Medicinal Plants of the World Volume 3

Chemical Constituents, Traditional and Modern Medicinal Uses

By Ivan A. Ross

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Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 eISBN: 1-59259-887-0 Preface

This volume of the series Medicinal Plants of the World: Chemical Constituents, Modern and Traditional Medicinal Uses contains information on 16 plant species and follows the same format as volumes 1 and 2. Some of the plants discussed in volume 3 may be considered controversial in their classification as “medicinal.” However, the Paracelsian dictum that “sola dosis fecit venenum” has been appreciated since ancient times, and throughout the ages many highly toxic materials used for lethal purposes have also found applications in modern medicine. It has been recognized that plants contain substances that are either harmful or toxic. However, it is wrong to think that there are plant toxins that are known or that are likely to have adverse effects on any and every form of life. A common feature of most toxic plants is that they are also known for their curative properties, and although they may provide the cure for an individual’s disease at one dose, they may cause the death of the same indi- vidual at another. Poisons are widespread in plants, and humans have tried to either get rid of them or convert them to their own advantage. By their very nature, poisons are biodynamic substances because they affect, or are intended to affect, the functioning of the victims’ body. This also means that they have been, and are, important sources of medicine. With such potentially dangerous substances, it also means that care in medication is essential, and it raises the question of the relationship between the toxic dose and the therapeutic dose. For full advan- tage to be taken of their properties, a combination of reliable sources of materials and effective methodologies is required to enable not only isolation of the substances responsible, but also the investigation of their mechanisms of action. As more sophisticated methods are evolved to elucidate their chemical and pharmacological natures, it will be possible to target more precisely the use of these substances as possible templates to produce medicinal agents. I am very grateful to a number of individuals for their valuable cooperation in this work. I owe sincere appreciation to Professor Ron Olowin of St. Mary’s College of California for granting me permission to use his photograph of Plantago ovata and Mr. Gary Monroe of Reno, Nevada for sharing his picture of Larrea tridentata. In work of this nature there is always room for improvement. Suggestions from readers are welcome and will be gratefully received. Ivan A. Ross

v Acknowledgments

I am very grateful to Dr. Diana E. Dyrda of the University of Agriculture, Lublin, Poland for her contribution in collecting data and working on the manuscript, and to Yvonne Gordon for editing this work. Also, to our families for enduring our absence in their lives.

vii Contents

Preface...... v Acknowledgments ...... vii List of Plants in Volumes 1 and 2 ...... xiii List of Color Plates ...... xv Abbreviations Used in the Chemical Constituents Section ...... xvii 1 Camellia sinensis ...... 1 Common Names ...... 1 Botanical Description ...... 2 Origin and Distribution ...... 2 Traditional Medicinal Uses ...... 2 Chemical Constituents ...... 2 Pharmacological Activities and Clinical Trials ...... 9 References...... 19 2 Cannabis sativa ...... 29 Common Names ...... 29 Botanical Description ...... 30 Origin and Distribution ...... 30 Traditional Medicinal Uses ...... 30 Chemical Constituents ...... 32 Pharmacological Activities and Clinical Trials ...... 39 References...... 94 3 Cocos nucifera ...... 117 Common Names ...... 117 Botanical Description ...... 118 Origin and Distribution ...... 119 Traditional Medicinal Uses ...... 119 Chemical Constituents ...... 120 Pharmacological Activities and Clinical Trials ...... 121 References...... 143 4 Coffea arabica ...... 155 Common Names ...... 155 Botanical Description ...... 156 Origin and Distribution ...... 156 Traditional Medicinal Uses ...... 156 Chemical Constituents ...... 157 Pharmacological Activities and Clinical Trials ...... 162 References...... 184 ix X CONTENTS

5 Daucus carota ...... 197 Common Names ...... 197 Botanical Description ...... 198 Origin and Distribution ...... 198 Traditional Medicinal Uses ...... 199 Chemical Constituents ...... 200 Pharmacological Activities and Clinical Trials ...... 202 References...... 210 6 Ferula assafoetida...... 223 Common Names ...... 223 Botanical Description ...... 224 Origin and Distribution ...... 224 Traditional Medicinal Uses ...... 224 Chemical Constituents ...... 225 Pharmacological Activities and Clinical Trials ...... 226 References...... 230 7 Hordeum vulgare ...... 235 Common Names ...... 235 Botanical Description ...... 235 Origin and Distribution ...... 236 Traditional Medicinal Uses ...... 236 Chemical Constituents ...... 237 Pharmacological Activities and Clinical Trials ...... 239 References...... 250 8 Larrea tridentata ...... 263 Common Names ...... 263 Botanical Description ...... 263 Origin and Distribution ...... 263 Traditional Medicinal Uses ...... 264 Chemical Constituents ...... 264 Pharmacological Activities and Clinical Trials ...... 265 References...... 268 9 Nicotiana tabacum ...... 271 Common Names ...... 271 Botanical Description ...... 272 Origin and Distribution ...... 272 Traditional Medicinal Uses ...... 272 Chemical Constituents ...... 273 Pharmacological Activities and Clinical Trials ...... 284 References...... 339 CONTENTS XI

10 Olea europaea...... 373 Common Names ...... 373 Botanical Description ...... 374 Origin and Distribution ...... 374 Traditional Medicinal Uses ...... 375 Chemical Constituents ...... 376 Pharmacological Activities and Clinical Trials ...... 379 References...... 388 11 Oryza sativa ...... 401 Common Names ...... 401 Botanical Description ...... 402 Origin and Distribution ...... 402 Traditional Medicinal Uses ...... 402 Chemical Constituents ...... 403 Pharmacological Activities and Clinical Trials ...... 405 References...... 410 12 Plantago ovata...... 419 Common Names ...... 419 Botanical Description ...... 419 Origin and Distribution ...... 420 Traditional Medicinal Uses ...... 420 Chemical Constituents ...... 420 Pharmacological Activities and Clinical Trials ...... 421 References...... 431 13 Saccharum officinarum ...... 437 Common Names ...... 437 Botanical Description ...... 438 Origin and Distribution ...... 438 Traditional Medicinal Uses ...... 438 Chemical Constituents ...... 439 Pharmacological Activities and Clinical Trials ...... 440 References...... 453 14 Serenoa repens ...... 461 Common Names ...... 461 Botanical Description ...... 461 Origin and Distribution ...... 462 Traditional Medicinal Uses ...... 462 Chemical Constituents ...... 462 Pharmacological Activities and Clinical Trials ...... 463 References...... 478 XII CONTENTS

15 Sesamum indicum ...... 487 Common Names ...... 487 Botanical Description ...... 488 Origin and Distribution ...... 488 Traditional Medicinal Uses ...... 488 Chemical Constituents ...... 490 Pharmacological Activities and Clinical Trials ...... 491 References...... 498 16 Zingiber officinale ...... 507 Common Names ...... 507 Botanical Description ...... 509 Origin and Distribution ...... 509 Traditional Medicinal Uses ...... 509 Chemical Constituents ...... 512 Pharmacological Activities and Clinical Trials ...... 517 References...... 543 Glossary...... 561 Cross Reference ...... 579 Index ...... 607 About the Author ...... 623 List of Plants Covered in Medicinal Plants of the World Volumes 1 and 2

Volume 1 1. Abrus precatorius 2. Allium sativum 3. Aloe vera 4. Annona muricata 5. Carica papaya 6. Cassia alata 7. Catharanthus roseus 8. Cymbopogon citratus 9. Cyperus rotundus 10. Hibiscus rosa-sinensis 11. Hibiscus sabdariffa 12. Jatropha curcas 13. Lantana camara 14. Macuna pruriens 15. Mangifera indica 16. Momordica charantia 17. Moringa pterygosperma 18. Persea americana 19. Phyllathus niruri 20. Portulaca oleracea 21. Psidium guajava 22. Punica granatum 23. Syzygium cumini 24. Tamarindus indica

xiii XIV CONTENTS

Volume 2 1. Allium cepa 2. Althaea officinalis 3. Anacardium occidentale 4. Ananas comosus 5. Angelica sinensis 6. Azadirachta indica 7. Echinacea angustifolia 8. Ephedra sinica 9. Eucalyptus globulus 10. Ginkgo biloba 11. Glycyrrhiza glabra 12. Hypericum perforatum 13. Laurus nobilis 14. Lycopersicon esculentum 15. Matricaria chamomilla 16. Morinda citrifolia 17. Musa sapientum 18. Myristica fragrans 19. Nelumbo nucifera 20. Pimpinella anisum 21. Ricinus communis 22. Tanacetum partheium 23. Tribulus terrestris 24. Vitex agnus-castus List of Color Plates

Color plates appear as an insert following page 270.

Plate 1. Camellia sinensis (see full discussion in Chapter 1). Plate 2. Cannabis sativa (see full discussion in Chapter 2). Plate 3. Cocos nucifera (see full discussion in Chapter 3). Plate 4. Coffea arabica (see full discussion in Chapter 4). Plate 5. Daucus carota (see full discussion in Chapter 5). Plate 6. Ferula assafoetida (see full discussion in Chapter 6). Plate 7. Hordeum vulgare (see full discussion in Chapter 7). Plate 8. Larrea tridentata (see full discussion in Chapter 8). Plate 9. Nicotiana tabacum (see full discussion in Chapter 9). Plate 10. Olea europaea (see full discussion in Chapter 10). Plate 11. Oryza sativa (see full discussion in Chapter 11). Plate 12. Plantago ovata (see full discussion in Chapter 12). Plate 13. Saccharum officinarum (see full discussion in Chapter 13). Plate 14. Serenoa repens (see full discussion in Chapter 14). Plate 15. Sesamum indicum (see full discussion in Chapter 15). Plate 16. Zingiber officinale (see full discussion in Chapter 16).

xv Abbreviations Used in Chemical Constituents Sections

Aer Aerial parts An Anther As Ash Bd Bud Bk Bark Bu Bulb Call Tiss Callus tissue Cr Crown Ct Coat Cx Calyx Cy Cotyledon Em Embryo EO Essential oil Ep Epidermis Fl Flower Fr Fruit Gel Jell Hu Hull Ju Juice Lf Leaf Lx Latex Pc Pericarp Pe Peel Pl Plant Pn Panicle Pt Part Pu Pulp Rh Rhizome Rt Root Sd Seed Sh Shoot St Stem Tr Trunk Tu Tuber Tw Twig

xvii CAMELLIA SINENSIS 1

1 Camellia sinensis L.

Common Names Aisiksikimi United States Te Denmark Caj Albania Te Faroe Islands Caj Croatia Te France Caj Czech Republic Te Italy Caj Hawaii Te Norway Caj Serbia Te Spain Cay Turkey Te Surinam Ceai Romania Te Switzerland Cha Brazil Te Wales Cha China Tea plant England Cha Hawaii Tea Australia Cha Japan Tea England Cha Pacific Islands Tea Guyana Cha Portugal Tea Hungary Chai Bulgaria Tea United States Chai Mozambique Tebusk Denmark Chai Russia Tebuske Sweden Chai Tanzania Tee Finland Chai Ukraine Tee Germany Chai Zaire Tee Netherlands Chaj Macedonia Tee South Africa Chayna roslina Ukraine Teepensas Finland Chinesischer tea Germany Tey The Isle of Man (Manx) Cunuc yacu Ecuador Teye Northern Sotho Eaj Czech Republic The France Eajovnik Czech Republic The Indonesia Herbata Poland The Malaysia Icayi Rwanda Thee Netherlands Ilitye Africa Theesoort Netherlands Itiye Africa Theestrauch Germany Oti United States Theestruik Netherlands Taa Germany Theler France Tae Ireland Ti Congo Te Cornwall Ti Samoa

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 1 2 MEDICINAL PLANTS OF THE WORLD

Ti Scotland Tra Vietnam Tii Greenland Tsa Philippines Tii New Zealand Yaku-q’oniwan Ecuador Tii Northwest Territories, Canada Zaya Turkmenistan

BOTANICAL DESCRIPTION TRADITIONAL MEDICINAL USES Camellia sinensis is an evergreen tree or India. Decoctions of the dried and fresh shrub of the THEACEAE family that grows buds and leaves are taken orally for head- to 10–15 m high in the wild, and 0.6–1.5 m ache and feverCS145. Powder or decoction of under cultivation. The leaves are short- the dried leaf is applied to teeth to prevent stalked, light green, coriaceous, alternate, tooth decayCS146. Fresh leaf juice is taken elliptic-obovate or lanceolate, with serrate orally for abortionCS155, and as a contracep- margin, glabrous, or sometimes pubescent tive and hemostaticCS147. beneath, varying in length from 5 to 30 cm, Mexico. Hot water extract of the leaf is and about 4 cm wide. Young leaves are pu- taken orally by nursing mothers to increase bescent. Mature leaves are bright green in milk productionCS148. color, leathery, and smooth. Flowers are Turkey. Leaves are taken orally to treat white, fragrant, 2.5–4 cm in diameter, soli- diarrheaCS149. tary or in clusters of two to four. They have China. Hot water extract of the dried leaf is numerous stamens with yellow anthers and taken orally as a sedative, an antihyperten- produces brownish-red, one- to four-lobed sive, and anti-inflammatoryCS108. capsules. Each lobe contains one to three Guatemala. Hot water extract of the dried spherical or flattened brown seeds. There leaf is used as eyewash for conjunctivitisCS154. are numerous varieties and races of tea. Kenya. Water extract of the dried leaf is There are three main groups of the cultivated applied ophthalmically to treat corneal forms: China, Assam, and hybrid tea, differ- opacitiesCS150. The infusion is used for ing in form. Camellia sinensis assamica, the chalzion and conjunctivitisCS151. source of much of the commercial tea crop Thailand. Hot water extract of the dried leaf of Ceylon is a tree that, unpruned, may attain is taken orally as a cardiotonic and a height of 15 m and has proportionally neurotonicCS152. Hot water extract of the longer, thinner leaves than typical species. dried seed is taken orally as an anti- CS153 ORIGIN AND DISTRIBUTION fungal . The cultivation and enjoyment of tea are CHEMICAL CONSTITUENTS recorded in Chinese literature of 2700 BC (ppm unless otherwise indicated) and in Japan about 1100. Through the Acetaldehyde, phenyl: Sh 1.52–1.78%CS100 Arabs, tea reached Europe about 1550. Acetaldehyde: LfCS073 Native to Assam, Burma, and the Chinese Acetamide, N-ethyl: LfCS027 province of Yunnan, it is highly regarded in Acetic acid: LfCS086 southern Asia and planted in India, south- Acetoin: LfCS068 ern Russia, East Africa, Java, Ceylon, Acetone: LfCS091 Sumatra, Argentina, and Turkey. China, Acetophenone, 2-4-dimethyl: LfCS027 India, Indonesia, and Japan produced about Acetophenone, 3-4-dimethoxy: LfCS027 a half of the total world production. Acetophenone, para-ethyl: LfCS027 CAMELLIA SINENSIS 3

Acetophenone: Headspace volatileCS044 Benzene, 1-2-5-trihydroxy: LfCS003 Actinidiolide, dihydro: Lf EOCS132 Benzene, 1-2-dimethoxy: LfCS077 Afzelechin, epi, (–): Lf 350CS084 Benzene, 1-2-dimethoxy-4-ethyl: LfCS077 Afzelechin, epi, 3-O-gallate (–): Lf 37CS005 Benzene, 1-2-dimethoxy-4-methyl: LfCS077 Afzelechin, epi, 3-O-gallate (4-b-6)-epi, Benzene, 1-3-diacetyl: LfCS027 gallocatechin-3-O-gallate: Lf 5.6CS008 Benzene, 1-4-diacetyl: LfCS027 Allantoic acid: PlCS033 Benzoic acid: Headspace volatileCS044 Allantoin: PlCS033 Benzothiazole, 2-methyl: LfCS036 Aluminium inorganic: LfCS028 Benzothiazole: LfCS036 Amyrin, D: Sd oilCS095 Benzoxazole: LfCS036 Amyrin, E: Sd oil 76CS095 Benzyl alcohol: Lf EO 1.01–1.6%CS136, Aniline, N-ethyl: LfCS027 Headspace volatileCS044, LfCS091, Aniline, N-methyl: LfCS027 Sh 0.09–0.14%CS100 Aniline: LfCS027 Benzyl butyrate: LfCS002 Apigenin: LfCS108 Benzyl ethyl ketone: LfCS002 Apigenin-6-8-di-C-E-D-arabinopyranosyl: Benzylaldehyde, 2-methyl: LfCS002 Lf 20CS156 Benzylaldehyde, 4-methoxy: LfCS002 Apigenin-6-8-di-C-glucoside: ShCS096 Benzylaldehyde: Headspace volatileCS044, Arbutin: Lf 0.2CS078 LfCS077, Sh 0.21–0.23%CS100 Aromadenrin: ShCS094 Benzylamine: N-N-dimethyl: LfCS027 Ascorbic acid: ShCS038, Lf 0.257%CS048 Bicyclo(4.3.0)non-8-en-7-one, 1-5-5-9- Assamicain A: Lf 58.2CS007 tetramethyl: LfCS002 Assamicain B: Lf 76.6CS007 Brassicasterol: Sd oilCS134 Assamicain C: Lf 33.6CS007 Brassinolide, 28-homo, 6-keto: LfCS135 Assamsaponin A: Sd 0.01%CS021 Brassinolide, 28-nor, 6-keto: LfCS135 Assamsaponin B: Sd 28.3CS021 Brassinolide, 28-nor: LfCS135 Assamsaponin C: Sd 36.5CS021 Brassinolide, 6-keto: LfCS135 Assamsaponin D: Sd 26.1CS021 Brassinolide: Lf 0.0046 ppbCS089 Assamsaponin E: Sd 11.1CS021 Brassinone, 24(S)-ethyl: Lf 30 ng/65 kgCS110 Assamsaponin F: Sd 14.1CS021 Brassinone, 24-ethyl: LfCS089 Assamsaponin G: Sd 79.1CS021 Brassinone: Lf 130 ng/65 kgCS110 Assamsaponin H: Sd 13.4CS021 Butan-2-ol: LfCS068 Assamsaponin I: Sd 98.5CS021 Butyrate, ethyl-3-hydroxy: LfCS068 Astragalin: LfCS139 Butyroin: LfCS068 Avicularin: LfCS058 Butyrospermol: Sd oilCS095 Barrigenol, A-1: PlCS118 Caffeine: Lf 0.381–9.9%CS114,CS049, ShCS038, Pl, Barringtogenol C, 3-O-E-D-galacto- Call TissCS050, SdCS093, Sd Ct, Peduncle, pyranosyl(1-2) E-D-xylopyranosyl PcCS102, Fl bud, Stamen, Pistil, FlCS107, An (1-2)D-l-arabinopyranosyl(1-3)E-D- 0.05–6.77 ppt, Stem call 0.64 pptCS099, glucuronopyranosyl-21-O-cinnamoyl- PetalCS117, FrCS037 16-22-di-O-acetyl: LfCS013 Camellia galactoglucan: LfCS067 Benzene, 1-2-3-trimethoxy: LfCS077 Camellia polysaccharide: LfCS122 Benzene, 1-2-3-trimethoxy-5-ethyl: LfCS077 Camellia saponin B, deacyl: LfCS081 Benzene, 1-2-3-trimethoxy-5-methyl: LfCS077 Camellia sinensis polysaccharide TSA: LfCS012 Benzene, 1-2-4-trihydroxy: LfCS003 Camellianin A: LfCS108 4 MEDICINAL PLANTS OF THE WORLD

Camellianin B: LfCS108 Catechin-3-O-gallate, epi(–): Lf 0.0086– Camelliaside A: Sd 656–2733.3CS011,CS119 6.6%CS053,CS049 Camelliaside B: Sd 291–3026.6 CS011,CS119 Catechin-gallate, (+): LfCS082 Camelliaside C: Sd 2.5CS011 Catechin-gallate: LfCS042 Campesterol: Sd oilCS134 Catechol, (+): PlCS138 Carvacrol: LfCS002 Catechol, epi(–): ShCS128, PlCS138 Castasterone: Lf 7.2 mg/65 kgCS110 Catechol, epi, gallate(–): ShCS128 Catechin-(4-D-8)-epi-gallocatechin: Catechol, epi-gallo(–): ShCS128 Lf 45.4CS008 Catechol, epi-gallo, gallate(–): ShCS128 Catechin-(4-D-8)-epi-gallocatechin-3- Catechol, gallo, (+): ShCS128 gallate: Lf 45.4CS008 Chasaponin: PlCS035 Catechin-(4-E-8)-epi-gallocatechin-3- Chlorogenic acid: Call TissCS087, LfCS139 gallate, epi: Lf 20.8CS008 Chondrillasterol: Sd oilCS130 Catechin, (+): Lf 0.0017–2.9%CS053,CS049, Citric acid: LfCS086 CS003 Call TissCS060. St callCS099, ShCS038, Cresol, meta: Lf CS003 An, StCS099 Cresol, ortho: Lf CS003 Catechin, epi (–): Lf 0.004–6.8%CS053,CS049, Cresol, para: Lf CS100 CS002 Call TissCS060, ShCS038, St call 0.07 pptCS099 Cyclocitral, E: Sh 0.08–0.1% , Lf Catechin, epi, 3-O-para-hydroxy-benzoate Cyclohex-2-en-1-4-dione, 2-6-6-trimethyl: CS002 (–): Lf 3.6CS005 Lf Catechin, epi, epi-gallo-catechin(4-E-8)- Cyclohex-2-en-1-one, 2-6-6-trimethyl: CS002 3-O-galloyl: Lf 50CS092 Lf CS002 Catechin, epi-gallo (–), 3-O-para- Damascenone, E: Lf CS002 coumaroate: Lf 83.3CS140 Damascone, D: Lf CS002 Catechin, epi-gallo (–): Lf 3269CS140 Damascone, E: Lf CS095 Catechin, epi-gallo, 3-3'-di-O-gallate(–): Dammaridienol: Sd oil 30 Deca-trans-2-cis-4-dien-1-al: LfCS002 LfCS140 Deca-trans-2-en-1-al: LfCS002 Catechin, epi-gallo, 3-4'-di-O-gallate(–): Dehydrogenase, NADP-dependent-alco- LfCS140 hol: SdCS031 Catechin, epi-gallo, 3-O-gallate (–): Demmarenol, 24-methylene: Sd oilCS095 Lf 0.8718%CS140 Diphenylamine: Lf 0.013–1.17%CS098 Catechin, epi-gallo, gallate(–): St call 0.02 Dodeca-trans-2-trans-6-10-trien-1-al, pptCS099, LfCS109 4-ethyl-7-11-dimethyl: LfCS002 Catechin, epi-gallo: LfCS140 Erucid acid: Sd oil LfCS134 Catechin-3-O-(3'-O-methyl)-gallate, Ethyl acetate: LfCS091 epi(–): Lf 0.08%CS010 Ethyl lactate: LfCS068 Catechin-3-O-(3-O-methyl)-gallate, Eugenol: Fr EOCS030 epi(–): Lf 70.6-96.2CS005,CS140 Euphol: Sd oilCS095 O O Catechin-3- -(4- -methyl)-gallate, Farnesene, , trans-trans: Lf EOCS115 CS005 D epi(–): Lf 16 Farnesol: LfCS091 Catechin-3-O-gallate-(4-E-6)-epi- Fluoride inorganic: Lf 188CS143 gallocatechin-3-O-gallate, epi: Fluorine, inorganic: LfCS043 CS008 Lf 5.8 Furan, 2-acetyl: LfCS002 Catechin-3- O-gallate-(4-E-8)-epi- Furan-3-one, tetrahydro, 2-methyl: LfCS068 CS008 gallocatechin-3-O-gallate, epi: Lf 3.6 Furocoumarin, angular, 4-hydroxy-2'- CS084 Catechin-3-O-gallate, (+): Lf 0.011% methoxy: LfCS014 CAMELLIA SINENSIS 5

Gadoleic acid: Sd oilCS134 Galloyl-E-D-glucose, 1-4-6-tri-O: Gallic acid: LfCS051 Lf 0.01%CS010 Gallocatechin gallate, (–): Lf 0.188%CS112 Galloylcatechin, epi (–): LfCS054 Gallocatechin gallate, (+): LfCS082 Geranic acid, trans: LfCS002 CS125 Gallocatechin gallate, epi(–): Lf Geraniol E-D-glucopyranoside: ShCS113 Gallocatechin gallate, epi(+): LfCS123 Geraniol: ShCS113, Lf EO 3.16-25.46%CS136, Gallocatechin-(4-D-8)-epi-catechin: LfCS109 Lf 36.6CS008 Geranyl-E-primeveroside, 8-hydroxy: Gallocatechin, (–): LfCS056 Lf 2.08CS018 Gallocatechin, (+): Lf 0.01–12.8%CS053,CS049 Germanicol: Sd oil 25CS095 Gallocatechin, epi(+): Lf 1.1%CS083 Germanicum inorganic: LfCS120 Gallocatechin, epi, (–): Lf 0.088- Gibberellin A-1: EndospermCS004 16.8%CS005,CS049, ShCS038 Gibberellin A-19: EndospermCS004 Gallocatechin, epi, (4-E-8)-epi-catechin- Gibberellin A-20: EndospermCS004 CS008 3-)-gallate: Lf 27.6 Gibberellin A-3, iso: EndospermCS004 Gallocatechin, epi, 3-O-cinnamate(–): Gibberellin A-3: EndospermCS004 CS005 Lf 13.2 Gibberellin A-38: EndospermCS004 Gallocatechin, epi, 3-3'-di-O-gallate(–): Gibberellin A-44: EndospermCS004 CS005 Lf 9 Gibberellin A-8: EndospermCS004 Gallocatechin, epi, 3-4'-di-O-gallate(–): Gibberellin A-S: EndospermCS004 CS005 Lf 9 Glucogallin, E: Lf 28.4CS008 Gallocatechin, epi, 3-O-gallate(–): Glucose, E-D, 1-0-galloyl-4-6-(–)- CS005 Lf 0.714% hexahyroxy-diphenoyl: Lf 30CS092 Gallocatechin, epi, 3-O-gallate-(4- -6)- CS092 E Glucose, -D, 1-4-6-tri-O-galloyl: Lf 5 CS008 E epi-catechin-3-O-gallate: Lf 4.2 Glutamic acid: N-para-coumaryl: LfCS133 Gallocatechin, epi, 3-O-gallate-(4-E-8)- Heptan-1-al: Sh 0.02–0.03%CS100 epi-catechin-3-O-gallate: Lf 44CS008 Heptan-2-ol: LfCS068 Gallocatechin, epi, 3-O-para- Heptan-2-one, 5-iso-propyl: LfCS002 coumaroate(–): Lf 38.4CS005 Heptan-2-one: LfCS002 Gallocatechin, epi, 8-C-ascorbyl-3-O- Heptan-3-ol: LfCS068 gallate: Lf 11.2CS008 Hepta-trans-2-trans-4-dien-1-al: Gallocatechin, epi: Lf 1.0867%CS101 Sh 0.06–0.1%CS100 Gallocatechin-3-5'-di-O-gallate, epi(–): Hept-trans-2-en-1-al: LfCS002 Lf 0.06%CS008 Hex-1-en-3-ol: LfCS068 Gallocatechin-3-O-(3'-O-methyl)-gallate, Hex-2-en-1-al, 5-methyl-2-phenyl: LfCS002 epi(–):Lf 38CS084 Hex-5-en-4-olide, 4-methyl: LfCS002 Gallocatechin-3-O-gallate (–): LfCS079 Hexadecane, N: LfCS091 Gallocatechin-3-O-gallate (+): LfCS157 Gallocatechin-3-O-gallate (4- -8) epi- Hexan-1-al: ChloroplastCS129, E CS100 catechin-gallate, epi: Lf 0.06%CS010 Sh 0.55–1.03% CS002 Gallocatechin-3-O-gallate, epi(–): Hexan-1-ol, 2-ethyl: Lf CS068 Lf 0.0328–21.3%CS053,CS049, ShCS038 Hexan-2-ol: Lf CS002 Gallocatechin-3-O-para-coumaroate, epi Hexa-trans-2-cis-4-dien-1-al: Lf CS034 (–): LfCS010 Hex-cis-3-en-1-al: Lf 370 CS091 Gallocatechin-gallate, (–): LfCS042 Hex-cis-3-en-1-ol acetate: Lf CS091 Gallocateuchin-3-O-gallate, epi (–): Hex-cis-3-en-1-ol butyrate: Lf CS091 Lf 5.33%CS010 Hex-cis-3-en-1-ol caproate: Lf 6 MEDICINAL PLANTS OF THE WORLD

Hex-cis-3-en-1-ol formate: LfCS002 Kaempferol: LfCS026, ShCS094 Hex-cis-3-en-1-ol hexanoate: Kaempferol-3-O-galactosyl-rhamnosyl- Sh 0.02–0.03%CS100 glucoside: LfCS058 Hex-cis-3-en-1-ol hex-trans-2-enoate: Kaempferol-3-O-glucosyl(1-3)rhamnosyl LfCS002 (1-6)galactoside: LfCS009 Hex-cis-3-en-1-ol propionate: LfCS002 Kaempferol-3-O-glucosyl-rhamnoside: Hex-cis-3-en-1-ol, E-D-glucoside: LfCS076 LfCS058 Hex-cis-3-en-1-ol: LfCS025, Lf EO 2.15– Kaempferol-3-O-glucosyl-rhamnosyl-galac- 15%CS136, Sh 0.09–0.13%CS100 toside: LfCS058 Hex-trans-2-en-1-al: LfCS065, Lf EO 1.13– Lauric acid: Sd oilCS134 25.48%CS136, Sh 2.09–3.1%CS100 Ligustrazine: LfCS027 Hex-trans-2-en-1-ol: Sh 0.04–0.06%CS100 Limonene: LfCS068 Hex-trans-2-enyl acetate: LfCS002 Linalool E-D-glucopyranoside: ShCS113 Hex-trans-2-enyl butyrate: LfCS002 Linalool oxide A: LfCS091 Hex-trans-2-enyl formate: LfCS002 Linalool oxide B: LfCS091 Hex-trans-2-enyl hexanoate: LfCS002 Linalool oxide C: LfCS091 Hex-trans-2-enyl propionate: LfCS002 Linalool oxide I: LfCS077 Hex-trans-3-enyl butyrate: LfCS002 Linalool oxide II: LfCS077 Hex-trans-3-enyl hex-cis-3-enoate: LfCS002 Linalool oxide III: LfCS077 Hex-trans-3-enyl propionate: LfCS002 Linalool oxide IV: LfCS077 Hex-trans-3-enyl-2-methyl butyrate: LfCS002 Linalool oxide: Headspace volatileCS044 Hexyl butyrate: LfCS002 Linalool, (R): LfCS074 Hexyl formate: LfCS002 Linalool, cis, oxide (furanoid): LfCS074 Hyperoside: LfCS058 Linalool, cis, oxide (pyranoid): LfCS074 Indole: LfCS109 Linalool, cis, oxide: Sh 0.06–0.16%CS100 Indole-3-methyl-ethanolate: LfCS015 Linalool, trans, oxide (furanoid): LfCS074 Inositol, myo, 2-O-E-L-arabinopyranosyl: Linalool, trans, oxide (pyranoid): LfCS074 Lf 0.4%CS116 Linalool, trans, oxide: Lf EO 3.18– Inositol, myo, 2-O-E-L-arabinopyranoside: 4.23%CS136, Sh 0.15–0.43%CS100 Lf 0.4%CS106 Linalool: LfCS121, Headspace volatileCS044, Inositol, myo, 2-O-E-L-arabinoside: LfCS077 ShCS113, Lf EO 8.2–19.84CS136 Ionone, D: Sh 0.03–0.05%CS100, LfCS068 Linoleic acid: Sd oilCS134, LfCS069 Ionone, E, 1'-2'-dihydro, 1'-2'-epoxy: Linolenic acid: LfCS069 Lf EOCS132 Loliolide: Lf EOCS132 Ionone, E, 1'-2'-dihydroxy, 1'-2'-threo: Lupeol: Sd oilCS062 Lf EOCS132 Malic acid: LfCS086 Ionone, E, 3'-oxo: Lf EOCS132 Malonic acid: LfCS086 Ionone, E: Lf EO 0.02–0.31%CS136, Menthol: LfCS068 Sh 0.17–0.29%CS100 Methionine, S-methyl: Lf 7–24.5 mg%CS158 Jasmonate, dihydro, methyl-trans: LfCS002 Methylamine: Lf 50CS141 Jasmone, cis: Lf EO 0.05–0.2%CS136 Morine: LfCS045 Jasmone: LfCS091 Myrcene: LfCS091 Jasmonic acid, (1R, 2R), (–): LfCS080 Myricetin: LfCS026 Jasmonic acid, (1R, 2S), (+): LfCS080 Myristic acid: Sd oilCS134, LfCS069 Jasmonic acid: PollenCS137, AnCS137, LfCS091 Naringenin: ShCS094 Kaempferitin: LfCS139 Naringenin-fructosyl-glucoside: LfCS063 CAMELLIA SINENSIS 7

Neral: LfCS002 Phenylethanol, 2: LfCS091 Nerolidol: LfCS109, Sh 0.08–0.12%CS100 Phenylethyl alcohol, 2: Sh 0.1–0.13%CS100 CS141 NH3 inorganic: Lf 400 Phenylethyl alcohol: Headspace Nicotiflorin: LfCS133 volatileCS044 Nicotine: Lf 15.5 ng/gCS047 Pheophytin A: LfCS088 Nonal-1-al: Sh 0.04–0.06%CS100 Pheophytin B: LfCS088 Nonal-2-ol: LfCS068 Pinene, a: LfCS068 Nonan-2-one: LfCS002 Pipecolic acid, L: FrCS030 Nona- trans-2-cis-4-dien-1-al: LfCS002 Pipecolic acid: LfCS037, FrCS037 Nona- trans-2-cis-6-dien-1-al: LfCS002 Polysaccharide T-B: LfCS111 Nona-trans-2-en-1-al: LfCS002 Procyanidin B-2 3'-O-gallate: Lf 166.7CS140 Nona-trans-2-trans-4-dien-1-al: LfCS002 Procyanidin B-2, 3-3'-di-O-gallate: Lf Oct-1-en-3-ol: LfCS068 0.00084–0.13%CS008,CS010 Octa-1-5-7-trien-3-ol, 3(S)-7-dimethyl: Procyanidin B-2: Lf 5.8CS008 Lf EOCS132 Procyanidin B-3, 3-O-gallate: LfCS070 Octa-1-5-diene-3-7-diol, 3(S)-7-dimethyl, Procyanidin B-3: Lf 0.21%CS010 (+): Lf EOCS132 Procyanidin B-4, 3'-O-gallate: Lf 141CS140 Octan-2-one: LfCS002 Procyanidin B-4: Lf 46.6CS008 Octan-3-ol: LfCS068 Procyanidin B-5, 3-3'-di- O-gallate: Lf 2.6CS008 Octanoate, ethyl: LfCS002 Procyanidin C-1: LfCS010 Octanoate, methyl: LfCS002 Prodelphinidin A-2, 3'-O-gallate: Lf 4.4CS008 Octa-trans-2-cis-4-dien-1-al: LfCS002 Prodelphinidin B-2, 3'-O-gallate: Lf 238CS008 Octa-trans-2-trans-4-dien-1-al: LfCS002 Prodelphinidin B-2, 3-3'-di-O-gallate: Octa-trans-3-cis-5-dien-2-one: LfCS002 Lf 18.4CS008 Oct-trans-2-enoic acid: LfCS002 Prodelphinidin B-2,3'-O-gallate: Lf 147.4CS140 Oleic acid: Sd oilCS134, LfCS069 Prodelphinidin B-4, 3'-O-gallate: Oolonghomobisflavan A: Lf 10.6CS008 Lf 63.8–1200CS008,CS010 Oolonghomobisflavan B: Lf 7.2CS008 Prodelphinidin B-4: Lf 56.8–800CS008,CS010 Oolongtheanin: Lf 1.8CS006 Prodelphinidin B-5, 3-3'-di-O-gallate: Oxalic acid: Lf 1.0%CS144 Lf 29.8CS008 Palmitic acid: Sd oilCS134, LfCS069 Proline, hydroxy: LfCS037, FrCS037 Pedunculagin: LfCS041 Propionamide, N-ethyl: LfCS027 Pent-1-en-3-ol: LfCS068, Sh 0.21–0.23%CS100 Propiophenone, 2-4-dimethyl: LfCS027 Pent-2-en-1-al, 4-methyl-2-phenyl: LfCS002 Propiophenone, para-ethyl: LfCS027 Pentadecane, 2-6-10-14-tetramethyl: LfCS091 Prunasin: LfCS059 Pentan-1-ol: Sh 0.06–0.11%CS100 Pyrazine, 2-3-dimethyl: LfCS027 Pentan-2-ol, methyl: LfCS068 Pyrazine, 2-5-dimethyl: LfCS027 Pentan-3-ol, methyl: LfCS068 Pyrazine, 2-6-dimethyl: LfCS027 Pentanoic acid: 2-amino-5-(N-ethyl- Pyrazine, 2-ethyl-3-5-dimethyl: LfCS027 carboxamido): Lf 120CS105 Pyrazine, 2-ethyl-3-6-dimethyl: LfCS036 Pent-cis-2-en-1-ol: Sh 0.1-0.14%CS100 Pyrazine, 2-ethyl-5-methyl: LfCS027 Pent-cis-3-en-1-al: LfCS002 Pyrazine, 2-ethyl-6-methyl: LfCS027 Phenol: LfCS003 Pyrazine, ethyl: LfCS027 Phenyl, acetate, ethyl: LfCS002 Pyrazine, methyl: LfCS027 Phenyl, acetate, hexyl: LfCS002 Pyrazine, trimethyl: LfCS027 Phenylacetic acid: LfCS002 Pyridine, 2-5-dimethyl: LfCS027 8 MEDICINAL PLANTS OF THE WORLD

Pyridine, 2-6-dimethyl: LfCS027 Tannic acid: Lf CS126 Pyridine, 2-acetyl: LfCS036 Tannin: LfCS024 Pyridine, 2-ethyl: LfCS027 Taraxasterol, Pseudo: Sd oilCS095 Pyridine, 2-ethyl-5-methyl: LfCS036 Taraxerol: Sd oil 20CS095 Pyridine, 2-ethyl-6-methyl: LfCS036 Tartaric acid: LfCS086 Pyridine, 2-methyl: LfCS027 Tea polysaccharides: LfCS055 Pyridine, 2-phenyl: LfCS027 Teasaponin B-1: LfCS057 Pyridine, 3-ethyl: LfCS027 Teasaponin B-2: LfCS040 Pyridine, 3-methoxy: LfCS036 Teasaponin B-3: LfCS040 Pyridine, 3-methyl: LfCS027 Teasaponin B-4: LfCS040 Pyridine, 3-N-butyl: LfCS036 Teasterone: LfCS090 Pyridine, 3-phenyl: LfCS027 Tectoquinone: RtCS039 Pyridine, 4-methyl: LfCS027 Terpineol, 4: LfCS002 Pyridine, 4-vinyl: LfCS036 Terpineol, D: Sh 0.07–0.1%CS100, LfCS068 Pyridine: LfCS027 Theacitrin A: Lf 0.08%CS016 Quercetin: LfCS026, ShCS094 Theaflagallin, epi, 3-O-gallate: Lf 17CS008 Quercetin-3-glucosyl(1-3)rhamnosyl Theaflagallin-3-O-gallate, epi: Lf 0.02%CS010 (1-6)galactoside: LfCS009 Theaflavate B: LfCS019 Quercetin-fructosyl-glucoside: LfCS063 Theaflavic acid, epi, gallate: LfCS064 Quercimeritrin: LfCS026 Theaflavic acid, epi: LfCS064 Quercitrin, iso: LfCS133 Theaflavin, digallate: LfCS071 Quercitrin: LfCS058 Theaflavin, iso: 3'-O-gallate: Lf 25CS019 Quinic acid, (–): LfCS104 Theaflavin, monogallate A: LfCS071 Quinoline, 2-4-dimethyl: LfCS027 Theaflavin, monogallate B: LfCS071 Quinoline, 2-6-dimethyl: LfCS027 Theaflavin, monogallate: LfCS124 Quinoline, 2-methyl: LfCS036 Theaflavin, neo: 3-O-gallate: Lf 30CS019 Quinoline, 3-N-butyl: LfCS027 Theaflavin: LfCS046, Sh 1.12–1.40%CS100, Quinoline, 3-N-propyl: LfCS027 FlCS159 Quinoline, 4-8-dimethyl: LfCS027 Theaflavin-3'-gallate: LfCS046 Quinoline, 6-methyl: LfCS036 Theaflavin-3'-O-gallate: FlCS159, Rutin: LfCS058 Lf 18.6–800CS008,CS010 Safranal: LfCS002 Theaflavin-3-3'- digallate: FlCS159 Safrole: LfCS002 Theaflavin-3-3'-di-O-gallate: Salicylic acid: Headspace volatileCS044 Lf 18.2–300CS008,CS010 Sesquiphelandrene, b: LfCS109 Theaflavin-3-gallate: LfCS046 Sitosterol, E: Sd oilCS134 Theaflavin-3-O-gallate: FlCS159, Spinasterol, 22-23-dihydro: Sd oilCS131 Lf 6-700CS008,CS010 Spinasterol, D, E-D-glucoside: RtCS039 Theaflavin-monogallate A: LfCS085 Spinasterol, D: RtCS039 Theaflavin-monogallate B: LfCS085 Spinasterol: Sd oilCS131 Theaflavonin, degalloyl: Lf 17.5CS010 Spinasterone, 22-23-dihydro: Sd oilCS131 Theaflavonin: Lf 11.5CS010 Spinasterone: Sd oilCS131 Theanaphthoquinone: LfCS023 Stearic acid: Sd oilCS134 Theanine: LfCS052, Call TissCS066, Seedling Rt Stigmasterol: Sd oilCS134 109, Sh 63, Cy 577 mg%CS097, St Call Strictinin: Lf 0.01%CS010 0.37 ppt, An 1.6-2.9%, St 34.9 pptCS099 Succinic acid: LfCS086 Thearubigin: Sh 13.56–15.74%CS100, LfCS139 CAMELLIA SINENSIS 9

Theasapogenol A, 22-O-angeloyl: SdCS020 Undeca-trans-2-en-1-al: LfCS002 Theasapogenol B, 22-O-angeloyl: SdCS020 Urea: PlCS033 Theasapogenol E, 22-O-angeloyl: SdCS020 Vitamin K-1: Lf 3.1-16.5CS072, Theasaponin B-1: LfCS081 Vitexin, iso, 2''-O-glucoside: LfCS103 Theasaponin E-1: Sd 75CS017 Vitexin: ShCS096 Theasaponin E-2: Sd 10CS017 Vomifeliol, dehydro: Lf EOCS132 CS061 Theasaponin, gluco: Sd PHARMACOLOGICAL ACTIVITIES Theasaponin: SdCS127, LfCS142 AND CLINICAL TRIALS Theasinensin A: Lf 0.01866–4.8718%CS006,CS140 Alcohol extract of Theasinensin B: Lf 128.2–600CS140,CS010 Antibacterial activity. black tea, assayed on Salmonella typhi and Theasinensin C: Lf 70.2 CS006 Salmonella paratyphi A, was active on all Theasinensin D: Lf 17.6CS006 strains of Salmonella paratyphi A, and only Theasinensin E: Lf 14.4CS006 42.19% of Salmonella typhi strains were Theasinensin F: Lf 19.6CS006 inhibited by the extractCS048. Hot water Theasinensin G: Lf 8CS006 extract of the dried entire plant and the tan- Theaspirane, dihydro, 6-7-epoxy: LfCS002 nin fraction, on agar plate, were active on Theaspirane, dihydro, 6-hydroxy: LfCS002 CS002 Escherichia coli, Pseudomonas aeruginosa, and Theaspirane: Lf CS160 CS132 Staphylococcus aureus . Theaspirone: Lf EO Catechin, adminis- CS029 CS050 Anticancer activity. Theobromine: Lf , Call Tiss , Sd, tered to pheochromocytoma cells in cell CS102 CS107 Pc , Fl Bd, Fl , Petal, Pistil, culture, was active. The cells were incu- CS117 CS099 CS033 Stamen , An, St, St Call , Pl , bated with different concentrations of cat- CS102 Seedcoat echin at short-term (2 days) and long-term CS008,CS010 Theogallin: Lf 6-55.5 (7 days) in Dulbecco’s modified Eagle CS093 Theophylline: Sd medium. The activity of superoxide dismu- CS036 Thiazole, 2-4-5-trimethyl: Lf tase was measured and its mRNA assayed by CS036 Thiazole, 2-4-dimethyl: Lf Northern blotting. After incubation for 2 CS036 Thiazole, 2-4-dimethyl-4-ethyl: Lf days, catechin significantly increased the Thiazole, 2-5-dimethyl: LfCS036 activity of copper/zinc superoxide dismu- Thiazole, 5-methyl: LfCS036 tase. However, it did not produce significant Thymol: LfCS002 effect at 7 days. The magnesium superoxide Tirucalla-7-24-dien-3-E-ol, 5-D: dismutase activity produced significant Sd oil 12CS062 changes in both short- and long-term treat- Tirucalla-7-24-dien-3-E-ol: Sd oilCS095 ment groups. The amount of mRNA also Tirucallol: Sd oilCS095 showed similar changesCS040. Toluidine, ortho: LfCS027 Anticarcinogenic activity. The anticar- Triacontan-1-ol: LfCS075 cinogenic activity of tea phenols has been Tricetin: ShCS094 demonstrated in rats and mice transplant- Tricetinidin: LfCS139 able tumors, carcinogen-induced tumors in Trifolin: LfCS058 digestive organs, mammary glands, hepato- Tr-saponin A: Rt 2.2CS022 carcinomas, lung cancers, skin tumors, leu- Tr-saponin B: Rt 5.9CS022 kemia, tumor promotion, and metastasis. Tr-saponin C: Rt 2.8CS022 The mechanisms of this effect indicated Typhasterol: LfCS090 that the inhibition of tumors may be the Umbelliferone: LfCS032 result of both extracellular and intracellular Undeca-2-one, 6-10-dimethyl: LfCS002 mechanisms indicating the modulation of 10 MEDICINAL PLANTS OF THE WORLD metabolism, blocking or suppression, modu- blotting methodsCS020. Green and black tea, lation of DNA replication and repair effects, administered orally to hairless mice in the promotion, inhibition of invasion and absence of any chemical initiators or pro- metastasis, and induction of novel mechan- moters, resulted in significantly fewer skin ismsCS002. The association of green tea and papillomas and tumors induced by UVA cancer has been investigated in 8552 Japa- and UVB light. Black tea however, provided nese women 40 years of age. After 9 years of better protection against UVB-induced follow-up study, 384 cases of cancer were tumors than green tea. Black tea consump- identified. There was a negative association tion was associated with a reduction in the between cancer incidence and green tea number of sunburn cells in the epidermis of consumption, especially among females mice 24 hours after irradiation, although consuming more than 10 cups of tea a day. there was no effect of green tea. Other indi- A slow down in increases of cancer inci- ces of early damage such as necrotic cells or dence with age was observed among females mitotic figures were not affected. Neutro- who consumed more than 10 cups phil infiltration as a measure of skin redness dailyCS010. Tea, taken by lung cancer was slightly lowered by tea consumption in patients at a dose of two or more cups per the UVB groupCS023. Epigallocatechin-3- day, reduced the risk by 95%. The protected gallate, in cell culture, activated proMMP- effect was more evident among Kreyberg I 2 in U-87 glioblastoma cells in the presence tumors (squamous cell and small cells) and of concanavalin A or cytochalasin D, two among light smokersCS011. The green tea potent activators of MT1-MMP, resulted in polyphenols, epi-gallocatechin-3-gallate, proMMP-2 activation that was correlated applied topically to human skin, prevented with the cell surface proteolytic processing penetration of ultraviolet (UV) radiation. of Mt1-MMP to it’s inactive 43 kDa form. This was demonstrated by the absence of Addition of epigallocatechin-3-gallate immunostaining for cyclobutane pyrimidine strongly inhibited the MT1-MMP-driven dimers in the reticular dermis. Topical migration in the cells. The treatment of administration to the skin of mice inhi- cells with non-cytotoxic doses of epigal- bited UVB-induced infiltration of CDIIb+ locatechin-3-gallate significantly reduced cells. The treatment also results in re- the amount of secreted pro MMP-2, and led duction of the UVB-induced immuno- to a concomitant increase in intracellular regulatory cytokine interleukin (IL)-10 in levels of that protein. The effect was similar the skin and draining lymph nodes, and an to that observed using well-characterized elevated amount of IL-12 in draining lymph secretion inhibitors such as brefeldin A and nodesCS015. Green tea extract, in human manumycin, indicative that epigallo- umbilical vein endothelial cells, did not catechin could also potentially act on intra- affect cell viability but significantly reduced cellular secretory pathwaysCS044. Green tea cell proliferation dose-dependently and pro- polyphenols, at a dose of 30 mg/mL, inhi- duced a dose-dependent accumulation of bited the photolabeling of P-glycoprotein cells in the gastrointestinal phase. The de- (P-gp) by 75% and increased the accumula- crease of the expression of vascular tion of rhodamine-123 in the multidrug-re- endothelial growth factor receptors fms-like sistant cell line CH(R)C5. This result tyrosine kinase and fetal liver kinase-I/ indicated that green tea polyphenols inter- kinase insert domain containing receptor in act with P-gp and inhibited its transport the cell culture by the extract was detected activity. The modulation of P-gp was a with immunohistochemical and Western reversible process. Epigallocatechin-3-gal- CAMELLIA SINENSIS 11 late potentiates the cytotoxicity of vinblas- nidermatum, and Rhizopus stoloniferCS162. tine in CH(R)C5 cells. The inhibitory ef- Saponin fraction of the leaf on agar plate fect on P-gp was also observed in human was active on Microsporum audonini, Caco-2 cellsCS045. minimum inhibitory concentration (MIC) Anticataract activity. Tea, administered in 10 mg/mL; Epidermophyton floccosum and culture to enucleated rat lens, reduced the Trichophyton mentagrophytes, MICs 25 Pg/ incidence of selenite cataract in vivo. The mLCS165. rat lenses were randomly divided into nor- Antihypercholesterolemic activity. Tea mal, control and treated groups and incu- supplemented with vitamin E, administered bated for 24 hours at 37qC. Oxidative stress to male Syrian hamsters, reduced plasma was induced by sodium selenite in the cul- low-density lipoprotein (LDL) cholesterol ture medium of the two groups (except the concentrations, LDL oxidation, and early normal group). The medium of the treated atherosclerosis compared to the consump- group was additionally supplemented with tion of tea alone by the hamsters. The anti- tea extract. After incubation, lenses were oxidant action of vitamin E is through the subjected to glutathione and malondial- incorporation of vitamin E into the LDL dehyde estimation. Enzyme activity of molecule. The hamsters were fed a semi- superoxide dismutase, catalase, and glu- purified hypercholesterolemic diet contain- tathione peroxidase were also measured in ing 12% coconut oil, 3% sunflower oil, and different sets of the experiment. In vivo 0.2% cholesterol (control), control and cataract was induced in 9-day-old rat pups 0.625% tea, control and 1.25% tea or con- of both control and treated groups by a trol and 0.044% tocopherol acetate for 10 single subcutaneous injection of sodium weeks. The hamsters fed the vitamin E diet selenite. The treated pups were injected compared to the different concentrations with tea extract intraperitoneally prior to of tea significantly lower plasma LDL cho- selenite challenge and continued for 2 con- lesterol concentrations, –18% (p < 0.007), secutive days thereafter. Cataract incidence –17% (p < 0.02), and –24% (p < 0.0001), was evaluated on 16 postnatal days by slit respectively. Aortic fatty streak areas were lamp examination. There was positive reduced in the vitamin E diet group com- modulation of biochemical parameters in pared to the control, –36% (p < 0.04) and the organ culture study. The results indi- low tea –45% (p < 0.01) diets. Lag phase of cated that tea act primarily by preserving conjugated diene production was greater in the antioxidant defense systemCS039. the vitamin E diet compared to the control, Antidiarrheal activity. Hot water extract low tea, and high tea diets, 41% (p < of tea, administered orally to rats, was effec- 0.0004), 40% (p < 0.0004), and 39% (p < tive in all the models of diarrhea used. 0.0008), respectively. Rate of conjugated Naloxone (0.5 mg/kg, ip) and loperamide diene production was reduced in the significantly inhibited the antidiarrheal vitamin E diet compared to the control, low activity of the extractCS029. tea, and high tea diets, –63% (p < 0.002), Antifungal activity. Ethanol (50%) extract –57% (p < 0.005), and –59% (p < 0.02), of the entire plant, in broth culture at a con- respectivelyCS005. Infusion of black tea centration of 1 mg/mL, was inactive on leaves was taken by 31 men (ages 47 r 14) Aspergillus fumigatus and Trichophyton men- and 34 females (ages 35 r 13) in a 4-week tagrophytesCS161. Hot water extract of the leaf study. Six mugs of tea were taken daily vs on agar plate at a concentration of 1.0% was placebo (water, caffeine, milk, and sugar) active on Alternaria tenuis, Pythium apha- and blood lipids, bowel habit, and blood 12 MEDICINAL PLANTS OF THE WORLD pressure measured during a run-in period p38-MAPK in chondrocytes. Epigallo- and at the end weeks 2, 3, and 4 of the test catechin-3-gallate did not alter the total period. Compliance was established by add- nonphosphorylated levels of either p38- ing a known amount of p-aminobenzoic acid MAPK or ERKp44/p42 in osteoarthritis to selected tea bags and then measure it chondrocytesCS033. Epigallocatechin-3-gal- excretion in the urine. Mean serum choles- late administered to primary human terol values during run-in, placebo and on osteoarthritis chondrocytes at a concentra- tea drinking were 5.67 r 1.05, 5.76 r 1.11, tion of 100 PM in cell Culture, inhibited the and 5.69 r 1.09 mmol/L (p = 0.16). There IL-I E-induced production of nitric oxide by were also no significant changes in diet, interfering with the activation of nuclear LDL-cholesterol, high-density lipoprotein factor (NF)NBCS042. Tea, in culture with (HDL) cholesterol, triacylglycerols, and bovine nasal and metacarpophalangeal blood pressure in the tea intervention cartilage and human nondiseased osteoar- period compared with placebo. Stool con- thritis and rheumatoid cartilage with and sistency was softened with tea compared without reagents known to accelerate carti- with the placebo, and no other differ- lage matrix breakdown, produced chon- ences were observed in bowel habit. The droprotective effect that may be beneficial results were unchanged within 15 “non- for the arthritis patient by reducing inflam- compliers” whose p-aminobenzoic acid mation and the slowing of cartilage break- excretion indicated that fewer than six tea down. Individual catechins were added to bags had been used, were excluded from the the cultures and the amount of released analysis, and when differenced between proteoglycan and type II collagen were mea- run-in and tea periods were considered sepa- sured by metachromatic assay and inhibi- rately for those who were given tea first or tion enzyme-linked immunosorbent assay secondCS167. (ELISA), respectively. Possible nonspecific Anti-inflammatory effect. Epigallocate- or toxic effects of the catechins were chin-3-gallate was shown to mimic its anti- assessed by lactate output and proteoglycan inflammatory effects in modulating the synthesis. Catechins, particularly those IL-I E-induced activation of mitogen acti- containing a gallate ester, were effective vated protein kinase in human chondro- at micromolar concentrations at inhibiting cytes. It inhibited the IL-I E-induced proteoglycan and type II collagen break- phosphorylation of c-Jun N-terminal kinase downCS043. (JNK) isoforms, accumulation of phospho- Antimutagenic activity. The anticarcino- c-Jun and DNA-binding activity of AP-1 in genic activity of tea phenols has been osteoarthritis chondrocytes, IL-I E but not demonstrated in rats and mice, transplant- epigallocatechin-3-gallate, and induced the able tumors, carcinogen-induced tumors in expression of JNK p46 without modulating digestive organs, mammary glands, hepato- the expression of JNK p54 in osteoarthritis carcinomas, lung cancers, skin tumors, leu- chondrocytes. In immune complex kinase kemia, tumor promotion, and metastasis. assays, epigallocatechin-3-gallate com- The mechanisms of this effect indicated pletely blocked the substrate phosphorylat- that the inhibition of tumors maybe the ing activity of JNK but not p38-mitogen result of both extracellular and intracellular activated protein kinase (MAPK). Epigallo- mechanisms indicting the modulation of catechin-3-gallate had no inhibitory effect metabolism, blocking or suppression, modu- on the activation of extracellular signal- lation of DNA replication and repair effects, regulated kinase p44/p42 (ERKp44/p42) or promotion, inhibition of invasion and CAMELLIA SINENSIS 13

Metastasis, and induction of novel mech- tagenic potency compared with the corre- anismsCS002. Green and black teas, adminis- sponding artificial teaCS019. Green and black tered orally to human adults, were effective. tea polyphenols, applied to the surfaces of Between 60 and 180 minutes after the teas ground beef before cooking, inhibited the were administered, the antimutagenic formation of the mutagens in a dose-related active compounds were recovered from the fashionCS025. Green or black tea polyphe- jejunal compartment by means of dialysis. nols sharply decreased the mutagenicity of a The dialysate appeared to inhibit the mu- number of aryl- and heterocyclic amines, of tagenicity of the food mutagen 2-amino-3,8- aflatoxin B1, benzo[a]pyrene, 1,2-dibromo- dimethylimidazo[4,5-f]quinoxaline on ethane, and more selectively of 2-nitropro- Salmonella typhimurium. The maximum pane, all involving an induced rat liver S9 inhibition was measured at 2 hours after fraction. Good inhibition was found with administration and was comparable for two nitrosamines that required a hamster S9 black and green teas. The maximum inhibi- fraction for biochemical activation. No tion observed with black tea was reduced by effect was found with 1-nitropyrene and 22, 42, and 78% in the presence of whole with the direct-acting (no S9) 2-chloro-4- milk, semi-skimmed milk, and skimmed methyl-thiobutanoic acidCS027. Hot water milk, respectively. Whole milk and skimmed extract on the leaf was evaluated in cell cul- milk abolished the antimutagenic activity of tures on various systems vs decaffeinated green tea by more than 90% and semi- and caffeinated teas. On mouse mammary skimmed milk by more than 60%. When a gland vs decaffeinated and caffeinated teas, homogenized breakfast was taken with black ICs50 were 10 mg/mL and 10 Pg/mL on CA- tea, the antimutagenic activity was elimi- A427, IC50 27 mg/mL and 31 Pg/mL, and nated. When tea and mutagen 2-amino-3,8- on epithelial cells, IC50 0.01 ng/mL and 0.3 dimethylimidazo[4,5-f]quinoxaline were ng/mLCS169. Hot water extract of the leaf, added to the system, 2-amino-3,8-dimethyl- on agar plate at a concentration of 1 mg/ imidazo[4,5-f]quinoxaline mutagenicity was plate, was active on Salmonella typhimu- efficiently inhibited, with green tea show- rium TA98 vs 2-amino-3-methylimidazo ing a slightly stronger antimutagenic activ- [4,5-f]quinoline-induced mutagenesis and ity than black tea. The addition of milk had produced weak activity vs benzo[a]pyrene- only a small inhibiting effect on the induced mutagenesisCS168. Infusion of the antimutagenicity. The antimutagenic activ- leaf, on agar plate at a concentration of 0.7 ity corresponded with reduction in antioxi- mg/plate, was active on Salmonella typhimu- dant capacity and with a decrease of rium TA98 and TA100 vs 2-amino-3- concentration of catechin, epigallocatechin methylimidazo[4,5-f]quinoline-; gallate, and epigallocatechinCS014. Chinese 3-amino-1,4-dimethyl-5H-pyrid[4,3- white tea, tested on rat liver S9 in assay for b]indole(Trp-1); aflatoxin B1-; 2-amino-6- methoxyresorufin O-demethylase, inhibited methyl-dipyrido[1,2-A:3,2-d]imidazole-, methoxyresorufin O-demethylase activity and benzo[a]pyrene-induced carcinogen- and attenuated the mutagenic activity of esisCS170. Infusion of the leaf, on agar plate 3-methylimidazo[4,5-f]quinoline (IQ) in at a concentration of 50 mg/plate, was absence of S9. Nine of the major constitu- active on Salmonella typhimurium TA98 vs ents found in green and white teas were 2-amino-3-methylimidazo[4,5-f]quinoline-; mixed to produce artificial teas according to 2-amino-3,4-dimethyl-imidazo[4,5- their relative levels in white and green teas. f]quinoline-;2-amino-3,8-dimethylimi- The complete tea exhibited higher antimu- dazo[4,5-f]quinoxaline-; 14 MEDICINAL PLANTS OF THE WORLD

2-amino-1-methyl-6-phenylimidazo[4,5-b]- in urine and lowered the esterified and total pyridine-;2-amino-3,7,8- cholesterol contents in plasma as compared trimethylimidazo[4,5-f]quinoxaline-; with a control group. TBARS contents in 2-amino-3,4,7,8-tetramethyl-3H-imidazo- liver, plasma, and cholesterol levels in the [4,5-f]quinoxaline-inoxaline-; 3-amino-1,4- liver were not affected. The lower plasma dimethyl-5H-pyrid[4,3-b]indole cholesterol concentration could not be (Trp-P-I)- and 3-amino-1-methyl-5H- explained by increased fecal excretion of pyrido [4,3-b]indole-induced mutagenesis. cholesterol or bile acids. On the other hand, Metabolic activation was required for posi- a relationship between decreased plasma tive resultsCS171. cholesterol and significantly higher acetate Anti-neoplastic effect. Green tea, admin- concentrations in the cecum, colon, and istered orally at a dose of 6 g per day in six portal blood of rats was assumed. Copper doses to 42 patients who were asymptom- absorption was significantly increased while atic and had manifested, progressive iron absorption was not affectedCS007. prostate specific antigen elevation with Epigallocatechin gallate, tea polyphenols, hormone therapy, produced limited anti- and tea extract were added to human plasma neoplastic activity. Continued use of lutein- and lipid peroxidation induced by the izing hormone-releasing hormone agonist water-soluble radical generator 2,2'-azobis was permitted. However, patients were (2-amidinopropane) dihydrochloride. Fol- ineligible if they had received other treat- lowing a lag phase, lipid peroxidation was ments for their disease in the preceding 4 initiated and it occurred at a rate that was weeks or if they had received a long-acting lower in a dose that was lowered in a dose- antiandrogen therapy in the preceding 6 dependent manner by the polyphenols. weeks. The patients were monitored Similarly, epigallocatechin gallate and the monthly for response and toxicity. Tumor extract added to plasma strongly inhibited response, defined as a decline of 50% or 2,2'-azobis(2-amidinopropane) greater in the baseline prostate-specific dihydrochloride-induced lipid peroxidation. antigen (PSA) value, occurred in a single The lag phase preceding detectable lipid patient, or 2% of The cohort (95% confi- peroxidation was the result of the antioxi- dence interval [CI], 1–14%). This one dant activity of endogenous ascorbate, response was not sustained beyond 2 which was more effective at inhibiting lipid months. At the end of the first month, the peroxidation than the tea polyphenols and median change in the PSA value from was not spared by these compounds. When baseline for the cohort increased by eight volunteers consumed the equiva- 43%CS031. Infusion of the leaf, administered lent of six cups of tea, the resistance of in the drinking of female mice at a concen- their plasma to lipid peroxidation did not tration of 1.25%, was active vs UV radia- increase over a period of 3 hoursCS009. Black tion-induced papillomas and tumorsCS172. tea leaves, administered to human red blood Leaves in the drinking water of female mice cells, was effective against damage by oxi- at a dose of 0.6% reduced lung tumor multi- dative stress induced by inducers such as plicity and volume in 4-(methylnitro- phenylhydrazine, Cu2+-ascorbic acid, and samine)-1-(3-pyridyl)-1-butanone (NNK) xanthine/xanthine oxidase systems. Lipid treated miceCS173. peroxidation of pure erythrocyte membrane Antioxidative effect. Tea, administered and of whole red blood cell was completely orally to rats, decreased the thiobarbituric prevented by black tea extract. Similarly, acid reactive substances (TBARS) contents the tea provided total protection against CAMELLIA SINENSIS 15 degradation of membrane proteins. Mem- Antispasmodic activity. Hot water extract brane fluidity studies as monitored by the and tannin fraction of the dried entire plant fluorescent probe 1,6-diphenyl-hexa-1,3,5- were active on the rabbit and rat intestines triene showed considerable disorganization vs pilocarpine-induced spasms and barium- of its architecture that could be restored induced contractionsCS160. back to normal on addition of black tea or Antiviral activity. Epigallocatechin-3-gal- free catechins. The tea extract in compari- late, administered to Hep2 cells in culture, son to free catechin seemed to be a better produced a therapeutic index of 22 and an protecting agent against various types of IC of 25 PM. The agent was the most CS013 50 oxidative stress . Ethanol/water (7:3) effective when added to the cells during the extract of green tea, tested on 2,2-azino-di- transition from the early to the late phase of 3-ethylbenzthiazoline sulphonate, produced viral infection suggesting that the polyphe- antioxidant activity compared with that nol inhibits one or more late steps in virus CS018 of ascorbic acid (10 mmol/L) . The infectionCS016. Nonpolyphenolic fraction of residual green Ethanol (50%) extract of the entire plant, tea (after hot water extraction) produced a in broth culture at a concentration of 50 Pg/ significant suppression against hydroperox- mL, was inactive on Raniket and Vaccinia ide generation from oxidized linoleic acid in virusesCS161. Hot water extract of the leaf in a dose-dependent manner. Using silica gel cell culture was active on Coxsackie A9, B1, TLC plate, chlorophylls a and b, pheo- B2, B3, B4, and B6 viruses, Echo type 9 phytins a and b, E-carotene, and lutein were virus, herpes simplex virus, poliovirus III, isolated. All of these constituents exhibited vaccinia virus, and REO type 1 virusCS163. significant antioxidant activites, the ranks Ethanol (50%) extract of suppressive activity against hydroperox- Anti-yeast activity. of the entire plant, in broth culture at a ide generation were chlorophyll a > lutein > pheophytin a > chlorophyll b > b-caro- concentration of 1 mg/mL, was inactive on tene > pheophytin bCS047. Candida albicans, Cryptococcus neoformans, CS161 Antiproliferative activity. Green tea frac- and Sporotrichum schenckii . Ethanol tions, tested on human stomach cancer extract of the leaf on agar plate produced CS164 (MK-1) cells, indicated six active flavan-3- MIC 9.3 mg/mL on Candida albicans . ols, epicatechin, epigallocatechin, epigal- Coronary heart disease prevention. Tea, locatechin gallate, gallocatechin, epicatechin taken by men and women age 30 to 70 years gallate, and gallocatechin gallate. Among at a dose of 480.0 mL per day, produced a the six active flavan-3-ols, epigallocatechin positive dose–response effectCS008. gallate and gallocatechin gallate produced Cytochrome P50 expression. Fresh leaves the highest activity. Epigallocatechin, of green, black, and decaffeinated black tea gallocatechin, and epicatechin gallate fol- enhanced lauric acid hydroxylation. The lowed next, and the activity of epicatechin decaffeinated black tea produced no signifi- was lowest. This suggests that the presence cant effect. Green tea and black tea but not of the three adjacent hydroxyl groups decaffeinated black tea, stimulated the O- (pyrogallol or galloyl group) in the molecule dealkylations of methoxy-, ethoxy-, and would be a key factor for enhancing the pentoxy-resorufin indicating upregulation activityCS032. of cytochrome P50 (CYP)1A and CYP2B. Antiprotozoan activity. Ethanol (50%) Immunoblot analysis revealed that green extract of the entire plant, in broth culture and black tea, but not decaffeinated black at a concentration of 125 Pg/mL, was inac- tea, elevated the hepatic CYP1A2 apopro- tive on Entamoeba histolyticaCS161. tein levels. Hepatic microsomes from green 16 MEDICINAL PLANTS OF THE WORLD and black tea-treated rats, but not those for tea and salivary pellicle components. from the decaffeinated black tea-treated Thirty-four percent of the fluoride was rats, were more effective than controls in retained in the oral cavity. Differences in converting IQ into mutagenic species in the retention at the tooth surface in the pres- Ames testCS001. ence and absence of an acquired pellicle Dental enamel erosion. Herbal tea and were not statistically significant at incisor conventional black tea, tested on teeth, or molar sites. Fluoride from tea showed resulted in erosion of dental enamel. After strong binding to enamel particles, which exposure to tea, sequential profilometric was only partially dissociated by solutions of tracings of the specimens were taken, super- ionic strength considerably greater than imposed, and the degree of enamel loss cal- that of salivaCS012. culated as the area of disparity between the Gastrointestinal effect. Green tea, admin- tracings before and after exposure. Tooth istered to rats fasted for 3 days, reverted to surface loss resulted from herbal tea (mean normal the mucosal and villous atrophy 0.05 mm2) was significantly greater than induced by fasting. Black tea ingestion had that which resulted from exposure to con- no effect. Ingestion of black tea, green tea, ventional black tea (0.01 mm2), and water and vitamin E before fasting protected the (0.00 mm2)CS022. Tannin, catechin, caffeine, intestinal mucosa against atrophyCS003. Char- and tocopherol, tested in vitro on tooth acterization of melanin extracted from tea enamel, demonstrated that these compo- leaves proved similarity of the original com- nents possess the property of increasing the pound to standard melanin. The Langmuir acid resistance of tooth enamel. The effects adsorption isotherms for gadolinium (Gd) increased dramatically when the compo- binding were obtained using melanin. Mela- nents were used in combination with fluo- nin–Gd preparation demonstrated low ride. A mixture of tannic acid and fluoride acute toxicity. LD50 for the preparation was showed the highest inhibitory effect (98%) in a range of 1.25–1.50 g/kg in mice. Mag- on calcium release to an acid solution. Tan- netic resonance imaging (MRI) properties nin in combination with fluoride inhibited of melanin itself and melanin-Gd com- the formation of artificial enamel lesions in plexes have been estimated. Gadolinium- comparison with acidulated phosphate free melanin fractions possess slighter fluoride (APF) as determined by electron relaxivity compared with its complexes. The probe microanalysis, polarized-light micros- relaxivity of lower molecular weight frac- copy, and Vickers microhardness measure- tion was 2 times higher than relaxivity of mentCS024. Gd(DTPA) standard. Postcontrast images DNA effect. Green tea extract, in cell cul- demonstrated that oral administration of ture at a dose of 10 mg/L corresponding to melanin complexes in concentration of 15 mmol/L EGCg for 24 hours, did not pro- 0.1 mM provides essential enhancement to tect Jurkat cells against H2O2-induced DNA longitudinal relaxation times (T[1])-weigh- damage. The DNA damage, evaluated by ted spin echo image. The required contrast the Comet assay, was dose-dependent. and delineation of the stomach wall dem- However, it reached plateau at 75 mmol/L onstrated uniform enhancement of MRI CS049 of H2O2 without any protective effect with proposed melanin complex . exerted by the extract. The DNA repair Hypocholesterolemic effect. Green tea, process, completed within 2 hours, was in human HepG2 cell culture, increased unaffected by supplementationCS021. both LDL receptor-binding activity and Fluoride retention. Tea, used as a mouth protein. The ethyl acetate extract, contain- rinse, demonstrated strong avidity of enamel ing 70% (w/w) catechins, also increased CAMELLIA SINENSIS 17

LDL receptor-binding activity, protein, and the insulin-potentiating activity for green mRNA, indicating that the effect was at the and oolong teas was owing to epigalloca- receptor level of gene transcription and that techin gallate. For black tea, the activity the catechins were the active constituents. was present in addition to epigallocatechin The mechanism by which green tea gallate, tannins, theaflavins, and other upregulated the LDL receptor was investi- undefined compounds. Several known com- gated. Green tea decreased the cell choles- pounds found in tea were shown to enhance terol concentration (–30%) and increased insulin with the greatest activity due to the conversion of the sterol-regulated ele- epigallocatechin gallate followed by ment binding protein (SREBP-1) from the epicatechin gallate, tannins, and thea- inactive precursor form to the active tran- flavins. Caffeine, catechin, and epicatechin scription-factor form. Consistent with this, displayed insignificant insulin-enhancing the mRNA of 3-hydroxy-3-methylglutaryl activities. Addition of lemon to the tea did coenzyme-A reductase, the rate limiting not affect the insulin-potentiating activity. enzyme in cholesterol synthesis, was also Addition of 5 g of 2% milk per cup increased by green teaCS050. decreased the insulin-potentiating activity Immunomodulatory effect. To determine one-third, and addition of 50 g of milk per the effects of tea on transplant-related cup decreased the insulin-potentiating immune function in vitro lymphocyte pro- activity approx 90%. Non-dairy creamers liferation tests using phytohemagglutinin, and soymilk also decreased the insulin- mixed lymphocytes culture assay, IL-2, and potentiating activityCS034. IL-10 production from mixed lymphocyte Iron absorption. Tea, administered by proliferation were performed. Tea had gastric intubation to rats, did not affect iron immunosuppressive effects and decreased absorption when tea was consumed for 3 alloresponsiveness in the culture. The days but when delivered in tea the absorp- immunosuppressive effect of tea was medi- tion was decreased. Rats maintained on a ated through a decrease in IL-2 produc- commercial diet were fasted overnight with tionCS038. Tea, assayed in cell culture, free access to water and then gavaged with enhanced neopterin production in unstimu- 1 mL of 59Fe labeled FeCl3 (0.1 mM or 1 mM) lated peripheral mononuclear cells, whereas and lactulose (0.5 M) in water or black tea. an effective reduction of neopterin forma- Iron absorption was estimated from Fe tion in cells stimulated with concanava- retention. Intestinal permeability was lin A, phytohemagglutinin or interferon evaluated by lactulose excretion in the (IFN)-J was observedCS041. Theaflavins urine. Iron absorption was lower with given potently suppressed IL-2 secretion, IL-2 with tea at both iron concentrations but tea gene expression, and the activation of did not affect lactulose excretionCS004. NF-NB in murine spleens enriched for Lipid peroxidation activity. Solubilized CD4(+) T-cells. Theaflavins also inhibited green tea, administered orally to rats for 5 the induction of IFN-J mRNA. However, weeks, reduced lipid peroxidation products. the expression of the T(H2) cytokines IL-4 The treatment produced increased activity and IL-5, which lack functional NF-NB sites of glutathione (GSH) peroxidase and GSH within their promoters was unexpectedly reductase, increased content of reduced suppressed by theaflavins as wellCS046. GSH, a marked decrease in lipid hydroper- Insulin-enhancing effect. Tea, as normally oxides and malondialdehyde in the liver, an consumed, was shown to increase insulin increase in the concentration of vitamin A activity more than 15-fold in vitro in an by about 40%. A minor change in the mea- epididymal fat cell assay. The majority of sured parameters was observed in the blood 18 MEDICINAL PLANTS OF THE WORLD serum. GSH content increased slightly, group (58.3%) were significantly better whereas the index of the total antioxidant than that of the control group (13.6%) (p < status increased significantly. In contrast, 0.005)CS035. the lipid peroxidation products, particularly P-glycoprotein activity. Green tea poly- malondialdehyde, was significantly dimin- phenols (30 Pg/mL) inhibited the photo- ished. In the central nervous tissue, the labeling of P-gp by 75% and increased the activity of superoxide dismutase and glu- accumulation of rhodamine-123 threefold tathione peroxidase decreased, whereas the in a multidrug-resistant cell line CH(R)C5, activity of GSH reductase and catalase indicating that the polyphenols interact increased after drinking green tea. More- with P-gp and inhibit its transport activity. over, the level of lipid hydroperoxides, 4- The modulation of P-gp transport by CS045 hydroksynonenal, and malondialdehyde polyphenols was a reversible process . decreased significantlyCS036. Photoprotection effect. Tea extracts, Neuromuscular-blocking action. Thearu- administered topically, produced a dose- bigin fraction of black tea was investigated dependent inhibition of the erythema for neuromuscular-blocking action of botu- response evoked by UV radiation. The (–)- linum neurotoxin types A, B, and E in the epigallocatechin-3-gallate and (–)-epica- mouse phrenic nerve-diaphragm prepara- techin-3-gallate polyphenolic fractions were most efficient at inhibiting erythema, tions. On binding, A (1.5 nM), B (6 nM), whereas (–)-epigallocatechin and (–)- and E (5 nM) abolished indirect twitches epicatechin had little effect. On histologi- within 50, 90, and 90 minutes, respectively. cal examination, skin treated with the Thearubigin fraction mixed with each toxin extracts reduced the number of sunburn protected against the neuromuscular-block- cells and protected epidermal Langerhans ing action of botulinum neurotoxin types A, CS037 cells from UV damage. The extract also B, and E by binding with the toxins . reduced damage that formed after UV Oral submucousal fibrosis effect. Tea, radiationCS006. Green tea polyphenols, administered orally to 39 patients with oral applied topically to the human skin, pre- submucous fibrosis, indicated that the treat- vented UVB-induced cyclobutane pyrimi- ment was effective for patients with abnor- dine dimers, which are considered to be mal hemorheology. The patients were mediators of UVB-induced immune sup- divided into control and experimental pression and skin cancer induction. The groups. The control group included 22 oral treatment, prior to exposure to UVB, pro- submucous fibrosis patients who were tected against UVB-induced local as well as treated by oral administration of vitamins A systemic immune suppression in laboratory and D, vitamin B complex, and vitamin E. animals. Additionally, treatment of mouse The experimental group included 17 skin inhibited UVB-induced infiltration patients who were treated with vitamins of CD11b cells. CD11b is a cell-surface and tea pigment after their examination of marker for activated macrophages and neu- hemorheology. The results showed that 7 of trophils, which are associated with induc- 12 patients in the experimental group with tion of UVB-induced suppression of contact abnormal hemorheology had average 7.9 hypersensitivity responses. The treatment mm improvement on the open degree also resulted in reduction of the UVB- (58.3%), and the open degree of the other induced immunoregulatory cytokine IL-10 five patients whose hemorheology was in skin as well as in draining lymph nodes, normal only increased 2 mm (20%). The and an elevated amount of IL-12 in drain- therapeutical results of the experimental ing lymph nodesCS026. CAMELLIA SINENSIS 19

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CS089 Ikekawa, N., S. Takatsuto, T. Kitsuwa, Effect of plucking intervals on the H. Saito, T. Morishita and H. Abe. chemical constituents of CTC black Analysis of natural brassinosteroids by tea. Agr Biol Chem 1986; 50(4): gas chromatography and gas chroma- 1039–1041. tography-mass spectrometry. J Chroma- CS101 Anon. Extraction of tannins especially togr 1984; 290(1): 289–302. catechins. Patent-Japan Kokai Tokkyo CS090 Abe, H., T. Morishita, M. Uchiyama, Koho-59 216,884 1984; 3 pp. S. Takatsuto and N. Ikekawa. A new CS102 Suzuki, T. and G. R. Waller. Purine brassinolide-related steroid in the alkaloids of the fruis of Camellia sinensis leaves of Thea sinensis. Agr Biol Chem L. and of Coffea arabica L. during fruit 1984; 1984(1): 2127–2172. development. Ann Bot (London) CS091 Lin, Z. K., Y. F. Hua and Y. H. Gu. 1985; 56(4): 537–542. Analysis of the aroma of Sichuan CS103 Chaboud, A., J. Rayaud, L. Debourcieu oolong tea. You-ji Hua Hsueh 1984; and J. Reynaud. The presence of 1984(1): 21–24. apigenin-2”-O-glucosyl-6-C- CS092 Nonaka, G. I., R. Sakai and I. Nishioka. glucosylapigenin or 2”-)-glucosylisovi- Hydrolysable tannins and proantho- texin in the leaves of Thea sinensis cyanidins from green tea. Phytochem- Sims. var. macrophylla. Pharmazie istry 1984; 23(8): 1753–1755. 1986; 41(10): 745–746. CS093 Skhiladze, N. R. and V. Y. Vachnadze. CS104 Sakata, K., S. Sakuraba, A. Yagi, K. Isolation of caffeine and theophylline Ina, T. Hara and T. Takeo. Isolation from ripe tea seeds. Chem Nat Comp and identification of (–)-quinic acid 1984; 20(5): 641. as an unidentified major tea–compo- CS094 Chkhikvishivili, I. D., V. A. Kurkin nent. Agr Biol Chem 1986; 50(7): and M. N. Zaprometov. Flavonoids of 1919–1921. Camellia sinensis. Chem Nat Comp CS105 Afzal, M., N. al-Sweedan, L. A. 1984; 20(5): 629–630. Massih, K. Takahashi and S. Shibata. CS095 Itoh, O., T. Uetsuki, T. Tamura and 2-amino-5-(N-ethylcarboxamido)- A. Matsumoto. Characterization of pentanoic acid from green tea leaves. triterpene alcohols of seed oils from Planta Med 1987; 53(1): 109–110. some species of Theaaceae, Phytolac- CS106 Sakata, K., H. Yamaguchi, A. Yagi and caceae and Sapotaceae. Lipids 1980; K. Ina. A new inositol glycoside, 2-O- 15(6): 407–411. beta-L-arabinopyranosyl-myo-inositol, CS096 Chkhikvishivili, I. D., V. A. Kurkin as a major tea component. Agr Biol and M. N. Zaprometov. Flavonids of Chem 1987; 51(6): 1737–1739. Camellia sinensis. II. Components of a CS107 Suzuki, T. Purine alkaloids in Camellia methanolic extract. Khim Prir Soedin sinensis flowers. Agr Biol Chem 1985; 1985; 21(1): 118–119. 49(9): 2803–2805. CS097 Tsushida, T. and T. Takeo. Occur- CS108 Cheng, G. R., J. L. Jin and Y. X. Wen. rence of theanine in Camelliajaponica The structures of two new flavonoid and Camellia sasanqua seedlings. Agr glycosides from bai-shui-cha, a kind of Biol Chem 1984; 48(11): 2861–2862. Camellia sinensis L. Yao Hsueh Hsueh CS098 Karawya, M. S., S. M. A. Wahab, M. Pao 1987; 22(3): 203–207. M. El-Olemy and N. M. Farrrag. CS109 Lee, M. H. and C. T. Lin. Changes of Diphenylamine, an antiyperglycemic flavor components of ti-kuan-yin tea agent from onion and tea. J Nat Prod during manufacturing. Chung-Kuo 1984; 47(5): 775–780. Nung Yeh Hua Hsueh Hui Chin CS099 Tsushida, T. and Y. Doi. Caffeine, 1985; 23(1/2): 127–132. theanine and catechin content in cal- CS110 Abe, H., T. Morishita, M. Uchiyama, luses of tea stem and anther. Nippon S. Takatsuto, N. Ikekawa, M. Ikeda, T. Nogei Kagaku Kaishi 1984; 58(11): Sassa, T. Kitsuwa and S. Marumo. 1131–1133. Occurrence of three new brassinoster- CS100 Barruah, S., M. Hhazarika, P. K. oids: brassinone, (24S)-24-etylbrassi- Mahanta, H. Horita and T. Mutai. none ad 28–norbrassinolide, in higher CAMELLIA SINENSIS 25

plants. Experientia 1983; 39(4): Chen. Determination of trace germa- 351–353. nium in herbal medicine by graphite fur- CS111 Shimizu, M., S. Wada, T. Hayashi, M. nace atomic absorption spectrometry. Arisawa, K. Ikegaya, S. Ogakum, S. Fenxi Shiyanshi 1991; 10(1): 30–31, 34. Yano and N. Morita. Studies on CS121 Owuoe, P. O. Differentiation of teas by hypoglycemic constituents of Japanese the variations of linalool and geraniol tea. Yakugaku Zasshi 1988; 108(10): contents. Bull Chem Soc Ethiopia 964–970. 1989; 3(1): 31–35. CS112 Taniguchi, S., Y. Miyashita, T. Ueyama, CS122 Wang, D. G. and S. R. Wang. Isola- K. Haji, Y. Hirase, T. Takemoto and S. tion, purification, analysis and anti- Arihara. Isolation of (–)-gallocatechin hyperlipidemia effect of green tea gallate from tea and pharmaceutical polysaccharide. Zhongguo Yaoke compositions containing it. Patent- Daxue Xuebao 1991; 22(4): 225–228. Japan Kokai Tokkyo Koho-63 30,418 CS123 Mukoyama, A., H. Ushijima, S. 1988; 5 pp. Nishimura, H. Koike, M. Toda, Y. CS113 Skobeleva, N. I., T. A. Petrova, A. A. Hara and T. Shimamura. Inhibition of Bezzubov and M. A. Bokuchava. Beta- rotavirus AND ENTEROVirus infec- D-glucosides of monoterpene alcohols tions by tea extracts. Jap J Med Sci in tea shoots. Soobshch Akad Nauk Biol 1991; 44(4): 181–186. Gruz SSR 1988; 131(2): 397–400. CS124 Namiki, K. Platelet aggregation inhibi- CS114 Tanizawa, H., S. Toda, Y. Sazuka, T. tory components of tea. Fragrance J Taniyama, T. Hayashi, S. Arichi and 1990; 18(11): 67–70. Y. T. Akino. Natural antioxidants. I. CS125 Park, S. N. and Y. C. Boo. Flavonoids Antioxidative components of tea leaf for protection of cells against chemi- (Thea sinensis L.). Chem Pharm Bull cally active species of oxygen, their 1984; 32(5): 2011–2014. extraction from plants, and their use in CS115 Nobumoto, Y., K. Kubota, A. Koba- cosmetics. Patent-Fr Demende-2,651,132 yashi and T. Yamanishi. Structure of 1991; 17 pp. alpha-farnesen in the essential oil of CS126 Wheeler, S. R. Tea and tannins. Sci- oolong tea. Agr Biol Chem 1990; ence 1978; 204: 6. 54(1): 247–248. CS127 Anisimov, M. M., E. B. Shentsova, V. CS116 Sakata, K., H. Yamauchi, A. Yagi, K. V. Shcheglov, Y. N. Shumilov, V. A. Ina, L. Parkanyi and J. Clardy. 2-O- Rasskazov, L. I. Strigina, N. S. (beta-L-arabinopyranosyl)-myo-inosi- Chetyrina and G. B. Elyakov. Mecha- tol as a main constituent of tea nism of cytotoxic action of some (Camellia sinensis). Agr Biol Chem triterpene glycosides. Toxicon 1978; 1989; 53(1): 2975–2979. 16: 207–218. CS117 Fujimori, N. and H. Ashihara. CS128 Dzhavelidze, T. A. Phenolic com- Adenine metabolism and the synthe- pounds in various parts of tea shoots. sis of purine alkaloids in flowers of Subtrop Kult 1978; 1978: 154–155. Camellia. Phytochemistry 1990; 29(11): CS129 Hatanaka, A., T. Kajiwara and J. 3513–3516. Sekiya. Biosynthesis of leaf alcohol: CS118 Furuya, T., Y. Orihara and Y. Tsuda. the oxygenative cleavage of linolenic Caffeine and theanine from cultured acid to cis-3-hexenal and 11-formyl- cells of Camellia sinensis. Phytochem- cis-9-undecenoic acid from linolenic istry 1990; 29(8): 2539–2543. acid in tea chloroplasts. Symp Chem CS119 Sekine, T., J. Arita, A. Yamaguchi, K. Nat Prod-22nd- Fukuoka, Japan 1979; Saito, S. Oknogi, N. Morisaki, S. 657–664. Iwasaki and I. Murakoshi. Two fla- CS130 Iida, T., T. M. Jeong, T. Tamura and vonol glycosides from seeds of Camel- T. Matsumoto. Identification of lia sinensis. Phytochemistry 1991; chondrillasterol in two Cucurbitaceae 30(3): 991–995. seed oils by proton nuclear magnetic CS120 Lin, W. Y., Y. H. He, J. H. Luo, L. J. resonance spectroscopy. Lipids 1980; Huang, K. Lin, S. R. Wu and J. H. 15: 66–68. 26 MEDICINAL PLANTS OF THE WORLD

CS131 Itoh, T., Y. Kikuchi, T. Tamura and T. mary and secondary amines in the Matsumoto. Two 3-oxo-steroids in human environment. Food Cosmet Thea sinensis seeds. Phytochemistry Toxicol 1977; 15: 275–282. 1981; 20: 175–176. CS142 Shecheglov, V. V., S. I. Baranova, M. CS132 Etoh, Hina, K. and M. Iguchi. Studies M. Anisimov, S. Antonov, S. S. on the aroma of tea. Part IV. 3S-(+)- Afiyatullov, E. V. Levina, V. F. 3,7-dimethyl-1,5-octadiene-3,7-diol Sharypov, V. A. Stonik and G. B. and ionone derivatives from tea. Agr Elyakov. Antimicrobial spectrum of Biol Chem 1980; 44: 2999–3000. some triterpene and steroid glyco- CS133 Imperato, F. N-P-coumarylglutamic sides. Antibiotiki (Moscow) 1979; 24: acid, an unusual hydroxycinnamic 270–273. acid–aminoacid derivative from black CS143 Sakai, T., K. Kobashi, M. Tsunezuka, tea. Chem Ind (London) 1980; 388. M. Hattori and T. Namba. Studies on CS134 Huq, M. S., B. K. Mondal and M. S. dental caries prevention by traditional Khan. Investigation on tea seed. Part Chinese medicine (part VI). On the I. Studies on the composition of the fluoride contents in crude drugs. oil. Bangladesh J Sci Ind Res 1980; Shoyakugaku Zasshi 1985; 39(2): 15(1): 125–129. 165–169. CS135 Takatsuto, S., N. Ikekawa, H. Abe, T. CS144 Nakahara, K. Oxalic acid content of Morishita, M. Uchiyama, M. Ikeda, T. vegetable foods. Eiyo To Shokuryo Sasa, S. Marumo and T. Kitsuwa. 1974; 27(1): 33–36 Microanalysis of brassinolide and its CS145 John, D. One hundred useful raw drugs application to the identification of of the Kani tribes of Trivandrum forest new brassinosteroids in plants. Proc division, Kerala, India. Int J Crude 25th Symp on the Chem of Nat Prod Drug Res 1984; 22(1): 17–39. Tokyo 1982; 290–297. CS146 Patel, V. K. and H. Venkatakrishna- CS136 Lin, Z., Y. Hua, Y. Gu, J. Ma, P. Chen Bhatt. Folklore therapeutic indigenous and Y. Xiao. Study on the chemical plants in periodontal disorders in In- constituents on the volatile oils from dia (Review, experimental and clinical the fresh leaves of Camellia sinensis. approach). Int J Clin Pharmacol Ther Chih Wu Hsueh Pao 1982; 24: 440–450. Toxicol 1988; 26(4): 176–184. CS137 Yamane, H., H. Abe and N. Takahashi. CS147 Jamir, N. S. Some interesting medici- Jasmonc acid and methyl jasmonate in nal plants used by Nagas. J Res Edu pollens and anthers of three Ind Med 1990; 9(2): 81–87. Camelliaspecies. Plant Cell Physiol CS148 Latorre, D. L. and F. A. Latorre. Plants 1982; 23: 1125–1127. used by the Mexican Kickapoo Indi- CS138 Bagratishvili, D. G. and M. N. ans. Econ Bot 1977; 31: 340–357. Zaprometov. Effect of light on the for- CS149 Yesilada, E., G. Honda, E. Sezike, M. mation of phenolic compounds in a Tabata, T. Fujita, T. Tanaka, Y. suspension of a tea plant cells. Akad Takeda and Y. Takaishi. Traditional Nauk Gruz 1982; 105: 581–584. medicine in Turkey. V. Folk medicine CS139 Ozawa, T. Separation of the compo- in the inner Taurus Mountains. J nents in black tea infusion by chroma- Ethnopharmacol 1995; 46(3): 133–152. tography on toyopearl. Agr Biol Chem CS150 Loewenthal, R. and J. Pe’er. Tradi- 1982; 46(4): 1079–1081. tional methods used in the treatment CS140 Nonaka, G. I., O. Kawahara and I. of ophthalmic diseases among the Nishioka. Tannins and related com- Turkana tribe in North West Kenya. J pounds. XV. A new class of dimeric Ethnopharmacol 1991; 33(3): 227–229. flavan-3-ol gallates, theasinensins A CS151 Klauss, V. and H. S. Adala. Traditional and B, and proanthocyanidin gallates herbal eye medicine in Kenya. World from green tea leaf. I. Chem Pharm Health Forum 1994; 15(9): 138–143. Bull 1983; 31(11): 3906–3914. CS152 Wasuwat, S. A list of Thai medicinal CS141 Neurath, G. B., M. Dunger, F. G. Pein, plants, ASRCT, Bangkok, Report No. D. Ambrosius and O. Schreiber. Pri- 1 on Res. Project. 17. Res Report, CAMELLIA SINENSIS 27

A.S.R.C.T., No 1 on Research Project and S. Kumagai. Epicallocatechin 17. 1067; 22 pp. gallate and gallocatechin gallate in CS153 Laohapaiboon, P. and P. Tosukhowong. green tea catechins inhibit extracellu- Antifungal activity of tea seed cake and lar release of vero toxin from entero- tea seed extract. Chulalongkorn Med J hemorrhagic Escherichia coli O157:H7. 1981; 24(4): 953–959. Biochim Biophys Acta 1999; 1472 CS154 Caceres, A., L. M. Giron, S. R. (1/2): 42–50. Alvarado and M. F. Torres. Screening CS158 Ohtsuki, K., M. Kawabata, K. Taguchi, of antimicrobial activity of plants H. Kokura and S. Kawamura. Determi- popularly used in Guatemala for the nation of S-methylmethionine, vita- treatment of dermatomucosal dis- min U, in various teas. Agr Biol Chem eases. J Ethnopharmacol 1987; 20(3): 1984; 48(10): 2471–2475. 223–237. CS159 Lin, Y. L., S. H. Tsai, S. Y. Lin-Shiau, CS155 Rao, R. R. and N. S. Jamir. Ethnobo- C. T. Ho and J. K. Lin. Theaflavin-3- tanical studies on Nagaland. I. Medi- 3-digallate from black tea blocks the cinal Plants. Econ Bot 1982; 36: nitric oxide synthase by down-regulat- 176–181. ing the activation of NF-KB in macro- CS156 Chaboud, A., J. Raynaud and L. phages. Eur J Pharmacol 1999; 367 Debourcieu. 6,8-Di-C-beta-D-arabino- (2/3): 379–388. pyranosyl apigenin from Thea sinensis CS160 Riso, P., D. Erba, F. Criscuoli and G. var. macrophylla. J Nat Prod 1986; Testolin. Effect of green tea extract on 49(6): 1145. DNA repair and oxidative damage due CS157 Sugita-Konishi, Y., Y. Hara-Kudo, F. to H2O2 in Jurkat T cells. Nutrition Amano, T. Okubo, N. Aoi, M. Iwaki Research 2002; 22(10): 1143–1150. CANNABIS SATIVA 29

2 Cannabis sativa L.

Common Names Almindelig hamp Denmark Harilik kanep Slovenia Asa Japan Haschischpflanze Germany Bang Egypt Hash United Kingdom Bhaang India Hashas Turkey Bhaango Nepal Hashish Morocco Canamo indico Spain Hemp United Kingdom Canapa indica Italy Hennep Netherlands Canhamo Portugal Hind kinnabi Turkey Cares Nepal Huo ma cao China Chanvre cultive France Huo ma China Chanvre de l’Inde France Indian hemp United Kingdom Chanvre France Indische hennep Netherlands Chanvrier sauvage France Indischer hanf Germany Charas India Indisk hamp Sweden Churras India Kannabis Finland Da ma cao China Kannabisu Japan Da ma ren China Kerp Albania Da ma China Kinnab Turkey Dagga South Africa Konopie siewne Poland Dansk pot Denmark Konopie Poland Echter hanf Germany Konoplja Slovenia Esrar Turkey Kultur hanf Germany Gaanjaa Nepal Maconha Portugal Gajiimaa Nepal Marihana Netherlands Ganja Guyana Marihouava Greece Ganja India Marihuana Poland Grifa Spain Marihuana Bulgaria Hachis Spain Marihuana Croatia Hamp Denmark Marihuana Czech Republic Hamp Norway Marihuana Denmark Hampa Sweden Marihuana France Hampjurt Iceland Marihuana Germany Hamppu Finland Marihuana Hungary Hanf Germany Marihuana Mexico

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 29 30 MEDICINAL PLANTS OF THE WORLD

Marihuana Russia Porkanchaa Thailand Marihuana Serbia Pot Denmark Marihuana Spain Qinnib Arabic countries Marihuana Ukraine Riesen hanf Germany Marihuana United States Seruma erva Portugal Marijuana France Taima Japan Marijuana Italy Til Arabic countries Marijuana Mexico Vrai chanvre France Marijuana Portugal Weed Guyana Marijuana Sweden Xian ma China Mashinin Japan Ye ma China Navadna konoplja Slovenia

BOTANICAL DESCRIPTION types of plants are numerous varieties that Cannabis sativa is an annual herb of the differ from the main one in height, extent MORACEAE family that grows to 5 m tall. of branching, and other characteristics. It is usually erect; stems variable, with res- ORIGIN AND DISTRIBUTION inous pubescence, angular, sometimes hol- Native to Central Asia and long cultivated low, especially above the first pairs of true in Asia, Europe, and China. Now a wide- leaves; basal leaves opposite, the upper spread tropical, temperate, and subarctic leaves alternate, stipulate, long petiolate, cultivar. Cannabis sativa has been cultivated palmate, with 3–11, rarely single, lan- for more than 4500 years for different pur- ceolate, serrate, acuminate leaflets up to 10 poses, such as fiber, oil, or narcotics. The cm long, 1.5 cm broad. Flowers are monoe- oldest use of hemp is for fiber, and later the cious or dioecious, the male in axillary and seeds were used for culinary purposes. Plants terminal panicles, apetalous, with five yel- yielding the drug were discovered in India, lowish petals and five poricidal stamens; the cultivated for medicinal purposes as early as female flowers germinate in the axils and 900 BC. In medieval times, it was brought to terminally, with one single-ovulate ovary. North Africa, where currently it is culti- Fruit is brown, shining achene, variously vated exclusively for hashish or kif. marked or plain, tightly embraces the seed with its fleshy endosperm and curved TRADITIONAL MEDICINAL USES embryo; late summer to early fall; year- Afghanistan. Hot water extract of the resin round in tropics. Drug-producing selections is taken orally to induce abortionCS235. grow better and produce more drugs in the China. Hot water extract of the inflores- tropics; oil- and fiber-producing plants cence is taken orally for wasting diseases, to thrive better in the temperate and subtropi- clear the blood, to cool the temperature, to cal areas. The form of the plant and the relieve fluxes, for rheumatism, to discharge yield of fiber from it vary according to cli- pus, and to stupefy and produce hallu- mate and particular variety. Varieties culti- cinationsCS035. The seed is taken orally as an vated for their fibers have long stalks, emmenagogueCS014. Decoction of the seed is branch very little, and yield only small taken orally as an anodyne, an emmenag- quantities of seed. Oil seed varieties are ogue, a febrifuge, for migraine, and for small, mature early, and produce large quan- cancerCS112. It is taken orally as a hallucino- tities of seed. Varieties grown for the drugs gen and externally for rheumatismCS109. are small, much branched with smaller dark- Guatemala. The leaves are used externally green leaves. Between these three main to relieve muscular painsCS106. CANNABIS SATIVA 31

India. Hot water extract of the dried entire unripe fruit is taken orally to induce plant is taken orally as a narcotic and to sleepCS192. relieve pain of dysmenorrheaCS210. Hot water Iran. Fluidextract of the dried flowering top extract of the dried flower and leaf is taken or the dried fruit is taken orally for abdomi- orally for dyspepsia and gonorrhea and as a nal pain associated with indigestion, for nerve stimulantCS217. Hot water extract of pain associated with cancer, for rheumatoid the inflorescence of female plants is taken arthritis, for gastric cramps or neuralgia, for orally as an abortifacientCS010. Hot water coughing, and as a hypnotic. Fluidextract of extract of the leaf is taken orally to relieve the dried fruit is taken orally for whooping menstrual painCS086. For cuts, boils, and blis- cough, as a hypnotic, and a tranquilizerCS034. ters, leaf paste is applied topically for 4 The dried seed is taken orally as a diuretic. daysCS098. Hot water extract of the bark is An infusion is taken orally as an analgesic taken orally for hydrocele and other in rheumatism or rheumatoid arthritis, a inflammationCS125. Extract of the leaves is sedative, a diaphoretic, and for hysteric con- used as an insect repellantCS246. Hot water ditions, gout, epilepsy, and cholera. The extract of the seed is taken orally as an seed oil is administered per rectum to reduce emmenagogueCS010. The powdered seed is cramps associated with lead poisoning asso- taken orally as an aid in conception. One ciated with constipation and vomiting. To gram of seeds is powdered, then mixed with reduce breast engorgement or reduce milk water, and given to women in the morning secretion, the seed oil is applied topically. before breakfast for 7 days after menstrua- In some cases, it would completely stop milk tion. The use of pepper and cane sugar is secretion. One to 2 g of seed oil is taken avoided. Paste of dried leaves is applied over orally several times a day for urinary the anus in the morning and evening for incontinencyCS034. pilesCS099. The dried leaf juice is used exter- Jamaica. Hot water extract of the flower, nally on cuts and piles and taken orally as leaf, and twig is taken orally as an antispas- an anthelminticCS143. To eliminate cough, modic and anodyneCS238. Hot water extract bronchitis, and other respiratory ailments, a of the resin is taken orally for diabetesCS198. half tablespoonful of powdered dried leaves Mexico. The aerial parts are smoked as a is mixed with an equal amount of honey and hallucinogenCS117. taken orally three times dailyCS193. Seed oil Morocco. The aerial parts are taken orally is used externally for burns. The oil is as a narcoticCS111. extracted by roasting the seedsCS213. Seeds are Nepal. Decoction of the leaf is taken orally taken orally for diabetes, hysteria, and by adults as an anthelminticCS090. The pow- sleeplessnessCS127. The aerial parts are dered leaf is mixed with cattle feed as a smoked to decrease nausea and vomiting treatment for diarrheaCS105. For headache, induced by anticancer drugsCS061. Hot water the dried leaves are ground with Datura extract of the aerial parts is taken orally by stramonium leaves and Picrorhiza schrophu- males as an aphrodisiacCS123. The dried aerial lariflora stem and water then applied parts are smoked by women to increase their externallyCS222. The leaf juice is used exter- amorous prowessCS181. The fresh leaves are nally as an antiseptic, as a hemostat on cuts taken orally for hemorrhoidsCS108. Hot water and wounds, and to treat swelling of extract of the dried leaf and seed is taken sprained jointsCS110. The seeds are crushed, orally for stomach troubles and indiges- mixed with curd, and taken orally for tionCS217. Fresh leaf juice is administered dysenteryCS090. Decoction of the seed is taken intraural to treat earacheCS143. The fruit is orally as an anthelminticCS104. To aid in par- used externally for skin diseasesCS227. The turition, 2 teaspoonfuls of powdered seeds 32 MEDICINAL PLANTS OF THE WORLD are made into a paste with sesame oil Apigenin glycoside: PlCS172 (Sesamum indicum L.) and applied intra- Apigenin-7-O-para-coumaroyl-glucoside: PlCS172 CS172 vaginally during laborCS100. Arabinic acid: Pl Arabinose: PlCS172 Hot water extract of the entire Pakistan. Arabitol: PlCS172 CS002 plant is taken orally as a parturifacient . Arachidic acid: PlCS172, SdCS134 Infusion of the leaf is taken orally for gen- Arginine: PlCS172 Aromadendrene, allo: PlCS172 eral weaknessCS113. Aspartic acid: PlCS172 Saudi Arabia. The aerial parts, mixed with Azelaic acid: PlCS172 honey, sugar, and nutmeg, are taken orally Behenic acid: PlCS172 CS156 CS172 as a psychotropicCS248. Benzaldehyde, para-ethyl: EO , Pl Benzene, 1-methyl-4-iso-propenyl: PlCS068, Senegal. The seed is taken orally as an CS172 CS011 emmenagogue . Benzo-(A)-anthracene: Lf Smoke 3.3 Pg/100 South Africa. Hot water extract of the CigCS088 entire plant is taken orally for asthmaCS107. Benzo-(A)-pyrene: Lf Smoke 4.2 Pg/100 Hot water extracts of the root and seed are CigCS088 taken orally to induce abortion, labor, and Benzo-(F)-fluoranthene: Lf Smoke 3 Pg/100 CS088 menstruationCS234, CS219. Cig Benzo-(G-H-I-)-perylene: Lf Smoke 0.7 g/ United States. Fluidextract of the inflores- P 100 CigCS088 cence is taken orally as a narcotic, antispas- Benzo-(K)-fluoranthene: Lf Smoke 1.1 Pg/100 CS015 modic, analgesic, and aphrodisiac . Hot CigCS088 water extract of the flowering top is taken Benzoic acid, 4-hydroxy methyl ester: PlCS033 orally as a potent antispasmodic, anodyne, Benzoic acid, 4-hydroxy-N-propyl ester: and narcotic. One teaspoon of plant mate- PlCS033 CS172 rial is steeped in 2 cups of boiling water, and Benzoic acid, 4-hydroxy: Pl 1 tablespoonful is taken two to four times a Benzoxocin-5-methanol, 2-(H)-1, 3-4-5-6- CS247 tetrahydro, 7-hydroxy-D-2-trimethyl-9-N- day . The dried aerial parts are smoked by propyl-2-6-methano: PlCS172 CS166 both sexes as an aphrodisiac . Benzyl acetate, para-ethyl: EOCS156, PlCS172 Vietnam. The seeds are taken orally as an Benzyl acetate: EOCS156,CS172 emmenagogueCS013. Bergamotene, D, trans: Lf EOCS062, ResinCS069, West Indies. Hot water extract of the entire InflorescenceCS036, PlCS172 CS196 plant is taken orally as an antispasmodicCS161. Bergamotene, D: Lf EO Betaine, iso-leucine, L-(+): PlCS172 Yugoslavia. Hot water extract of the seed is CS202 CS169 Bibenzyl, 3-4-5-trihydroxy: Resin 596.5 taken orally for diabetes . Bibenzyl, 3-4-dihydroxy-5-5-dimethoxy-3-(3- Zimbabwe. Hot water extract of the aerial methyl-but-2-enyl): AerCS155 parts is taken orally as a treatment for Bibenzyl, 3-4-dihydroxy-5-methoxy: AerCS155, malariaCS238. Lf 2CS157 Bibenzyl,3-3-dihydroxy-4-5-dimethoxy: CHEMICAL CONSTITUENTS Lf 5CS157, AerCS155 (ppm unless otherwise indicated) Bisabolene: PlCS068 Acetaldehyde: PlCS172 Bisabolol, D: PlCS172, Fl EOCS196 Acetone: PlCS172 Borneol acetate: PlCS172, EOCS156 Actinidiolide, dihydro: EOCS156, PlCS172 Borneol, (–): PlCS068 Alanine: PlCS172 Borneol: ResinCS069, EOCS156 Aldotetronic acid, 2-C-methyl: PlCS172 Bornesitol, D, (+): PlCS172 Aldotetronolactone, 2-C-methyl: PlCS172 Butylamine, iso: PlCS172 Anethole, cis: EOCS156, PlCS172 Butylamine, N: PlCS172 Anethole, trans: EOCS156, PlCS172 Butylamine, sec: PlCS172 CANNABIS SATIVA 33

Butyraldehyde, iso: PlCS172 Cannabielsoin, C-3: ResinCS132 Cadaverine: PlCS172 Cannabielsoin: PlCS172 Cadinene, ': PlCS172, EOCS156 Cannabifuran, dehydro: ResinCS239, PlCS172 Cadinene, J: PlCS172, EOCS156 Cannabifuran: PlCS172, ResinCS239 Calamenene: PlCS172, Lf EOCS062 Cannabigerol monomethyl ether: PlCS172 Campest-4-en-3-one: PlCS172 Cannabigerol: ResinCS084, PlCS044 Campest-5-en-3-E-ol-7-one: PlCS172 Cannabigerolic acid monoethyl ether: Campestanol: SdCS076 Lf 20CS004, PlCS172 Campesterol: SdCS076, Call TissCS083, RtCS050 Cannabigerolic acid: Lf 40CS032, PlCS172, Camphene hydrate: EOCS156, PlCS172 InflorescenceCS218 Camphene: Inflorescence EOCS036, Lf EOCS062, Cannabigerovarin: PlCS172 ResinCS069 Cannabigerovarinic acid: PlCS172 Camphor: Lf EOCS062, PlCS172 Cannabinerolic acid: Lf 7.6CS032 Canabispiran: Lf CS091 Cannabinodiol: ResinCS020 Cannabamine B: Lf CS070 Cannabinodivarin: PlCS172 Cannabamine C: Lf CS070 Cannabinol methyl ether: ResinCS018 Cannabamine D: Lf CS070 Cannabinol monomethyl ether: PlCS172 Cannabamine: Lf CS070 Cannabinol, '-6(A)-10(A)-tetrahydro, Cannabicclovarin: PlCS172 10-oxo: ResinCS239, PlCS172 Cannabichromanone, C-3: ResinCS132 Cannabinol, '-6(A)-10(A)-tetrahydro, Cannabichromanone: Resin 59CS150 8-9-dihydroxy (DL): AerCS158 Cannabichromene, propyl: ResinCS137 Cannabinol, '-6(A)-10(A)-tetrahydro, Cannabichromene: RtCS145, ResinCS009, 9-10-dihydroxy (DL): AerCS158 AerCS049,CS206 Cannabinol, '-6(A)-10(A)-tetrahydro, Cannabichromenic acid: InflorescenceCS218, 9-hydroxy-10-ethoxy: AerCS118 ResinCS055, Lf CS073 Cannabinol, '-6(A)-10(A)-tetrahydro, Cannabichromevarin: PlCS172 cis: PlCS172 Cannabichromevarinic acid: PlCS172 Cannabinol, '-8-tetrahydro, trans (–): Cannabicitran: PlCS172 AerCS064 Cannabicoumaronic acid: Resin 84CS150 Cannabinol, '-8-tetrahydro, trans: PlCS172 Cannabicoumaronone: PlCS172 Cannabinol, '-8-tetrahydro: PlCS038, Cannabicyclol: AerCS064, Lf CS057, FlCS074, ResinCS055, RtCS145, InflorescenceCS218 ResinCS043 Cannabinol, '-9-tetrahydro, 6(A)-7-10(A)- Cannabicyclolic acid: InflorescenceCS218 trihydroxy: PlCS172 Cannabidihydrophenanthrene: Lf 20CS001 Cannabinol, '-9-tetrahydro, cis: Lf 2CS114, Cannabidiol monomethyl ether: PlCS172 Lf/FlCS074 Cannabidiol, C-4: PlCS172 Cannabinol, '-9-tetrahydro, methyl ether: Cannabidiol, propyl: ResinCS137 ResinCS137 Cannabidiol: LfCS040, AerCS039, ResinCS045, Cannabinol, '-9-tetrahydro, propyl: InflorescenceCS052 ResinCS137 Cannabidiolic acid: PlCS172 Cannabinol, '-9-tetrahydro, trans (–): PlCS172 Cannabidiolic acid-tetrahydro-cannabitriol Cannabinol, '-9-tetrahydro, trans: Fl/LfCS074, ester: PlCS172 PlCS172, ResinCS137 Cannabidiorcol: PlCS172 Cannabinol, '-9-tetrahydro: PlCS041, Cannabidivarin: PlCS172 ResinCS048, BkCS046, Sd 16.5CS126, Call Tiss Cannabidivarol: PlCS146,CS172 65CS188, Fr 0.5653%CS089, Fl tops 4%CS136, Cannabidivarolic acid: PlCS146 LfCS060, RtCS145 Cannabielsoic acid A: PlCS172, ResinCS056 Cannabinol, '-9-tetrahydroxylic acid: Cannabielsoic acid B, C-3: PlCS172, ResinCS132 ResinCS019 Cannabielsoic acid B: PlCS172, ResinCS056 Cannabinol, hexahydro: AerCS064 Cannabielsoic acid, C-3: PlCS172 Cannabinol, propyl: ResinCS137 Cannabielsoin I, dehydro: ResinCS239 Cannabinol, tetrahydro, iso, propyl: ResinCS137 34 MEDICINAL PLANTS OF THE WORLD

Cannabinol, tetrahydro, iso: ResinCS137 Cannabisperenone, iso: PlCS172 Cannabinol, tetrahydro: PlCS133 Cannabispiradienone: Lf 5–6CS185, CS001 Cannabinol: ResinCS009, Sd 8CS148, Cannabispiran, dehydro: Lf 2.3CS091, CS209 Fr 0.1275%CS089, PlCS038 Cannabispiran, iso: LfCS180 Cannabinol-C-4, '-9-tetrahydro, trans: Cannabispiran: Lf 20–245.7CS080, CS209 PlCS172 Cannabispiranol, D: Lf 0.3CS185 Cannabinol-C-4: PlCS172 Cannabispiranol, E: Lf 8–80CS209, CS091 Cannabinolic acid A, '-9-tetrahydro, trans Cannabispiranol: Lf 18CS157 (–): AerCS064 Cannabispirenone A, (–): Lf 30CS185 Cannabinolic acid A, '-9-tetrahydro, trans: Cannabispirenone A, (DL): Lf 30CS185 PlCS172 Cannabispirenone B: Lf CS185 Cannabinolic acid A, '-9-tetrahydro: LfCS004 Cannabispirenone: Lf 210CS185 Cannabinolic acid B, '-9- tetrahydro, trans Cannabispirenone: Lf 61CS157, Aer 10CS124 (–): AerCS064 Cannabispirol, acetyl: PlCS172 Cannabinolic acid B, '-9-tetrahydro, trans: Cannabispirone: Aer 30CS124, PlCS172, PlCS172 Lf 40CS157 Cannabinolic acid B, '-9-tetrahydro: Cannabistilbene I: Lf 0.4CS204 ResinCS055 Cannabistilbene II: LfCS204 Cannabinolic acid, '-1-tetrahydro: Cannabitetrol: PlCS205 Lf 1.4333%CS032 Cannabithrene I: Lf 4CS185 Cannabinolic acid, '-8-tetrahydro, trans: Cannabithrene II: Lf 8CS185 PlCS172 Cannabitriol, (+): AerCS118, PlCS172 Cannabinolic acid, '-8-tetrahydro: Cannabitriol, (+): PlCS172 InflorescenceCS218 Cannabitriol, (DL): Lf 2.7CS203 Cannabinolic acid, '-9-tetrahydro: Cannabitriol, trans (DL): LfCS194 InflorescenceCS218, LfCS151,CS179 Cannabitriol: Aer 250CS079 Cannabinolic acid, tetrahydro: LfCS179, PlCS041, Cannabivarichromene: ResinCS017 PollenCS067 Cannabivarin, '-9-tetrahydro, trans (–): Cannabinolic acid: LfCS004, ResinCS055, PlCS172, AerCS064 InflorescenceCS218, PlCS172 Cannabivarin, '-9-tetrahydro, trans: PlCS172 Cannabinolic acid-C-4, '-9-tetrahydro, trans: Cannabivarin, tetrahydro: Fl/LfCS074 PlCS172 Cannabivarin: PlCS172 Cannabiol, '-6(A)-10(A)-tetrahydro, 9-10- Cannabivarinic acid, '-9-tetrahydro, trans (–): dihydroxy (DL): PlCS172 AerCS064 Cannabiorcol, '-9-tetrahydro, trans: PlCS172 Cannabivarinic acid, '-9-tetrahydro, trans: Cannabiorcol: PlCS172 PlCS172 Cannabiorcolic acid, '-9-tetrahydro, trans: Cannabivarol, '-9-tetrahydro: PlCS146 PlCS172 Cannabivarol, tetrahydro: PlCS041 Cannabipinol: PlCS172 Cannabivarol: Fl topsCS211 Cannabiprene: Lf 26.8CS091 Cannabivarolic acid, tetrahydro: PlCS041 Cannabiripsol: PlCS172, AerCS165 Cannflavin A: Aer 190CS028 Cannabisativine, anhydro: PlCS172 Cannflavin B: Aer 30CS028 Cannabisativine: Rt 2CS085 Cannflavin: Lf 138.5CS027 Cannabiscoumaranone: Resin 140CS150 Cannflavone 2: AerCS226 Cannabisin A: Fr 74CS029 Canniflavone 1: Lf 0.8CS185 Cannabisin B: Fr 812CS030 Canniflavone 2: 6CS185 Cannabisin C: Fr 0.267%CS030 Canniprene: Lf 27-1490CS209, CS182, PlCS172 Cannabisin D: Fr 59.8CS030 Car-3-ene: InflorescenceCS036, EOCS156, PlCS172 Cannabisin E: Fr 120CS031 Car-4-ene: PlCS172, CS068 Cannabisin F: Fr 45CS031 Carbazole: Lf (smoke)CS054 Cannabisin G: Fr 20CS031 Carvacrol: Lf EOCS062, PlCS172 Cannabisiradienone: PlCS172 Carveol acetate, dihydro: PlCS172, EOCS156 CANNABIS SATIVA 35

Carvone, dihydro: RtCS122, EOCS156, PlCS172 Docosane, N: PlCS172 Carvone: RtCS122, EOCS156, PlCS172 Dodecan-1-al: EOCS156, PlCS172 Caryophyllene alcohol, D: EOCS156, PlCS068 Dodecan-2-one: PlCS172, EOCS156 Caryophyllene epoxide,E: Lf EO, Fl EOCS196 Dodecane, N: PlCS172 Caryophyllene epoxide: Lf EOCS062 Dotriacontane, 2-methyl: PlCS172 Caryophyllene oxide: Fl topsCS211, Lf EOCS053, Dotriacontane, N: PlCS172 PlCS172 Edestin: PlCS172 Caryophyllene, D: PlCS172, CS068 Edestinase: PlCS172 Caryophyllene, E: PlCS172, ResinCS069, Fl Eicosadienoic acid: PlCS172 EOCS196, InflorescenceCS036 Eicosane, N: PlCS172 Caryophyllene, iso: PlCS172, Inflorescence Eicosenoic acid: PlCS172 EOCS036 Elemene,J: EOCS156, Fl EO, Lf EOCS196, PlCS172 Caryophyllene: Lf EOCS062 Ereptase (peptidase): PlCS172 Caryophyllenol: PlCS172 Ergostan-3-one, 5-D: Call TissCS083 Castasterone: SdCS071 Ergosterol: PlCS172 Cedrene, D: PlCS172, EOCS156 Erythritol: PlCS172, Cellulose, hemi: PlCS172 Essential oil: Aer 0.09–0.11%CS156, Cholest-4-en-3-one, 24-methyl: SdCS077 Lf 0.15%CS062, InflorescenceCS036 Cholestan-3-one, 5-D, 24-methyl: SdCS077 Ethanol: PlCS172 Cholesterol: SdCS076 Ethanolamine: PlCS172 Choline: Rt, Fl topsCS070, LfCS177, PlCS172 Ethylamine, (DL): PlCS172 Chrysene: Lf (smoke) 5 Pg/100 CigCS088 Ethylamine: PlCS172 Cineol, 1-4: PlCS172, Lf EOCS062 Eudesmol,J: EOCS156, PlCS172 Cineol, 1-8: Lf EOCS062, PlCS172 Eugenol methyl ether: EOCS156, PlCS172 Cinnamic acid, trans: LfCS006, PlCS172 Eugenol, iso: EOCS156, PLCS172 Cinnamide, N-(para-hydroxy-E-phenylethyl)- Eugenol: EOCS156, PlCS172 para-hydroxy-(trans): PlCS172 Farnesene, D trans, trans: EOCS156, PlCS172 Citric acid, iso: PlCS172 Farnesene, D: Fl EO, Lf EOCS196 Citric acid: PlCS172 Farnesene, E, cis: PlCS172 Citronellol: EOCS156, PlCS172 Farnesene, E, trans: Fl EOCS196, Lf EOCS062, CS196 Copaene, D: Lf EOCS062, PlCS172 Farnesene, E: ResinCS069, Inflorescence Cosmosioside: PlCS172 EOCS036, EOCS156, PlCS172 Coumaric acid, para: PlCS172 Farnesene: PlCS172 Cubebene, D: PlCS172, EOCS156 Farnesol: PlCS172, EOCS156 Curcumene, D: PlCS172, Lf EOCS062 Farnesyl-acetone: EOCS156, PlCS172 Curcumene, E: PlCS172,CS068 Fatty acids: SdCS059 Curcumene: EOCS156 Fenchol: Lf EOCS062, PlCS068 Cyclocitral, E: PlCS172, EOCS156 Fenchone: EOCS156, PlCS172 Cyclohex-5-enone, 2-2-6-trimethyl: PlCS172, Fenchyl alcohol: ResinCS069, EOCS156, PlCS172 EOCS156 Ferulic acid: PlCS172 Cyclohexanone, 2-2-6-trimethyl: EOCS156, Flavocannabiside: AerCS121 PlCS172 Flavone, 4-5-7-trihydroxy-3-methoxy-6- Cyclolanost-24-methylene-3-E-acetate: PlCS033 geranyl: Lf 6CS182 Cymen-8-ol, para: EOCS156, PlCS172 Flavosativaside: AerCS121 Cymene, para: PlCS172, CS068, EOCS156, Friedelanol, epi: PlCS172, CS068 InflorescenceCS036 Friedelin: PlCS172, CS033, CS068, RtCS122 Cystine: PlCS172 Friedelinol, epi: PlCS172, RtCS122 Dec-3-en-5-one: EOCS156, PlCS172 Fructose: PlCS172 Decan-1-al: PlCS172, EOCS156 Furfural, 5-methyl: EOCS156 Decan-2-one: EOCS156, PlCS172 Furo-(1,2,A)-4-N-pentyl-7-7-10-trimethyl- Decane, N: PlCS172 dibenzopyran, 2-methyl: Lf (smoke)CS195 Dibenz-(A-1)-anthracene: Lf (smoke) 0.3 Pg/ Furo-(1,2,A)-4-N-pentyl-7-7-10-trimethyl- CigCS088 dibenzopyranyl: Lf (smoke)CS195 36 MEDICINAL PLANTS OF THE WORLD

Furo-(1,2-A)-4-N-pentyl-7-7-10-trimethyl- Hexyl acetate: EOCS156 dibenzopyran, 2-3-dimethyl: Hexyl iso-butyrate: EOCS156 Lf (smoke)CS195 Histamine: PlCS172 Galactitol: PlCS172 Histidine: PlCS172 Galactosamine: PlCS172, Lf/St 1.9%CS081 Hordenine: LfCS051, PlCS172 Galactose: PlCS172 Humulene oxide I: PlCS172 Galacturonic acid: PlCS172 Humulene oxide II: PlCS172 Geraniol: Lf EOCS062, PlCS172 Humulene oxide: EOCS156 Geranyl acetone: PlCS172, EOCS156 Humulene,D: Lf EO, Fl EOCS196 Glucaric acid: PlCS172 Humulene,E: PlCS172, Inflorescence EOCS036, Gluconic acid: PlCS172 EOCS156 Glucosamine: PlCS172 Humulene: Lf EOCS062, ResinCS069 Glucose, D (D): PlCS172 Indan-1-spiro-cyclohexane, 5-7-dihydroxy: Glucose, E(D): PlCS172 ResinCS026 Glutamic acid: PlCS172 Indan-1-spiro-cyclohexane, 5-hydroxy-7- Glyceric acid: PlCS172 methoxy: ResinCS026 Glycerol, (D), D-manno-octulose: PlCS172 Indan-1-spiro-cyclohexane, 7-hydroxy-5- Glycerol: PlCS172 methoxy: ResinCS026 Glycine: PlCS172 Indole: Lf (smoke)CS054 Glycoprotein (Cannabis sativa): Lf CS119 Inositol, (+): PlCS172 Grossamide: Fr 8CS029 Inositol, myo: PlCS172, Fl/LfCS082 Guaiol: PlCS172 Ionone, E: EOCS172, PlCS172 Gurjunene,D: Fl EOCS196, ResinCS069, PlCS172 Kaempferol: AerCS241 Heneicosane, 3-methyl: PlCS172 Ledol: PlCS172, EOCS156 Heneicosane, N: PlCS172 Leucine, iso: PlCS172 Hentriacontane, 2-methyl: PlCS172 Leucine: PlCS172 Hentriacontane, 3-methyl: PlCS172 Lignanamide I: FrCS093 Hentriacontane, N: PlCS172 Limonene: PlCS172, Fl EOCS196, ResinCS069, Hept-2-3n-6-one, 2-methyl: PlCS172 Inflorescence EOCS036 Hept-5-en-2-one, 6-methyl: EOCS156 Linalool, cis, oxide: EOCS156, PlCS172 Heptacosane, 3-methyl: PlCS172 Linalool, trans, oxide: PlCS172 Heptacosane, N: AerCS063, PlCS172 Linalool: PlCS172, ResinCS069, Lf EOCS062 Heptadecane, 3-6-dimethyl: PlCS172 Linoleic acid methyl ester: PlCS172 Heptadecane, 3-7-dimethyl: PlCS172 Linoleic acid: PlCS172, SdCS134 Heptadecane, N: PlCS172 Linolenic acid methyl ester: EOCS156 Heptan-1-al: PlCS172, EOCS156 Linolenic acid: PlCS172, SdCS134 Heptan-2-one: EOCS156, PlCS172 Longifolene, (+): PlCS068 Heptatriacontane, N: PlCS172 Longifolene: PlCS172, EOCS156, Inflorescence Heptulose, sedo: PlCS172 EOCS036 Hexacosane, 2-methyl: PlCS172 Lysine: PlCS172 Hexacosane, N: PlCS172 Malic acid: PlCS172 Hexadecanamide: ResinCS116 Malonic acid: PlCS172 Hexadecane, N: PlCS172 Maltose: PlCS172 Hexadecane-1-ol: PlCS172, EOCS156 Mannitol: PlCS172 Hexan-1-al: EOCS156, PlCS172 Mannose: PlCS172 Hexan-1-ol acetate: PlCS172 Mentha-1-8(9)-dien-5-ol, meta: PlCS172 Hexan-1-ol butyrate: PlCS172 Methanol: PlCS172 Hexan-1-ol caproate: PlCS172 Methionine: PlCS172 Hexan-1-ol iso-butyrate: PlCS172 Methyl acetate: PlCS172 Hexatriacontane, N: PlCS172 Methylamine, di: PlCS172 Hex-cis-3-en-1-ol caproate: EOCS156 Methylamine: PlCS172 Hex-cis-3-enol caproate: PlCS172 Muscarine: PlCS172 CANNABIS SATIVA 37

Myrcene: Fl EOCS196, ResinCS069, Inflorescence Perillene: EOCS156, PlCS172 EOCS036, PlCS068 Peroxidase: PlCS172 Myristic acid: PlCS172, EOCS156 Perylene: Lf (smoke) 0.9 Pg/CigCS088 Nerol: EOCS062, PlCS172 Phellandrene,D: Inflorescence EOCS036, PlCS172 Nerolidol: Lf EOCS062, PlCS172 Phellandrene,E: Lf EOCS062, PlCS172 Neurine: PlCS172, RtCS070 Phenethylamine, E: PlCS172 Nonacosane, N: AerCS063, PlCS172 Phenol, 2-6-di-tert-butyl-4-methyl: EOCS156 Nonadecane, N: PlCS172 Phenol, 3-[2-(3-hydroxy-4-methoxy-phenyl)- Nonan-1-al: PlCS172, EOCS156 ethyl]-5-methoxy: PlCS172 Nonan-1-ol: PlCS172, EOCS156 Phenol, 3-[2-(3-hydroxy-4-methoxy-phenyl)- Nonane, N: PlCS172 ethyl]-ethyl-5-methoxy: PlCS172 Nonatriacontane, N: PlCS172 Phenol, 3-[2-(3-iso-prenyl-4-hydroxy-5- Ocimene, E, cis: PlCS172, EOCS156 methoxy-phenyl)-ethyl]-5-methoxy: PlCS172 Ocimene, E, trans: Lf EOCS062, PlCS172, CS068 Phenol, 3-[2-(4-hydroxy-phenyl)-ethyl]-5- Ocimene, cis: Inflorescence EOCS036 methoxy: PlCS172 Ocimene, trans: Inflorescence EOCS036 Phenol, 4-vinyl: AerCS159 Oct-1-en-3-ol: PlCS172, EOCS156 Phenol, 5-methoxy-3-[2-(3-hydroxy-4- Octacosane, 2-methyl: PlCS172 methoxy-phenyl)-ethyl]: Lf 1.9CS209 Octacosane, 9-methyl: PlCS172 Phenylalanine: PlCS172 Octacosane, N: PlCS172 Phloriglucinol, E-D-glucoside: StCS102 Octadecane, 3-6-dimethyl: PlCS172 Phosphatase, adenosine-5: PlCS172 Octadecane, 3-7-dimethyl: PlCS172 Phosphoric acid: PlCS172 Octadecane, N: PlCS172 Phthalate, N-butyl: EOCS156 Octan-1-al: EOCS156, PlCS172 Phthalate, N-propyl: EOCS156 Octan-1-ol caproate: PlCS172 Phytol: EOCS156, PlCS172 Octan-1-ol: EOCS156, PlCS172 Pinene, D, oxide: EOCS172, PlCS172 Octan-3-ol: EOCS156, PlCS172 Pinene, D: ResinCS069, Inflorescence EOCS036, Octan-3-one: EOCS156, PlCS172 Lf EOCS062, PlCS172 Octatriacontane, N: PlCS172 Pinene,E: Lf EOCS062, ResinCS069, Inflorescence Octyl caproate: EOCS156 EOCS036, PlCS172 Oleic acid methyl ester: Call TissCS083 Pinocarveol: EOCS156, PlCS172 Oleic acid: PlCS172, SdCS134 Pinocarvone: EOCS156, PlCS172 Olivetol: AerCS226 Piperidine: Fl top, LfCS070, PlCS172 Orientin: AerCS121, PlCS172 Piperitenone oxide: EOCS156, PlCS172 Orientin-2-O-E-D-glucoside: PlCS172, Piperitenone: ResinCS069, EOCS156, PlCS172 Aer 4.2CS131 Piperitone oxide: EOCS156, PlCS172 Orientin-7-O-D-L-rhamnosyl glucoside: PlCS172 Proline, L: RtCS070 Orientin-7-O-E-D-glucoside: PlCS172 Proline: PlCS172 Oxidase, polyphenol: PlCS172 Prop-1-ene, 3-phenyl-2-methyl: PlCS172, Palmitic acid methyl ester: Call TissCS083, EOCS156 EOCS156, PlCS172 Prospylamine, N: PlCS172 Palmitic acid: SdCS134, PlCS172 Pulegone: EOCS156, PlCS172 Palmitoleic acid: PlCS172 Pyrano-(3-4-B)-benzofuran, 1-4 5-hydroxy-7- Pectin: PlCS172 pentyl-1-(A)-D-3-3-trimethyl-ethano-1- Pentacosane, 3-methyl: PlCS172 (H): AerCS115 Pentacosane, N: PlCS172 Pyrene: Lf (smoke) 6.6 Pg/CigCS088 Pentadecan-2-one, 6-10-14-trimethyl: PlCS172, Pyroglutamic acid: PlCS172 EOCS156 Pyrrolidine: PlCS172 Pentadecan-2-one: EOCS156, PlCS172 Quebrachitol, (+): PlCS172 Pentadecane, N: PlCS172 Querachitol: Fl/LfCS082 Pentan-1-al: EOCS156, PlCS172 Quercetin: AerCS241 Pentatriacontane, N: PlCS172 Raffinose: PlCS172 38 MEDICINAL PLANTS OF THE WORLD

Rhamnose: PlCS172 Terpineol, D: PlCS172, ResinCS069, Lf EOCS062, Ribitol: PlCS172 EOCS068 Ribose: PlCS172 Terpineol, E: EOCS156, PlCS172 Sabinene, trans: PlCS172, EOCS156 Terpinolene: Fl EOCS062, Lf EOCS062, Inflores- Sabinene: EOCS156, PlCS172 cence EOCS036, PlCS172 Safranal: EOCS156, PlCS172 Tetracosane, 2-methyl: PlCS172 Salicyclic acid methyl ester: EOCS156, PlCS172 Tetracosane, N: PlCS172 Santalene, E, epi: PlCS172, EOCS156 Tetradecane, 2-6-dimethyl: PlCS172 Sativic acid: PlCS172 Tetradecane, N: PlCS172 Scyllitol: Fl/LfCS082 Tetratriacontane, N: PlCS172 Selina-3-7(11)-diene: PlCS172, Inflorescence Threonic acid: PlCS172 EOCS036 Threonine: PlCS172 Selina-4(14)-7(11)-diene: Inflorescence Thujene, D: PlCS172, CS068, EOCS156 EOCS036, PlCS172 Thujol alcohol: PlCS172, EOCS156 Selinene,D: PlCS172, Inflorescence EOCS036, Triacontane, 3-methyl: PlCS172 EOCS156 Triacontane, N: PlCS172 Selinene,E: Inflorescence EOCS036, PlCS172, Tricosane, 3-methyl: PlCS172 EOCS156 Tricosane, N: PlCS172 Serine: PlCS172 Tridecan-1-al: EOCS156, PlCS172 Sitostanol: SdCS076 Tridecane, 3-6-dimethyl: PlCS172 Sitosterol, E: RtCS122, SdCS076, Call TissCS083, Tridecane, N: PlCS172 PlCS172 Trigonelline: PlCS172, FL topCS070 Skatole: Lf (smoke)CS054 Tritriacontane, N: PlCS172 Sorbitol: PlCS172 Tryptophan: PlCS172 Spiro-(cyclohexane-1-3-(4-6-dihydroxy)- Tyramine, feruloyl: Sd 2.5, Rt, Resin, indan): Fl topCS135 LfCS149,CS230 Spiro-(cyclohexane-1-3-(4-hydroxy-6- Tyramine, N-(para-coumaroyl): Fr 111CS029, methoxy)-indan): Fl topCS135 Sd 111CS092 Spiro-(cyclohexane-1-3-(6-hydroxy-4- Tyramine, N-trans-caffeoyl: Fr 47.1CS029 methoxy)-indan): Fl topCS135 Tyramine, N-trans-feruloyl: Fr 78.5CS029 Stearic acid methyl ester: Call TissCS083 Tyramine, para-coumaroyl: Sd 0.5CS230, Rt, Lf, Stearic acid: PlCS172, SdCS134 ResinCS149,CS230 Stigmast-22-en-3-one, 5-D: Call TissCS083 Tyramine: PlCS172 Stigmast-4-en, 3-one: PlCS172, RtCS050 Tyrosine: PlCS172 Stigmast-5-en-3-E-ol-7-one: RtCS050, PlCS172 Undecan-1-al: EOCS156, PlCS172 Stigmasta-4-22-diene-3-one: RtCS050, PlCS172 Undecan-2-one, 6-10-dimethyl: EOCS156, Stigmasta-5-22-dien-3-E-ol-7-one: RtCS050 PlCS172 Stigmasta-7-24(28)-dien-3-E-ol, 5-D: PlCS172 Undecan-2-one: EOCS156, PlCS172 Stigmastan-3-one, 5-D: Call TissCS083 Undecane, N: PlCS172 Stigmasterol: SdCS076, PlCS172 Valine: PlCS172 Stilbene, dihydro 3'-5-dihydroxy-3-4- Vanillic acid: PlCS172 dimethoxy: LfCS185 Vitamin K: PlCS172 Stilbene, dihydro 4’-5-dihydroxy-3-methoxy: Vitexin, iso, 7-O-D-L-rhamnosyl-glucoside: LfCS185 PlCS172 Succinic acid: PlCS172 Vitexin, iso, 7-O-E-D-glucosyl-arabinoside: Sucrose: PlCS172 PlCS172 Terpinen-4-ol, D: PlCS172 Vitexin, iso: PlCS172 Terpinen-4-ol: Lf EOCS062, PlCS172 Vitexin-2-E-D-glucoside: PlCS172, Aer 4CS131 Terpinene, D: Lf EOCS062, PlCS172, Inflores- Vitexin-7-O-E-D-(6-glucoside): PlCS172 cence EOCS036 Vomifoliol, dihydroxylan: PlCS172 Terpinene, J: PlCS172, ResinCS069, EOCS156, Vomifoliol: PlCS172 Inflorescence EOCS036 Xylitol: PlCS172 CANNABIS SATIVA 39

Xylose: PlCS172 ence of measurable levels of '-9-THC in the Zeatin nucleoside: PlCS172 blood of drivers in the absence of alcohol or CS172 Zeatin: Pl other drugs, by surveys of driving under the PHARMACOLOGICAL ACTIVITIES influence of cannabis, and by significantly AND CLINICAL TRIALS higher accident culpability risk of drivers Abortifacient activity. Alcohol extract of using cannabis. Evidence demonstrated that the dried leaf, administered intragastrically cannabis dependence, both behavioral and to pregnant rats at a dose of 125 mg/kg, pro- physical, occurred in about 7–10% of regu- duced teratogenic effectsCS233. Water extract lar users, and that early onset of use—espe- of the dried leaf, administered intragastri- cially of weekly or daily use—is a strong cally to pregnant rats at variable dosage lev- predictor of future dependence. Cognitive els on days 6–15 of pregnancy was activeCS228. impairments of various types are readily Acute cardiovascular fatalities. Six cases demonstrable during acute cannabis intoxi- of possible acute cardiovascular death in cation, but there is no suitable evidence yet young adults were reported where very available to permit a decision as to whether recent cannabis ingestion was documented long-lasting or permanent functional losses by the presence of '-9-tetrahydrocannab- can result from chronic heavy use in inol ('-9-THC) in postmortem blood adultsCS265. The gender effects on progression samples. A broad toxicological blood analy- to treatment entry and on the frequency, sis could not reveal other drugsCS392. severity, and related complications of the Acute panic reaction (Koro). Koro, an Diagnostic and Statistical Manual of Mental acute panic reaction related to the percep- Disorders, 3rd edition revised drug and alco- tion of penile retraction, was once consid- hol dependence among 271 substance- ered limited to specific cultures. Over 70 dependent patients (mean age: 32.6 years; American men responded by telephone to 156 women) was studied. There was no gen- report negative reactions to cannabis. Three der difference among patients in the age at of them (Caucasians aged 22–26 years with onset of regular use of any substance. considerable experience with cannabis) Women experienced fewer years of regular spontaneously mentioned experiencing use of opioids and cannabis and fewer years symptoms of Koro after smoking cannabis. of regular alcohol drinking before entering All three cases occurred after the partici- treatment. Although the severity of drug pants had heard about cannabis-induced and alcohol dependence did not differ by Koro and used the drug in a novel setting or gender, women reported more severe psy- atypical way. Two of the men had body chiatric, medical, and employment com- dysmorphia, which may have contributed to plicationsCS285. In a 3-day, double-blind, symptoms. All three decreased their can- randomized, counterbalanced study, the nabis consumption after the Koro experi- behavioral, cognitive, and endocrine effects ence. Several factors may have interacted to of 2.5 and 5 mg intravenous '-9-THC were create the symptoms. These include previ- characterized in 22 healthy individuals, who ous knowledge of cannabis-induced Koro, had been exposed to cannabis but had never the use of cannabis in a way that might been diagnosed with a cannabis abuse disor- heighten a panic reaction, and poor body der. Prospective safety data at 1, 3, and 6 imageCS393. months post-study was also analyzed. '-9- Adverse effects. A causal role of acute can- THC produced schizophrenia-like positive nabis intoxication in motor vehicle and and negative symptoms, altered perception, other accidents has been shown by the pres- increased anxiety and plasma cortisol, 40 MEDICINAL PLANTS OF THE WORLD euphoria, disrupted immediate and delayed of CB1 receptor has been shown to block word recall, sparing recognition recall, voluntary alcohol intake in miceCS255. impaired performance on tests of distract- Allergenic effect. An “All India Coordi- ibility, verbal fluency, and working memory, nated Project on Aeroallergens and Human but did not impair orientationCS287. This Health” was undertaken to discover the study examined the behavioral and neuro- quantitative and qualitative prevalence of chemical (cannabinoid CB1 receptor gene aerosols at 18 different centers in the coun- expression) changes induced by spontane- try. Predominant airborne pollens were ous cannabinoid withdrawal in mice. Ces- Holoptelea, Poaceae, Asteraceae, Eucalyp- sation of CP-55,940 treatment in tolerant tus, Casuarina, Putanjiva, Cassia, Quercus, mice induced a spontaneous time-depen- Cocos, Pinus, Cedrus, Ailanthus, Cheno/Ama- dent behavioral withdrawal syndrome ranth, Cyperus, Argemone, Xanthium, Parthen- consisting of marked increases (140%) in ium, and others. Clinical and immunological motor activity, number of rearings (170%), evaluations revealed some allergenically decreases in grooming (57%), wet-dog important taxa. Allergenically important shakes (73%), and rubbing behaviors (74%) pollens were Prosopis juliflora, Ricinus com- on day 1, progressively reaching values simi- munis, Morus, Mallotus, Alnus, Querecus, lar to vehicle-treated mice on day 3. This Cedrus, Argemone, Amaranthus, Chenopo- spontaneous cannabinoid withdrawal dium, Holoptelea, Brassica, Cocos, Cannabis, resulted in CB1 gene expression up-regula- Parthenium, Cassia, and grassesCS317. In the tion (20–30%) in caudate-putamen, ventro- multitest routine skin-test battery, 78 of 127 medial hypothalamic nucleus, central patients tested (61%) were cannabis-test amygdaloid nucleus, and CA1, whereas in positive. Thirty of the 78 patients were ran- the CA3 field of hippocampus, a significant domly selected to determine if they had decrease (15–20%) was detectedCS293. allergic rhinitis and/or asthma symptoms Alcohol interaction. The complementary during the cannabis pollination period. By DNA and genomic sequences encoding G history, 22 (73%) claimed respiratory symp- protein-coupled cannabinoid receptors toms in July through September. All 22 of (CB1 and CB2) from several species were these subjects were also skin test-positive to cloned. This has facilitated discoveries of weeds pollinating during the same period as endogenous ligands (endocannabinoids). cannabis (ragweed, pigweed, cocklebur, Two fatty acid derivatives characterized to Russian thistle, marsh elder, or kochia)CS411. be arachidonylethanolamide and 2-arachi- Alkaline phosphatase stimulation. Etha- donylglycerol isolated from both nervous nol (95%) extract of the dried resin, admin- and peripheral tissues mimicked the phar- istered intraperitoneally to toads at a dose macological and behavioral effects of '-9- of 10 mg/day for 14 days, was active. The THC. The down-regulation of CB1 receptor results were significant at p < 0.01 levelCS216. function and its signal transduction by Aminopyrene-N-demethylase induction. chronic alcohol was demonstrated. The ob- Ethanol (95%) extract of the dried aerial served down-regulation of CB1 receptor- parts, administered intraperitoneally to rats binding and its signal transduction resulted at a dose of 2 mg/kg for 15 days, was active. from the persistent stimulation of receptors A dose of 20 mg/kg for 7 days was also by the endogenous CB1 receptor agonists activeCS141. arachidonylethanolamide and 2-arachi- Amnesic syndrome. A 26-year-old woman donylglycerol, whose synthesis is increased suffered disseminated intravascular coagula- by chronic alcohol treatment. The deletion tion (DIC) and a brief respiratory arrest fol- CANNABIS SATIVA 41

lowing recreational use of 3,4-methylene- effective dose (ED)50 35.5 mg/kg and hot CS052 dioxymethamphetamine (MDMA, or “ec- plate method, ED50 53 mg/kg . Petroleum stasy”) together with amyl nitrate, lysergic ether and ethanol (95%) extracts of the acid (LSD), cannabis, and alcohol. She was dried aerial parts, administered intragastri- left with residual cognitive and physical cally to mice, was active vs phenylbenzo- deficits, particularly severe anterograde quinone-induced writhing, inhibitory memory disorder, mental slowness, severe concentration (IC)50 0.013 mg/kg and 0.045 ataxia, and dysarthria. Follow-up investiga- mg/kg, respectivelyCS140. tions have shown that these have persisted, Analgesic effect. Ajulemic acid (AJA, although there has been some improvement CT-3, or IP-751), administered to healthy in verbal recognition memory and in social human adults and patients with chronic functioning. Magnetic resonance imaging neuropathic pain, demonstrated a complete and quantified positron emission tomogra- absence of psychotropic actions. It proved phy investigations revealed severe cerebel- to be more effective than placebo in reduc- lar atrophy and hypometabolism accounting ing this type of pain as measured by the for the ataxia and dysarthria; thalamic, visual analog scale. Signs of dependency retrosplenial, and left medial temporal were not observed after withdrawal at the hypometabolism to which the anterograde end of the 1-week treatment periodCS274. amnesia can be attributed. There was some Forty women undergoing elective abdomi- degree of frontotemporal–parietal hypome- nal hysterectomy were investigated in a ran- tabolism, possibly accounting for the cogni- domized, double-blind, placebo-controlled, tive slowness. The putative relationship of single-dose trial. Randomization took place these abnormalities to the direct and indi- when postoperative patient-controlled rect effects of MDMA toxicity, hypoxia, and analgesia was discontinued on the second ischemia was consideredCS394. postoperative day. When patients requested Amyotrophic lateral sclerosis. One hun- further analgesia, they received a single, dred thirty one respondents with amyo- identical capsule of either 5 mg of oral '-9- trophic lateral sclerosis—13 of whom THC (n = 20) or placebo (n = 20) in a reported using cannabis in the last 12 double-blind fashion. The primary outcome months—were examined. The results indi- measure was summed pain intensity differ- cated that cannabis might be moderately ence (SPID) at 6 hours after administration effective at reducing symptoms of appetite of the study medication derived from visual loss, depression, pain, spasticity, and drool- analog pain scores on movement and at rest. ing. Cannabis was reported ineffective in Secondary outcome measures were time-to- reducing difficulties with speech and swal- rescue medication and adverse effects of lowing, and sexual dysfunction. The long- study medication. Mean (standard devia- est relief was reported for depression (approx tion [SD]) visual analog scale pain scores 2–3 hours)CS296. before medication in the placebo and '-9- Analgesic activity. Ethanol (50%) extract THC groups were 6.3(2.6) and 6.4(1.3) cm of the entire plant, administered intraperi- on movement, and 3.2(1.9) and 3.3(0.9) at toneally to mice at a dose of 250 mg/kg, was rest, respectively. There were no significant active vs tail pressure methodCS007. Flavonoid differences in mean (95% confidence inter- fraction of the leaf, administered intraperi- val [CI] of the difference) SPID at 6 hours toneally to mice, was activeCS242. The inflo- between the groups (placebo 7.9, '-9-THC rescence, administered orally to male rats, 4.3[–1.8 to 9] cm per hour on movement; produced weak activity vs paw pressure test, placebo 8.8, '-9-THC 4.9[–0.2 to 8.1] cm 42 MEDICINAL PLANTS OF THE WORLD per hour at rest) and time to rescue analge- were studied. Seventy-two (35%) subjects sia (placebo 217, '-9-THC 163[–22 to 130] reported ever having used cannabis. Thirty- minutes). Increased awareness of surround- two (15%) subjects reported having used ings was reported more frequently in pa- cannabis for pain relief (pain users), and 20 tients receiving '-9-THC (40 vs 5%, p = (10%) subjects were currently using can- 0.04). There were no other significant dif- nabis for pain relief. Thirty-eight subjects ferences with respect to adverse eventsCS326. denied using cannabis for pain relief (recre- THC, morphine, and a THC–morphine ational users). Compared with nonusers, combination were administered to 12 pain users were significantly younger (p = healthy subjects using experimental pain 0.001) and were more likely to be tobacco models (heat, cold, pressure, and single and users (p = 0.0001). The largest group of repeated transcutaneous electrical stimula- patients using cannabis had pain caused by tion). THC (20 mg), morphine (30 mg), trauma and/or surgery (51%), and the site THC–morphine (20 mg THC + 30 mg mor- of pain was predominantly neck/upper body phine), or placebo were given orally as and myofascial (68 and 65%, respectively). single dose. Reaction time, side effects (vi- The median duration of pain was similar in sual analog scales), and vital functions were both pain users and recreational users (8 vs monitored. For the pharmacokinetic profil- 7 years; p = 0.7). There was a wide range of ing, blood samples were collected. THC did amounts and frequency of cannabis use. Of not significantly reduce pain. In the cold the 32 subjects who used cannabis for pain, and heat tests, it even produced hyperalge- 17 (53%) used four puffs or less at each dos- sia, which was completely neutralized by ing interval, eight (25%) smoked a whole THC–morphine. A slight additive analge- cannabis cigarette (joint), and four (12%) sic effect was observed for THC–morphine smoked more than one joint. Seven (22%) in the electrical stimulation test. No anal- of these subjects used cannabis more than gesic effect resulted in the pressure and heat once daily, five (16%) used it daily, eight test, with neither THC nor THC–mor- (25%) used it weekly, and nine (28%) used phine. Psychotropic and somatic side effects it rarely. Pain, sleep, and mood were most (sleepiness, euphoria, anxiety, confusion, frequently reported as improving with can- nausea, dizziness, etc.) were common, but nabis use, and “high” and dry mouths were usually mildCS330. Three cannabis-based the most commonly reported side effectsCS351. extracts '-9-THC, cannabidiol [CBD], and Patients with chronic pain completed a a 1:1 mixture of them both) were given over questionnaire about the type of cannabis a 12-week period in a randomized, double- used, the mode of administration, the blind, placebo-controlled, crossover trial. amount used and the frequency of use, and Extracts, which contained THC, proved their perception of the effectiveness of most effective in symptom control. Regi- cannabis on a set of pain-associated symp- mens for the use of the sublingual spray toms and side effects. Fifteen patients (10 emerged and a wide range of dosing require- males) were interviewed (median age, 49.5 ments was observed. Side effects were com- years; range, 24–68 years). All patients mon, reflecting a learning curve for both smoked herbal cannabis for therapeutic patient and study team. These were gener- reasons (median duration of use, 6 years; ally acceptable and little different to those range, 2 weeks–37 years). Seven patients seen when other psychoactive agents are only smoked at night (median dose eight used for chronic painCS294. Over a 6-week puffs, range two to eight puffs), and eight period 209 chronic noncancer pain patients patients used cannabis mainly during the CANNABIS SATIVA 43 day (median dose of three puffs; range, two that a flare might last anywhere from a few to eight puffs); the median frequency of use days to a few weeks and relief from flare were was four times per day (range, 1 to 16 times/ by analgesic injections (including opiates), day). Twelve patients reported improve- relaxation, sleep, and cannabis (three indi- ment in pain and mood, whereas 11 viduals). Three-quarters of the groups reported improvement in sleep. Eight agreed that there was no long-term effect on patients reported a “high;” six denied a the ankylosing sponylitis following a “high.” Tolerance to cannabis was not flareCS378. reportedCS368. THC was administered to six Anti-anaphylactic activity. Water extract patients with chronic pain at doses 5–20 of the dried fruit, at a concentration of 1 Pg/ mg/day. A sufficient pain relief had been mL, produced weak activity on the rat achieved in three patients. The other three Leuk-RBL 2H3 vs biotinyl immunoglobulin suffered from intolerable side effects, such E-avidin complex-induced degranulation as nausea, dizziness, and sedation without a of E-hexosaminidaseCS103. reduction of pain intensity. In these cases, Anti-androgenic effect. Ethanol (95%) the treatment was continued with other extract of the aerial parts, administered analgesicsCS391. intraperitoneally to castrated mice at a dose Anaphrodisiac effect. Tincture of the of 2 mg/animal, produced strong activityCS012. resin, administered intraperitoneally to The dried leaf, smoked by 13 male adults for male mice at a dose of 12.5 mg/kg, produced 21 days, was inactiveCS208. a significant reduction in mounts and Anti-arthritic effect. Oral administration attempted mounts. Other behaviorial of AJA, a cannabinoid acid devoid of activities were unaffectedCS153. psychoactivity, reduced joint tissue damage Angiotensin-converting enzyme inhibi- in rats with adjuvant arthritis. Peripheral tion. Ethanol (100%) extract of the dried blood monocytes (PBM) and synovial leaf at a concentration of 333.3 Pg/mL pro- fluid monocytes (SFM) were isolated from duced weak activity, and the water extract healthy subjects and patients with inflam- was inactiveCS129. matory arthritis, respectively, treated with Ankylosing spondylitis. Ankylosing spon- AJA (0–30 mM) in vitro, and then stimu- dylitis is a systemic disorder occurring in lated with lipopolysaccharide. Cells were genetically predisposed individuals. The dis- harvested for messenger RNA (mRNA), ease course appears to be characterized by and supernatants were collected for bouts of partial remission and flares. There cytokine assay. Addition of AJA to PBM were 214 patients questioned (169 men, 45 and SFM in vitro reduced both steady-state women; average disease duration, 25 years; levels of interleukin-1J (IL-1J) mRNA and age of disease onset, 22 years). The main secretion of IL-1J in a concentration-de- symptoms of flare were pain (all groups), pendent manner. Suppression was maximal immobility (90%), fatigue (80%), and emo- (50.4%) at 10 mM AJA (p < 0.05 vs un- tional symptoms, such as depression, with- treated controls, n = 7). AJA did not drawal, and anger, (75%). All of patients influence tumor necrosis factor-D (TNF-D) experienced between one and five localized gene expression in or secretion from flares per year. Fifty-five percent of the PBMCS358. groups contained patients (n = 85) who Antibacterial activity. Essential oil, on experienced a generalized flare. The main agar plate, was active on Staphylococcus perceived triggers of flare were stress (80%) aureus and Streptococcus faecalis, minimum and “overdoing it” (50%). Patients reported inhibitory concentration (MIC) 0.5 mg/mL, 44 MEDICINAL PLANTS OF THE WORLD and produced weak activity on Pseudomonas perazine, haloperidol, domperidone, or fluorescens and Escherichia coli, MIC 10 mg/ alizapride. Relative risk was 1.38 (95% CI mL and 5 mg/mL, respectivelyCS152. 1.18–1.62), number-needed-to-treat (NNT) Anticonvulsant activity. Ethanol (95%) was 6 for complete control of nausea; rela- extract of the entire plant, administered tive risk was 1.28 (CI 1.08–1.51), NNT 8 subcutaneously to male mice and rats at a for complete control of vomiting. Cannab- dose of 2–4 mL/kg, was active vs metrazole inoids were not more effective in patients and electroshock, respectively. A dose of 4 receiving very low or very high emetogenic mL/kg was inactive vs strychnine convul- chemotherapy. In crossover trials, patients sions in miceCS005. The entire plant, smoked preferred cannabinoids for future chemo- by 29 patients with epilepsy under the age therapy cycles: relative risk 2.39 (2.05– of 30 years, was active. It must be noted that 2.78), NNT 3. Some potentially beneficial in some species, cannabinoids can precipi- side effects occurred more often with can- tate epileptic seizuresCS120. Tincture of the nabinoids: “high” 10.6 (6.86–16.5), NNT 3; resin, administered intraperitoneally to sedation or drowsiness 1.66 (1.46–1.89), mice at a dose of 25 mg/kg, produced 80% NNT 5; euphoria 12.5 (3–52.1), NNT 7. protection vs pentylenetetrazole convul- Harmful side effects also occurred more of- sionsCS058. ten with cannabinoids: dizziness 2.97 (2.31– Antidiuretic activity. After ingesting the 3.83), NNT 3; dysphoria or depression 8.06 aerial parts, a 55-year-old man developed (3.38–19.2), NNT 8; hallucinations 6.10 urinary retention that required catheteriza- (2.41–15.4), NNT 17; paranoia 8.58 (6.38– tion for reliefCS154. 11.5), NNT 20; and arterial hypotension Anti-emetic activity. In a qualitative study 2.23 (1.75–2.83), NNT 7. Patients given of self-care in pregnancy, birth, and lacta- cannabinoids were more likely to withdraw tion within a nonrandom sample of 27 because of side effects (relative risk 4.67 women in British Columbia, Canada, 20 [3.07–7.09]; NNT 11)CS400. women (74%) experienced pregnancy- Anti-estrogenic effect. Ethanol (95%) induced nausea. Ten of these women used extract of the dried aerial parts, adminis- antiemetic herbal remedies, which included tered intragastric to rats at variable doses ginger, peppermint, and cannabis. Only gin- was inactiveCS231. Petroleum ether extract of ger has been subjected to clinical trials the dried leaf, administered intraperito- among pregnant women, although the three neally to female rats at a dose equivalent to herbs were clinically effective against nau- 10 mg/kg tetrahydrocannabinol (THC) on sea and vomiting in other contexts, such as 11–21 days of age, was activeCS175. chemotherapy-induced nausea and post- Antifertility effect. Petroleum ether ex- operative nauseaCS311. CBD, a major non- tract of the entire plant, administered by psychoactive cannabinoid administered by gastric intubation to female mice at doses oral infusion to rats with nausea elicited by of 75 mg/kg and 150 mg/kg, was active. A lithium chloride, and with conditioned nau- dose of 3 mg/kg, produced weak activityCS170. sea elicited by a flavor paired with lithium Resin, administered by gastric intubation to chloride, was activeCS382. Oral nabilone, oral male mice at variable dosage levels, was dronabinol (THC), and intramuscular inactiveCS189. levonantradol were administered to 1366 Antifungal activity. Ethanol (50%) extract patients. Cannabinoids were more effec- of the dried leaf was active on Rhizoctonia tive antiemetics than prochlorperazine, solani, mycelial inhibition was 65.99%CS229. metoclopramide, chlorpromazine, thiethyl- Water extract of the fresh leaf on agar plate CANNABIS SATIVA 45 at a concentration of 1:1 was active on ity, production of oxygen-derived free radi- Fusarium oxysporumCS096. The water extract cals, and nitric oxide ([NO], nitrite/nitrate also produced strong activity on Ustilago content) after three doses of CBD. The maydis and Ustilago nudaCS212. Water extract effect on NO seemed to depend on a lower of the fresh shoot on agar plate was inactive expression of the endothelial isoform of NO on Helminthosporium turcicumCS237. synthaseCS303. Antiglaucomic activity. Water extract of Antimalarial activity. The dried leaf was the dried entire plant, administered intra- inactive on Plasmodium falciparum D-6 and CS095 venously to Rhesus monkeys and rabbits at W-2, IC50 greater than 1000 nmols . a dose of 0.01 Pg/animal, was active. The Antimycobacterial activity. Essential oil, intraocular pressure rose for 24 hours on agar plate, was active on Antimyco- postinjection, then fell for 3 days. A dose of bacterium smegmatis, MIC 0.1 mg/mLCS152. 25 Pg/animal, administered intravenously to Anti-nematodal activity. Water extract of rabbits, was also active. The effect was not the dried leaf at variable concentrations influenced by atropine, scopolamine, produced strong activity on Meloidogyne methysergide, haloperidol, chlorpromazine, incognitaCS200. spironolactone, yohimbine or dexametha- Antioxidant activity. Methanol extract of sone. Partial inhibition was seen when the stem, at concentration 50 PL, produced galactose, glucose or mannose were admin- strong activityCS101. istered intravenously, concurrentlyCS232. Antispasmodic activity. Ethanol (50%) Water extract of the dried leaf and stem, ap- extract of the entire plant was active on the plied opthalmically to rabbits was activeCS072. guinea pig ileum vs acetylcholine and hista- Antigonadotropin effect. Ethanol (80%) mine-induced spasmsCS007. The resin antago- extract of the dried aerial parts, adminis- nized serotonin contractions of the rat tered intragastrically to male langurs at a intestine and non-pregnant uterusCS003. dose of 14 mg/kg daily for 90 days produced Antispermatogenic effect. Sixteen healthy equivocal effectCS173. chronic marijuana smokers were associated Anti-inflammatory activity. Petroleum with a decline in sperm concentration and ether and ethanol (95%) extracts of the total sperm count during the fifth and sixth dried aerial parts, applied externally on mice weeks after 4 weeks of high-dose smoking at a dose of 100 Pg/ear, was active vs tissue (8–20 cigarettes/day)CS164. The dried aerial plasminogen activator-induced erythema of part, taken by inhalation daily, decreases the earCS140. CBD was administered orally to the quantity as well as quality of sper- rats at doses of 5–40 mg/kg daily for 3 days matozoaCS181. Ethanol (80%) extract of the after the onset of acute inflammation in- dried aerial parts, administered intra- duced by intraplantar injection of 0.1 mL gastrically to langurs at a dose of 14 mg/kg carrageenan (1% w/v in saline). CBD had a daily for 90 days, was equivocalCS173. Ethanol time- and dose-dependent antihyperalgesic (95%) extract of the dried aerial parts, effect after a single injection. Edema follow- administered intraperitoneally to mice at a ing carrageenan peaked at 3 hours and lasted dose of 2 mg/animal daily for 45 days, pro- 72 hours. A single dose of CBD reduced duced a complete arrest of spermatogenesis. edema in a dose-dependent fashion and sub- The effect was reversibleCS244. sequent daily doses produced further time- Antistress activity. The leaf smoke, in and dose-related reductions. There were combination with hashish smoke, adminis- decreases in prostaglandin E2 (PGE2) tered to rats housed in a wire cage inside a plasma levels, tissue cyclo-oxygenase activ- larger cage with a cat, was equivocal. The 46 MEDICINAL PLANTS OF THE WORLD rats’ brains were dissected and measured Cannabinoids are usually well tolerated, and for protein and catecholamine levelsCS214. do not produce the generalized toxic effects Anti-tumor activity. Arachidonyl ethanol- of conventional chemotherapiesCS328. amide, in three cervical carcinoma (CxCa) Anti-ulcer activity. Petroleum ether extract cell lines at increasing doses with or with- of the dried aerial parts, administered intra- out antagonists to receptors to arachidonyl peritoneally to male rats, was activeCS097. ethanolamide, induced apoptosis of CxCa Antiviral activity. Hot water extract of the cell lines via aberrantly expressed vanilloid dried fruit, in vero cell culture at a concen- receptor-1. Arachidonyl ethanolamide- tration of 0.5 mg/mL, was inactive on her- binding to the classical CB1 and CB2 can- pes simplex 1 virus, measles virus, and nabinoid receptors mediated a protective poliovirus 1CS094. effect. A strong expression of the three Anxiolytic activity. AEA, a primary endo- forms of arachidonyl ethanolamide recep- genous ligand of the brain cannabinoid tors was observed in ex vivo CxCa biop- receptors, is released in selected regions of siesCS297. Three cannabis constituents, CBD, the brain and is deactivated through a two- '-8-THC, and cannabinol displayed anti- step process consisting of transport into cells proliferative activity in several human can- followed by intracellular hydrolysis. Phar- cer cell lines in vitro. They were oxidized to macological blockade of the enzyme fatty their respective paraquinones 2, 4, and 6. acid amide hydrolase (FAAH), which is Quinone 2 significantly reduced cancer responsible for intracellular AEA degrada- growth of HT-29 cancer in nude miceCS275. tion, produced anxiolytic-like effects in rats '-9-THC binds and activates membrane without causing the wide spectrum of receptors of the 7-transmembrane domain, behavioral responses typical of direct-acting G protein-coupled superfamily. Several cannabinoid agonists. These findings sug- putative endocannabinoids have been iden- gest that AEA contributes to the regulation tified, including anandamide (AEA), 2- of emotion and anxiety, and that FAAH arachidonyl glycerol, and noladin ether. might be the target for a novel class of Synthesis of numerous cannabinomimetics anxiolytic drugsCS323. has expanded the repertoire of cannabinoid Aphrodisiac activity. The leaf, smoked by receptor ligands with the pharmacodynamic adults of both sexes, was activeCS171. properties of agonists, antagonists, and Attention deficit hyperactivity disorder. inverse agonists. These ligands have proven Attention defict hyperactivity disorder has to be powerful tools both for the molecular been considered a mental and behavioral characterization of cannabinoid receptors disorder of childhood and adolescence. It is and the delineation of their intrinsic signal- being increasingly recognized in adults, who ing pathways. Much of the understanding of may have psychiatric comorbidity with sec- the signaling mechanisms activated by can- ondary depression, or a tendency to drug nabinoids has been derived from studies of and alcohol abuse. A 32-year-old woman receptors expressed by tumor cellsCS318. Can- known for years as suffering from borderline nabinoids and their derivatives exerted personality disorder and drug dependence palliative effects in cancer patients by pre- (including cannabis, LSD, and ecstasy) and venting nausea, vomiting, and pain and by alcohol abuse that did not respond to treat- stimulating appetite. These compounds ment was reported. Only when correctly have been shown to inhibit the growth of diagnosed as attention defict hyperactivity tumor cells in culture and animal models by disorder and appropriately treated with the modulating key cell-signaling pathways. psychotropic stimulant methylphenidate CANNABIS SATIVA 47

(Ritalin®), was there significant improve- took ecstasy, 10% took tranquillizers, 9% ment. She succeeded academically, which used hypnotics, 4% used creatine, and 41% had not been possible previously, her crav- used vitamins against fatigue. Beliefs about ing for drugs diminished, and a drug-free doping did not differ among doping agent state was reachedCS446. users and nonusers, except for the associated Auditory function. Eight male subjects health risks, which were minimized by users. (aged 22–30 years) who had previously used Users of doping agents stated that the cannabis were investigated. They performed quality of the relations that they main- air conduction pure tone audiometry in tained with their parents was sharply both ears over 0.5–8 kHz. A simple test of degraded, and they reported that they were frequency selectivity by detecting a 4-kHz susceptible to influence and difficult to live tone under two masking noise conditions with. More often than nondoping-agent was also carried out in one ear. Three test users, these adolescents were neither happy, sessions at weekly intervals were carried out, nor healthy, although paradoxically, they at the start of which they ingested a capsule seemed less anxious and were more self- containing either placebo, 7.5, or 15 mg of confidentCS302. Maternal exposure to '-9- THC. These were administered in a ran- THC in rats resulted in alteration in the domized cross-over, double-blind manner. pattern of ontogeny of spontaneous locomo- Auditory testing was carried out 2 hours tor and exploratory behavior in the off- after ingestion. Blood samples were also spring. Adult animals exposed during obtained at this time point and assayed for gestational and lactational periods exhib- '-9-THC and 11-hydroxy-THC levels. No ited persistent alterations in the behavioral significant changes in threshold or fre- response to novelty, social interactions, quency resolution were seen with the dos- sexual orientation, and sexual behavior. ages employed in this studyCS367. They also showed a lack of habituation and Barbiturate potentiation. Flavonoid frac- reactivity to different illumination condi- tion of the leaf, administered intraperito- tions. Adult offspring of both sexes also neally to mice, was activeCS242. Petroleum displayed a characteristic increase in spon- ether extract of the dried entire plant, taneous and water-induced grooming administered intraperitoneally to pigs at a behavior. Some of the effects were depen- dose of 250 mg/kg, was inactiveCS022. dent on the sex of the animals being studied, Behavioral effect. A four-page, self-com- and the dose of cannabinoid administered pleted questionnaire was designed to deter- to the mother during gestational and lacta- mine the drugs used (licit, illicit, and doping tional periods. Maternal exposure to low substances) along with beliefs about doping doses of THC sensitized the adult offspring and the psychosociological factors associ- of both sexes to the reinforcing effects of ated with their consumption. The question- morphine, as measured in a conditioned naire was distributed to high school students place preference paradigmCS462. enrolled in a school sports association in E-Endorphin interaction. '-9-THC ad- eastern France. The completed forms were ministered to rats produced large increases received from 1459 athletes: 4% stated that in extracellular levels of E-endorphin in they had used doping agents at least once in the ventral tegmental area and lesser their life (their main source of supply being increases in the shell of the nucleus peers and health professionals). Thirty-four accumbens (Nac). In rats that had learned percent of the sample smoked some tobacco, to discriminate injections of THC from 66% used alcohol, 19% used cannabis, 4% injections of vehicle, the opioid agonist 48 MEDICINAL PLANTS OF THE WORLD morphine did not produce THC-like dis- ketocannabinoid, CBD, and a combined criminative effects, but markedly increased oral application of both substances on bin- discrimination of THC. The opioid antago- ocular depth inversion and behavioral states nist naloxone reduced the discriminative were investigated in nine healthy male vol- effects of THC. Bilateral microinjections of unteers. A significant impairment of bin- E-endorphin directly into the ventral teg- ocular depth perception was found when mental area, but not into the shell of the nabilone was administered, but combined Nac, markedly increased the discriminative application with CBD revealed reduced effects of ineffective threshold doses of effects on binocular depth inversionCS414. THC, but had no effect when given alone. Birth-weight effect. A total of 32,483 can- The increase was blocked by naloxoneCS280. nabis-using women giving birth to live-born Binocular depth inversion reduction. A infants were investigated. The largest reduc- study to assess whether the binocular depth tion in mean birth-weight for any cannabis inversion illusion (BDII) could detect subtle use during pregnancy was 48 g (95% CI, 83– cognitive impairment owing to regular can- 14 g), with considerable heterogeneity nabis use was conducted. Ten regular can- among the five studies. Mean birth-weight nabis users and 10 healthy controls from the was increased by 62 g (95% CI, 8-g reduc- same community sources, matched for age, tion – 132-g increase; p heterogeneity, 0.59) sex, and premorbid intelligence quotient among infrequent users (Յ weekly), (IQ) were evaluated. The subjects were also whereas cannabis use at least four times per compared on measures of executive func- week had a 131-g reduction in mean birth- tioning, memory, and personality. Regular weight (95% CI 52–209-g reduction; p het- cannabis users were found to have signifi- erogeneity, 0.25). From the five studies of cantly higher BDII scores for inverted low birth-weight, the pooled odds ratio for images. This was not to the result of a prob- any use was 1.09 (95% CI 0.94–1.27; p het- lem in the primary processing of visual erogeneity, 0.19)CS437. In a cohort study con- information, as there was no significant sisted of a multiethnic population of 7470 difference between the groups for depth pregnant women. Information on the use of perception of normal images. There was drugs was obtained from personal interviews no relationship between BDII scores for at entry to the study and assays of serum inverted images and time since the last dose, obtained during pregnancy. Pregnancy suggesting that the measured impairment of outcome data (low birth-weight [<2500 g], BDII more closely reflected chronic than pre-term birth [<37 weeks gestation], and acute effects of regular cannabis use. There abruptio placentae) were obtained with a were no significant differences between the standardized study protocol. A total of 2.3% groups for other neuropsychological mea- of the women used cocaine and 11% used sures of memory or executive function. A cannabis during pregnancy. Cannabis use positive relationship was found between was not associated with low birth-weight psychoticism as defined by the revised (1.1, 0.9–1.5), pre-term delivery (adjusted Eysenck Personality Questionnaire and can- odds ratio [OR] 1.1, CI 0.8–1.3), or abrup- nabis, tobacco, and alcohol use. Cannabis tio placentae (1.3, 0.6–2.8)CS465. users also used significantly larger amounts Bladder dysfunction. Two whole-plant of alcohol. No relationship was found extracts of Cannabis sativa were adminis- between BDII scores and drug use other tered to patients with advanced multiple than cannabis or psychoticismCS332. Nabi- sclerosis (MS) and refractory troublesome lone, a psychoactive synthetic 9-trans- lower urinary tract symptoms. The patients CANNABIS SATIVA 49 took the extracts containing '-9-THC and lower caffeine consumption group exhib- CBD (2.5 mg of each per spray) for 8 weeks ited AA protection during both phases. followed by THC-only (2.5 mg THC per Covariates (neuroticism, extraversion and spray) for a further eight weeks, and then depression scores, age, sex, body mass index) into a long-term extension. Assessments were not significantCS377. included urinary frequency and volume Blood-borne sexually transmitted infec- charts, incontinence pad weights, cysto- tions. Substance use, including alcohol and metry, and visual analog scales for second- illicit drugs, increases the risk for the acqui- ary troublesome symptoms. Twenty-one sition and transmission of sexually transmit- patients were recruited and data from 15 ted infection (STI). The prevalence of were evaluated. Urinary urgency, the num- blood-borne STI including human immuno- ber and volume of incontinence episodes, deficiency virus (HIV), human T-cell frequency, and nocturia all decreased lymphotrophic virus type 1, hepatitis B significantly following treatment (p < virus, and syphilis in residents of a detoxifi- 0.05, Wilcoxon’s signed rank test). Daily cation and rehabilitation unit in Jamaica total voided, catheterized and urinary were investigated. The demographic char- incontinence pad weights also decreased acteristics and the results of laboratory significantly for both extracts. Patient self- investigations for STI in 301 substance assessment of pain, spasticity, and quality abusers presented during a 5-year period of sleep improved significantly (p < 0.05, were reviewed. The laboratory results were Wilcoxon’s signed rank test) with pain im- compared with those of 131 blood donors. provement continuing up to a median of 35 The substances used by participants were weeks. There were few troublesome side alcohol, cannabis, and cocaine. None of effects, suggesting that cannabis-based the clients was an intravenous drug user. medicinal extracts are a safe and effective Female substance abusers were at higher risk treatment for urinary and other problems in for STI. The prevalence of STI in substance patients with advanced MSCS269. abusers did not differ significantly from that Blood pressure stress reactivity effect. in blood donors (12% vs 10%). The preva- Data from an ascorbic acid (AA) trial lence of syphilis in substance abusers was (Cetebe 3 g/day for 14 days, n = 108) were significantly higher than that in blood compared by substance use level regarding donors (6% vs 3%, p < 0.05). The preva- systolic blood pressure (SBP) stress reactiv- lence of syphilis was dramatically increased ity to the anticipation and actual experience in female substance abusers and female phases of a standardized psychological stres- blood donors (30%, p < 0.001 and 13%, p < sor (10 minutes of public speaking and 0.05, respectively). An excess of human arithmetic). Self-reported never users of T-cell lymphotrophic virus type 1 was also cannabis, persons not currently smoking to- observed in female compared with male sub- bacco, and persons consuming three or more stance abusers. Unemployment was identi- caffeine beverages daily all exhibited AA fied also as a risk factor for sexually SBP stress reactivity protection to the actual transmitted disease in substance abusersCS401. stressor, but not during the anticipation Brain aging effect. The impact of duration phase. Self-reported ever cannabis users, of education, cannabis addiction and smok- current tobacco smokers, and persons con- ing on cognition and brain aging was stud- suming less than three caffeine beverages ied in 211 healthy Egyptian volunteers with daily exhibited the AA SBP protection dur- mean age of 46.4 r 3.6 years (range, 20–76 ing the anticipation phase, but only the years). The subjects were classified into two 50 MEDICINAL PLANTS OF THE WORLD groups: Gr I (n = 174; mean age, 49.9 r 3.8 etic cells and has only 44% overall nucle- years; range, 20–76 years), nonaddicts, otide sequence identity with the CB1 recep- smokers, and nonsmokers, educated and tor. The existence of this receptor provided noneducated, and Gr II cannabis addicts the molecular basis for the immunosuppres- (n = 37; mean age, 43.6 r 2.6 years; range, sive actions of cannabis. The CB1 receptor 20–72 years) all smokers, educated and mediates inhibition of adenylate cyclase, noneducated. Outcome measures included inhibition of N- and P/Q-type calcium the Paced Auditory Serial Addition test for channels, stimulation of potassium chan- testing attention and the Trailmaking test nels, and activation of mitogen-activated A and Trailmaking test B (TMb) for testing protein kinase. The CB2 receptor mediates psychomotor performance. Age corre- inhibition of adenylate cyclase and activa- lated positively with score of TMb in the tion of mitogen-activated protein kinase. nonaddict group and in the addict group The discovery of endogenous cannabinoid (Trailmaking test A and TMb). Years of receptor ligands, AEA (N-arachidonyl- education correlated negatively with scores ethanolamine), and 2-arachidonylglycerol of TMb in the nonaddict group (Gr I) but made the notion of a central cannabinoid not the addict group (Gr II). Cannabis neuromodulatory system plausible. AEA is addicts (Gr II) had significantly poorer released from neurons on depolarization attention than nonaddict normal volun- through a mechanism that requires calcium- teers (Gr I). It was determined that impair- dependent cleavage from a phospholipid ment of psychomotor performance is age precursor in neuronal membranes. The related whether in normal nonaddicts or in release of AEA is followed by rapid uptake cannabis addicts. A decline in attention into the plasma and hydrolysis by fatty-acid was detected in cannabis addicts and has amidohydrolase. The psychoactive cannab- been considered a feature of pathological inoids increase the activity of dopaminergic agingCS448. neurons in the ventral tegmental area– Brain cannabinoid receptor. In humans, mesolimbic pathway. Because these dopam- psychoactive cannabinoids produce eupho- inergic circuits are known to play a pivotal ria, enhancement of sensory perception, role in mediating the reinforcing (reward- tachycardia, antinociception, difficulties in ing) effects of the most drugs of abuse, the concentration, and impairment of memory. enhanced dopaminergic drive elicited by The cognitive deficiencies persist after the cannabinoids is thought to underlie the withdrawal. The toxicity of cannabis has reinforcing and abuse properties of can- been underestimated for a long time, since nabis. Thus, cannabinoids share a final com- recent findings revealed that '-9-THC- mon neuronal action with other major drugs induced cell death with shrinkage of neu- of abuse such as morphine, ethanol, and rons and DNA fragmentation in the nicotine in producing facilitation of the hippocampus. The acute effects of cannab- mesolimbic dopamine systemCS423. Hippoc- inoids, as well as the development of toler- ampal slices from humans, guinea pigs, rats, ance, are mediated by G protein-coupled and mice, and cerebellar, cerebrocortical, cannabinoid receptors. The CB1 receptor and hypothalamic slices from guinea pigs and its splice variant, CB1A, are found pre- were incubated with [3H] noradrenaline and dominantly in the brain with highest densi- then superfused. Tritium overflow was ties in the hippocampus, cerebellum, and evoked either electrically (0.3 or 1 Hz) or striatum. The CB2 receptor is found pre- by introduction of Ca2+ ions (1.3 PM) into dominantly in the spleen and in hemopoi- Ca2+-free, K+-rich medium (25 PM) contain- CANNABIS SATIVA 51 ing 1 PM of tetrodotoxin. The cyclic adeno- 141716 (0.1 PM; apparent pA2 8.3), that sone monophosphate (cAMP) accumula- by itself did not affect cAMP accumulation. tion stimulated by 10 PM of forskolin was In conclusion, cannabinoid receptors of the determined in guinea pig hippocampal CB1 subtype occur in the human hippoc- membranes. The following drugs were used: ampus, where they may contribute to the the cannabinoid receptor-agonists (-)-cis- psychotropic effects of cannabis, and in the 3-[2-hydroxy-4-(1,1- dimethylheptyl)phen- guinea pig hippocampus, cerebellum, cere- yl]-trans-4-(3-hydroxypropyl)cyclo-hexanol bral cortex, and hypothalamus. The CB1 (CP-55,940) and R(+)-[2,3-dihydro-5-me- receptor in the guinea pig hippocampus is thyl-3-[(morpholinyl)methyl]pyrrolo[1,2, located presynaptically, was activated by 3-de]-1,4-benzoxazinyl]-(1-naphthalen- endogenous cannabinoids, and may be yl)methanone (WIN 55,212-2 [WIN]), the negatively coupled to adenylyl cyclaseCS442. inactive S(-)-enantiomer of the latter (WIN The acute administration of AEA or THC 55,212-3) and the CB1 receptor antagonist in rats increased the maximum binding ca-

N-piperidino-5-(4-chlorophenyl)-1-(2,4- pacity (Bmax) of cannabinoid receptors in the dichlorophenyl)-4-methyl-3-pyrazole- cerebellum and, particularly, in the hippoc- carboxamide (SR 141716). The electrically ampus. This effect was also observed after 5 evoked tritium overflow from guinea pig days of a daily exposure to AEA or THC. hippocampal slices was reduced by WIN The increase in the Bmax after the acute (peak inhibitory concentration 30%, 6.5) treatment seemed to be caused by changes but not affected by WIN 55,212-3 up to 10 in the receptor affinity (high Kd). The mM. The concentration–response curve of increase after the chronic exposure may be WIN was shifted to the right by SR 141716 attributed to an increase in the density of (0.032-PM) (apparent pA2 8.2), which by receptors. The [3H]CP-55,940 binding to itself did not affect the evoked overflow. cannabinoid receptors in the striatum, the WIN (1 PM) also inhibited the Ca2+-evoked limbic forebrain, the mesencephalon, and tritium overflow in guinea pig hippocampal the medial basal hypothalamus was not slices and the electrically evoked overflow altered after the acute exposure to AEA or in guinea pig cerebellar, cerebrocortical, THC. The chronic exposure to THC sig- and hypothalamic slices, as well as in hu- nificantly decreased the Bmax of these recep- man hippocampal slices, but not in rat and tors in the striatum and nonsignificantly in mouse hippocampal slices. SR 141716 (0.32 the mesencephalon. This effect was not PM) markedly attenuated the WIN-induced elicited after the chronic exposure to AEA inhibition in guinea pig and human brain and was not accompanied by changes in the CS463 slices. SR 141716 (0.32 PM) by itself Kd . increased the electrically evoked tritium Bronchoconstrictor activity. Water extract overflow in guinea pig hippocampal slices, of seed, administered by inhalation to human but failed to do so in slices from the other adults, was activeCS147. brain regions of the guinea pig and in Bronchodilator activity. Petroleum ether human hippocampal slices, but failed to do extract of the aerial parts, administered so in slices from the other brain regions of orally to adults of both sexes, was inac- the guinea pig and in human hippocampal tiveCS078. slices. The cAMP accumulation stimulated Cannabinoid hyperemesis. Nineteen pa- by forskolin was reduced by CP-55,940 and tients were identified with chronic cannabis WIN. The concentration-response curve of abuse and a cyclical vomiting illness. Fol- CP-55,940 was shifted to the right by SR low-up was provided with serial urine drug 52 MEDICINAL PLANTS OF THE WORLD screen analysis and regular clinical consul- amygdala, periaqueductal gray, and the tation to chart the clinical course. Of the paraventricular nucleus of the hypothala- 19 patients, five refused consent and were mus) and reward-related sites (Nac and lost to follow-up, and five were excluded pedunculopontine tegmental nucleus). In a based on cofounders. In all cases, chronic further experiment, Wistar rats and Lewis cannabis abuse predated the onset of the rats did not differ in the amount of Fos im- cyclical vomiting illness. Cessation of can- munoreactivity produced by cocaine (15 nabis abuse led to cessation of the cyclical mg/kg). These results indicate that Lewis vomiting illness in seven cases. Three cases rats are less sensitive to the behavioral, did not abstain and continued to have physiological and neural effects of canna- recurrent episodes of vomiting. Three cases binoidsCS396. rechallenged themselves after a period of Cannabis withdrawal effect. A 35-year- abstinence and suffered a return to illness. old male was cognitively assessed prior to Two of these cases abstained again and cessation of 18 years of daily cannabis use became, and remain, well. The third case and monitored for several weeks post- did not and remains ill. A novel finding was cessation. Brain event-related potential that 9 of the 10 patients, including the pre- measures of selective attention reflecting a viously published case, displayed an abnor- difficulty in filtering out complex irrel- mal washing behavior during episodes of evant information showed no indication of active illnessCS258. improvement over 6 weeks of abstinence. Cannabinoid-induced Fos expression. When tested in the acutely intoxicated state Cannabinoid CB1 receptor agonist CP- prior to cessation of use, a dramatic normal- 55,940 in Lewis and Wistar rats was investi- ization of the event-related potential signa- gated. A moderate (50 Pg/kg) and a high ture was observed. A treatment program (250 Pg/kg) dose level were used. The 250- based on supportive–expressive psycho- Pg/kg dose caused locomotor suppression, therapy was administered and depression, hypothermia, and catalepsy in both strains, anxiety, and general psychological health but with a significantly greater effect in were monitored over the course of with- Wistar rats. The 50-Pg/kg dose provoked drawal from cannabisCS466. moderate hypothermia and locomotor sup- Cannabis–amphetamine interaction. Can- pression but in Wistar rats only. CP-55,940 nabinoid–amphetamine interactions were caused significant Fos immunoreactivity in studied as follows: 24 out of 33 brain regions examined. The 1. 30 minutes after acute injection of (-)-'- most dense expression was seen in the 9-THC (0.1 or 6.4 mg/kg, intraperito- paraventricular nucleus of the hypothala- neally). mus, the islands of Calleja, the lateral sep- 2. 30 minutes after the last injection of 14- tum (ventral), the central nucleus of the daily treatment with (-)-'-9-THC (0.1 or amygdala, the bed nucleus of the stria 6.4 mg/kg). terminalis (lateral division), and the vent- 3. 24 hours after the last injection of 14- rolateral periaqueductal gray. Despite daily treatment with (-)-'-9-THC (6.4 having a similar distribution of CP-55,940- mg/kg). induced Fos expression, Lewis rats showed Acute cannabinoid exposure antagonized less overall Fos expression than Wistar rats the amphetamine-induced dose-dependent in nearly every brain region counted. This increase in locomotion, exploration, and held equally true for anxiety-related brain the decrease in inactivity. Chronic treat- structures (e.g., central nucleus of the ment with (-)-'-9-THC resulted in toler- CANNABIS SATIVA 53 ance to this antagonistic effect on locomo- conservative wound dressings and second- tion and inactivity but not on exploration, ary prostacyclin therapy a complete healing and potentiated amphetamine-induced ste- of digital necrosis was observed. There was reotypes. Lastly, 24 hours of withdrawal no recurrence during the 6-month follow- after 14 days of cannabinoid treatment upCS336. Young men were presented with dis- resulted in sensitization to the effects of tal arteriopathy of the lower limbs in three D-amphetamine on locomotion, explora- cases, and of the left upper limb in the tion, and stereotypesCS431. remaining patient. Symptoms occurred pro- Cannabis-induced coma. Two cases of gressively, distal pulses had disappeared, and cannabis-induced coma were reported fol- distal necrosis was constant. Three patients lowing accidental ingestion of cannabis suffered from Raynauld’s phenomenon, cookies. The possibility of cannabis inges- none of them presented with venous throm- tion should be considered in cases of unex- bosis. Radiological evaluation revealed dis- plained coma in a previously healthy young tal abnormalities in all cases, and proximal child if signs of conjunctival hyperemia, arterial thrombosis in one case. The four pupillary dilatation, and tachycardia were patients were cannabis smokers for at least present and other causes, such as central four years. With cannabis interruption and nervous system infection or trauma were symptomatic treatment, lesions improved unlikelyCS458. for three patients. For one of them, recur- Cannabis-related arteritis. A 19-year-old rence of arteriopathy occurred when he man who presented with plantar claudica- resumed smoking cannabis. For the fourth tion associated with necrosis in a toe under- who never stopped cannabis, an amputation went diagnostic arteriography and surgery was necessaryCS349. Ten male moderate for popliteal artery entrapment type III was tobacco smokers and regular cannabis users studied. Surgical clearance resolved the with a median age of 23.7 years, developed popliteal artery entrapment but left the subacute distal ischemia of the lower or clinical symptoms unchanged. Closer ques- upper limbs, leading to necrosis in the toes tioning disclosed a history of cannabis con- and/or fingers and sometimes to distal limb sumption and intravenous vasodilatory gangrene. Two of the patients also pre- therapy was started. After the 21-day course sented with venous thrombosis and three of vasodilator agents, the pain disappeared patients were suffering from a recent and the toe necrosis regressed. The patient Raynauld’s phenomenon. Biological test stopped taking cannabis and had no signs of results did not show evidence of the classi- recurrenceCS308. A 24-year-old woman who cal vascular risk factors for thrombosis. was a heavy cannabis smoker with progres- Arteriographic evaluation in all of the cases sive Raynauld’s phenomenon and digital revealed distal abnormalities in the arteries necrosis, was investigated. Systemic sclero- of feet, legs, forearms, and hands resembling sis and other connective tissue disorders, as those of Buerger’s disease. A collateral cir- well as arteriosclerosis and arterial emboli culation sometimes with opacification of were excluded with appropriate laboratory the vasa nervorum was noted. In some cases, examinations. Arteriography revealed mul- arterial proximal atherosclerotic lesions and tiple forearm, palmar and digital occlusions venous thrombosis were observed. Despite with corkscrew-shaped vessels. Based on the treatment with ilomedine and heparin in all characteristic arteriography and clinical cases, five amputations were necessary in findings, the diagnosis of cannabis arteritis four patients. The vasoconstrictor effect of was retained. With careful necrectomy, cannabis on the vascular system has been 54 MEDICINAL PLANTS OF THE WORLD known for a long time. It has been shown patients were current tobacco smokers, 19 that '-8-THC and '-9-THC may induce were current cannabis users, and none were peripheral vasoconstrictor activity. Can- currently using opioids other than pre- nabis arteritis resembles Buerger’s disease, scribed methadone. Abnormalities of respi- but patients were moderate tobacco smok- ratory function were defined as those results ers and regular cannabis usersCS406. outside the 95% confidence interval of ref- Cannabis-related flashback. A young erence values for normal subjects adjusted man who offended a friend without any for age, weight, height, and sex. Thirty-one objective reason was reported. The report of (62%) MMT patients had reduced carbon the forensic psychiatrist demonstrated that monoxide transfer factor; 17 (34%) had el- the offense was committed under the influ- evated single breath alveolar volume, and ence of a cannabis flashback. The last time 43 (86%) had a reduced carbon monoxide the offender had consumed cannabis was 2 transfer factor–alveolar volume ratio. Six weeks before the acts. A plasmatic detection patients (12%) had reduced forced expira- was realized and showed a level of 6 ng/mL, tory volume in 1 second (FEV1); one (2%) 30 minutes after the beginning of the had reduced forced vital capacity (FVC); flashbackCS383. and nine (18%) had an obstructive ventila- Capgras syndrome. A report describes an tory defect. Ten (20%) patients had arterial apparently greater incidence of Capgras syn- CO2 pressure higher than 45 mmHg and 14 drome among the Maori population com- (28%) had alveolar to arterial oxygen gradi- pared with the European population. Five ent higher than 15 mmHg. Chest X-ray, cases of Capgras syndrome were identified echocardiography, and electrocardiogram in the eastern catchment area where 19% of showed no significant abnormalitiesCS256. the population identified as Maori, 75% as The potent cannabinoid receptor agonists European, and 6% as other or nonspecified. WIN55,212-2 (0.05, 0.5, or 5 pmol/50 nL) All of the cases occurred in Maori patients. and HU-210 (0.5 pmol/50 nL) or the CB1 No cases were identified in the western receptor antagonist/inverse agonist AM281 catchment area where 12% of the popula- (1 pmol/100 nL) were microinjected into tion identified as Maori, 87% as European, the rostral ventrolateral medulla oblongata and 1% as other or nonspecified. Four of five (RVLM) of urethane-anesthetized, immobi- cases were females. Two cases had a history lized and mechanically ventilated male of cannabis use. Three cases had exhibited Sprague–Dawley rats (n = 22). Changes in dangerous behavior towards family mem- splanchnic nerve activity, phrenic nerve bersCS410. activity, mean arterial pressure, and heart Carcinogenic activity. The dried leaf, rate in response to cannabinoid administra- administered intraperitoneally to rats of tion were recorded. The CB1 receptor gene both sexes at a dose of 7 mg/kg/week, was was expressed throughout the ventrolateral active. The animals were irradiated with J medulla oblongata. Unilateral microinjec- radiation between 40 and 50 days of age and tion of WIN 55,212-2 into the RVLM observed for 78 weeks. There was a greater evoked short-latency, dose-dependent in- incidence of tumors in animals given mari- creases in splanchnic nerve activity (0.5 juana extract and J radiation than either pmol; 175 r 8%, n = 5) and mean arterial marihuana or J radiation aloneCS223. pressure (0.5 pmol; 26 r 3%, n = 8), and Cardiorespiratory effect. Fifty stable abolished phrenic nerve activity (0.5 pmol; patients (25 males, 25 females) with me- duration of apnea: 5.4 r 0.4 seconds, n = 8), thadone maintenance treatment (MMT) with little change in heart rate (p < 0.005). programs were investigated. Forty-six MMT HU-210, structurally related to '-9-THC, CANNABIS SATIVA 55 evoked similar effects when microinjected layers of the membrane, with particularly into the RVLM (n = 4). Prior microinjec- strong expression in the amniotic epithe- tion of AM281 produced agonist-like lium and reticular cells and cells of the effects, and significantly attenuated the maternal decidua layer. Moderate expres- response to subsequent injection of WIN sion was observed in the chorionic cyto- (0.5 pmol, n = 4)CS331. trophoblasts. The expression of FAAH was Cardiovascular effects. The leaf, smoked highest in the amniotic epithelial cells, by adults of both sexes, at a dose of 600 mg/ chorionic cytotrophoblast, and maternal person (1–1.5% THC), produced no decidua layer. The results suggest that the adverse effects on blood pressure, electrocar- human placenta is a likely target for cannab- diogram, and the heartCS065. Cannabis and '- inoid action and metabolism. This is con- 9-THC increase heart rate, slightly increase sistent with a placental site of action of supine blood pressure, and on occasion pro- endocannabinoids and cannabis being duced marked orthostatic hypotension. Car- responsible, at least in part, for the poor out- diovascular effects in animals are different, comes associated with cannabis consump- with bradycardia and hypotension the most tion and pathology in the endocannabinoid typical responses. Cardiac output increases, system during pregnancyCS327. and peripheral vascular resistance and maxi- Central nervous system depressant activ- mum exercise performance decrease. Toler- ity. Fluidextract of the aerial parts, admin- ance to most of the initial cardiovascular istered intraperitoneally to rats at a dose of effects appears rapidly. With repeated expo- 25 mg/kg, was active. The fluidextract, sure, supine blood pressure decreases administered orally to dogs, produced slightly, orthostatic hypotension disappears, ataxiaCS240. The leaf, smoked by human blood volume increases, heart rate slows, adults, produced a decrease in psychomotor and circulatory responses to exercise and performanceCS066. Valsalva maneuver are diminished, consis- Central nervous system effect. '-9-THC tent with centrally mediated, reduced sym- activates the two G protein-coupled recep- pathetic, and enhanced parasympathetic tors CB1 and CB2. The endogenous ligands activity. Receptor-mediated and probably of these receptors were identified as lipid nonneuronal sites of action account for can- metabolites of arachidonic acid, named nabinoid effects. The endocannabinoid sys- endocannabinoids. The two most studied tem appears important in the modulation of endocannabinoids are AEA and 2-arachi- many vascular functions. Cannabis’ cardio- donyl-glycerol. The CB1 receptor is mas- vascular effects are not associated with sively expressed throughout the central serious health problems for most young, nervous system, whereas CB2 expression healthy users, although occasional myocar- seems restricted to immune cells. Following dial infarction, stroke, and other adverse endocannabinoid binding, CB1 receptors cardiovascular events are reportedCS362. modulate second messenger cascades (inhi- Cataleptic effect. Petroleum ether extract bition of adenylate cyclase, activation of of the dried entire plant, administered mitogen-activated protein kinases and of intraperitoneally to guinea pigs at a dose of focal-adhesion kinases), as well as ionic 100 mg/kg, was activeCS022. conductances (inhibition of voltage-depen- CB1 cannabinoid receptor in human pla- dent calcium channels, activation of several centa. CB1 (G protein-coupled) receptor potassium channels). Endocannabinoids and FAAH expression in human term pla- transiently silenced synapses by decreasing centa were investigated by immunohis- neurotransmitter release. They play major tochemistry. CB1 receptor was found in all roles in various forms of synaptic plasticity 56 MEDICINAL PLANTS OF THE WORLD because of their ability to behave as retro- increases correlated with regional cerebral grade messengers and activate noncanna- blood flow in the cerebellum. Results indi- binoid receptors (such as vanilloid receptor cate that smoking cannabis appears to type-1)CS305. Mice strain with a disrupted accelerate a cerebellar clock-altering self- CB1 gene (CB1 knockout mice) appeared paced behaviorsCS343. healthy and fertile, but they had a signifi- Clinical endocannabinoid deficiency. cantly increased mortality rate. They also Clinical endocannabinoid deficiency, and displayed reduced locomotor activity, the prospect that it could underlie the increased ring catalepsy, and hypoalgesia in pathophysiology of migraine, fibromyalgia, hotplate and formalin tests. '-9-THC- irritable bowel syndrome, and other func- induced ring catalepsy, hypomobility, and tional conditions alleviated by clinical can- hypothermia were completely absent in nabis were studied. Migraine has numerous CB1 mutant mice. In contrast, '-9-THC- relationships to endocannabinoid function. induced analgesia in the tail-flick test and AEA potentiated 5-hydroxytrayptamine other behavioral (licking of the abdomen) (HT1A) and inhibited 5-HT2A receptors and physiological (diarrhea) responses supporting therapeutic efficacy in acute and after '-9-THC administration were found. preventive migraine treatment. Cannab- Results indicate that most, but not all, cen- inoids also demonstrated dopamine-block- tral nervous system effects of '-9-THC are ing and anti-inflammatory effects. AEA is mediated by the CB1 receptorCS425. tonically active in the periaqueductal gray Central nervous system stimulant activ- matter, a migraine generator. THC modu- ity. The resin, ingested by a 4-year-old girl, lated glutamatergic neurotransmission via showed signs of stupor alternating with brief N-methyl-D-aspartic acid-receptors. Fibro- intervals of excitation and foolish laughing myalgia is now conceived as a central sensi- with atactic movements. Her temperature, tization state with secondary hyperalgesia. blood pressure, pulse, hemoglobin, leuko- Cannabinoids have similarly demonstrated cytes, serum electrolytes, and serum urea the ability to block spinal, peripheral and were normal. Respiratory rate was 12 beats gastrointestinal mechanisms that promote per minute. Blood sugar elevated. Recovery pain in headache, fibromyalgia, irritable was complete within 24 hours with no bowel syndrome and related disordersCS288. treatmentCS047. Cognitive functioning. Cognitive perfor- Cerebellar clock-altering effect. Twelve mance was examined in 145 adolescents volunteers who smoked cannabis recrea- aged 13–16 years for whom prenatal expo- tionally about once weekly, and 12 volun- sure to cannabis and cigarettes had been teers who smoked daily for a number of ascertained. The subjects were from a low- years performed a self-paced counting task risk, predominantly middle-class sample during positron emission tomography im- participating in an ongoing, longitudinal aging, before and after smoking cannabis study. The assessment battery included tests and placebo cigarettes. Smoking cannabis of general intelligence, achievement, increased regional cerebral blood flow in the memory, and aspects of executive function- ventral forebrain and cerebellar cortex in ing. Consistent with results obtained at ear- both groups, but resulted in significantly less lier ages, the strongest relationship between frontal lobe activation in chronic users. prenatal maternal cigarette smoking and Counting rate increased after smoking can- cognitive variables was seen with overall nabis in both groups, as did a behavioral intelligence and aspects of auditory func- measure of self-paced tapping, and both tioning, whereas prenatal exposure to mari- CANNABIS SATIVA 57 juana was negatively associated with tasks tual performance. On the second day, sub- that required visual memory, analysis, and jects received a regular cigarette or one con- integrationCS344. A multisite, retrospective, taining 290 mg/kg body weight of THC. cross-sectional, neuropsychological study Physical and psychological assessments were was conducted among 102 near-daily can- performed immediately (15 minutes) after nabis users (51 long-term users: mean, 23.9 subjects smoked their cigarettes. Twenty- years of use; 51 shorter-term users: mean, four hours later, physical and psychological 10.2 years of use), compared with 33 non- examinations were repeated. Results suggest user controls. Measures from nine standard that perceptual motor speed and accuracy, neuropsychological tests that assessed atten- two very important parameters of driving tion, memory, and executive functioning ability, seem to be impaired immediately were administered prior to entry into a after cannabis consumptionCS420. The analy- treatment program following a median 17- ses included 1318 participants under age 65 hour abstinence. Long-term cannabis users years who completed the Mini-Mental State performed significantly less well than Examination (MMSE) during three study shorter-term users and controls on tests of waves in 1981, 1982, and 1993–1996. Indi- memory and attention. On the Rey Audi- vidual MMSE score differences between tory Verbal Learning Test, long-term users waves two and three were calculated for recalled significantly fewer words than each study participant. After 12 years, study either shorter-term users (p = 0.001) or con- participants’ scores declined a mean of 1.20 trols (p = 0.005). There was no difference points on the MMSE (standard deviation, between shorter-term users and controls. 1.90), with 66% having scores that declined Long-term users showed impaired learning by at least one point. Significant numbers (p = 0.007), retention (p = 0.003), and of scores declined by three points or more retrieval (p = 0.002) compared with con- (15% of participants in the 18–29-year-old trols. Both user groups performed poorly on age group). There were no significant dif- a time estimation task (p < 0.001 vs con- ferences in cognitive decline between heavy trols). Performance measures often corre- users, light users, and nonusers of cannabis. lated significantly with the duration of There were also no male–female differences cannabis use, being worse with increasing in cognitive decline in relation to cannabis years of use, but were unrelated to with- useCS426. From 250 individuals consuming drawal symptoms and persisted after con- cannabis regularly, 99 healthy, free of any trolling for recent cannabis use and other other past or present drug abuse, or history drug useCS388. A patient with a history of trau- of neuropsychiatric disease cannabis users matic brain injury along with current mood were selected. After an interview, physical disorder and cannabis use was reported. The examination, analysis of routine laboratory impact of cannabis use appeared to have a parameters, plasma/urine analyses for drugs, detrimental effect on his mood. Treatment and Minnesota Multiphasic Personality of the mood disorder resulted in larger cog- Inventory testing, users and respective con- nitive gainsCS415. Sixty healthy volunteers (a trols were subjected to a computer-assisted negative urine drug-screening test was pre- attention test battery comprising visual requisite) were investigated. On the first scanning, alertness, divided attention, flex- day, baseline data were obtained from a ibility, and working memory. Of the poten- physical examination and a psychological tial predictors of test performance within test battery for the investigation of visual the user group, including present age, age of and verbal memory and cognitive percep- onset of cannabis use, degree of acute 58 MEDICINAL PLANTS OF THE WORLD intoxication (THC + THC–OH plasma lev- abuse/dependence. The results indicated els), and cumulative toxicity (estimated that patients with dysthymia and SRD have total life dose), an early age of onset turned exposure to most substances of abuse that out to be the only predictor, predicting was comparable to patients with SRD only. impaired reaction times exclusively in visual They selectively use certain substances less scanning. Early-onset users (onset before often than patients with SRD onlyCS433. A age 16; n = 48) showed a significant impair- course and severity of SRD among 642 ment in reaction times in this function, patients with comorbid major depressive whereas late-onset users (onset after age 16; disorder (MDD) was analyzed by means of n = 51) did not differ from controls (n = both retrospective and concurrent data. 49)CS428. Male volunteers (n = 5) with histo- Data on course included lifetime use, age at ries of moderate alcohol and cannabis use first use, years of use, use in the last year, were administered three doses of alcohol periods of abstinence, and current diagno- (0.25, 0.5, or 1 g/kg), three doses of cannabis sis. Data on severity included two measures (4.8, or 16 puffs of 3.55% '-9-THC), and of SRD-associated problems, substance placebo in random order under double blind abuse vs dependence, self-help activities, conditions in seven separate sessions. Blood and number of substances being abused. alcohol concentration (10–90 mg/dL) and SRD-MDD patients tended to manifest THC levels (63–188 ng/mL) indicated that lower levels of cannabis, opiate, and cocaine active drug was delivered to subjects dose use, and more SRD-only patients were abus- dependently. Alcohol and cannabis pro- ing three or more substances. Men with duced dose-related changes in subjective SRD-MDD demonstrated longer mean measures of drug effect. Ratings of perceived durations of abstinence compared with men impairment were identical for the high with SRD-only, whereas SRD-MDD women doses of alcohol and cannabis. Both drugs demonstrated shorter mean durations of produced comparable impairment in digit– abstinence, compared with women with symbol substitution and word recall tests, SRD-only. MDD-SRD patients showed but had no effect in time perception and slightly less substance abuse, but SRD reaction time tests. Alcohol, but not can- severity was comparable with SRD-only nabis, slightly impaired performance in a patientsCS441. number recognition testCS444. Covariation among risk behaviors. A Comorbid dysthymia and substance dis- sample of 913 sexually active high school order. A total of 642 patients were assessed. students completed a self-administered Thirty-nine had substance-related disorder questionnaire that required mainly “yes” or and dysthymia (SRD-dysthymia) and 308 “no” answers to questions involving par- had SRD only. Data on past use were ticipation in a range of risk behaviors. Con- collected by a research associate using a traceptive nonuse was not significantly questionnaire. The patients with SRD- associated with use of cigarettes, alcohol, or dysthymia and SRD did not differ with re- inhalants; perpetration or being a victim of gard to use of alcohol, tobacco, and violence; exposure to risk of physical injury; benzodiazepines. The patients with SRD- and suicidality. For males only, there was a dysthymia started caffeine use at an earlier significant inverse association between age, had shorter “use careers” of cocaine, contraceptive nonuse and use of cannabis amphetamines, and opiates, and had fewer in the previous month. This was not the days of cocaine and cannabis use in the last case for lifetime cannabis use for either year. They also had a lower rate of cannabis genderCS404. CANNABIS SATIVA 59

Cyclo-oxygenase inhibition. Ethanol such as cisplatin. THC-induced cell death (100%) extract and essential oil of the aerial was preceded by significant changes in the parts were active, IC50 6.7 mg/L and 7.5 mg/ expression of genes involved in the mito- L, respectivelyCS226. gen-activated protein kinase signal trans- Cytochrome P450 and 2C6 expression. duction pathways. Both apoptosis and gene Hashish (cannabis) and heroin effect on the expression changes were altered indepen- expression of cytochrome P450 2E1 (CYP dent of p53 and the cannabinoid 1 and 2 2E1) and cytochrome P450 2C6 (CYP 2C6) receptors (CB1-R and CB2-R)CS261. was measured after single (24 hours) and re- Depressant activity. Heavy cannabis use peated-dose treatments (four consecutive and depression are associated and evidence days). The expression of CYP 2E1 was from longitudinal studies suggests that slightly induced after single-dose treatments heavy cannabis use may increase depressive and markedly induced after repeated-dose symptoms among some usersCS321. Partici- treatments of mice with hashish (10 mg/kg pants (n = 1920) were reassessed as part of a body weight). It is believed that N-nitro- follow-up study. The analysis focused on samines are activated principally by CYP two cohorts: those who reported no depres- 2E1 and the activity of N-nitrosodime- sive symptoms at baseline (n = 849) and thylamine was found to be increased after those with no diagnosis of cannabis abuse at single- and repeated-dose treatments of baseline (n = 1,837). Symptoms of depres- mice with hashish by 23 and 41%, respec- sion, cannabis abuse, and other psychiatric tively. Hashish treatments of mice increased disorders were assessed with the Diagnostic the total hepatic content of CYP by 112 and Interview Schedule. In participants with no 206%, respectively; aryl hydrocarbon baseline depressive symptoms, those with a hydroxylase activity by 110 and 165%, diagnosis of cannabis abuse at baseline were respectively; nicotinamide adenine dinucle- four times more likely than those with no otide phosphate–cytochrome c reductase cannabis abuse diagnosis to have depressive activity by 21 and 98%, respectively, and symptoms at the follow-up assessment, after glutathione level by 81 and 173%, respec- adjusting for age, gender, antisocial symp- tively. The level of free radicals (thio- toms, and other baseline covariates. These barbituric acid-reactive substances) was participants were more likely to have expe- potentially decreased after single- or rienced suicidal ideation and anhedonia repeated-dose treatments with either hash- during the follow-up period. Among the ish or heroinCS333. participants who had no diagnosis of can- Cytotoxic activity. Ethanol (50%) extract nabis abuse at baseline, depressive symp- of the entire plant, in cell culture, was inac- toms at baseline failed to significantly tive on CA-9KB, ED50 greater than 20 Pg/ predict cannabis abuse at the follow-up mLCS007. Water extract of the dried seed, in assessmentCS395. The relationship between cell culture at a concentration of 500 Pg/ depressive symptoms and polydrug use mL, was inactive on CA-mammary-micro- (alcohol, cannabis, and cocaine) among alveolarCS144. blacks in a high-risk community was stud- Cytotoxic effect. THC, in leukemic cell ied. A street sample (n = 570) from four lines (CEM, HEL-92, and HL60) and in high-risk communities was collected peripheral blood mononuclear cells, 6 hours through personal interviews. Interviewers after exposure induced apoptosis, even at asked respondents about their drug use one times the IC50. THC did not appear to behavior during the past 30 days and their act synergistically with cytotoxic agents, depressive symptoms during the past week. 60 MEDICINAL PLANTS OF THE WORLD

Odds ratios and logistic regressions, adjusted Discriminative stimulus effect. Rhesus for age and sex, were used to assess the rela- monkeys, trained to discriminate '-9-THC tionship between depressive symptoms and from vehicle in a two-lever drug discrimina- drug and polydrug use (drug use involving tion procedure, were tested with a variety of cocaine). Results showed that depressive psychoactive drugs, including cannabinoids symptoms are significantly associated with or drugs from other classes. The results indi- polydrug use. Depressive symptoms were not cated that '-9-THC discrimination showed associated with alcohol use or with the com- pharmacological specificity, in that none of bination of alcohol and cannabis useCS440. the noncannabinoid drugs fully substituted Diabetic ketoacidosis. One hundred fifty- for '-9-THC. The classical cannabinoids, eight young adults, aged 16–30 years, with '-9-THC and '-8-THC, and the novel type 1 diabetes, attending an urban diabetes cannabinoids, WIN and 1-butyl-2-methyl- clinic, were sent an anonymous confi- 3-(1-naphthoyl)indole, produced full dose- dential postal questionnaire to determine dependent substitution for '-9-THC in all the prevalence of street drug use. Eighty- monkeys. A heptyl indole derivative failed five completed responses were received. to substitute for '-9-THC, but it also did Twenty-nine percent of respondents admit- not displace [3H] CP-55,940 from its bind- ted to using street drugs. Of those, 68% ing siteCS461. habitually took street drugs more than once DNA synthesis inhibition. Ethanol (95%) a month. Seventy-two percent of users were extract of the dried resin, administered unaware of the adverse effects on diabetes. intraperitoneally to toads at a dose of 10 mg/ Results indicated that the street drug usage day for 14 days, was active. The results were in young adults with type 1 diabetes is com- significant at p < 0.01 levelCS216. mon and may contribute to poor glycemic Dopamine metabolism. The effect of control and serious complications of repeated administrations of THC or WIN, a diabetesCS299. synthetic cannabinoid receptor agonist, on Digital necrosis. An 18-year-old woman, dopamine turnover in the prefrontal cortex, with a history of severe anorexia nervosa of striatum, and Nac in rats, was investi- 5 years’ duration, who acknowledged regu- gated. THC or WIN (twice daily for seven lar use of tobacco and cannabis, was hospi- or 14 days) caused a persistent and selec- talized for necrosis of the left index and tive reduction in medial prefrontal corti- thumb that had occurred shortly after left cal dopamine turnover. No significant radial artery puncture for blood gas analysis. alterations of dopamine metabolism were Acrocyanosis of the four limbs had been observed in the Nac or striatum. These present since the onset of anorexia nervosa. dopaminergic deficits in the prefrontal cor- Arteriography of the upper limbs showed tex were observed after a drug-free period of major spasm of the left radial and cubital up to 14 days. The cognitive dysfunction arteries and thromboses in the left inter- produced by heavy, long-term cannabis use digital arteries of the left index and thumb. may be subserved, in part, by drug-induced The distal portions of the arteries were then alterations in frontal cortical dopamine on the left and on the right. The necrotic turnoverCS346. Two weeks’ administration of lesions healed after intravenous adminis- THC to rats, reduced dopamine transmis- tration of ilomedine and interruption of sion in the medial prefrontal cortex, tobacco and cannabis. Acrocyanosis of the whereas dopamine metabolism in striatal four limbs persistedCS398. regions was unaffectedCS434. CANNABIS SATIVA 61

Dopamine release. A 38-year-old drug- Then a randomized, placebo-controlled free schizophrenic patient took part in a crossover study was performed, in which 19 single photon emission computerized tomo- patients with PD were randomized to graphic study of the brain, and smoked can- receive oral cannabis extract followed by nabis secretively during a pause in the placebo or vice versa. Each treatment phase course of an imaging session. Cannabis had lasted for 4 weeks with an intervening 2- an immediate calming effect, followed by a week washout phase. The primary outcome worsening of psychotic symptoms a few measure was a change in Unified Parkin- hours later. A comparison of the two sets of son’s Disease Rating Scale (UPDRS) (items images, obtained before and immediately 32 to 34) dyskinesia score. Secondary out- after smoking cannabis, indicated a 20% come measures included the Rush scale, decrease in the striatal dopamine D2 recep- Bain scale, tablet arm drawing task, and tor-binding ratio, suggestive of increased total UPDRS score following a levodopa synaptic dopaminergic activityCS399. challenge, as well as patient-completed Dopamine transmission modulation. The measures of a dyskinesia activities of daily endogenous cannabinoid system is a new living scale, the PDQ-39, on–off diaries, and signaling system composed by the central a range of category rating scales. Seventeen (CB1) and the peripheral (CB2) receptors, patients completed the study. Cannabis and several lipid transmitters including was well tolerated and had no pro- or anti- AEA and 2-arachidonylglycerol. Cannab- parkinsonian action. There was no evidence inoid CB1 receptors are present in dopam- for a treatment effect on L-DOPA-induced ine projecting brain areas. In primates and dyskinesia as assessed by the UPDRS, or certain rat strains it is also located in any of the secondary outcome mea- dopamine cells of the A8, A9, and A10 mes- suresCS259. An anonymous questionnaire encephalic cell groups, as well as in hypo- sent to all patients attending the Prague thalamic dopaminergic neurons controlling Movement Disorder Center revealed that prolactin secretion. CB1 receptors co-local- 25% of 339 respondents had taken cannabis ize with dopamine D1/D2 receptors in and 45.9% of these described some form of dopamine projecting fields. Manipulation of benefitCS262. 2,4,5-Trihydroxyphenethyla- dopaminergic transmission is able to alter mine (6-hydroxydopamine)-lesioned rats the synthesis and release of AEA, as well as were treated with the enantiomers of the the expression of CB1 receptors. CB1 recep- synthetic cannabinoid 7-hydroxy-'6-THC tors can switch their transduction mecha- 1,1-dimethylheptyl. Treatment with its (-)- nism to oppose to the ongoing dopamine (3R, 4R) enantiomer (code name HU-210), signaling. Acute blockade of CB1 receptor a potent cannabinoid receptor type 1 ago- potentiates the facilitatory role of dopam- nist, reduced the rotations induced by ine D2 receptor agonists on movement. CB1 L-DOPA/carbidopa or apomorphine by 34 stimulation results in sensitization to the and 44%, respectively. Treatment with the motor effects of indirect dopaminergic (+)- (3S, 4S) enantiomer (code name agonistsCS291. HU-211), an N-methyl-D-aspartate antago- Dyskinetic activity. A 4-week dose escala- nist, and the psychotropically inactive can- tion study was performed to assess the nabis constituent: CBD and its primary safety and tolerability of cannabis in six metabolite, 7-hydroxy-cannabinol, did not patients with Parkinson’s disease (PD) with show any reduction of rotational behavior. levodopa (L-DOPA)-induced dyskinesia. The results indicate that activation of the 62 MEDICINAL PLANTS OF THE WORLD

CB1 stimulates the dopaminergic system serum prolactin abruptly. None of the can- ipsilaterally to the lesion, and may have nabinoid receptor agonists affected serum implications in the treatment of PDCS338. growth hormoneCS420. Dystonic activity. The neural mechanisms Environmental stress and cannabinoids underlying dystonia involve abnormalities interaction. Anxiety and panic are the within the basal ganglia—in particular, most common adverse effects of cannabis overactivity of the lateral globus pallidus. intoxication. Data suggest that cannabinoid Cannabinoid receptors are located presyn- CB1 receptor modulation of amygdalar aptically on J-aminobutyric acid receptor activity contributes to these phenomena. (GABA) terminals within the globus palli- Using Fos as a marker, it was tested the dus internus, where their activation reduces hypothesis that environmental stress and GABA reuptake. Cannabinoid receptor CB1 cannabinoid receptor activity interact stimulation may thus reduce overactivity of in the regulation of amygdalar activation in the globus pallidus, and thereby reduce dys- male mice. Both 30 minutes of restraint and tonia. A double-blind, randomized, pla- CB1 receptor agonist treatment ('-9-THC cebo-controlled, crossover study using the [2.5 mg/kg]) or CP-55,940 (0.3 mg/kg); by synthetic cannabinoid receptor agonist intraperitoneal injection) produced barely nabilone in patients with generalized and detectable increases in Fos expression segmental primary dystonia showed no sig- within the central amygdala (CeA). The nificant reduction in dystonia following combination of restraint and CB1 agonist treatment with nabiloneCS390. administration produced robust Fos induc- Embryotoxic effect. Resin, administered tion within the CeA, indicating a synergis- orally to pregnant rabbits at a dose of 1 mL/ tic interaction between environmental kg, was activeCS167. stress and CB1 receptor activation. An Endocrine effect. Animal models have inhibitor of endocannabinoid transport, demonstrated that cannabinoid administra- AM404 (10 mg/kg), produced an additive tion acutely altered multiple hormonal sys- interaction with restraint within the CeA. tems, including the suppression of the In contrast, FAAH inhibitor-treated mice gonadal steroids, growth hormone, prolac- (URB597, 1 mg/kg) and FAAH (–/–) mice tin, and thyroid hormone and the activation did not exhibit any differences in amygdalar of the hypothalamic–pituitary–adrenal activation in response to restraint compared (HPA) axis. These effects were mediated by with control mice. In the basolateral binding to the endogenous cannabinoid amygdala (BLA) and medial amygdala, receptor in or near the hypothalamus. restraint stress produced a low level of Fos Despite these findings in animals, the effects induction, which was unaffected by cannab- in humans have been inconsistent, and dis- inoid treatment. The CB1 receptor antago- crepancies were likely owing in part to the nist SR141716 dose-dependently increased development of toleranceCS363. Intravenous Fos expression in the BLA and CeACS272. administration of three cannabinoid ago- Epileptic effect. '-9-THC at a dose of 1 PM, nists (AEA, methanandamide, and WIN) significantly depressed evoked depolariz- to nine castrated male calves under stress- ing postsynaptic potentials (PSPs) in rat free conditions provoked immediate olfactory cortex neurones. A standardized increases of serum cortisol and respiration cannabis extract (SCE) and '-9-THC-free rate, and produced rapid hypoalgesia to SCE significantly potentiated evoked PSPs cutaneous pain and thermal stimuli. AEA (all results were fully reversed by the CB1 and methanandamide did not affect serum receptor antagonist SR141716A, 1 PM). prolactin. Administration of WIN increased The potentiation by '-9-THC-free SCE CANNABIS SATIVA 63 was greater than that produced by SCE. intubation to rats at a dose of 75 mg/kg for On comparing the effects of '-9-THC-free 70 days, was activeCS224. SCE on evoked PSPs and artificial PSPs Estrogen receptors stimulating effect. (aPSPs; evoked electrotonically following THC, CBD, and desacetyllevonantradol, in brief intracellular current injection), PSPs estrogen-induced MCF-7 breast cancer cells were enhanced, whereas aPSPs were unaf- at concentrations of no more than 10 PM, fected, suggesting that the effect was not re- produced no effect. THC failed to antago- sulting from changes in background input nize the response to estradiol under condi- resistance. Similar recordings made using tions in which the antiestrogen LY156758 CB1 receptor-deficient knockout mice and (keoxifene; raloxifene) was effective. The wild-type littermate controls revealed can- phytoestrogen formononetin behaved as an nabinoid or extract-induced changes in estrogen at high concentrations, and this membrane resistance, cell excitability and response was antagonized by LY156758. synaptic transmission in wild-type mice that THC, desacetyllevonantradol, or CBD did were similar to those seen in rat neurones, not stimulate transcription of an EREtkCAT but no effect on these properties were seen reporter gene transiently transfected into in CB1 receptor-deficient knockout mice MCF-7 cellsCS452. cells. Results indicated that the unknown Estrogenic effect. Petroleum ether extract extract constituent(s) effects over-rode the of the resin was active on the rat non-preg- suppressive effects of '-9-THC on excita- nant uterusCS130. Resin, in the ration of tory neurotransmitter release, which may immature and ovariectomized rats at a con- explain some patients’ preference for herbal centration equivalent to 250 ppm THC/ani- cannabis rather than isolated '-9-THC mal, was inactive CS236,CS162. (owing to attenuation of some of the cen- Estrous cycle disruption effect. Ethanol tral '-9-THC side effects) and possibly (95%) extract of the dried aerial parts, account for the rare incidence of seizures in administered intraperitoneally to gerbils at some individuals taking cannabis recrea- a dose of 2.5 mg/animal daily for 60 days, tionallyCS278. A SCE with pure '-9-THC, at was activeCS184. Petroleum ether extract of matched concentrations of '-9-THC, and a the dried aerial, administered intraperi- '-9-THC-free extract ('-9-THC-free SCE) toneally to mice and rats at doses of 1 and 5 in in vitro rat brain slice model of epilepsy mg/animal, respectively, for 64 days, was were examined. In the in vitro epilepsy activeCS174. Petroleum ether extract of the model, in which sustained epileptiform aerial parts, administered intraperitoneally seizures were induced by the muscarinic to female rats, produced weak activityCS016. receptor agonist oxotremorine-M in imma- Petroleum ether extract of the entire plant, ture rat piriform cortical brain slices, SCE administered by gastric intubation to female was a more potent and again more rapidly- mice at doses of 75 mg/kg and 150 mg/kg, acting anticonvulsant than isolated '-9- was active. A dose of 3 mg/kg produced THC. '-9-THC-free extract also exhibited weak activityCS170. Petroleum ether extract of anticonvulsant activity. CBD did not the resin, administered intraperitoneally to inhibit seizures, nor did it modulate the female rats at doses of 10 and 20 mg/kg, was activity of '-9-THC in this model. These activeCS187. Resin, administered orally to results demonstrated that not all of the female rats at doses of 3, 15, and 75 mg/kg therapeutic actions of cannabis herb might daily for 72 days, was activeCS168. be a result of the '-9-THC contentCS312. Familial Mediterranean fever. A patient Estrogen cycle disruption effect. The with familial Mediterranean fever was pre- dried aerial part, administered by gastric sented with chronic relapsing pain and 64 MEDICINAL PLANTS OF THE WORLD inflammation of gastrointestinal origin. restrictive symptoms only, 17 with purging After determining a suitable analgesic dos- symptoms. The rates of drug use between age, a double-blind, placebo-controlled, subjects and their comparison groups were crossover trial was conducted using 50 mg compared by Z-scores, with the level of sig- of '-9-THC daily in five doses in the active nificance set at 0.05. During the preceding weeks and measuring effects on parameters year, restrictors used significantly less to- of inflammation and pain. Although no bacco, alcohol, and cannabis than grade- anti-inflammatory effects of '-9-THC were and sex-matched comparison populations, detected during the trial, a highly signifi- and purgers used these substances at rates cant reduction (p < 0.001) in additional similar to those of comparison subjects. analgesic requirements was achievedCS447. Other drugs seen frequently in the purgers Fish poison. Ethanol (95%) extract of the included hallucinogens, tranquilizers, dried aerial parts at a concentration of 1:1 stimulants, LSD, phencyclidine, cocaine, was active. The water extract was inac- and ecstasy. Both groups used caffeine and tiveCS243. laxatives, but few used diet pills. Restrictors Follicle-stimulating hormone release said they did not use substances because inhibition. Ethanol (95%) extract of the they were bad for their health, tasted dried resin, administered intraperitoneally unpleasant, were contrary to their beliefs, to toads at a dose of 10 mg/day for 14 days, and were too expensive. Purgers generally was active. The results were significant at used substances to relax, relieve anger, avoid p < 0.01 levelCS216. eating, and “get away” from problems. Food intake modulation. Cannabis sativa Female adolescents with eating disorders stimulates appetite, especially for sweet and who have restrictive symptoms use sub- palatable food. Cannabinoid action has stances less frequently than the general ado- proposed a central role of the cannabinoid lescent population but do not abstain from system in obesityCS352. Dronabinol, a com- their use. Those with purging symptoms use mercially available form of a THC, has been substances with a similar frequency to that used successfully for increasing appetite in found in the general adolescent popu- patients with HIV wasting disease. Cannab- lationCS372. inoid receptor antagonist may reduce Gastric secretory inhibition. Petroleum obesityCS353. To determine the prevalence of ether extract of the dried aerial parts, substance use in adolescents with eating dis- administered intraperitoneally to male rats, orders, the results of a data set of Ontario was activeCS097. high school students were compared. One Gene expression effect. Cannabinoids can hundred and one female adolescents who cross the placental barrier and be secreted met the Diagnostic and Statistical Manual of in the maternal milk. Through this way, Mental Disorders, 4th edition’s criteria for an cannabinoids affect the ontogeny of various eating disorder were followed up in a tertiary neurotransmitter systems leading to changes care pediatric treatment center. They were in different behavioral patterns. Dopamine asked to participate in a cross-sectional and endogenous opioids are among the neu- study using a self-administered question- rotransmitters that result more affected by naire assessing substance use and investigat- perinatal cannabinoid exposure, which, ing reasons for use and nonuse; 95 agreed to when animals mature, produce changes in participate and 77 completed the question- motor activity, drug-seeking behavior, naire (mean age, 15.2 years). The patients nociception, and other processes. These dis- were divided into two groups: 63 with turbances are likely originated by the capa- CANNABIS SATIVA 65 bility of cannabinoids to influence the culture via sustained ceramide accumula- expression of key genes for both neurotrans- tion, extracellular signal-regulated kinase mitters, in particular, the enzyme tyrosine activation and Akt inhibition. Cannab- hydroxylase and the opioid precursor pro- inoid treatment inhibited angiogenesis of enkephalin. Cannabinoids seem to be able gliomas in vivo. Cannabinoids killed glioma to influence the expression of genes encod- cells selectively and could protect ing for neuroglia cell adhesion molecules, nontransformed glial cells from deathCS273. which supports a potential influence of Glucosidase inhibition. Ethyl acetate and cannabinoids on the processes of cell prolif- water-soluble fractions of the dried aerial eration, neuronal migration or axonal elon- parts were inactive on the intestineCS128. gation in which these proteins are involved. Gynecomastic effect. A retrospective CB1 receptors, which represent the major analysis was carried out on 175 men over the targets for the action of cannabinoids, are age of 16 years who were presented with abundantly expressed in certain brain breast enlargement and/or “lumps” during a regions, such as the subventricular areas, 7-year period to a single surgeon. The which have been involved in these pro- patients had complete biochemical assess- cesses during brain development. Cannab- ment (liver function tests, J-glutamyl inoids might also be involved in the transferase, prolactin, D-fetoprotein, and E- apoptotic death that occurs during brain human chorionic gonadotropin), and development, possibly by influencing the mammography and/or ultrasound with fine- expression of Bcl-2/Bax system. CB1 recep- needle biopsy if indicated. Thirty-nine of tors are transiently expressed during brain the patients had bilateral true gynecomastia development in different group of neurons and 88 had unilateral gynecomastia (53% which do not contain these receptors in the left). Carcinoma of the breast was diagnosed adult brainCS254. in eight, pseudo-gynecomastia in 18, 13 had Glaucoma effect. Nine patients with glau- physiological pubertal changes only, and 9 coma unresponsive to treatment were had other diagnoses. Adverse drug reactions treated with orally administered '-9-THC were possibly implicated in the etiology of capsules or inhaled cannabis in addition to 47 patients, alcohol in seven patients, can- their existing therapeutic regimen. An ini- nabis in one patient, testicular malignancy tial decrease in intraocular pressure was in four patients, and hepatocellular carci- observed in all patients, and the investi- noma in one patient. Five patients were gator’s therapeutic goal was met in four of found to have hyperprolactinemia. Twenty- the nine patients. The decreases in intra- four percent of patients were reassured with- ocular pressure were not sustained, and the out intervention; 18% failed to attend patients elected to discontinue treatment follow-upCS348. within 1–9 months for various reasonsCS359. Hair stimulant effect. Ethanol (50%) Gliomatous effect. Gliomas, in particular extract of the dried seed, applied externally glioblastoma multiform or grade IV astrocy- to mice at a dose of 0.33 g/mL for 14 days, toma, are the most frequent class of malig- was inactiveCS139. nant primary brain tumors and one of the Hemagglutinin activity. Saline extract of most aggressive forms of cancer. Cannab- the dried seed at a concentration of 10% was inoids and their derivatives slowed the inactive on the human red blood cell CS207. growth of different types of tumors, includ- Hepatitis C risk factor. The study of a ing gliomas, in laboratory animals. Cannab- dually diagnosed population estimated the inoids induced apoptosis of glioma cells in prevalence of hepatitis C virus (HCV) to be 66 MEDICINAL PLANTS OF THE WORLD

29.7% or 16 times higher than that in the a significantly higher number of women general population. A high correlation was used cannabis for pain management. The found between the use of tobacco and HCV most commonly reported reason for medici- infection. This appears to be beyond the risk nal cannabis use was appetite stimulation/ factor conveyed by intravenous drug use. weight gain. Male gender and history of Of the patients whose primary diagnoses intravenous drug use were predictive of any were cocaine, opiate, amphetamine, or cannabis use. Age, gender, HIV clinical polysubstance dependence (drugs often status, antiretroviral use, and history of used intravenously), 42% of the tobacco intravenous drug use were not significant users were HCV-positive, whereas only predictors of medicinal cannabis use. 20% of the nontobacco using patients with Despite the frequency of medicinal use, similar primary diagnoses were HCV-posi- minimal changes in the pattern of cannabis tive. The association of tobacco use with use on HIV diagnosis were reported with HCV was found to be strong for females 80% of current medicinal users also indicat- with alcohol, sedative/hypnotic, inhalant, ing recreational consumptionCS289. HIV or cannabis dependence, as none of the patients (n = 252) were recruited via 17 nontobacco using female patients with consecutive sampling in public health care these diagnoses were HCV-positive, whereas clinics. Structured interviews assessed pat- 14 of the 45 (31%) tobacco-using females terns of recent cannabis use, including its with these diagnoses did test positive perceived benefit for symptom relief. for HCVCS306. Associations between cannabis use and Hepatotoxic activity. Ethanol (95%) demographic and clinical variables were extract of the dried resin, administered examined using univariate and multivariate intraperitoneally to toads at a dose of 10 mg/ regression analyses. Overall prevalence of day for 14 days, was active. The results were smoked cannabis in the previous month was significant at p < 0.01 levelCS216. 23%. Reported benefits included relief of Histamine release stimulation. Water anxiety and/or depression (57%), improved extract of the seed, administered intrader- appetite (53%), increased pleasure (33%), mally to human adults, was active on human and relief of pain (28%). Recent use of can- basophilsCS147. nabis was positively associated with severe HIV involvement. The prevalence, predic- nausea (OR = 4, p = 0.004) and recent use tors, and patterns of cannabis use—specifi- of alcohol (OR = 7.5, p < 0.001) and nega- cally medicinal cannabis use among patients tively associated with being Latino (OR = with HIV—were examined. Any cannabis 0.07, p < 0.001). No associations between use in the year prior to interview and self- cannabis use and pain symptoms were defined medicinal use were evaluated. A observedCS315. No safety problems specific to cross-sectional multicenter survey and ret- HIV or protease inhibitors were found in a rospective chart review were conducted to study in which volunteers stayed in a evaluate overall drug utilization in HIV, research hospital 24 hours a day and were including cannabis use. HIV-positive adults randomly assigned to either smoke can- were identified through the HIV Ontario nabis, take oral THC, or take an oral Observational Database; 104 consenting placebo. Cannabis and THC use was associ- patients were interviewed. Forty-three per- ated with weight gainCS369. cent of the patients reported cannabis use, Hyperglycemic activity. Ethanol (95%) whereas 29% reported medicinal use. Rea- extract of the leaf, administered intrave- sons for use were similar by gender although nously to rats at a dose of 300 mg/kg, pro- CANNABIS SATIVA 67 duced an increase of 40 mg percentage 2 made, using automated immunoassays, of hours postinjection and a corresponding de- the presence of cannabis, cocaine, amphet- crease in liver glycogenCS163. Ethanol (95%) amine, methamphetamine, MDMA, methyl- extract of the dried leaf, administered by enedioxyethylamphetamine (MDE), and gastric intubation to rabbits, produced an opiates. Positive results were confirmed by increase followed by a gradual decrease in gas chromatography–mass spectrometry. blood sugar levelsCS021. The dried leaves, Eleven US plasma units were found to be smoked by human adults, produced elevated positive for cocaine (14.6%), whereas all glucose levels in two out of four subjects and German samples were cocaine-negative (p no impairment of insulin release or changes = 0.0007). Fifteen US plasma units (20%) in growth hormone levelsCS024. and one German unit (1.3%) were con- Hypertensive activity. Ethanol (95%) and firmed as positive for cannabis (p = 0.0003). water extracts of the dried aerial parts, Three out of 75 US plasma units were posi- administered intravenously to cats, were tive for both cannabis and cocaine. In none inactive. The ethanol extract stimulated of the 150 samples were amphetamine, respiration and the water extract had no methamphetamine, MDMA, MDE, or opi- effect on respirationCS243. ates detected CS355. Hypoglycemic activity. Ethanol (95%) Immunomodulatory effect. The smoking extract of the dried leaf, administered by of cannabis showed a significant local gastric intubation to rabbits, produced an immunosuppression of the bactericidal increase, followed by a gradual decrease, in activity of human alveolar macrophages. In blood sugar levelsCS021. Extract of the dried animal studies, cannabinoids were identi- leaf, administered subcutaneously to rabbits fied as potent modulators of cytokine pro- at a dose of 0.5 mL/kg (approx 0.6 mg THC) duction, causing a shift from T-helper-1 for 9 weeks, further enhanced hypoglycemia (Th1) to Th2 cytokines. In consequence, induced by insulin. No hypoglycemic effect a compromised cellular immunity was was seen in normal animalsCS025. Hot water observed in these animals, resulting in extract of the resin, administered by gastric enhanced tumor growth and reduced intubation to dogs at a dose of 20 g of air- immunity to viral infections. In vitro, dried resin/animal, produced weak immunosuppressive effects were shown activityCS198. The dried leaf, smoked by adults in all immune cells, but only at high micro- at a dose of 2 g/person, was inactiveCS023. molar cannabinoid concentrations not Hypotensive activity. Ethanol (50%) reached under normal clinical conditions. extract of the entire plant, administered In conclusion, there was no evidence that intravenously to dogs at a dose of 50 mg/kg, cannabinoids induce a serious, relevant was activeCS007. Ethanol (95%) and water immunosuppression in humans, with the extracts of the dried aerial parts, adminis- exception of cannabis smoking, which may tered intravenously to cats, were inactive. affect local bronchoalveolar immunityCS279. The ethanol extract stimulated respiration, The immune function in 16 MS patients and the water extract had no effectCS243. treated with oral cannabinoids was mea- Ilicit drug in plasmapheresis donors. Sev- sured. A modest increase of tumor necrosis enty-five US plasma units from 10 different factor (TNF)-D in lipopolysaccharide- states in the United States and 75 German stimulated whole blood was found during plasma units that had been analyzed princi- cannabis plant-extract treatment (p = pally for their protein composition were 0.037), with no change in other cytokines. screened for drugs. Determinations were In the subgroup of patients with high 68 MEDICINAL PLANTS OF THE WORLD adverse event scores, an increase in plasma sudden infant death syndrome (SIDS); 58% IL-12p40 was found (p = 0.002). The results were positive for drugs, predominantly indicate pro-inflammatory disease-modify- cocaine. The odds ratio for SIDS among ing potential of cannabinoids in MSCS347. drug-positive infants was 1.5 (CI = 0.46– THC and their metabolites inhibited pro- 5.01) and 1.9 (CI = 0.58–6.2) among duction of IL-1 and J-interferon, decreased cocaine-positive infantsCS445. a 33% of the lymphocytes activity and Infant neurobehavioral effect. The sub- inhibited 66% of the lymphocytes adenyl- jects and controls in this study were full- cyclase activity. The consumption of can- term infants of appropriate gestational age nabis decreased immunological competence with no medical problems. At 1–2 days of of macrophages, and alternated their essen- age, 20 infants exposed to cocaine, alcohol, tial role of trophicity of the central nervous cannabis, and cigarettes, 17 infants exposed system. Inhibiting actions of cannabinoids to alcohol and/or cannabis and cigarettes, on the cyclo-oxygenase, promoted produc- and 20 drug-free infants were evaluated by tion of arachidonic acid degradation prod- using the Neonatal Intensive Care Unit ucts. This compound mimics the action of Network Neurobehavioral Scale. Cocaine- histamine, induced a raise of the vascular exposed (CE) infants showed increased tone permeability and bronchospasm, and con- and motor activity, more jerky movements, tributed at delayed reaction of anaphy- startles, tremors, back arching, and signs of laxiaCS427. central nervous system and visual stress than Infant mortality. For a period of 11 months, unexposed infants. They also showed poorer 2964 infants were enrolled and screened at visual and auditory following. There were birth for exposure to cocaine, opiate, or can- no differences in how the examination was nabinoid by meconium analysis. At birth, administered to CE and nonexposed infants. 44% of the infants tested positive for drugs, Reduced birth-weight and length were also 30.5% positive for cocaine, 20.2% for opi- observed in CE infants. Differences attrib- ate, and 11.4% for cannabinoids. Compared utable to CE infants were related to muscle with the drug-negative group, a significantly tone and motor performance, following dur- higher percentage (p < 0.05) of the drug- ing orientation, and signs of stress. CE positive infants had lower weight and infants were not more difficult to test, nor smaller head circumference and length at did they require an alteration in the exami- birth and a higher percent of their mothers nation. Both neurobehavioral patterns of were single, multigravid, multiparous, and excitability and lethargy were observed. The had little to no prenatal care. Within the findings may have been a result of the syn- first 2 years of life, 44 infants died: 26 were ergistic effects of cocaine with alcohol and drug-negative (15.7 deaths per 1000 live cannabisCS456. births) and 18 were drug-positive (13.7 Inflammatory effect. A case of a 17-year- deaths per 1000 live births). The mortality old male regular cannabis user who devel- rate among cocaine, opiate, or cannabinoid- oped a large swollen uvula (uvulitis) and positive infants were 17.7, 18.4, and 8.9 per partial upper airway obstruction after 1000 live births, respectively. Among smoking cannabis was evaluated. Symp- infants with birth-weight of 2500 g or less, toms resolved with the administration of infants who were positive for both cocaine corticosteroids and antihistaminesCS380. A and morphine had a higher mortality rate healthy 17-year-old man who inhaled (OR = 5.9, CI = 1.4–24) than drug-nega- cannabis prior to general anesthesia is tive infants. Eleven infants died from the described. In the recovery room, after an CANNABIS SATIVA 69 uneventful general anesthetic, acute uvular were added prior to ethanol extract of can- edema resulted in postoperative airway nabis to determine their effect on Na+ and obstruction and admission to the hospital. Cl– movement. The results suggested that The uvular edema was treated successfully the extract may affect the Cl– movement with dexamethasoneCS455. more directly than Na+ movement in the Information-processing effect. Informa- intestinal epithelial cellsCS307. tion processes are thought to represent the Intraocular pressure reduction. Polysac- basic building blocks of higher order cogni- charide fraction of the dried entire plant, tive processes. The inspection time task was administered intravenously to rabbits at a used to investigate the effects of acute and dose of 1 Pg/animal was activeCS138. Water subacute cannabis use on information pro- extract of the dried aerial parts, adminis- cessing in 22 heavy users compared with 22 tered intravenously to rabbits at a dose of nonusers. The findings indicated that users 250 Pg/animal, was activeCS142. A dose of 5 in the subacute state display significantly Pg/animal was inactive on Rhesus monkeys slowed information-processing speeds and active on rabbits. A dose of 10 mg/ani- (longer inspection times) compared with mal, administered per rectum to Rhesus controls. This deficit appeared to be nor- monkeys and rabbits, was inactiveCS191. malized while users were in the acute state. IQ effect. Cannabis use for 70 individuals These results may be explained as a with- aged 17–20 years was determined through drawal effect, but may also be owing to tol- self-reporting and urinalysis. IQ scores were erance development because of long-term calculated by subtracting each person’s IQ cannabis useCS276. score at 9–12 years (before initiation of drug Insecticidal activity. Leaf extract, admin- use) from his or her score at 17–20 years. istered to larvae of Chironomus samoensis, The difference in IQ scores of current heavy produced paralysis leading to death. The users (at least five joints per week), current extract brought a drastic change in the mor- light users (less than five joints per week), phology of sensilla trichoidea, the general former users (who had not smoked regularly body cuticle, and a significant reduction in for at least 3 months), and nonusers (who the concentration of magnesium and iron, never smoked more than once per week and whereas manganese showed only slight no smoking in the past 2 weeks) was com- average increase. Because the sensilla pared. Current cannabis use was signifi- trichoidea has nerve connections, it was cantly correlated (p < 0.05) in a dose-related assumed that the toxic principle of the leaf fashion with a decline in IQ over the ages extract has affected the central nervous studied. The comparison of the IQ differ- systemCS267. ence scores showed an average decrease of Intestinal motility activity. Rat intestinal 4.1 points in current heavy users (p < 0.05) epithelia mounted in an Ussing chamber compared with gains in IQ points for light attached with voltage/current clamp were current users (5.8), former users (3.5), and used for measuring changes of the short-cir- nonusers (2.6)CS385. cuit current across the epithelia. The intes- Lactate inhibition. The dried leaf, smoked tinal epithelia were activated with current by adults at a dose of 2 g/person, decreased raised by serosal administration of forskolin blood lactic acidCS023. 5 PM. Ethanol extracts of cannabis aug- Leutinizing hormone-release inhibition. mented the current additively when each The dried aerial part, smoked by meno- was added after forskolin. In subsequent pausal women at a dose of 1 g/person, was experiments, ouabain, and bumetanide inactiveCS225. When administered to normal 70 MEDICINAL PLANTS OF THE WORLD and castrated male rats, at a dose of 75 mg/ years. Cannabis and tobacco smoking were kg, was activeCS215. documented at each age using a standard- Lower limb occlusive arteriopathy. Sev- ized interview. Lung function, as measured enty-three patients (60 males and 13 by the FEV1–vital capacity (VC) ratio, was females less than 50 years of age) were obtained by simple spirometry. A fixed divided into four groups: Buerger’s disease effects regression model was used to analyze (thromboangiitis obliterans [TAO]), the data and to account for confounding atheromatous juvenile peripheral obstruc- factors. When the sample was stratified for tive arterial diseases (POAD), autoimmune cumulative use, there was evidence of a POAD, and arteriopathy of undetermined linear relationship between cannabis use origin. The first symptoms occurred at 38 r and FEV1–VC (p < 0.05). In the absence of 8 years of age. Fourteen patients (20%) had adjusting for other variables, increasing can- TAO, 51 (70%) atheromatous POAD, 4 nabis use over time was associated with a (5%) POAD with systemic or autoimmune decline in FEV1–VC with time; the mean disease, and 4 (5%) undetermined POAD. FEV1–VC among subjects using cannabis Age of onset was earlier in TAO (35 r 8 vs on 900 or more occasions was 7.2, 2.6 and 40 r 8 years, p = 0.046), smoking was greater 5% less than nonusers at ages 18, 21, and in the atheroma group (33 r 16 vs 24 r 14 26, respectively. After controlling for pack/years, p = 0.033). Fifty-three patients potential confounding factors (age, tobacco with POAD had dyslipidemia and 26% had smoking, and weight) the negative effect of hypertension. Regular cannabis intake was cumulative cannabis use on mean FEV1– more frequent in the TAO group (21% vs VC was only marginally significant (p < 8%). At the time of medical care, Fontaine’s 0.09). Age (p < 0.001), cigarette smoking stage was more frequently stage II in (p < 0.05), and weight (p < 0.001) were all atheroma patients (57% vs 14%) and stage significant predictors of FEV1–VC. Can- IV in TAO patients (86% vs 35%). TAO nabis use and daily cigarette smoking acted was diagnosed in 43% cannabis users and additively to influence FEV1–VC. Results in 19% nonusers. Results indicated that indicated that longitudinal observations the main etiology of juvenile POAD is over 8 years in young adults revealed a dose- atheroma, followed by TAO. Cannabis dependent relationship between cumula- users accounted for at least 10% of these tive cannabis consumption and decline patients. They were characterized by lower in FEV1–VC. When confounders were tobacco intake, more distal lesions, more accounted for the effect was reduced and frequent involvement of the upper limbs. was only marginally significant, but given They presented more frequently as TAOCS379. the limited time frame over which observa- A case of a 30-year-old woman who smoked tions were made, the trend suggests that cannabis and developed intermittent clau- continued cannabis smoking has the poten- dication of the lower limbs was reported. tial to result in clinically important impair- Results indicated that cannabis could be ment of lung functionCS371. involved not only in the pathogenesis of Luteolytic effect. The aerial parts, smoked juvenile obstructive arteriopathy, but by a chronic high-dose user, were inac- also in the development of atheromatous tiveCS160. lesionsCS409. Memory impairment. The effects of com- Lung function. A group of over 900 young bined exposure to ethanol and '-9-THC in adults derived from a birth cohort of 1037 a memory task was investigated in rats. subjects were studied at age 18, 21, and 26 Ethanol, voluntarily ingested in alcohol- CANNABIS SATIVA 71 preferring rats, and THC, given by intrap- enhanced the ability of cell-mediated type eritoneal injection, had a synergic action to hypersensitivity and nonspecific immune impair object recognition when a 15-minute responses in normal miceCS334. interval was adopted between the sample Mitochondrial function disruption. '-9- phase and the choice phase of the test. THC in the pulmonary transformed cell line Ingestion of ethanol, or 2 or 5 mg/kg of A549 produced a rapid and extensive THC were not able to modify object recog- depletion of cellular energy stores. Adenos- nition in these experimental conditions. ine 5'-triphosphatase levels declined dose

When voluntary ethanol ingestion was dependently with an IC50 of 7.5 Pg/mL of combined with administration of these THC after 24 hours of exposure. Cell death doses of THC, object recognition was mark- was observed only at concentrations greater edly impaired. THC impaired object recog- than 10 Pg/mL. Studies using JC-1, a fluo- nition only at the dose of 10 mg/kg, when rescent probe for mitochondrial membrane its administration was not combined with potential, revealed diminished mitochon- that of ethanol. The selective cannabinoid drial function at THC concentrations as CB1 receptor antagonist SR 141716A (N- low as 0.5 Pg/mL. At concentrations of (piperidin-1-yl)-5-(4-chlorophenyl)-1(2, 4- 2.5 and 10 Pg/mL of THC, a decrease in dichloro-phenyl)-4-methyl-1H-pyrazole mitochondrial membrane potential was ob- carboxamide HCl) at the dose of 1 mg/kg served 1 hour after THC exposure. Mito- reversed the amnesic effect of 10 mg/kg of chondrial function remained diminished THC. This indicated that the effect is for at least 30 hours after THC exposure. mediated by the receptor subtype. The syn- Flow cytometry studies on cells exposed to ergism of ethanol and THC was not particulate smoke extracts indicated that detected when an intertrial interval of 1 JC-1 red fluorescence was fivefold lower in minute was adoptedCS370. cells exposed to cannabis smoke extract Memory improvement. Extract from fruc- compared with tobacco smoke-exposed tus cannabis (EFC), administered intra- cells. Comparison with a variety of mito- gastrically to mice with drug-induced chondrial inhibitors demonstrated that dysmnesia at doses of 0.2, 0.4, and 0.8 g/kg, THC produced effects similar to that of for 7 days, prolonged the latency and carbonyl cyanide p-trifluoromethoxyphe- decreased the number of errors in the step- nylhydrazone, suggesting uncoupling of down test, and enhanced the spatial resolu- electron transport. Loss of red JC-1 fluores- tion of amnesic mice in water maze test. cence by THC was suppressed by cyclo- EFC at the dose of 0.2 g/kg overcame amne- sporin A, suggesting mediation by the sia of three stages of memory process. EFC mitochondrial permeability transition pore. activated calcineurin activity at a concen- This disruption of mitochondrial function tration range of 0.01–100 g/L. The maximal was sustained for at least 24 hours after re- value of EFC on calcineurin activity (35% moval of THC by extensive washingCS360. r 5 %) appeared at a concentration of 10 g/ Mitogenic effect. The resin was inactive LCS320. EFC with activation of calcineurin, on the human and rat white blood cellsCS037. extracted from Chinese traditional medi- Molluscicidal activity. Ethanol (95%) and cine, was used to determine the effects on water extracts of the dried flowering tops, at memory and immunity in mice. In the step- a concentration of 1000 ppm, produced down-type passive avoidance test, the plant weak activity on Biomphalaria straminea and extract (0.2 g/kg) significantly improved Biomphalaria glabrataCS245. Water saturated amnesia induced by drugs, and greatly with essential oil of the aerial parts, at a con- 72 MEDICINAL PLANTS OF THE WORLD centration of 1:2, produced weak activity on (p = 0.0111)CS257. A cannabis-based medici- Biomphalaria glabrataCS201. nal extract (CBME) was administered to Motor function. Nine cannabis smokers 160 patients with multiple sclerosis experi- and 16 controls were studied to determine encing significant problems from at least the attentional areas related to motor func- one of the following: spasticity, spasms, tion, and primary and supplementary motor bladder problems, tremor, or pain. The cortices. Echo planar images and high-reso- interventions were oromucosal sprays of lution molecular resonance images were ac- matched placebo, or whole plant CBME quired. The challenge paradigm included containing equal amounts of '-9-THC and left and right finger sequencing. Group dif- CBD at a dose of 2.5–120 mg of each daily, ferences in cerebral activation were exam- in divided doses. The primary outcome mea- ined for Brodmann areas (BA) 4, 6, 24, and sure was a Visual Analogue Scale (VAS) 32 using region of interests analyses in sta- score for each patient’s most troublesome tistical parametric mapping. Cannabis users, symptom. Additional measures included tested within 4–36 hours of discontinuation, VAS scores of other symptoms, and mea- exhibited significantly less activation than sures of disability, cognition, mood, sleep controls in BA 24 and 32 bilaterally during and fatigue. Following CBME the primary right- and left-sided sequencing and for BA symptom score reduced from mean 74.36 6 in all tasks except for left-sided sequenc- (11.1) to 48.89 (22.0) following CBME and ing in the left hemisphere. There were no from 74.31 (12.5) to 54.79 (26.3) following statistically significant differences for BA 4. placebo. Spasticity VAS scores were signifi- None of these regional activations corre- cantly reduced by CBME (Sativex®) in com- lated with urinary cannabis concentration parison with placebo (p = 0.001). There and verbal IQ for smokers. The results sug- were no significant adverse effects on cog- gested that recently abstinent chronic can- nition or mood and intoxication was gener- nabis smokers produce reduced activation in ally mildCS268. A SCE with pure '-9-THC, at motor cortical areas in response to finger matched concentrations of '-9-THC, and a sequencing compared with controlsCS250. '-9-THC-free extract ('-9-THC-free SCE) Multiple sclerosis. One hundred fifty- in a mouse model of MS, were examined. seven drug-naïve, first-episode schizophrenic Although SCE inhibited spasticity in the patients were examined. A significantly mouse model of MS to a comparable level, elevated brain-derived neurotrophic factor it caused a more rapid onset of muscle relax- (BDNF) serum concentrations in patients ation and a reduction in the time to maxi- with chronic cannabis abuse (n = 35, p < mum effect compared with '-9-THC alone. 0.001) or multiple substance abuse (n = 20, The '-9-THC-free extract or CBD caused p < 0.001) prior to disease onset were no inhibition of spasticityCS312. In an found. Drug-naïve schizophrenic patients experimental allergic encephalomyelitis without cannabis consumption showed (EAE), an animal model of MS, it was similar results to normal controls and demonstrated that the cannabinoid sys- cannabis controls without schizophrenia. tem is neuroprotective during EAE. Mice, Elevated BDNF serum levels were not deficient in the cannabinoid receptor CB1, related to schizophrenia and/or substance tolerated inflammatory and excitotoxic abuse itself but may reflect a cannabis- insults poorly, and developed substantial related idiosyncratic damage of the schizo- neurodegeneration following immune phrenic brain. Disease onset was 5.2 years attack in EAE. Exogenous CB1 agonists can earlier in the cannabis-consuming group provide significant neuroprotection from CANNABIS SATIVA 73 the consequences of inflammatory central killer cell activity on the effect of viruses nervous system disease in an experimental were similar to those of infected but can- allergic uveitis modelCS339. nabis-free counterparts, but on the level of Mutagenic activity. Petroleum ether uninfected cells treated with cannabis. The extract of the aerial parts, in the ration of effects of cannabis and retrovirus were addi- Drosophila at concentrations of 0.5, 1, and tive resulting in anergy of natural-killer 5% of the diet, was activeCS190. Petroleum cellsCS432. ether extract of the dried leaf, administered Neonatal abstinence syndrome. The by gastric intubation to male mice at a dose relationship of maternal drug abuse to symp- of 50 mg/kg, was activeCS183. Water and toms, the effectiveness of pharmacological methanol extracts of the seed, on agar plate agents in controlling symptoms, and the at a concentration of 100 mg/mL, were length of in-patient stay were investigated inactive on Bacillus subtilis H-17 (Rec+) and in infants with neonatal abstinence syn- Salmonella typhimurium TA100 and TA98. drome. Pharmacological treatment was oral Metabolic activation had no effect on the morphine sulphate (0.2 mg four to six times resultsCS199. hourly), phenobarbitone (3–7 mg/kg/day), Myocardial infarction. A young man who or combination of the two were adminis- suffered a myocardial infarction after taking tered to infants with a serial Finnegan score Viagra® in combination with cannabis was greater than 8. The average maternal age investigated. Viagra is metabolized pre- was 24.6 years, (18–34 years). Drug use vol- dominantly by the CYP450 3A4 hepatic unteered by the mothers was methadone microsomal isoenzyme. Cannabis is a known alone in 6 cases, methadone and benzodiaz- inhibitor of CYP450 3A4 isoenzyme. The epines in 14, methadone and heroin and effect of the Viagra was thus potentiated by benzodiazepines in 7, methadone and the effect of cannabisCS387. heroin in 10, heroin alone in 2, and other Natural-killer cells effect. Leukemia sus- multiple drug use including oral morphine ceptible BALB/c and resistant C57BL/6 sulphate, dothiepin, and cannabis in 4. mice were infected with Friend leukemia Average gestational age was 40.3 (35–42 virus complex and its helper component weeks). The average birth-weight was 2.81 Rowson-Parr virus. At different time points, kg (1.89–3.91 kg). Time-to-onset of with- their natural-killer cells were separated from drawal symptoms was 2.8 (1–13) days. The spleens and treated with 0–10 Pg/mL of duration of pharmacological treatment (oral THC, subsequently mixed with Yac-1 tar- morphine sulphate and/or phenobarbitone) get cells for 4 and 18 hours. The natural- was 21.8 (1–62) days. The total hospital stay killer cell activity in both mouse strains for the 43 infants was 1011 daysCS424. infected by either virus complex or helper Neuroendocrine abnormalities. Prolactin virus weakened on days 2–4 postinfection, response to D-fenfluramine was assessed in normalized by day 8 and enhanced on days abstinent ecstasy (MDMA) users with con- 11–14. Natural-killer cell activity on the comitant use of cannabis only (13 males, 11 effect of low concentration (1–2.5 Pg/mL) females) and in two control groups: healthy of THC slightly increased in BALB/c, was nonusers (13 females) and exclusive can- unaffected in C57BL/6, especially in the 18 nabis users (seven males). Prolactin hour assays. In the combined effects of can- response to D-fenfluramine was slightly nabis and retrovirus, damages by cannabis blunted in female ecstasy users. Both male dominated over those of retroviruses. Inhi- user samples exhibited a weak prolactin bition or reactive enhancement of natural- response to D-fenfluramine, but this was 74 MEDICINAL PLANTS OF THE WORLD weaker in the group of cannabis users. less of current analgesic therapy. They Baseline prolactin and prolactin response to entered a baseline period of 2 weeks, fol- D-fenfluramine were associated with the lowed by three, 2-week treatment periods; extent of previous cannabis use. The results during each period they received one of indicated that the endocrinological abnor- three oromucosal spray preparations. These malities of ecstasy users might be closely were placebo and two whole plant extracts related to their coincident cannabis of C. sativa L.: GW-1000-02 (Sativex®), useCS381. containing '-9-THC: CBD in an approx 1:1 Neurogenic symptoms alleviation. Whole- ratio and GW-2000-02, containing prima- plant extracts of '-9-THC, CBD, 1:1 CBD: rily THC. The primary outcome measure THC, or placebo were self-administered by was the mean pain severity score during the sublingual spray to 24 patients with MS last 7 days of treatment. Secondary outcome (n = 18), spinal cord injury (n = 4), brachial measures included pain related quality of life plexus damage (n = 1), and limb amputa- assessments. The primary outcome measure tion owing to neurofibromatosis (n = 1), at failed to fall by the two points defined in doses determined by titration against symp- our hypothesis. Both this measure and mea- tom relief or unwanted effects within the sures of sleep showed statistically significant range of 2.5–120 mg/24 hours for 2 weeks. improvements. The study medications were The patients recorded symptoms, well- well tolerated with the majority of adverse being, and intoxication scores on a daily events, including intoxication type mild to basis using visual analog scales. At the end moderate in severity and resolving sponta- of each two-week period an observer rated neous reactionsCS251. severity and frequency of symptoms on Neuroprotective effect. The effect of can- numerical rating scales, administered stan- nabidiol on E-amyloid peptide-induced tox- dard measures of disability (Barthel Index), icity in cultured rat pheocromocytoma mood, cognition, and recorded adverse PC12 cells was investigated. Following events. Pain relief associated with both exposure of cells to E-amyloid peptide (1 Pg/ THC and CBD was significantly superior to mL), a marked reduction in cell survival was placebo. Impaired bladder control, muscle observed. This effect was associated with spasms, and spasticity were improved by increased reactive oxygen species produc- cannabis medicinal extract (CME) in some tion and lipid peroxidation, and caspase 3 patients with these symptoms. Three (a key enzyme in the apoptosis cell-signal- patients had transient hypotension and ling cascade) appearance, DNA fragmenta- intoxication with rapid initial dosing of tion, and increased intracellular calcium. THC-containing CME. The results indi- Treatment of the cells with CBD (10–7–10–4 cated that cannabis could improve neuro- mol) prior to E-amyloid peptide exposure, genic symptoms unresponsive to standard significantly elevated cell survival, whereas treatments. Unwanted effects were predict- it decreased reactive oxygen species produc- able and generally well toleratedCS354. tion, lipid peroxidation, caspase 3 levels, Neuropathic pain relief. Forty-eight pa- DNA fragmentation, and intracellular tients with at least one avulsed root and calciumCS298. CBD and other cannabinoids baseline pain score of four or more on an were examined as neuroprotectants in rat 11-point ordinate scale participated in a cortical neuron cultures exposed to toxic randomized, double-blind, placebo-con- levels of glutamate. The psychotropic can- trolled, three-period crossover study. The nabinoid receptor agonist '-9-THC and patients had intractable symptoms regard- cannabidiol, reduced N-methyl-D-aspartate, CANNABIS SATIVA 75

D-amino-3-hydroxy-5-methyl-4-isoxazole paw tremor, and scratches. In both experi- propionic acid and kainate receptor medi- mental conditions, the global withdrawal ated neurotoxicities. Neuroprotection was score was significantly attenuated by '-9- not affected by cannabinoid receptor THC administration. The effect of '-9- antagonist, indicating a (cannabinoid) THC was not to the result possible adaptive receptor-independent mechanism of action. changes induced by chronic nicotine on CBD demonstrated a reduction in hydrop- CB1 cannabinoid receptors. The density eroxide toxicity in neurons. In this trial of and functional activity of these receptors the abilities of various antioxidants to pre- were not modified by chronic nicotine vent glutamate toxicity, cannabidiol was administration in the different brain struc- superior to both D-tocopherol and ascorbate tures investigated. The consequences of '- in protective capacityCS412. 9-THC administration on c-Fos expression Neuropsychological effect. Cerebral blood in several brain structures after chronic flow was measured in 12 long-term can- nicotine administration and withdrawal nabis users shortly after cessation of can- were examined. c-Fos was decreased in the nabis use (mean 1.6 days). The findings caudate putamen and the dentate gyrus showed significantly lower mean hemi- after mecamylamine precipitated nicotine spheric blood flow values and significantly withdrawal. '-9-THC administration did lower frontal values in the cannabis subjects not modify c-Fos expression under these compared with normal controls. The results experimental conditions. '-9-THC also indicated that the functional level of the reversed conditioned place aversion associ- frontal lobes was affected by long-term can- ated to naloxone precipitated nicotine nabis useCS397. withdrawal. The results indicated that '-9- Neurotransmission inhibition. The BLA THC administration attenuated somatic or the medial prefrontal cortex (PFC) signs of nicotine withdrawal and this effect stimulation in urethane-anesthetized rats was not associated with compensatory induced generation of action potentials in changes on CB1 cannabinoid receptors dur- the Nac neurons. This excitatory effect was ing chronic nicotine administration. '-9- strongly inhibited by the synthetic cannab- THC also ameliorated the aversive inoid agonists WIN (0.062–0.25 mg/kg, iv motivational consequences of nicotine [intravenously]) and HU-210 (0.125–0.25 withdrawalCS253. mg/kg, iv), or '-9-THC (1 mg/kg, iv). D1 Night vision improvement. In a double- or D2 dopamine receptor antagonists blind study, graduated THC administration (SCH23390 0.5–1 mg/kg, sulpiride 5–10 at doses of 0–20 mg (as Marinol) on mea- mg/kg, iv) or the opioid antagonist nalox- sures of dark adaptometry and scotopic sen- one (1 mg/kg, iv) were not able to reverse sitivity was evaluated. Field studies of night the action of cannabinoids. The selective vision were performed among Jamaican and CB1 receptor antagonist/reverse agonist Moroccan fishermen, and mountain dwell- SR141716A (0.5 mg/kg, iv) fully suppressed ers with the LKC Technologies Scotopic the action of cannabinoid agonists, whereas Sensitivity Tester-1 (SST-1). Improve- per se had no significant effectCS374. ments in night vision measures were noted Nicotine and '-9-THC interaction. '-9- after THC or cannabis. The effect was dose- THC administration to mice significantly dependent and cannabinoid-mediated at decreased the incidence of several nicotine the retinal levelCS286. withdrawal signs precipitated by mecamy- Nocturnal sleep effect. Eight healthy vol- lamine or naloxone, such as wet-dog-shakes, unteers (four males, four females; aged 21– 76 MEDICINAL PLANTS OF THE WORLD

34 years) were taking placebo, 15 mg '-9- preceded his stroke. Except for cigarette THC, 5 mg THC combined with 5 mg smoking and slight dyslipidemia, classical CBD, and 15 mg THC combined with 15 risk factors for stroke/embolism were mg CBD. These were formulated in 50:50 absent. The family history for cerebrovas- ethanol to propylene glycol and adminis- cular events, blood pressure, clotting tests, tered using an oromucosal spray during a examinations for thrombophilia, vasculitis, 30-minute period from 10 PM. Electroen- extracranial and intracranial arteries, and cephalogram was recorded during the sleep cardiac investigations were normal or period (11 PM to 7 AM). Performance, sleep respectively negative; the stroke was attri- latency, and subjective assessments of buted to the chronic cannabis consump- sleepiness and mood were measured from tionCS271. 8:30 AM (10 hours after drug administra- Oral cancer. A study of 116 patients aged tion). There were no effects of 15 mg THC 45 years and younger, diagnosed with squa- on nocturnal sleep. With the concomitant mous cell carcinoma of the mouth was con- administration of the drugs (5 mg THC and ducted. Two hundred and seven controls 5 mg CBD to 15 mg THC and 15 mg CBD), who had never had cancer, matched for age, there was a decrease in stage 3 sleep, and sex, and area of residence, were recruited. with the higher dose combination, wake- The self-completed questionnaire con- fulness was increased. The next day, with a tained items about exposure to the follow- 15-mg THC dose, memory was impaired, ing risk factors: tobacco products, cannabis, sleep latency was reduced, and the subjects alcohol, and diet. Conditional logistic reported increased sleepiness and changes in analyses were conducted adjusting for social mood. With the lower dose combination, class, ethnicity, tobacco, and alcohol hab- reaction time was faster on the digit recall its. All tests for statistical significance were task, and with the higher dose combination, two-sided. The majority of oral cancer subjects reported increased sleepiness and patients reported exposure to the major risk changes in mood. Fifteen milligrams of factors of tobacco and alcohol even at the THC appeared to be sedative, and 15 mg younger age. The estimated risks associated CBD appeared to have alerting properties as with tobacco or alcohol were low (OR it increased waking activity during sleep and range: 0.6–2.5) among both males and counteracted the residual sedative activity females. Only smoking for 21 years or more of the 15 mg THCCS290. produced significantly elevated odds ratios Occipital stroke. A right occipital (OR = 2.1; 95% CI: 1.1–4). Exposure asso- ischemic stroke occurred in a 37-year-old ciated with other major risk factors did not Albanese man with a previously uneventful produce significant risks in this sample. medical history, 15 minutes after smoking a Long-term consumption of fresh fruits and cigarette with approximately 250 mg of can- vegetables in the diet appeared to be pro- nabis. Clinical manifestations of the stroke tective for both males and femalesCS310. were left-sided hemiparesis, hemihypesthe- Oral cytological effect. The effects of can- sia and blurred vision, which vanished spon- nabis, methaqualone, or tobacco smoking taneously and almost completely after 3 on the epithelial cells in 16 patients were days. The patient has been smoking can- evaluated. The site samples included the nabis regularly from the age of 27, with a buccal mucosa (left and right sides), the pos- frequency of two to three cigarettes/can- terior dorsum of the tongue, and the ante- nabis per week during the 6 months that rior floor of the mouth. There was a CANNABIS SATIVA 77 significant prevalence of bacterial cells in with agoraphobia diagnosis did not affect the smears and a greater number of degener- the treatment response in either group. ate and atypical squamous cells in cannabis There were no significant differences in users compared with controls. Epithelial weight gain, sexual side effects, or relapse cells in smears taken from cannabis users rates between patients according to gender and tobacco-smoking controls showed or comorbid diagnosisCS300. koilocytic changesCS376. Paroxysmal atrial fibrillation. A healthy Ovulation inhibition effect. Petroleum young subject was observed for paroxysmal ether extract of the aerial parts, admin- atrial fibrillation following cannabis intoxi- istered orally to rats, produced weak cation. The abuse of this substance was the activityCS087. most possible and identifiable risk factorCS407. Pancreatic effect. Place conditioning effect. THC was A 29-year-old man presented with acute administered to female rats at doses of 1, 5, pancreatitis after a period of heavy cannabis or 20 mg/kg) during gestation and lacta- smoking. Other causes of the disease were tion. Maternal exposure to low doses of ruled out. The pancreatitis resolved itself THC (1 and 5 mg/kg), relevant for human after the cannabis was stopped and this was consumption, produced an increased confirmed by urinary cannabinoid metabo- response to the reinforcing effects of a mod- lite monitoring in the community. There erate dose of morphine (350 Pg/kg), as mea- were no previous reports of acute pancreati- sured in the place-preference conditioning tis associated with cannabis use in the gen- paradigm (CPP) in the adult male off- eral population. Drugs of all types are related spring. These animals also displayed an en- to the etiology of pancreatitis in approxi- hanced exploratory behavior in the mately 1.4–2% of casesCS313. defensive withdrawal test. Only females Pancreatic toxicity. The dried leaf, smoked born from mothers exposed to THC at a by a 19-year-old woman, was active. The dose of 1 mg/kg exhibited a small increment subject was hospitalized with pancrea- in the place conditioning induced by mor- titisCS220. phine. The possible implication of the HPA Panic disorder. Sixty-six panic disorder was analyzed by monitoring plasma levels of patients were included in a study. All of adrenocorticotropic hormone (ACTH) and whom met the DSM-IV diagnosis of panic corticosterone in basal and moderate-stress disorder (n = 45) or panic disorder with ago- conditions (after the end of the CPP test). raphobia ([PDA]; n = 21). Twenty-four Female offspring perinatally exposed to patients experienced their first panic attack THC (1 or 5 mg/kg) displayed high basal within 48 hours of cannabis use and then levels of corticosterone and a blunted adre- went on to develop panic disorder. All the nal response to the HPA-activating effects patients were treated with paroxetine of the CPP test. Male offspring born from (gradually increased up to 40 mg/day). The mothers exposed to THC (1 or 5 mg/kg) dis- two groups responded equally well to played the opposite pattern: normal to low paroxetine treatment as measured at the 8 basal levels of corticosterone, and a sharp weeks and 12 months follow-up visits. adrenal response to the CPP challengeCS436. There were no significant effects of age, sex, THC administration to rats at a low dose and duration of illness as covariates with (1.5 mg/kg) resulted in failing to develop response rates between the two groups. In place conditioning, and developing a place addition, panic disorder or panic disorder aversion at a high dose (15 mg/kg). Admin- 78 MEDICINAL PLANTS OF THE WORLD istration of the cannabinoid antagonist Assessment Scale administered at 1–3 days SR141716A induced a CPP at both a low of age. Adjusting for cannabis exposure had (0.5 mg/kg) and a high (5 mg/kg) doseCS451. no effect on these relationships between Plant germination effect. Methyl chloride plasma NE and the depressed and orienta- extract of the dried seed produced weak tion clustersCS449. activity on Amaranthus spinosus (25.8%) Pneumonic effect. A case–control study inhibitionCS176. Methyl chloride extract of was conducted in 7001 individuals. Odds the dried leaves produced 17.5% inhibition ratios were calculated by conditional logis- of Amaranthus spinosusCS176. tic regression with substance use and social Plasma norepinephrine concentration. factors as cofounders. Pneumonia was not Forty-six newborn infants participated in a associated with kava use. Crude odds ratios prospective study of the neonatal and long- = 1.26 (0.74–2.14, p = 0.386) increased after term effects of prenatal cocaine exposure. controlling for confounders (OR = 1.98, Based on maternal self-report, maternal 0.63–6.23, p = 0.237) but was not signifi- urine screening, and infant meconium cant. Adjusted odds ratios for pneumonia analysis, 24 infants were classified as CE and cases involving kava and alcohol users was 22 as unexposed. Between 24 and 72 hours 1.19 (0.39–3.62, p = 0.756). Crude odds postpartum, plasma samples for norepi- ratios for associations between pneumonia nephrine (NE), epinephrine, dopamine, and cannabis use (OR = 2.27, 1.18–4.37, and dihydroxyphenylalanine analysis were p = 0.014) and alcohol use (OR = 1.95, obtained. The Neonatal Behavioral Assess- 1.07–3.53, p = 0.026) were statistically ment Scale was administered at 1–3 days of significant and approached significance for age and at 2 weeks of age by examiners petrol sniffing (OR = 1.98, 0.99–3.95, masked to the drug exposure status of the p = 0.056)CS335. newborns. The CE newborns had increased Postural syncope. Twenty-nine volunteers plasma NE concentrations when compared participated in a randomized, double-blind, with the unexposed infants (geometric placebo-controlled study. Cerebral blood mean, 923 pg/mL vs 667 pg/mL). There velocity, pulse rate, blood pressure, skin per- were no significant differences in plasma fusion on forehead and plasma '-9-THC epinephrine, dopamine, or dihydroxyphe- levels were quantified during reclining and nylalanine concentrations. Analysis for the standing for 10 minutes before and after effect of potential confounding variables THC infusions and cannabis smoking. Both revealed that maternal cannabis use was also THC and cannabis induced postural dizzi- associated with increased plasma NE, ness, with 28% reporting severe symptoms. although birth-weight, gender, and mater- Intoxication and dizziness peaked immedi- nal use of alcohol or cigarettes were not. ately after drug. The severe dizziness group Geometric mean plasma NE was 1164 pg/ showed the most marked postural drop in mL in those infants with in utero exposure cerebral blood velocity and blood pressure to both cocaine and cannabis compared to and showed a drop in pulse rate after an ini- 812 pg/mL in those exposed to only cocaine tial increase during standing. Postural dizzi- and 667.0 pg/mL in those exposed to nei- ness was unrelated to plasma levels of THC ther. Among the CE infants, plasma NE and other indicesCS340. concentration correlated with an increased Prenatal exposure. Data collected from the score for the depressed cluster (r = 0.53) and National Household Survey on Drug Abuse, a decreased score for the orientation cluster a nationally representative sample survey of (r = –0.43) of the Neonatal Behavioral 22,303 noninstitutionalized women aged CANNABIS SATIVA 79

18–44 years, of whom 1249 were pregnant, week before and throughout pregnancy were analyzed. During the 2-year study were 90 g lighter than the offspring of other period, 6.4% of the non-pregnant women of women. No significant adjusted effects were childbearing age and 2.8% of the pregnant seen for birth length and head circum- women reported that they used illicit drugs. ferenceCS389. In two hospitals, 12,885 preg- Of the women who used drugs, the relative nant women answered questionnaires proportion of women who abstained from regarding consumption of alcohol, tobacco, illicit drugs after recognition of pregnancy cannabis, and other drugs. The prevalence increased from 28% during the first trimes- of cannabis use was 0.8%. Women using ter of pregnancy to 93% by the third trimes- cannabis, but no other illicit drugs were ter. However, because of postpregnancy each retrospectively matched with four ran- relapse, the net pregnancy-related reduction domly chosen pregnant women in the same in illicit drug use at postpartum was only period and the same age group and with 24%. Cannabis accounted for three-fourths same parity. Eighty-four cannabis users were of illicit drug use, and cocaine accounted for included. These women were socioeco- one-tenth of illicit drug use. Of those who nomically disadvantaged and had a higher used illicit drugs, over half of pregnant and prevalence of present and past use of alco- two-thirds of non-pregnant women used hol, tobacco, and other drugs. No signifi- cigarettes and alcohol. Among the cant difference in pregnancy, delivery, or sociodemographic subgroups, pregnant and puerperal outcome was found. Children of non-pregnant women who were young (18– women using cannabis were 150 g lighter, 30 years) or unmarried, and pregnant 1.2 cm shorter, and had 0.2 cm smaller head women with less than a high school educa- circumference than the control infantsCS418. tion had the highest rates of illicit drug A 27-year-old woman who smoked a joint useCS357. Over 12,000 women at 18–20 weeks (cannabis) and 20 cigarettes (tobacco) daily of gestation were enrolled in an Avon Lon- up to the time of a positive pregnancy test gitudinal Study of Pregnancy and Child- at 7 weeks and 4 days, was evaluated. On hood. Five percent of the mothers reported day 20 of pregnancy, she had a LSD smoking cannabis before and/or during minitrip. The patient had a spontaneous pregnancy; they were younger, of lower par- term delivery. The baby boy weight was ity, better educated, and more likely to use between the 5th and the 50th percentile, alcohol, cigarettes, coffee, tea, and hard length between the 50th and the 90th per- drugs. Cannabis use during pregnancy was centile, normal umbilical arterial and unrelated to risk of perinatal death or need venous pH values, and Apgar scores of 7/9/ for special care, but the babies of women 10. There were no visible abnormalities, and who used cannabis at least once per week behavior was normalCS419. Eight hundred before and throughout pregnancy were 216 seven consecutive positive-pregnancy test g lighter than those of nonusers, had signifi- urine samples were screened for a range of cantly shorter birth lengths, and smaller drugs, including cotinine as an indicator of head circumferences. After adjustment for maternal smoking habits. A positive test for confounding factors, the association cannabinoids was found in 117 (14.5%) of between cannabis use and birth-weight the samples. Smaller numbers of samples failed to be statistically significant (p = were positive for other drugs: opiates (11), 0.056) and was clearly nonlinear. The benzodiazepines (4), cocaine (3), and one adjusted mean birth-weights for babies of each for amphetamines and methadone. women using cannabis at least once per Polydrug use was detected in nine individu- 80 MEDICINAL PLANTS OF THE WORLD als. Only two samples tested positive for sivity were assessed using a Continuous Per- ethanol. The proportion with a urine coti- formance Task. Second and third trimester nine level indicative of active smoking was of tobacco exposure and first trimester of 34.3%. The outcome of the pregnancy was cocaine use predicted increased omission traced for 288 of the subjects. Cannabis use errors. Second trimester cannabis use pre- was associated with a lower gestational age dicted more commission errors and fewer at delivery (p < 0.005), an increased risk of omission errors. There were no significant prematurity (p < 0.02), and reduction in effects of prenatal alcohol exposure. Lower birth-weight (p < 0.002). Maternal smoking Stanford-Binet Intelligence Scale compos- was associated with a reduction in infant ite scores, male gender, and an adult male birth-weight (p < 0.05). This was less pro- in the household predicted more errors of nounced than the effect of other substance commission. Lower Standford-Binet Intel- misuseCS422. A sample of low-income women ligence Scale composite scores, younger attending a prenatal clinic was assessed. The child age, maternal work/school status, and majority of the women decreased their use higher maternal hostility scores predicted of cannabis during pregnancy. The assess- more omission errorsCS429. The neurophysi- ments of child behavior problems included ological effects of prenatal cannabis expo- the Child Behavior Checklist, Teacher’s sure on response inhibition were assessed in Report Form, and the Swanson, Noland, thirty-one participants aged 18–22. Ottawa and Pelham checklist. Multiple and logistic Prenatal Prospective Study performed a regressions were employed to analyze the blocked design Go/No-Go task while neu- relations between cannabis use and behav- ral activity was imaged with functional mag- ior problems of the children at age 10, while netic resonance imaging. The Ottawa controlling for the effects of other extrane- Prenatal Prospective Study is a longitudinal ous variables. Prenatal cannabis use was sig- study that provides a unique body of infor- nificantly related to increased hyperactivity, mation collected from each participant over impulsivity, and inattention symptoms as 20 years, including prenatal drug history, measured by the Swanson, Noland, and detailed cognitive/behavioral performance Pelham, increased delinquency as mea- from infancy to young adulthood, and cur- sured by the Child Behavior Checklist, and rent and past drug usage. The functional increased delinquency and externalizing magnetic resonance imaging results showed problems as measured by the Teacher’s that with increased prenatal cannabis expo- Report Form. The pathway between prena- sure, there was a significant increase in neu- tal cannabis exposure and delinquency was ral activity in bilateral PFC and right mediated by the effects of cannabis exposure premotor cortex during response inhibition. on inattention symptomsCS413. Attention There was also an attenuation of activity in and impulsivity of prenatally substance- left cerebellum with increased prenatal exposed 6-year-olds were assessed as part of exposure to cannabis when challenging the a longitudinal study. Most of the women response inhibition neural circuitry. Prena- were light-to-moderate users of alcohol and tally exposed offspring had significantly cannabis who decreased their use after the more commission errors than non-exposed first trimester of pregnancy. Tobacco was participants, but all participants were able used by a majority of women and did not to perform the task with more than 85% change during pregnancy. The women, accuracy. The findings were observed when recruited from a prenatal clinic, were of low controlling for present cannabis use and pre- socioeconomic status. Attention and impul- natal exposure to nicotine, alcohol, and CANNABIS SATIVA 81 caffeine, and suggest that prenatal cannabis unchanged in most of the gray-matter exposure was related to changes in neural structures analyzed (cerebral cortex, BAL activity during response inhibition that last nucleus, hippocampus, thalamic and hypo- into young adulthoodCS282. The effects of pre- thalamic nuclei, basal ganglia, and sub- natal cannabis and alcohol exposure on ventricular zones) and also in a few school achievement at 10 years of age were white-matter structures (fornix and fascicu- examined. Women were interviewed about lus retroflexus). The increase in L1-mRNA their substance use at the end of each tri- levels reached statistical significance only in mester of pregnancy, at 8 and 18 months, '-9-THC-exposed males but not females, and at 3, 6, 10, 14, and 16 years. The women where only trends or no effects were were of lower socioeconomic status, high detected. The results supported evidence on school-educated, and light-to-moderate a sexual dimorphism, with greater effects in users of cannabis and alcohol. At the 10-year male fetuses, for the action of cannabinoids follow-up, the effects of prenatal exposure in the developing brainCS295. Fetal cannabis to cannabis or alcohol on the academic per- exposure has no consistent effect on out- formance of 606 children were assessed. come. Prenatal cocaine exposure has not Exposure to one or more cannabis joints per been shown to have any detrimental effect day during the first trimester predicted on cognition, except as mediated through deficits in Wide Range Achievement Test- cocaine effects on head size. Although fetal Revised reading and spelling scores and a cocaine exposure has been linked to numer- lower rating on the teachers’ evaluations of ous abnormalities in arousal, attention, and the children’s performance. This relation neurological and neurophysiological func- was mediated by the effects of first-trimester tion, most such effects appear to be self-lim- cannabis exposure on the children’s depres- ited and restricted to early infancy and sion and anxiety symptoms. Second-trimes- childhood. Opiate exposure elicits a well- ter cannabis use was significantly associated described withdrawal syndrome affecting with reading comprehension and under- the central nervous, autonomic, and gas- achievement. Exposure to alcohol during trointestinal systems, which is most severe the first and second trimesters of pregnancy among methadone-exposed infantsCS319. predicted poorer teachers’ ratings of overall Executive functioning in cocaine/polydrug school performance. Second-trimester binge (cannabis, alcohol, and tobacco)-exposed drinking predicted lower reading scores. infants was assessed in a single session, There was no interaction between prenatal occurring between 9.5 and 12.5 months of cannabis and alcohol exposure. Each was an age. In an A-not-B task, infants searched— independent predictor of academic perfor- after performance-adjusted delays—for an manceCS283. Pregnant rats were treated daily object hidden in a new location. The CE with '-9-THC from the fifth day of gesta- infants did not differ from non-CE controls tion up to the day before birth (GD21). recruited from the same at-risk population. Then rats were sacrificed and their pups Comparison of heavier-CE (n = 9) with the removed for analysis of the neural adhesion combined group of lighter-CE (n = 10) and molecule L1-mRNA levels in different non-CE (n = 32) infants revealed significant brain structures. The levels of L1 transcripts differences on A-not-B performance, as well were significantly increased in the fimbria, as on global tests of mental and motor stria terminalis, stria medullaris, corpus cal- development. Covariates investigated losum, and in gray-matter structures (sep- included socioeconomic status, marital sta- tum nuclei and the habenula). It remained tus, race, maternal age, years of education, 82 MEDICINAL PLANTS OF THE WORLD weeks of gestation, and birth-weight, as well the follicular phase. The results were signifi- as severity of prenatal cannabis, alcohol, cant at p < 0.01 levelCS221. and tobacco exposure. The relationship of Propiospinal myoclonus. A 25-year-old heavier-CE status to motor development woman with clusters of myoclonus induced was mediated by length of gestation, and the by a single exposure to inhaled cannabis was relationship of heavier-CE status to mental evaluated. Investigations excluded a struc- development was confounded with mater- tural abnormality of the spine. Multichan- nal gestational use of cigarettes. The rela- nel surface electromyogram with parallel tionship of heavier-CE status to A-not-B frontal electroencephalogram recording performance remained significant after con- confirmed the diagnosis of propriospinal trolling for potentially confounded variables myoclonusCS284. and mediators, but was not statistically sig- Prostaglandin synthetase inhibition. nificant after controlling for the variance Chromatographic fraction of the aerial parts associated with global mental develop- was active on the bull seminal vesiclesCS159. mentCS341. Weight, height, and head circum- Protein synthesis inhibition. Ethanol ference were examined in children from (95%) extract of the dried resin, adminis- birth to early adolescence for whom prena- tered intraperitoneally to toads at a dose tal exposure to cannabis and cigarettes had of 10 mg/day for 14 days, was active. The been ascertained. The subjects were from a results were significant at p < 0.01 levelCS216. low-risk, predominantly middle-class sam- Psoriatic effect. Hot water extract of the ple participating in an ongoing longitudinal dried seed, taken orally by 108 human adults study. The negative association between with psoriasis at variable dosage level, was growth measures at birth and prenatal ciga- active. After 3–4 weeks of treatment, there rette exposure was overcome, sooner in was significant improvement. The extract males than females, within the first few was taken in combination with Rehmannia years, and by the age of 6 years, the children glutinosa (rhizome), Salvia miltiorrhiza (root), of heavy smokers were heavier than control Scrophularia ningpoensis (root), Isatis tinctoria subjects. Pre- and postnatal environmental (branch and leaf), Sophora subprostrata tobacco smoke did not have a negative (root), Dictamnus dasycarpus (rootbark), effect on the growth parameters; how- Polygonum bistorta (rhizome), and Forsythia ever, the choice of bottlefeeding or shorter suspensa (fruit)CS197. duration of breastfeeding by women who Psychosocial morbidity association. Can- smoked during pregnancy appeared to play nabis dependence is a prevalent comorbid an important positive role in the catch-up substance use disorder among patients early observed among the infants of smokers. in the course of a schizophrenia-spectrum Prenatal exposure to cannabis was not sig- disorder. Among 29 eligible patients, 18 nificantly related to any growth measures at participated in the study. First-episode birth, although a smaller head circumfer- patients with comorbid cannabis depen- ence observed at all ages reached statistical dence (n = 8) reported significantly greater significance among the early adolescents childhood physical and sexual abuse com- born to heavy cannabis usersCS417. pared with those without comorbid can- Prolactin inhibition. The dried leaves, nabis dependence (n = 10). The result smoked by healthy female volunteers at a indicated the preliminary evidence of an dose of 1 g/person, produced a decrease in association between childhood maltreat- plasma prolactin levels during the luteal ment and cannabis dependence among this phase of the menstrual cycle but not during especially vulnerable population. Child- CANNABIS SATIVA 83 hood physical and sexual abuse may be a risk symptoms. The brain mechanisms underly- factor for the initiation of cannabis depen- ing the association have to be elucidated; dence and other substance use disorders in they may implicate deregulation of cannab- the early course of schizophreniaCS249. inoid and dopaminergic systems. Cannabis Psychotic effect. Thirty five hundred rep- exposure may be a risk factor for psychotic resentatives 19 years of age were examined disorders by interacting with a preexisting in a cohort study. The subjects completed a vulnerability for these disordersCS277. 40-item Community Assessment of Psychic Refractory neuropathic pain. Seven Experiences, measuring subclinical positive patients (three women and four men) aged (paranoia, hallucinations, grandiosity, first- 60 r 14 years suffering from chronic refrac- rank symptoms) and negative psychosis tory neuropathic pain, received oral THC dimensions, depression, and drug use. Use titrated to the maximum dose of 25 mg/day of cannabis was associated positively with (mean dose: 15 r 6 mg) during an average both positive and negative dimensions of of 55.4 days (range: 13–128). Various com- psychosis, independent of each other and of ponents of pain (continuous, paroxysmal, depression. An association between can- and brush-induced allodynia) were assessed nabis and depression disappeared after using visual analog scale scores. Health- adjustment for the negative psychosis related quality of life was evaluated using dimensions. First use of cannabis younger the Brief Pain Inventory, and the Hospital than age 16 years was associated with a Anxiety and Depression scale was used to much stronger effect than first use after age measure depression and anxiety. THC did 15 years, independent of lifetime frequency not induce significant effect on the various of use. The association between cannabis pain, health-related quality of life and anxi- and psychosis was not influenced by the dis- ety and depression scores. Numerous side tress associated with the experiences, indi- effects (notably sedation and asthenia) were cating that self-medication may be an observed in five out of seven patients, unlikely explanation for the entire associa- requiring premature discontinuation of tion between cannabis and psychosisCS264. the drug in three patientsCS361. Cross-sectional epidemiological studies Reproductive effect. Cannabis use during indicated that individuals with psychosis pregnancy in developed nations is estimated use cannabis more often than other indi- to be approx 10%. Recent evidence suggests viduals in the general population. It has that the endogenous cannabinoid system, long been considered that this association now consisting of two receptors and mul- was explained by the self-medication tiple endocannabinoid ligands, may also hypothesis, postulating that cannabis is used play an important role in the maintenance to self-medicate psychotic symptoms. This and regulation of early pregnancy and hypothesis has been recently challenged. fertilityCS316. Drugs of abuse, like alcohol, Several prospective studies carried out in opiates, cocaine, and cannabis, are used by population-based samples, showed that can- many young people for their presumed nabis exposure was associated with an aphrodisiac properties. The opioids inhibit increased risk of psychosis. A dose–response the hypothalamus–pituitary–gonads axis relationship was found between cannabis (HPG), and increase the prolactin levels, exposure and risk of psychosis, and this which interferes with the male and female association was independent from potential sexual response. Cannabis, at high doses, confounding factors, such as exposure to could inhibit the HPG axis and reduce other drugs and preexistence of psychotic fertilityCS350. Cannabis initially increases 84 MEDICINAL PLANTS OF THE WORLD libido and potency, but chronic use causes for lactation and causes a diminution in the sexual inversionCS364. Long-term use of can- volume of the mammary glands. Significant nabis has been found to cause physiological amounts of the drug have been detected in changes that can alter individual reproduc- both mothers’ milk and the blood of new- tive potential. The effects of cannabis borns. Animal studies indicate that THC depend on the dose and can include death crosses the placenta, achieving concentra- from depression of the respiratory system. tions in the fetus as high as those in the Cannabis is absorbed rapidly and eliminated mother. Animal studies also demonstrated very slowly. '-9-THC is highly liposoluble increasing frequency of abortions, intrauter- and fixes to the serum proteins, passing to ine death, and declines in fetal weight. The the lungs and liver for metabolization and effects were probably caused by an alteration to the kidneys and liver for excretion. As in placental function. A human study like- with estrogens, there is an enterohepatic wise showed that cannabis use during preg- circuit for reabsorption and elimination. nancy was significantly related to poor fetal Ninety percent is eliminated in the feces, development, low birth-weight, diminished 65% within 48 hours. Because of the size, and decreased cephalic circumference. enterohepatic circuit and liposolubility, Congenital malformations have been elimination requires 1 week for completion. observed in experimental animals exposed The other important biotransformation of to THC. Declines in sperm volume and the active principle is hydroxylation. The count and abnormal sperm motility have hydroxylated derivatives are responsible for been observed in chronic cannabis users. In the psychoactivity of cannabis. Cannabis vitro studies show that THC produces a affects both neuroendocrine function and marked degeneration of human spermCS365. the germ cells. Studies on experimental ani- Among sexually experienced girls, 39% (n mals have indicated that THC can cause a = 123) reported using oral contraceptive decline in the pituitary hormones, follicle pills(OCPs), 5.4% (n = 17) used Depo- stimulating hormone, luteinizing hormone, Provera® (medroxyprogesterone acetate) or and prolactin, and in the steroids progester- Norplant® (levonorgestrel), and 55.6% (n = one, estrogen, and androgens. Human stud- 175) used no hormonal method. Logistic ies have shown that chronic users have regression analysis revealed that the factors decreased levels of serum testosterone. most significantly associated with the use of Because steroidogenesis can be restimulated hormonal methods were older age (OR = with human chorionic gonadotropin, it 1.19; 95% CI, 1.07–1.33), not using a con- appears that THC does not directly affect dom at last intercourse (OR = 0.55; CI, steroid production by the corpus luteum, but 0.34–0.90), and having had a well visit that its action is mediated by the hypothala- within 1 year (OR = 2.11; CI, 1.12–3.70). mus. Because of its potent antigonadotropic OCP users were less likely than Depo- action, THC is under study as an anovula- Provera or Norplant users to have used al- tory agent. The same animal studies have cohol (p = 0.041), cigarettes (p = 0.002), or shown that ovulation returns to normal 6 cannabis (p = 0.018) in the past 30 days. months after termination of use. High rates OCP users were less likely than nonusers of of anovulation and luteal insufficiency have hormonal methods to have smoked ciga- been observed in women smoking cannabis rettes (p = 0.034) or cannabis (p = 0.052). at least three times weekly. THC accumu- The school-based clinic had a greater pro- lates in the milk. Animal studies have shown portion of subjects using long-acting that THC depresses the enzymes necessary progestins (p < 0.001)CS443. CANNABIS SATIVA 85

Respiratory effect. Smoking a “joint” of sured. Ninety-one subjects (9.7%) were cannabis resulted in exposure to signifi- cannabis-dependent and 264 (28.1%) were cantly greater amounts of combusted mate- current tobacco smokers. After controlling rial than with a tobacco cigarette. The for tobacco use, respiratory symptoms asso- histopathological effects of cannabis-smoke ciated with cannabis dependence included exposure included changes consistent with wheezing apart from colds, exercise-induced acute and chronic bronchitis. Cellular dys- shortness of breath, nocturnal wakening plasia has also been observed, suggesting with chest tightness, and early morning that, like tobacco smoke, cannabis exposure sputum production. These were increased has the potential to cause malignancy. by 61, 65, 72 (all p < 0.05), and 144% (p < Symptoms of cough and early morning spu- 0.01) respectively, compared with non- tum production are common (20–25%) tobacco smokers. The frequency of respira- even in young individuals who smoke can- tory symptoms in cannabis-dependent nabis alone. Almost all studies indicated subjects was similar to tobacco smokers of that the effects of cannabis and tobacco 1–10 cigarettes per day. The proportion of smoking are addictive and independentCS342. cannabis-dependent study members with an A small group of current male cannabis pro- FEV1/FVC ratio of less than 80% was 36% cessors with a mean age of 43 years was stud- compared with 20% for nonsmokers (p = ied. Questionnaire data, lung function, 0.04). These outcomes occurred indepen- serial FEV1 and blood were collected from dently of coexisting bronchial asthmaCS405. all workers. Seven workers (64%) com- Reversal of cannabinoid addiction. '-9- plained of at least one respiratory symptom THC was administered orally to mice at a (one with byssinosis). The mean percentage dose of 10 mg/kg twice daily for 6 days to predicted FEV1 was 91.5, FVC 97.7, peak make them dependent on cannabinoids. expiratory flow 92.1, and forced expiratory Other groups of mice were administered flow between 25 and 75% of FVC 79.5. orally with a '-9-THC and benzoflavone Serial FEV1 measurements in the two work- from Passiflora incarnata at doses of 10 or 20 ers with work-related respiratory symptoms mg/kg twice daily for 6 days. Mice receiving revealed a mean change in FEV1 on the first the '-9-THC and Passiflora incarnata working day of –12.9%. This contrasted extract developed significantly less depen- with +6.25% on the last working day. dence, worse locomotor activity, and less of Respective values for the two workers with- typical withdrawal effects like paw tremors out work-related symptoms were –1.4 and and headshakes, compared with mice +3.2%CS402. Nine hundred forty-three young receiving '-9-THC alone. Administration adults from a birth cohort of 1037 were stud- of SR-141716A, a selective cannabinoid- ied at age 21 years. Standardized respiratory receptor antagonist (10 mg/kg, orally), to symptom questionnaires were administered. all groups on the seventh day resulted in an Spirometry and methacholine challenge artificial withdrawal. Administration of tests were undertaken. Cannabis depen- 20 mg/kg of the Passiflora incarnata benzo- dence was determined using DSM-III-R cri- flavone moiety to mice showing symptoms teria. Descriptive analyses and comparisons of withdrawal owing to administration of between cannabis-dependent, tobacco- SR-141716A produced a marked attenua- smoking, and nonsmoking groups were tion of withdrawal effectsCS375. undertaken. Adjusted odds ratios for respi- Schizophrenic effect. The nerve growth ratory symptoms, lung function, and airway factor (NGF) serum levels of 109 consecu- hyperresponsiveness (PC20) were mea- tive drug-naïve schizophrenic patients were 86 MEDICINAL PLANTS OF THE WORLD measured and compared with those of tion. During eight test sessions, 55 male vol- healthy controls. The results were corre- unteers made repeated ratings of subjective lated with the long-term intake of cannabis “high,” sedation, and stimulation, as well as and other drugs. Mean (r standard devia- rating their perceptions of motivation and tion) NGF serum levels of 61 control performance on cognitive tests. The long, persons (33.1 r 31 pg/mL) and 76 schizo- relative to the short, breath-holding dura- phrenics who did not consume illegal drugs tion increased “high” ratings after smoking (26.3 r 19.5 pg/mL) did not differ signifi- cannabis, but not placebo. Cannabis smok- cantly. Schizophrenic patients with regular ing increased sedation and a perception of cannabis intake (> 0.5 g per day on average worsened test performance, and decreased for at least 2 years) had significantly raised motivation with respect to test perfor- NGF serum levels of 412.9 r 288.4 pg/mL mance. Paradoxical subjective effects were (n = 21) compared with controls and schizo- observed in those subjects reporting some phrenic patients not consuming cannabis stimulation, as well as sedation after smok- (p < 0.001). In schizophrenic patients who ing cannabis, particularly with the long abused not only cannabis, but also addi- breath-holding duration. Breath-holding tional substances, NGF concentrations were duration did not produce any subjective as high as 2336.2 r 1711.4 pg/mL (n = 12). effects that were independent of the drug On average, heavy cannabis consumers suf- treatment (i.e., occurred equally after smok- fered their first episode of schizophrenia 3.5 ing of cannabis and placebo)CS438. years (n = 21) earlier than schizophrenic Sexual headache. Sexual headaches usu- patients who abstained from cannabis. ally develop during orgasm. The case of a These results indicate that cannabis is a pos- young man and heavy cannabis smoker who sible risk factor for the development of suffered posterior cerebral artery infarction schizophrenia. This might be reflected in during his first episode of coital headache the raised NGF-serum concentrations when was reportedCS386. both schizophrenia and long-term cannabis Sexual receptivity. The effects of THC on abuse prevailCS304. sexual behavior in female rats and its influ- Schizotypy correlation. Two hundred ence on steroid hormone receptors and neu- eleven healthy adults who used cannabis rotransmitters in the facilitation of sexual showed higher scores on schizotypy, border- receptivity was examined. Results revealed line, and psychoticism scales than never- that the facilitatory effect of THC was users. Multivariate analysis, covarying lie inhibited by antagonists to both progester- scale scores, age, and educational level indi- one and dopamine D(1) receptors. To test cated that high schizotypal traits best further the idea that progesterone receptors discriminated subjects who had used (PR) and/or dopamine receptors (D[1]R) in cannabis from never-users, whether or not the hypothalamus were required for THC- they reported having used other recre- facilitated sexual behavior in rodents, ational drugs. The results indicated that antisense, and sense oligonucleotides to cannabis use was related to a personality PR and D(1)R were administered intra- dimension of psychosis-proneness in healthy cerebroventricularly into the third cerebral peopleCS457. ventricle of ovariectomized, estradiol ben- Sedative and stimulant effects. A double- zoate-primed rats. Progesterone- and THC- blind, placebo-controlled study assessed facilitated sexual behavior was inhibited in subjective effects of smoking cannabis with animals treated with antisense oligonucle- either a long or short breath-holding dura- otides to PR or to D(1)R. Antagonists to CANNABIS SATIVA 87 cannabinoid receptor-1 subtype (CB1), but toneally to rats at a dose of 0.89 mg/kg, was not to cannabinoid receptor-2 subtype active vs corneo-palpebral reflexCS022. (CB2) inhibited progesterone- and dopam- Smooth muscle stimulant activity. Hot ine-facilitated sexual receptivity in female water extract of the dried leaf was active on ratsCS408. Adult female and male rats that had the rabbit and guinea pig intestineCS177. been perinatally exposed to hashish extracts Water extract of the dried aerial parts at a were investigated. Adult males perinatally concentration of 1:1 was equivocal on the exposed to hashish extracts exhibited guinea pig ileumCS243. marked changes in the behavioral patterns Spasticity treatment. Standardized plant executed in the sociosexual approach extract was administered orally to 57 MS behavior test; these changes did not exist in patients with poorly controlled spasticity, at females. Control males first visited the a dose of 2.5 mg of THC and 0.9 mg of CBD. incentive male and took longer to visit the Patients in group A started with a drug incentive female, whereas hashish-exposed escalation phase from 15 to a maximum of males followed the opposite pattern. Hash- 30 mg of THC by 5 mg per day if well toler- ish-exposed males spent more time in the ated, being on active medication for 14 days vicinity of the incentive female, whereas before starting placebo. Patients in group B they decreased their frequency of visits to, started with placebo for 7 days, crossed to and the time spent in, the male incentive the active period (14 days), and closed with area. This behavior was observed during the a three-day placebo period (active drug-dose first third of the test, but became normal- escalation and placebo sham escalation as ized and even inverted during the last two- in group A). Measures used included daily thirds. In the social interaction test, the self-report of spasm frequency and symp- normal reduction in the time spent in active toms, Ashworth Scale, Rivermead Mobility social interaction following the exposure to Index, 10-meter timed walk, nine-hole peg a neophobic situation (high light levels) in test, paced auditory serial addition test, and controls did not occur in hashish-exposed the digit span test. There were no statisti- males, although these exhibited a response cally significant differences associated with in the dark-light emergence test similar to active treatment compared with placebo, that of their corresponding controls. No but trends in favor of active treatment were changes were seen in spontaneous locomo- seen for spasm frequency, mobility, and get- tor activity in both tests. These behavioral ting to sleep. In the 37 patients (per-proto- alterations observed in hashish-exposed col set) who received at least 90% of their males were paralleled by a significant prescribed dose, improvements in spasm decrease in L-3,4-dihydroxyphenylacetic frequency (p = 0.013) and mobility after acid contents in the limbic forebrain; this excluding a patient who fell and stopped suggests a decreased activity of mesolimbic walking were seen (p = 0.01). Minor adverse dopaminergic neurons. No effects were seen events were slightly more frequent and in femalesCS459. severe during active treatment, and toxicity Smooth muscle relaxant activity. Ethanol symptoms, which were generally mild, were (95%) and water extracts of the dried aerial more pronounced in the active phaseCS270. parts, at a concentration of 1:1, produced Six hundred thirty participants with stable weak activity on the rabbit duodenum. The MS and muscle spasticity were treated with ethanol extract was equivocal on the guinea oral cannabis extract (n = 211), '-9-THC pig ileumCS243. Petroleum ether extract of the (n = 206), or placebo (n = 213) for 15 weeks. dried entire plant, administered intraperi- Six hundred eleven of 630 patients were 88 MEDICINAL PLANTS OF THE WORLD followed up for the primary end point. No Spontaneous pneumomediastinum. Spon- treatment effect of cannabinoids on the taneous pneumomediastinum is defined as primary outcome (p = 0.40) was noted. The pneumomediastinum in the absence of an estimated difference in mean reduction in underlying lung disease. It is the second total Ashworth score for participants taking most common cause of chest pain in young, cannabis extract compared with placebo healthy individuals (<30 years) necessi- was 0.32 (95% CI, –1.04 to 1.67), and for tating hospital visits. Inhalational drug use those taking '-9-THC vs placebo it was (cocaine and cannabis) has been associ- 0.94 (–0.44 to 2.31). There was an evidence ated with a significant number of cases, of a treatment effect on patient-reported although cases with no apparent etiological spasticity and pain (p = 0.003), with or incriminating factors are well-recognized. improvement in spasticity reported in 61% A case of an 18-year-old high school student (n = 121, 95% CI, 54.6–68.2), 60% (n = with spontaneous pneumomediastinum was 108, 52.5–66.8), and 46% (n = 91, 39–52.9) evaluatedCS421. of participants on cannabis extract, '-9- Sudden cardiac death. An 18-year-old THC, and placebo, respectivelyCS322. male suffered sudden cardiac death follow- Spatial working memory effect. Func- ing the use of cocaine, cannabis, and tional magnetic resonance imaging was used ethanolCS439. to examine brain activity in 12 long-term Sudden infant death syndrome. In a heavy cannabis users, 6–36 hours after last nationwide case–control study of 369 cases use, and in 10 control subjects while they and 1558 controls, two-thirds of SIDS performed a spatial working memory task. deaths occurred at night (between 10 PM Regional brain activation was analyzed and and 7:30 AM). The odds ratio (95% CI) for compared using statistical parametric map- prone sleep position was 3.86 (2.67–5.59) ping techniques. Compared with controls, for deaths occurring at night, and 7.25 cannabis users exhibited increased activa- (4.52–11.63) for deaths occurring during tion of brain regions typically used for spa- the day; the difference was significant. The tial working memory tasks (such as PFC and odds ratio for maternal smoking and SIDS anterior cingulate). Users also recruited deaths occurring at night was 2.28 (1.52– additional regions not typically used for 3.42), and for the day, 1.27 (0.79–2.03). If spatial working memory (such as regions in the mother was single, the odds ratio was the basal ganglia). The findings remained 2.69 (1.29–3.99) for a nighttime death, and essentially unchanged when reanalyzed 1.25 (0.76–2.04) for a daytime death. Both using the subjects ages as a covariate. Brain interactions were significant. The interac- activation showed little or no significant tions between time of death and bed shar- correlation with subjects years of education, ing, not sleeping in a cot or bassinet, verbal IQ, lifetime episodes of cannabis use, ethnicity, late timing of prenatal care, binge or urinary cannabinoid levels at the time of drinking, cannabis use, and illness in the scanningCS281. baby were also significant. All were more Spermicidal effect. Petroleum ether strongly associated with SIDS occurring at extract of the dried aerial parts at a concen- nightCS366. In a nationwide case–control tration of 0.74 mmol was active on the study, 393 cases and 1592 controls were ana- human spermatozoaCS186. lyzed. Adjusting for ethnicity and maternal Spontaneous activity reduction. Petro- tobacco use, the SIDS odds ratio for weekly leum ether extract of the dried entire plant, maternal cannabis use since the infant’s administered intraperitoneally to guinea birth was 2.23 (95% CI = 1.39, 3.57) com- pigs at a dose of 100 mg/kg, was activeCS022. pared with nonusers, and the multivariate CANNABIS SATIVA 89 odds ratio was 1.55 (95% CI = 0.87, environmental vulnerabilities predisposing 2.75)CS403. to both outcomes. In contrast, associations Suicidal effect. Standardized interview as- between cannabis dependence and suicidal sessments were conducted with 2311 youths behaviors cannot be entirely explained by aged 8–15 years who used drugs before age common predisposing genetic and/or shared 16. Approximately 15 years after recruit- environmental predispositionCS260. ment, 1695 persons (mean age = 21 years) Synergic cytotoxicity. THC, in A549 lung were reassessed. One hundred fifty-five of tumor cells culture at concentrations of less them made suicide attempts (SA) and 218 than 5 Pg/mL, produced no cytotoxic effect. had onset of depression-related suicide ide- At higher levels it induced cell necrosis, ation (SI). The relative risk, from survival with a lethal concentration (LC)50 of 16–18 analysis and logistic regression models, to Pg/mL. Butylated hydroxyanisole ([BHA], a study early use of tobacco, alcohol, can- food additive)alone at concentrations of nabis, and inhalants, with covariate adjust- 10–200 PM, produced limited cell toxicity ments for age, sex, race/ethnicity, and other and significantly enhanced the necrotic pertinent covariates were examined. Early- death resulting from concurrent exposure to onset of cannabis use and inhalant use for THC. In the presence of BHA at 200 PM, females, but not for males, signaled a mod- the LC50 for THC decreased to 10–12 Pg/ est excess risk of SA (cannabis-associated mL. Similar results were obtained with RR = 1.9; p = 0.04; inhalant-associated RR smoke extracts prepared from cannabis ciga- = 2.2; p = 0.05). Early-onset of cannabis use rettes, but not with extracts from tobacco or by females (but not for males) signaled placebo cannabis cigarettes (containing no excess risk for SI (RR = 2.9; p = 0.006). THC). Experiments were repeated in the Early-onset alcohol and tobacco use were presence of either diphenyleneiodonium or not associated with later risk of SA or SICS252. dicumarol as inhibitors of the redox cycling Two hundred seventy-seven same-sex twin pathway. Neither of the compounds pro- pairs (median age: 30 years) discordant for tected cells from the effects of combined cannabis dependence and 311 pairs discor- THC and BHA, but rather enhanced dant for early-onset cannabis use (before age necrotic cell death. Measurements of cellu- 17 years) were examined. Individuals who lar ATP revealed that both THC and BHA were cannabis-dependent had odds of SI reduced ATP levels in A549 cells, consis- and SA that were 2.5–2.9 times higher tent with toxic effects on mitochondrial than those of their noncannabis-dependent electron transport. The combination was co-twin. Cannabis dependence was associ- synergistic in this respect, reducing ATP ated with elevated risks of major depressive levels to less than 15% of the control. disorder (MDD) in dizygotic, but not in Exposure to cannabis smoke in conjunction monozygotic twins. Twins who initiated with BHA may promote deleterious health cannabis use before age 17 years of age had effects in the lungCS373. elevated rates of subsequent SA (OR, 3.5, Teratogenic activity. Resin, administered 95% CI, 1.4–8.6) but not of MDD or SI. orally to pregnant rabbits at a dose of 1 mL/ Early MDD and SI were significantly associ- kg, was activeCS167. Alcohol extract of the ated with subsequent risks of cannabis dried leaves, administered intragastrically to dependence in discordant dizygotic pairs, pregnant rats at a dose of 125 mg/kg from but not in discordant monozygotic pairs. days 7 to 16 of gestation, was active. The The results indicated that the comorbidity fetuses showed several gross abnormali- between cannabis dependence and MDD ties, visceral anomalies, and skeletal mal- likely arises through shared genetic and formationsCS233. Water extract of the dried 90 MEDICINAL PLANTS OF THE WORLD leaf, administered intragastrically to preg- sible explanation for the clinically observed nant rats at doses of 125, 200, 400, and 800 relation between the cannabinoid system mg/kg, produced various types of malforma- and TSCS292. A single-dose, cross-over study tions in the fetusesCS228. Petroleum ether ex- in 12 patients, and a 6-week, randomized tract of the aerial parts, administered orally trial in 24 patients, demonstrated that '9- to rats and rabbits, was inactiveCS087. THC, the most psychoactive ingredient of Tourette syndrome. Tourette syndrome cannabis, reduced tics in TS patients. No se- (TS) is a complex inherited disorder of rious adverse effects occurred and no impair- unknown etiology, characterized by mul- ment on neuropsychological performance tiple motor and vocal tics. Involvement of was observedCS329. In the randomized, the central cannabinoid (CB1) system was double-blind, placebo-controlled study, 24 suggested because of therapeutic effects of patients with TS, according to DSM-III-R cannabis consumption and '-9-THC-treat- criteria, were treated over a 6-week period ment in TS patients. The central cannab- with up to 10 mg/day of THC. Tics were inoid receptor (CNR1) gene encoding the rated at six visits (visit 1, baseline; visits 2–4, CNR1 was considered as a candidate gene during treatment period; visits 5–6, after for TS and systematically screened by withdrawal of medication) using the Tour- single-strand conformation polymorphism ette Syndrome Clinical Global Impressions analysis and sequencing. Compared with the scale (TS-CGI), the Shapiro Tourette-Syn- published CNR1 sequence, three single-base drome Severity Scale (STSSS), the Yale substitutions were identified: 1326ToA, Global Tic Severity Scale (YGTSS), the 1359GoA, 1419 + 1GoC. The change at self-rated Tourette Syndrome Symptom List position 1359 is a common polymor-phism (TSSL), and a videotape-based rating scale. (1359 G/A) without allelic association with Seven patients dropped out of the study or TS. 1326ToA was present in only one TS had to be excluded, but only one because of patient and is a silent mutation, which does side effects. Using the TS-CGI, STSSS, not change codon 442 (valine). 1419 + YGTSS, and video rating scale, there was a 1GoC affects the first nucleotide immedi- significant difference (p < 0.05) or a trend ately following the coding sequence. It was toward a significant difference (p < 0.1) first detected in three of 40 TS patients and between THC and placebo groups at visits none of 81 healthy controls. This statisti- 2, 3, and/or 4. Using the TSSL at 10 treat- cally significant association with TS (p = ment days (between days 16 and 41) there 0.034) could not be confirmed in two subse- was a significant difference (p < 0.05) quent cohorts of 56 TS patients (one het- between both groups. Analysis of variance erozygous for 1419 + 1GoC) and 55 controls, also demonstrated a significant difference and 64 patients and 66 controls (one het- (p = 0.037). No serious adverse effects erozygous for 1419 + 1GoC), respectively. occurredCS345. In the randomized, double- Transcript analysis of lymphocyte RNA blind, placebo-controlled study, the effect of from five 1419 + 1GoC carriers revealed a treatment with up to 10 mg '-9-THC over no systematic influence on the expression a 6-week period on neuropsychological per- level of the mutated allele. In addition, seg- formance in 24 patients suffering from TS regation analysis of 1419 + 1GoC in af- was investigated. During medication and fected families gave evidence that 1419 + immediately, as well as 5–6 weeks after, 1GoC does not play a causal role in the eti- withdrawal of '-9-THC treatment, no det- ology of TS. It was concluded that genetic rimental effect was seen on learning curve, variations of the CNR1 gene are not a plau- interference, recall and recognition of word CANNABIS SATIVA 91 lists, immediate visual memory span, and Her temperature, blood pressure, pulse, divided attention. A trend towards a signi- hemoglobin, leukocytes, serum electrolytes, ficant immediate verbal memory span and serum urea were normal. Respiratory improvement during and after treatment rate was 12 beats per minute. Blood sugar was foundCS356. A randomized double-blind elevated. Recovery was complete within 24 placebo-controlled crossover single-dose hours with no treatmentCS047. Four patients trial of '-9-THC (5, 7.5, or 10 mg) in 12 suffered gastrointestinal disorders and psy- adult TS patients was performed. Tic sever- chological effects after eating salad prepared ity was assessed using the TSSL and exam- with hemp seed oil. The concentration of iner ratings (STSSS, YGTSS, TS-CGS). THC in the oil far exceeded the recom- Using the TSSL, patients also rated the mended tolerance doseCS450. From January severity of associated behavioral disor- 1998 to January 2002, 213 incidences were ders. Clinical changes were correlated to recorded of dogs that developed clinical maxi-mum plasma levels of THC and its signs following oral exposure to cannabis, metabolites 11-OH-THC and 11-nor-'-9- with 99% having neurological signs and tetrahydrocannabinol-9-carboxylic acid. 30% exhibiting gastrointestinal signs. The Using the TSSL, there was a significant cannabis ingested ranged from 0.5 to 90 g. improvement of tics (p = 0.015) and obses- The lowest dose at which signs occurred was sive-compulsive behavior (p = 0.041) after 84.7 mg/kg and the highest reported dose treatment with '-9-THC compared with was 26.8 g/kg. Onset of signs ranged from 5 placebo. Examiner ratings demonstrated a minutes to 96 hours, with most signs occur- significant difference for the subscore “com- ring within 1–3 hours after ingestion. The plex motor tics” (p = 0.015) and a trend signs lasted from 30 minutes to 96 hours. towards a significant improvement for the Management consisted of decontamination, subscores “motor tics” (p = 0.065), “simple sedation (with diazepam as drug of choice), motor tics” (p = 0.093), and “vocal tics” fluid therapy, thermoregulation, and general (p = 0.093). No serious adverse reactions supportive care. All followed animals made occurred. Five patients experienced mild, full recoveriesCS309. The suspension prepared transient side effects. There was a signifi- from the benzene washing solution of can- cant correlation between tic improvement nabis seeds, administered intravenously to and maximum 11-OH-THC plasma con- mice at a dose of 3 mg/kg, produced hypoth- centrationCS384. ermia, catalepsy, pentobarbital-induced Toxic effect. Petroleum ether extract of the sleep prolongation, and suppression of loco- dried leaf, administered by gastric intuba- motor activity. These pharmacological tion to pregnant rats at a dose of 150 mg/kg, activities of benzene washing solution of produced a reduction of food and water con- cannabis seeds were significantly higher sumption and maternal weight gain. The than those of '-9-THC (3 mg/kg, iv)CS435. weight of pups at birth was reduced by Toxicity assessment. Ethanol (50%) approx 10% of the litter size, and pup mor- extract of the entire plant, administered tality at birth was not affected signifi- intraperitoneally to mice, produced a maxi- cantlyCS178. Water extract of the aerial parts, mum tolerated dose of 500 mg/kgCS007. administered intravenously to male adults, Transient global amnesia. A 6-year-old was activeCS042. The resin, ingested by a 4- boy became intoxicated after ingesting year-old girl, showed signs of stupor alter- cookies laced with cannabis. He was pre- nating with brief intervals of excitation and sented with retentive memory deficit of sud- foolish laughing with atactic movements. den onset that was later diagnosed as 92 MEDICINAL PLANTS OF THE WORLD transient global amnesia. Transient global accidents and interpersonal violence, amnesia owing to cannabis intoxication is respectively, were positive for cannabis an extremely rare eventCS266. compared with 43 and 27% for alcohol, Transient ischemic attack. A 22-year-old respectively. There was no significant man with a 5-year history of drug and alco- difference in hospital stay or injury severity hol abuse was presented with a left hemi- score between substance users and non- paresis preceded by three transient ischemic usersCS416. attacks. Two of the attacks occurred while Trigeminovascular system effect. Arachi- smoking cannabis. Substance abuse was the donylethanolamide is believed to be the only identifiable risk factor for the cere- endogenous ligand of the cannabinoid CB1 brovascular diseaseCS454. and CB2 receptors. Known behavioral Trauma injuries. An association between effects of AEA are antinociception, cata- combat-related posttraumatic stress disorder lepsy, hypothermia, and depression of motor (C-PTSD) and other mental disorders was activity, similar '-9-THC, the psychoactive studied in co-twin (male monozygotic twin constituent of cannabis. A role of the CB1 pairs in the Vietnam Era Twin Registry). receptor in the trigeminovascular system, Logistic regression analyses demonstrated using intravital to study the effects of AEA that combat exposure, adjusted for C- against various vasodilator agents was PTSD, was significantly associated with examined. AEA inhibited dural blood ves- increased risk for alcohol and cannabis sel dilation brought about by electrical dependence and that C-PTSD mediated the stimulation by 50%, calcitonin gene-related association between combat exposure and peptide (CGRP) by 30%, capsaicin by 45%, both major depression and tobacco depen- and NO by 40%. CGRP(8–37) attenuated denceCS325. Sera from 111 patients with NO-induced dilation by 50%. The AEA trauma injuries who presented during a 3- inhibition was reversed by the CB1 recep- month period were screened for blood alco- tor antagonist AM251. AEA also reduced hol. Urine specimens were analyzed for the blood pressure changes caused by CGRP metabolites of cannabis and cocaine. Sixty- injection, this effect was not reversed by two percent of patients were positive for at AM251CS314. least one substance and 20% for two or Tumor-promoting effect. A 28-year-old more. Positivity rates were as follows: can- man who abused alcohol, nicotine, and can- nabis, 46%; alcohol, 32% (with 71% of nabis for several years was investigated. He these having blood alcohol levels >80 mg/ suffered simultaneously from a squamous dL); and cocaine (6%). Substance usage was cell carcinoma of the hypopharynx with most prevalent in the third decade of life. bilateral cervical metastases, an adenocar- The patients who yielded a positive result cinoma of the transverse colon and a were significantly younger than those nega- primary hepatocellular carcinoma. There tives. There was no significant difference in were occurrences of three separate malig- age or substance usage between the victims nant tumors with different histologies in the of interpersonal violence or road traffic aerodigestive tract, which could be related accidents. In the group designated “other to a chronic abuse of cannabisCS460. accidents,” patients were significantly older Turning behavior. Cannabinoid agonists: and had a lower incidence of substance WIN (1–100 ng/mouse), CP-55,940 (0.1– usage than the other two groups. Cannabis 50 ng/mouse), and AEA (0.5–50 ng/mouse), was the most prevalent substance in all administered unilaterally into the mouse groups. Fifty and 55% of victims of road striatum, dose-dependently induced turning CANNABIS SATIVA 93 behavior. SR 141716A [N-(piperidin-1-yl) cannabis use for both maternal self- and -5-(4-chlorophenyl)-1-(2,4-dichlorophe- paternal proxy report, although the associa- nyl)-4-methyl-1H- pyrazole-3-carboxamide tion was significant only for maternal self- hydrochloride], the selective antagonist of reportCS301. CB1 receptor, antagonized the three can- Visuospatial memory effect. Twenty-five nabinoid receptor agonists-induced turning college students who were heavy cannabis with similar effective dose50 (0.13–0.15 mg/ smokers (who had smoked a median of 29 of kg, intraperitoneally). Spiroperidol (a D2 the last 30 days) were compared with 30 receptor blocker), (+)-SCH 23390 (a D1 light smokers (1 day in the last 30 days). receptor blocker), or prior 6-hydroxy- The subjects were tested after a supervised dopamine lesions of the striatum blocked period of abstinence from cannabis and WIN- and CP-55,940-induced turning, thus other drugs lasting at least 19 hours. Differ- suggesting the involvement of DA transmis- ences between the overall groups of heavy sion in cannabinoid-induced turningCS464. and light smokers did not reach statistical Tyrosinase inhibition. Methanol (80%) significance on the four subtests of attention extract of the dried aerial parts, at a con- administered. On examining data for the centration of 100 Pg/mL, produced weak two sexes separately, marked and significant activityCS075. differences were found between heavy- and Uterine stimulant effect. Ethanol (50%) light-smoking women on the subtest exam- extract of the entire plant was inactive on ining visuospatial memory. On this test, the rat uterusCS007. Ethanol (95%) and water subjects were required to examine a 6 u 6 extracts of the dried aerial parts, at a con- “checkerboard” of squares in which certain centration of 1:1, produced strong activity squares were shaded. The shaded squares on the non-pregnant rat uterusCS243. Water were then erased and the subject was extract of the flowering tops produced required to indicate with the mouse which strong activity on the rat uterusCS008. squares had formerly been shaded. Increas- Ventricular septal defect. A Birth Defect ing numbers of shaded squares were pre- Case–Control Study was used to identify sented at each trial. The heavy-smoking 122 isolated simple ventricular septal defect women remembered significantly fewer (VSD) cases and 3029 control infants. squares on this test, and they made signifi- Exposure data on alcohol, cigarette, and il- cantly more errors than the light-smoking licit drug use were obtained through stan- women. These differences persisted despite dardized interviews with mothers and different methods of analysis and consider- fathers. Associations between lifestyle fac- ation for possible confounding variablesCS453. tors and VSD were calculated using mater- Weight loss. The dried leaves, adminis- nal self-reports; associations were also tered by gastric intubation to male rats at a calculated using paternal proxy reports of dose of 75 mg/kg, was activeCS215. the mother’s exposures. Maternal self-report Wilson’s disease. A patient with general- of heavy alcohol consumption and paternal ized dystonia owing to Wilson’s disease ob- proxy report of the mother’s moderate alco- tained mrked improvement in response to hol consumption were associated with iso- smoking cannabisCS263. lated simple VSD. A twofold increase in risk Winiwarter-Buerger disease. Two young of isolated simple VSD was identified for men aged 18 and 20 years with juvenile maternal self- and paternal proxy-reported endarteritis were evaluated. Both developed cannabis use. Risk of isolated simple VSD acute distal ischemia of the lower or upper increased with regular (Ն3 days per week) limbs with arteriographic evidence sugges- 94 MEDICINAL PLANTS OF THE WORLD tive of Winiwarter-Buerger disease. Both CS009 Segelman, A. B., F. H. Pettler and N. smoked regularly but not excessively, and R. Farnsworth. Cannabis sativa (mari- both used cannabis regularly. In one case, huana). A correction of reported thin- layer chromatography data. Pharm the therapeutic response to withdrawal of Wkly 1970; 105: 1360–1362. cannabis was good. In the second, use of CS010 Saha, J. C., E. C. Savini and S. cannabis continued and arterial disease per- Kasinathan. Ecbolic properties of sisted. The main clinical and radiographical Indian medicinal plants. Part 1. Indian features in this condition are the same as in J Med Res 1961; 49: 130-151. CS011 Berhault, J. Flore Illustree du Senegal Winiwarter-Buerger diseaseCS430. II. Govt. 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CS386 Alvaro, L. C., I. Iriondo, and F. J. CS397 Lundqvist, T., S. Jonsson, and S. Villaverde. Sexual headache and Warkentin. Frontal lobe dysfunction stroke in a heavy cannabis smoker. in long-term cannabis users. Neuro- Headache 2002; 42(3): 224–226. toxicol Teratol 2001; 23(5): 437–443. CS387 McLeod, A. L., C. J. McKenna, and D. CS398 Launay, D., V. Queyrel, P. Y. Hatron, B. Northridge. Myocardial infarction U. Michon-Pasturel, E. Hachulla, and following the combined recreational B. Devulder. Digital necrosis in a use of Viagra and cannabis. Clin patient with anorexia nervosa. Asso- Cardiol 2002; 25(3): 133–134. ciation of vasculopathy and radial CS388 Solowij, N., R. S. Stephens, R. A. artery injury Presse Med 2000; 29(34): Roffman et al. Cognitive functioning 1850–1852. of long-term heavy cannabis users seek- CS399 Voruganti, L. N., P. Slomka, P. Zabel, ing treatment. JAMA 2002; 287(9): A. Mattar, and A. G. Awad. Cannabis 1123–1131. induced dopamine release: an in-vivo CS389 Fergusson, D. M., L. J. Horwood, and SPECT study. Psychiatry Res 2001; K. Northstone. Maternal use of can- 107(3): 173–177. nabis and pregnancy outcome. BJOG CS400 Tramer, M. R., D. Carroll, F. A. 2002; 109(1): 21–27. Campbell, D. J. Reynolds, R. A. CS390 Fox, S. H., M. Kellett, A. P. Moore, A. Moore, and H. J. McQuay. Cannab- R. Crossman, and J. M. Brotchie. inoids for control of chemotherapy Randomised, double-blind, placebo- induced nausea and vomiting: quanti- controlled trial to assess the potential tative systematic review. BMJ 2001; of cannabinoid receptor stimulation in 323(7303): 16–21. the treatment of dystonia. Mov Disord CS401 Dowe, G., M. F. Smilkle, C. Thesiger, 2002; 17(1): 145–149. and E. M. Williams. Bloodborne sexu- CS391 Elsner, F., L. Radbruch, and R. ally transmitted infections in patients Sabatowski. Tetrahydrocannabinol for presenting for substance abuse treat- treatment of chronic pain. Schmerz ment in Jamaica. Sex Transm Dis 2001; 15(3): 200–204. 2001; 28(5): 266–269. CS392 Bachs, L. and H. Morland. Acute car- CS402 Fishwick, D., L. J. Allan, A. Wright, diovascular fatalities following can- C. M. Barber, and A. D. Curran. Res- nabis use. Forensic Sci Int 2001; piratory symptoms, lung function, and 124(2–3): 200–203. cell surface markers in a group of hemp CS393 Earleywine, M. Cannabis-induced fiber processors. Am J Ind Med 2001; Koro in Americans. Addiction 2001; 39(4): 419–425. 96(11): 1663–1666. CS403 Scragg, R. K., E. A. Mitchell, R. P. CS394 Kopelman, M. D., L. J. Reed, P. Ford, J. M. Thompson, B. J. Taylor, Marsden, et al. Amnesic syndrome and and A. W. Stewart. Maternal cannabis severe ataxia following the recre- use in the sudden death syndrome. ational use of 3,4-methylene-dioxy- Acta Paediatr 2001; 90(1): 57–60. methamphetamine (MDMA, ‘ecstasy’) CS404 Flisher, A. J. and D. O. Chalton. Ado- and other substances. Neurocase 2001; lescent contraceptive non-use and 7(5): 423–432. covariation among risk behaviors. J CS395 Bovasso, G. B. Cannabis abuse as a risk Adolesc Health 2001; 28(3): 235–241. factor for depressive symptoms. Am J CS405 Taylor, D. R., R. Poulton, T. E. Psychiatry 2001; 158(12): 2033–2037. Moffitt, P. Ramankutty, and M. R. CS396 Arnold, J. C., A. N. Topple, P. E. Mal- Sears. The respiratory effects of can- let, G. E. Hunt, and I. S. McGregor. nabis dependence in young adults. The distribution of cannabinoid- Addiction 2000; 95(11): 1669–1677. induced Fos expression in rat brain: CS406 Disdier, P., B. Granel, J. Serratrice, et differences between the Lewis and al. Cannabis arteritis revisited—ten Wistar strain. Brain Res 2001; 921 new case reports. Angiology 2001; (1–2): 240–255. 52(1): 1–5. CANNABIS SATIVA 113

CS407 Kosior, D. A., K. J. Filipiak, P. Stolarz, injuries. West Indian Med J 1999; and G. Opolski. Paroxysmal atrial 48(4): 200–202. fibrillation in a young female patient CS417 Fried, P. A., B. Watkinson, and R. following marijuana intoxication—a Gray. Growth from birth to early case report of possible association. Med adolescence in offspring prenatally Sci Monit 2000; 6(2): 386–389. exposed to cigarettes and marijuana. CS408 Mani, S. K., A. Mitchell, and B. W. Neurotoxicol Teratol 1999; 21(5): O’Malley. Progesterone receptor and 513–525. dopamine receptors are required in CS418 Balle, J., M. J. Olofsson, and J. Hilden. Delta 9-tetrahydrocannabinol modula- Cannabis and pregnancy. Ugeskr tion of sexual receptivity in female Laeger 1999; 161(36): 5024–5028. rats. Proc Natl Acad Sci USA 2001; CS419 Von Mandach, U., M. M. Rabner, J. 98(3): 1249–1254. Wisser, and A. Huch. LSD and can- CS409 Schneider, F., N. Abdoucheli-Baudot, nabis abuse in early pregnancy with M. Tassart, F. Boudghene, and P. good perinatal outcome. Case report Gouny. Cannabis and tobacco: cofac- and review of the literature. Gynakol tors favoring juvenile obliterative Geburtshilfliche Rundsch 1999; arteriopathy. J Mal Vasc 2000; 25(5): 39(3): 125–129. 388–389. CS420 Zenor, B. N., G. D. Weesner, and P. V. CS410 Mackirdy, C. and D. Shepherd. Malven. Endocrine and other Capgras syndrome: possibly more com- responses to acute administration of mon among the Maori of New cannabinoid compounds to non- Zealand. Aust NZ J Psychiatry 2000; stressed male calves. Life Sci 1999; 34(5): 865–868. 65(2): 125–133. CS411 Stokes, J. R., R. Hartel, L. B. Ford, and CS421 Okereke, U. N., B. E. Weber, and R. T. B. Casale. Cannabis (hemp) posi- H. Israel. Spontaneous pneumome- tive skin tests and respiratory symp- diastinum in an 18-year-old black toms. Ann Allergy Asthma Immunol Sudanese high school student. J Natl 2000; 85(3): 238–240. Med Assoc 1999; 91(6): 357–359. CS412 Hampson, A. J., M. Grimaldi, M. CS422 Sherwood, R. A., J. Keating, V. Lolic, D. Wink, R. Rosenthal, and J. Kavvadia, A. Greenough, and T. J. Axelrod. Neuroprotective antioxi- Peters. Substance misuse in early dants from marijuana. Ann N Y Acad pregnancy and relationship to fetal Sci 2000; 899: 274–282. outcome. Eur J Pediatr 1999; 158(6): CS413 Goldschmidt, L., N. L. Day, and G. A. 488–492. Richardson. Effects of prenatal mari- CS423 Ameri, A.The effects of cannabinoids juana exposure on child behavior prob- on the brain. Prog Neurobiol 1999; lems at age 10. Neurotoxicol Teratol 58(4): 315–348. 2000; 22(3): 325–336. CS424 Coghlan, D., M. Milner, T. Clarke, et CS414 Leweke, F. M., U. Schneider, M. al. Neonatal abstinence syndrome. Ir Radwan, E. Schmidt, and H. M. Med J 1999; 92(1): 232–233, 236. Emrich. Different effects of nabilone CS425 Zimmer, A., A. M. Zimmer, A. G. and cannabidiol on binocular depth Hohmann, M. Herkenham, and T. I. inversion in Man. Pharmacol Bio- Bonner. Increased mortality, chem Behav 2000; 66(1): 175–181. hypoactivity, and hypoalgesia in can- CS415 Payne, H. C. Traumatic brain injury, nabinoid CB1 receptor knockout mice. depression and cannabis use—assess- Proc Natl Acad Sci USA 1999; ing their effects on a cognitive per- 96(10): 5780–5785. formance. Brain Inj 2000; 14(5): CS426 Lyketsos, C. G., E. Garrett, K. Y. 479–489. Liang, and J. C. Anthony. Cannabis CS416 McDonald, A., N. D. Duncan, and D. use and cognitive decline in persons I. Mitchell. Alcohol, cannabis and under 65 years of age. Am J Epidemiol cocaine usage in patients with trauma 1999; 149(9): 794–800. 114 MEDICINAL PLANTS OF THE WORLD

CS427 Masset, D., J. H. Bourdon, J. Arditti- rahydrocannabinol facilitates mor- Djiane, and J. Jouglard. Impact of phine-induced place conditioning in delta-9-tetrahydrocannabinol and its adult male offspring. Pharmacol metabolites on the immune system. Biochem Behav 1998; 61(3): 229–238. Acta Clin Belg Suppl 1999; 1: 39–43. CS437 English, D. R., G. K. Hulse, E. Milne, CS428 Ehrenreich, H., T. Rinn, H. J. Kunert, C. D. Holman, and C. I. Bower. et al. Specific attentional dysfunction Maternal cannabis use and birth in adults following early start of can- weight: a meta-analysis. Addiction nabis use. Psychopharmacology (Berl) 1997; 92(11): 1553–1560. 1999; 142(3): 295–301. CS438 Block, R. I., W. J. Erwin, R. Farinpour, CS429 Leech, S. L., G. A. Richardson, L. and K. Braverman. Sedative, stimu- Goldschmidt, and N. L. Day. Prenatal lant, and other subjective effects of substance exposure: effects on atten- marijuana: relationships to smoking tion and impulsivity of 6-year-olds. techniques. Pharmacol Biochem Neurotoxicol Teratol 1999; 21(2): Behav 1998; 59(2): 405–412. 109–118. CS439 Daisley, H., A. Jones-Le Cointe, G. CS430 Disdier, P., L. Swiader, J. Jouglard, et Hutchinson, and V. Simmons. Fatal al. Cannabis-induced arteritis vs. cardiac toxicity temporally related to Buerger disease. Nosologic discussion poly-drug abuse. Vet Hum Toxicol apropos of two new cases. Presse Med 1998; 40(1): 21–22. 1999; 28(2): 71–74. CS440 Wang, M. Q., C. B. Collins, R. J. CS431 Gorriti, M. A., F. Rodriguez de DiClemente, G. Wingood, and C. L. Fonseca, M. Navarro, and T. Palomo. Kohler. Depressive symptoms as corre- Chronic (-)-delta9-tetrahydrocannab- lates of polydrug use for blacks in a inol treatment induces sensitization to high-risk community. South Med J the psychomotor effects of amphet- 1997; 90(11): 1123–1128. amine in rats. Eur J Pharmacol 1999; CS441 Westermeyer, J., S. Kopka, and S. 365(2–3): 133–142. Nugent. Course and severity of sub- CS432 Ongradi, J., S. Specter, A. Horvath, stance abuse among patients with and H. Friedman. Additive effect of comorbid major depression. Am J marihuana and retrovirus in the anergy Addict 1997; 6(4): 284–292. of natural killer cells in mice. Orv CS442 Schlicker, E., J. Timm, J. Zentner, and Hetil 1999; 140(2): 81–84. M. Gothert. Cannabinoid CB1 recep- CS433 Eames, S. L., J. Westermeyer, and R. tor-mediated inhibition of noradre- D. Crosby. Substance use and abuse naline release in the human and among patients with comorbid dys- guinea-pig hippocampus. Naunyn thymia and substance disorder. Am J Schmiedebergs Arch Pharmacol 1997; Drug Alcohol Abuse 1998; 24(4): 356(5): 583–589. 541–550. CS443 Middleman, A. B., L. M. Robertson, R. CS434 Jentsch, J. D., C. D. Verrico, D. Le, and H. DuRant, V. Chiou, and S. J. Emans. R. H. Roth. Repeated exposure to delta Use of hormonal methods of birth con- 9-tetrahydrocannabinol reduces pre- trol among sexually active adolescent frontal cortical dopamine metabolism girls. J Pediatr Adolesc Gynecol 1997; in the rat. Neurosci Lett 1998; 246(3): 10(4): 193–198. 169–172. CS444 Heishman, S. J., K. Arasteh, and M. L. CS435 Matsunaga, T., K. Watanabe, H. Stitzer. Comparative effects of alcohol Yoshimura, and I. Yamamoto. Quanti- and marijuana on mood, memory, and tative analysis and pharmaco-toxicity performance. Pharmacol Biochem of cannabinoids in commercially avail- Behav 1997; 58(1): 93–101. able cannabis seeds. Yakugaku Zasshi CS445 Ostrea, E. M. Jr., A. R. Ostrea, and P. 1998; 118(9): 408–414. M. Simpson. Mortality within the first CS436 Rubio, P., F. Rodriguez de Fonseca, J. 2 years in infants exposed to cocaine, L. Martin-Calderon, et al. Maternal opiate, or cannabinoid during gesta- exposure to low doses of delta9-tet- tion. Pediatrics 1997; 100(1): 79–83. CANNABIS SATIVA 115

CS446 Durst, R. and P. Rebaudengo-Rosca. CS457 Williams, J. H., N. A. Wellman, and J. Attention deficit hyperactivity disor- N. Rawlins. Cannabis use correlates der, facilitating alcohol and drug abuse with schizotypy in healthy people. in an adult. Harefuah 1997; 132(9): Addiction 1996; 91(6): 869–877. 618–622, 680. CS458 Boros, C. A, D. W. Parsons, G. D. CS447 Holdcroft, A., M. Smith, A. Jacklin, Zoanetti, D. Ketteridge, and D. et al. Pain relief with oral cannab- Kennedy. Cannabis cookies: a cause of inoids in familial Mediterranean fever. coma. J Paediatr Child Health 1996; Anaesthesia 1997; 52(5): 483–486. 32(2): 194–195. CS448 Elwan, O., A. A. Hassan, M. Abdel CS459 Navarro, M., R. de Miguel, F. Rodri- Naseer et al. Brain aging in a sample of guez de Fonseca, J. A. Ramos, and J. J. normal Egyptians cognition, educa- Fernandez-Ruiz. Perinatal cannabinoid tion, addiction and smoking. J Neurol exposure modifies the sociosexual Sci 1997; 148(1): 79–86. approach behavior and the mesolimbic CS449 Mirochnick, M., J. Meyer, D. A. Frank, dopaminergic activity of adult male H. Cabral, E. Z. Tronick, and B. rats. Behav Brain Res 1996; 75(1–2): Zuckerman. Elevated plasma norepi- 91–98. nephrine after in utero exposure to co- CS460 Richter, B., N. Marangos, A. Jeron, caine and marijuana. Pediatrics 1997; and S. Irscheid. 3 different malignan- 99(4): 555–559. cies of the aerodigestive tract after CS450 Meier, H. and H. J. Vonesch. Can- chronic abuse of cannabis products. nabis poisoning after eating salad. HNO 1995; 43(12): 728–731. Schweiz Med Wochenschr 1997; CS461 Wiley, J. L., J. W. Huffman, R. L. 127(6): 214–218. Balster, and B. R. Martin. Pharma- CS451 Sanudo-Pena, M. C., K. Tsou, E. R. cological specificity of the discrimi- Delay, A. G. Hohman, M. Force, and native stimulus effects of delta 9-tet- J. M. Walker. Endogenous cannab- rahydrocannabinol in rhesus monkeys. inoids as an aversive or counter- Drug Alcohol Depend 1995; 40(1): rewarding system in the rat. Neurosci 81–86. Lett 1997; 223(2): 125–128. CS462 Navarro, M., P. Rubio, and F. R. de CS452 Ruh, M. F., J. A. Taylor, A. C. Fonseca. Behavioural consequences of Howlett, and W. V. Welshons. Failure maternal exposure to natural cannab- of cannabinoid compounds to stimu- inoids in rats. Psychopharmacology late estrogen receptors. Biochem (Berl) 1995; 122(1): 1–14. Pharmacol 1997; 53(1): 35–41. CS463 Romero, J., L. Garcia, J. J. Fernandez- CS453 Pope, H. G. Jr., A. Jacobs, J. P. Mialet, Ruiz, M. Cebeira, and J. A. Ramos. D. Yurgelun-Todd, and S. Gruber. Evi- Changes in rat brain cannabinoid dence for a sex-specific residual effect binding sites after acute or chronic of cannabis on visuospatial memory. exposure to their endogenous agonist, Psychother Psychosom 1997; 66(4): anandamide, or to delta 9-tetrahydro- 179–184. cannabinol. Pharmacol Biochem CS454 Lawson, T. M. and A. Rees. Stroke and Behav 1995; 51(4): 731–737. transient ischaemic attacks in associa- CS464 Souilhac, J., M. Poncelet, M. Rinaldi- tion with substance abuse in a young Carmona, G. Le Fur, and P. Soubrie. man. Postgrad Med J 1996; 72(853): Intrastriatal injection of cannabinoid 692–693. receptor agonists induced turning CS455 Mallat, A., J. Roberson, and J. G. behavior in mice. Pharmacol Biochem Brock-Utne. Preoperative marijuana Behav 1995; 51(1): 3–7. inhalation—an airway concern. Can J CS465 Shiono, P. H., M. A. Klebanoff, R. P. Anaesth 1996; 43(7): 691–693. Nugent, et al. The impact of cocaine CS456 Napiorkowski, B., B. M. Lester, M. C. and marijuana use on low birth weight Freier, et al. Effects of in utero substance and preterm birth: a multicenter exposure on infant neurobehavior. study. Am J Obstet Gynecol 1995; Pediatrics 1996; 98(1): 71–75. 172(1 Pt. 1): 19–27. 116 MEDICINAL PLANTS OF THE WORLD

CS466 Solowij, N., B. F. Grenyer, G. study of acute and chronic cognitive Chesher, and J. Lewis. Biopsycho- effects, withdrawal and treatment. social changes associated with cessa- Life Sci 1995; 56(23–24): 2127– tion of cannabis use: a single case 2134. COCOS NUCIFERA 117

3 Cocos nucifera L.

Common Names Anaargeel Iran Kelapa Malaysia Arre kokosi Albania Khokhonate South Africa Bahia coconut palm Brazil Klapper Netherlands Boko Philippines Klapperboom Netherlands Cno coco England Kobari India Cno coco Ireland Kobbai India Cocco Italy Kobbai Sri Lanka Coco da Bahia Brazil Kobbera India Coco da India Portugal Kobbera Sri Lanka Coco fruto Spain Kok mak phao Laos Coco Portugal Kokas Ethiopia Coco Spain Kokkofoinika Greece Coconut Guyana Koko yashi Japan Cocotera Spain Koko Spain Cocotier France Kokonet Ethiopia Cocotier Romania Kokos orekonosnyi Russia Coqueiro da Bahia Brazil Kokos Bulgaria Coqueiro Portugal Kokos Croatia Cro bainney The Isle of Man Kokos Czech Republic Daab India Kokos Germany Dafu Kenya Kokos Netherlands Dafu Mozambique Kokos Russia Dafu Tanzania Kokos Sweden Dafu Zaire Kokos Ukraine Dua Vietnam Kokosa Slovenia Gawz el Hindi Arabic countries Kokoshneta Iceland Hentgagan engouz Armenia Kokosnoed Denmark Hindistancevizi Turkey Kokosnoot Netherlands I kokosit Albania Kokosnot Sweden Kafa Turkey Kokosnus Israel Karida Greece Kokosnuss Germany Karyda Greece Kokosnut Netherlands Ke ke ye zi Taiwan Kokosnut Spain Kelapa Indonesia Kokosov orah Croatia

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 117 118 MEDICINAL PLANTS OF THE WORLD

Kokosov orah Serbia Narial India Kokosov orech Bulgaria Narikela India Kokosov Bulgaria Narikol India Kokosova palma Slovenia Narival Nepal Kokosovaia pal’ma Russia Nariyal India Kokosovy orech Czech Republic Narkel India Kokosovy orech Slovakia Natsume yashi Japan Kokosovyj orech Ukraine Nazi Mozambique Kokosovyj orjekh Russia Nazi Tanzania Kokospalm Netherlands Nazi Zaire Kokospalm Sweden Niyog Philippines Kokospalme Denmark Niyok Hawaii Kokospalme Germany Niyok Pacific Islands Kokronoto Surinam Noce di cocco Italy Kokus Israel Noix de coco France Kokusnod Faeroe Islands Noz de coco Portugal Kokuszdio Hungary Nuca de cocos Romania Kookospahkina Finland Nuez de coco Spain Kookospalm Estonia Nyior Malaysia Kookospalmu Finland Palma de coco Spain Kronto Surinam Palma del cocco Italy Lag Guyana Palma kokosowa Poland Ma phra on Thailand Palmera de coco Spain Maak muu Thailand Polgaha Sri Lanka Mak un on Myanmar Qoqus Israel Maphrao Thailand T’ha’ari Tahiti Mar India Tenkaya India Mnazi Mozambique Tenkaya Sri Lanka Mnazi Southeastern Africa Tennai marama India Mnazi Tanzania Tennai marama Sri Lanka Mnazi Zaire Thenga India Naarakel India Thenga Malaysia Naariyal kaa per India Thenga Sri Lanka Naariyal kaa per Pakistan Thenginkai India Naariyal India Thengu India Naariyal Pakistan Thengu Sri Lanka Nadiya India Thenkaii India Nalikeran Malaysia Thenkaii Sri Lanka Nanivaara India Ungbin Myanmar Naral India Ye shu China Nargil Arabic countries Ye zi China Nargil Iran

BOTANICAL DESCRIPTION straight or gently curved, with marked fo- Cocos nucifera is an unbranched monoe- liar scars, 30–50 cm in diameter, rises from a cious plant of the PALMAE family. It grows thickened base, and increases in height at a to 30 m tall, with a crown of 25–35 pari- decreasing rate with age. The leaves are pinnate leaves, producing 12–16 new leaves horizontal or somewhat hanging, 4–8 m in per year. There is a central bud, which if cut length and divided. Segments of leaves are off, leads to the death of tree. The trunk is numerous, linear-lanceolate, 0.5–1 m long COCOS NUCIFERA 119 and tapering. In the axil of each leaf is a Phyllanthus virgatus, is rubbed around the ear spathe enclosing a long, stout, straw, or an for ear infections. Extract of different dried orange-colored spadix. The spadix is com- parts of the palm are taken orally for filari- posed of up to 40 branches, each bearing up asis. A water solution of the crushed dried to 300 small, fragrant, male flowers, and a bark or husk and grated bark of Hibiscus few female, 2 cm long, globose flowers. The tiliaceus is used externally to soak fractures male and female flowers are produced sepa- and sprains. Crushed aerial root tips of Ficus rately in the leaf axils, usually on a long prolixa are fried with coconut cream made of stalk. Approximately one-third of the female fresh endosperm, and the resulting oil is flowers develop into four to eight ripe fruits taken orally as a laxative in treating serious in 12–13 months, per inflorescence. The fruit diseasesCN047. is ovoid, three-angled drupe, up to 30 cm Ecuador. Hot water extract of the plant is long, usually with thick, fibrous mesocarp taken orally by females for sterilityCN055. (husk) and a hard, green-brown endocarp Fiji. Oil is used externally to prevent hair (shell) enclosing one seed. The seeds consist loss. The oil is warmed with crushed onion of 10 to 20 mm-thick white, fleshy endo- and garlic and applied aurally for sperm (meat), covered by thin brown testa, earacheCN049. Water of the unripe fruit is surrounding a cavity party filled with a wa- taken orally for kidney problemsCN049. tery, sweet fluid (coconut water or milk). The Ghana. Coconut milk is taken orally for latter is found mainly in immature fruits. diarrheaCN098. ORIGIN AND DISTRIBUTION Guatemala. Hot water extract of the dried fruit is taken orally as a febrifuge and sudo- Evidence has been found that the place of rific and for renal inflammation and origin is “submerged land to the north west scrofula. Hot water extract of the dried fruit of New Guinea.” The major coconut areas is applied externally on wounds, ulcers, lie between 20q N and 20q S of the equator. bruises, sores, skin infections, mucosa, der- Although it is found beyond this region, 27q matitis, inflammations, abscesses, and N and 27q S, cultivation has not been suc- furunclesCN056. cessful and the palm does not fruit. Many Haiti. Decoction of the dried pericarp is varieties are found in Melanesian region. It taken orally for amenorrhea. Fresh essential is most widely cultivated in the tropics: In- oil is applied externally on burnsCN051. dia, Ceylon, Malaysia, Indonesia, Philip- Hawaii. Water extract of the fruit is taken pines, South Sea Islands in the Pacific, East orally for asthmaCN024. Africa, and Central and South Americas, up India. Infusion of the inflorescence is taken to 800 m above sea level, on humus-rich and orally every morning for 3 days, coinciding porous soil or pure sand in coastal regions. with the menstrual cycle for leukorrhea and TRADITIONAL MEDICINAL USES problems associated with the menstrual Admiralty Islands. The young root or cycleCN026. A dose of 50 g daily of a mixture leaves of the coconut plant are chewed for of Cocos nucifera fruit and Ficus- benghalensis diarrheaCN044. latex is taken for 3 months to increase Brazil. Decoction of the husk fiber is used sexual potency in menCN041. Fruit is taken to treat diarrhea and arthritisCN070. orally as a remedy for tapewormsCN059. Cook Islands. Water extract of grated en- Indonesia. Coconut oil is applied exter- dosperm and Citrus aurantium juice is used nally to treat wounds and injuries by the to soak affected part in fractures and ethnic group of NgadaCN159. Shell is used as sprainsCN047. Endosperm is taken orally for incenseCN057. Hot water extract of the root is astheniaCN051. Oil, mixed with crushed taken orally for fever, bloody diarrhea, and 120 MEDICINAL PLANTS OF THE WORLD dysentery. Milk is taken orally by adults for women to treat severe bleeding during early poisoningCN042. Fruit milk is taken orally by pregnancy. Infusion of fresh kernel, taken females as a contraceptiveCN006. Fruit juice is twice daily with “tongan oil” prepared from believed to diminish libido or fertilityCN008. Aleurites moluccana is used for dysuria caused Seed oil with lemon juice and various tree by “kahi,” a locally described syndrome roots is taken orally as an abortifacientCN016. affecting the gastrointestinal and genitouri- Fruit ointment is applied externally for nary systemsCN045. swollen legs. Fresh flowers, chewed with Trinidad. Hot water extract of the root is Borassus flbellifer, are used for gonorrheaCN042. taken orally for amenorrheaCN015. Jamaica. Hot water extract of the dried Vanuatu. Hot water extract of the fruit, shell is taken orally for diabetesCN043. Hot drunk in large quantities when very hot, is water extract of the root, with seven other said to induce abortionCN005. Juice of the plants, wine, and rum, is used as a tonicCN060. crushed root mixed with water is drank after Extract of different parts are taken orally for delivery to restore strenghCN023. diabetesCN025. West Indies. Hot water extract of the root Marquesas Islands. Fruit juice is mixed is taken orally for amenorrhea. Hot water with Cordia subcordata and other plants and extract of the mesocarp is taken orally by used for general menstrual disordersCN003. females for dysmenorrhea, amenorrhea, and Mexico. A plaster made of fresh milk mixed menorrhagiaCN038. with egg white is applied externally to pre- CHEMICAL CONSTITUENTS vent miscarriageCN046. (ppm unless otherwise indicated) Mozambique. Fruit is eaten by males as an 14-O-(3-O-[E-D-galactopyranosyl-(1o2)-D- aphrodisiac and used for relief of tumorsCN027. galactopyranosyl-(1o3)-D-L- Papua New Guinea. The fresh root of a arabinofuranosyl]-4-O-(D-L-arabino-furanosyl)- young coconut is dug out and washed, then E-D- galactopyranosyl)-trans-zeatin-riboside: chewed and swallowed to relieve stomach- MilkCN087 acheCN022. Fruit milk of Cocos nucifera is Acetoin: EndospermCN030 Alanine, phenyl: LfCN032 taken orally together with leaves of Cleroden CN001 sp., Pouzolzia microhylla, or Macaranga Alanine: Endosperm Aluminium inorganic: LfCN011 tanarius by pregnant women as an abortifa- Amyrin, D: Sd oilCN221 CN004 cient agent . Amyrin, E: Sd oilCN221 Peru. Hot water extract of the fresh fruit is Arginine: EndospermCN001 taken orally for blennorrhagia and asthma Aspartic acid: EndospermCN001 and as a diuretic, tenifuge, and galac- Butane-2-3-diol: EndospermCN030 CN030 tagogueCN054. Butane-2-3-dione: Endosperm Butyric acid, 2-methyl, methyl ester: FrCN220 Thailand. Hot water extract of the fresh Butyroin: FrCN220 fruit juice is taken orally as a cardiotonic Campesterol: Sd oilCN221 CN062 and neurotonic . Caproic acid: EndospermCN030 Tonga. Infusion of fresh kernel of coconut Catechins: HuskCN066 and Euodia hortensis are taken orally to Cocamide diethanoloamide: Sd oilCN082 treat retention of blood clots in the uterus Cocamidopropyl betaine: Sd oilCN214. Cocos II protein: PollenCN114 after childbirth (locally called “toka-ala”). CN114 A mixture of Cocos nucifera, Glochidion Cocos IIa protein: Pollen Cocos VI protein: PollenCN114 concolor, Vigna marina, Morinda citrifolia, Cocos VII protein: PollenCN114 Euodia hortensis, and Premna taitensis with Cycloartenol, 24-methylene: Sd oilCN221 lemon juice is taken orally by pregnant Cycloartenol: Sd oilCN221 COCOS NUCIFERA 121

Decalactone, G: EndospermCN030 Terpineol, D: FrCN220 Decanoic acid: EndospermCN030 Tetracosane, N: Sd oilCN221 Docosane, N: Sd oilCN221 Threonine: LfCN032 Dodecalactone, G: EndospermCN030 Tocopherol, D: Sd oilCN010 Dotriacontane, N: Sd oilCN221 Triacontane, N: Sd oilCN221 Eicosane, N: Sd oilCN221 Triclosane, N: Sd oilCN221 Ethyl lactate: FrCN220 Tyrosine: LfCN032 Fructose: Milk 2.22%CN050, RtCN029 Valine: EndospermCN001, LfCN032 Galactitol: EndospermCN028 Gentisic acid: LfCN009 PHARMACOLOGICAL ACTIVITIES Glucose: Milk 1.97%CN050, RtCN029 AND CLINICAL TRIALS Glutamic acid: EndospermCN001, LfCN032 Acquired immunodeficiency syndrome Glycine: EndospermCN001, LfCN032 activity. Coconut oil and “monolaurin”—a Heneicosane, N: Sd oilCN221 coconut oil byproduct—were administered CN221 Heptacosane, N: Sd oil to 12 women and 3 men who were in the Heptadecane, N: Sd oilCN221 Heptan-2-ol: FrCN220 early stage of human immunodeficiency vi- Hexacosane, N: Sd oilCN221 rus infection. Ten patients took different Histidine: LfCN032 doses of monolaurin, and five patients took Lactose: RtCN029 coconut oil. It was believed that the treat- Lauric acid: EndospermCN030 ment would lead to higher CD4 counts and Leucine, iso: EndospermCN001, LfCN032 a lower viral load. The trial was abandoned CN032 Leucine: Lf because it received only lukewarm approval Ligustrazine: EndospermCN030 from the governmentCN155. Limonene: FrCN220 Linamarase: EndospermCN013 Allergenic activity. Dried fruit juice, admin- Lysine: EndospermCN001, LfCN032 istered intraperitoneally to guinea pigs at a Menthol: FrCN220 dose of 10 mL/animal, was active. Dried Methionine: EndospermCN001, LfCN032 fruit juice, administered intravenously to Myristic acid: Sd oilCN031 guinea pigs at a dose of 5 mL/animal, was CN221 Nonacosane, N: Sd oil activeCN036. A patient with coconut anaphy- Nonadecane, N: Sd oilCN221 laxis was confirmed by skin prick test. In Octacosane, N: Sd oilCN221 Octalactone,G: EndospermCN030 vitro serum specific immunoglobulin E Octanoic acid: EndospermCN030 (IgE) was presentCN065. Two patients with Pentacosane, N: Sd oilCN221 allergy manifested by life-threatening sys- Phaseic acid, dihydro: SapCN040 temic reaction after consumption of coco- Phaseic acid, hydroxy: SapCN040 nut were investigated. Sera IgE from both Proline, hydroxy: EndospermCN001 CN032 patients indicated reduced coconut aller- Proline: Lf gens with molecular weight of 35 and 36.5 Purin-6-one, 2-(3-methyl-but-2-enyl-amino): MilkCN039 kDa. IgE from 1 patient also bound a 55-kDa Pyrasine, 2-3-5-trimethyl: EndospermCN030 antigen. Preabsorption of sera with nut ex- Raffinose: RtCN029 tracts suppressed IgE binding to coconut Serine: EndospermCN001, LfCN032 proteins. Preabsorption of sera with coconut Sitosterol, E: Sd oilCN221 produced a disappearance of IgE binding to CN028 Sorbitol: Endosperm protein bands at 35 and 36 kDa on a reduced CN221 Squalene: Sd oil immunoblot of walnut protein extract in Stigmasterol: Sd oilCN221 Succinic acid: RtCN029 one patient and suppression of IgE bind- Sucrose: Milk 0.43%CN050 ing to a protein at 36 kDa in another Tannin (Cocos nucifera): PlCN061 patientCN078. Three cases of individuals aller- 122 MEDICINAL PLANTS OF THE WORLD gic to cocamide diethanolamide were inves- pollen extract immunotherapy. Serological tigated. In two of the cases, multiple other study indicated a significant reduction of cutaneous allergies were present. In both specific IgE and elevation of specific IgG in instances, cocamide diethanolamide was posttherapeutic patients’ sera. There was no present in several personal care products correlation between symptom-mediation used by the patients. In the third case, occu- scores and changes in specific serum IgE or pational exposure was suspectedCN082. Coco- IgG levelsCN097. Proteins from fresh coconut nut diethanolamide, administered to six and commercial extracts of coconut, admin- patients with occupational contact derma- istered to a patient with coconut anaphy- titis caused by coconut diethanolamide, pro- laxis, produced a positive skin prick test. In duced sensitization from a barrier cream in vitro serum-specific IgE was present for two patients, hand-washing liquid in three, coconut, hazelnut, Brazil nut, and cashew. and one had been exposed to a hand-wash- Immunoblots demonstrated IgE binding to ing liquid and to a metalworking fluid con- 35- and 50-kDa protein bands in the coco- taining coconut diethanolamide. Leave-on nut and hazelnut extracts. Inhibition assays products (hand-protection foams) produced using coconut demonstrated complete inhi- sensitization more rapidly (2–3 months) bition of hazelnut specific IgE, but inhibi- than rinse-off products (5–7 years). There tion assays using hazelnut showed only was no contact allergy to another coconut- partial inhibition of coconut-specific oil-derived sensitizer (cocamidopropyl IgECN135. A total of 100 patients (59 females betaine)CN214. Coconut diethanolamide, ad- and 41 males, aged 10–59 years, mean age ministered to a dentist, produced an occu- 27.9 years) with allergic rhinitis under- pational allergic contact dermatitis for went a skin prick test with 30 aeroaller- hand-washing liquidsCN216. Pollen extract, gens. Coconut produced 12% of positive administered to 24 patients with allergy, resultsCN194. Oil, administered to E-lactoglo- asthma, and rhinitis produced positive skin bulin-treated brown Norway rats at a dose prick test in all cases, and 19 of them were of 10% of diet supplemented with 0.5% phadezym radioallergosorbent test-positive. curcumin for 3 weeks, lowered the circula- Bronchial provocation test was positive in tory release of rat chymase II in response to seven out of eight patients, and no late antigenCN205. The triethanolamine (TEA) response or nonspecific reactions were salt of the condensation product of coconut observedCN090. An 8-month-old baby fed fatty acids with a complex of polypeptides from birth with maternal milk was investi- and amino acids derived from collagen gated. The first milk induced a severe gas- (TEA-Coco-hydrolyzed protein), adminis- trointestinal disorder, which disappeared tered to a 21-year-old woman, produced a when second milk was used. The third milk severe dermatitis of the face after using a caused a relapse. The allergen was coconut, proprietary skin cleanser. Patch testing which was physicochemically modified in revealed delayed hypersensitivity to TEA- the second milk. It was confirmed by posi- Coco-hydrolyzed protein but not to other tive reintroduction test, positive skin test, ingredients of the cleanser and positive and positive specific IgE testCN091. Pollen results with other condensates of fatty acids extract immunotherapy was studied in 96 and protein hydrolysatesCN218. allergic patients for 6–12 months. The clini- Aminopeptidase activity influence. Oil, cal status measured by the symptom-medi- administered to mice testis using acryl- cation scores demonstrated that the patients amides as substrates, produced no difference had significant clinical improvement after in soluble glutamyl-aminopeptidase (AP) COCOS NUCIFERA 123 angiotensin among the groups tested. genesCN166. Hydrogenated oil, administered Soluble aspartyl-AP and soluble pyroglut- to Listeria monocytogenes-infected mice, amyl-AP progressively decreased with the produced a significant increase in perito- degree of saturation of the fatty acids used neal cells of coconut oil-fed mice and a in the diet. Membrane-bound glutamyl-AP reduction of bacterial recovery from the progressively increased with the degree of spleenCN186. Oil, administered to mice inject- saturation of the fatty acids used in the diet. ed with a nonlethal dose of Escherichia For membrane-bound aspartyl-AP activity, coli at a dose of 20% by weight for 5 weeks, mice that were fed diets containing fish oil produced a decrease of peak plasma tu- showed significantly higher levels than mor necrosis factor (TNF)-D, interleukin those fed sunflower oil, olive oil, and lard, (IL)-1 E, and IL-6 concentrations. Peak but not those fed coconut oilCN164. plasma IL-10 concentrations were higher in Analgesic activity. Ethanol (50%) extract the coconut-fed group than in those fed of the leaf, administered intraperitoneally to the other diets, coconut oil diminished pro- mice at a dose of 0.375 mg/kg, was inactive duction of proinflammatory cytokines in vs tail pressure methodCN036. vivoCN187. Anti-ancylostomiasis activity. Milk and Anticarcinogenic effect. Coconut cake, meat of one nut eaten early in the morning administered to rat with 1,2-dimethylhydra- by 22 adults on empty stomach was inac- zine-induced colon cancer at a dose of 25% tiveCN059. of diet for 30 weeks, produced a significant Antibacterial activity. Ethanol (50%) decrease of the incidence and number of extracts of the leaf, on agar plate at concen- tumors, and E-glucuronidase and mucinase trations above 25 Pg/mL, were inactive on activitiesCN134. Hydrogenated oil, adminis- Bacillus subtilis, Escherichia coli, Salmonella tered to Wistar female rats at doses of 8% typhosa, and Staphylococcus aureusCN058. Tinc- and 24%, with or without a 24 mg/day/rat ture of the dried fruit (10 g plant material in phytosterol supplement, produced no sig- 100 mL ethanol), on agar plate at a concen- nificant influence. Colonic glands were tration of 30 PL/disc, was inactive on found in area of lymphoid follicles in all the Pseudomonas aeruginosa and Staphylococ- groups but were more frequently in rats on cus aureus and produced weak activity on high-fat dietCN170. Escherichia coliCN056. Water extract of the Anticonvulsant activity. Ethanol (50%) husk fiber and fractions from adsorption extract of the leaf, administered intraperi- chromatography were active on Staphylococ- toneally to mice at a dose 0.375 mg/mL, was cus aureusCN070. Hydrogenated oil, adminis- inactive vs electroshock-induced convul- tered orally to Balb/c mice at a dose of 20% sionsCN058. by weight for 4 wk and then infected with Antidiarrheal activity. Water extract of Listeria monocytogenes or treated with N- coconut water, administered orally to acetyl-L-cysteine (25 mg/mL intraperito- adults, produced equivocal effectCN019. neally), produced no effect on survival. Antifungal activity. Ethanol (50%) extract N-acetyl-L-cysteine reduced the recovery of of the leaf, on agar plate at a concentration Listeria monocytogenes from the spleen of the of 25 Pg/mL or more, was inactive on mice fed coconut oil dietCN145. There was a Microsporum canis and Trichophyton menta- reduction in lymphocyte proliferation. An grophytesCN058. Oil, on agar plate at a concen- important increase in the production of tration of 05 mL/plate, was active on Absidia reactive oxygen species was found after 12 h corymbifera, Aspergillus flavus, Aspergillus of the incubation with Listeria monocyto- niger, and Penicillium nigricansCN017. Ethanol 124 MEDICINAL PLANTS OF THE WORLD

(95%) extract of the dried shell, on agar senger (m)RNA level in the liver of coco- plate at a concentration of 100 Pg/mL, was nut-fed rats, but not in those fed corn active on Microsporum audouini, Micro- oilCN142. Structured lipids (10%) synthesized sporum canis, Microsporum gypseum, Tricho- from oil triglycerides, coconut oil, and phyton mentagrophytes, Trichophyton rubrum, coconut oil–safflower oil blends (1:0.7 w/w) Trichophyton tonsurans, Trichophyton viola- were administered to rats for 60 days. The ceum, and Epidermophyton floccosumCN033. All structured lipids lowered serum and liver fractions of the husk fiber, from adsorption cholesterol levels. Most of the decrease chromatography, were inactive on Candida observed in serum was found in LDL albicans, Fonsecaea pedrosoi, and Cryptococ- fractionCN143. Oil, administered orally to cus neoformansCN070. male Wistar rats at a dose of 11% w/w for Antihypercholesterolemic activity. Oil 6 months, produced a significant increase was administered orally to male Wistar rats of serum total cholesterol (twofold), serum at doses of 12 or 24% of diet ad libitum for 4 triglycerides (92.6%), LDL cholesterol weeks. Absorption of oleic acid in rats fed (92.3%), and body weight gain (2.8-fold)CN147. 24% oil was significantly greater than in Anti-inflammatory activity. Ethanol controls during 0–8 hours but was not sig- (50%) extract of the leaf, administered nificantly different during 0–24 hours. orally to male rats at a dose of 0.375 Pg/kg, There were no differences among groups in 1 hour before carrageenin injections, was the distribution of cholesterol and oleic acid inactive vs carrageenin-induced pedal either in the lymph lipoproteins or in the edemaCN058. lipid classesCN097. Oil was administered to 61 Antilipidemic activity. Triglycerides struc- healthy males and 22 females aged 20–34 tured lipids from coconut oil, administered years, group I received a coconut–palm– to rats at a dose of 10% of diet for 60 days, coconut dietary sequence; group II, coco- produced a 15% decrease in total choles- nut–corn–coconut; group III, coconut oil terol and a 23% decrease in LDL cholesterol during all three 5-week dietary periods. levels in the serum compared to coconut oil- Compared with entry-level values, coconut fed rats. Total and free cholesterol levels in oil raised the serum total cholesterol con- the liver of structured lipid-fed rats were centration greater than 10% in all three lowered by 31 and 36%, respectively. The groups. The entry level of the ratio of low- triglycerides in the serum and liver were density lipoprotein (LDL) to high-density decreased by 14 and 30%, respectivelyCN140. lipoprotein (HDL) was not altered by coco- Anti-nociceptive activity. Aqueous ex- nut oilCN107. Oil was administered to 6- tract of the husk fiber, administered orally month-old ovariectomized rats with or to mice at doses of 200 or 400 mg/kg, pro- without taurine for 28 days. Body mass gain, duced an inhibition of the acetic acid- food intake, liver weight, and plasma induced writhing responseCN063. apoliprotein (apo) A-I, apo B, LDL, and Antioxidant activity. Aqueous extract of very low-density lipoprotein (VLDL) con- the husk fiber, in cell culture, was active vs centrations were not affected by the diet. 2,2-diphenyl-1-picryl-hydrazyl-hydrate Taurine lowered the plasma total choles- radicalsCN063. Juice, in cell culture, was active terol and increased liver total lipid and trig- vs 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino- lyceride in rats that were fed corn oil but bis(3-ethylbenz-thiazoline-6-sulfonic acid) not in those fed coconut oil. Taurine and superoxide radicals but promoted the increased the 3-hydroxy-3-methylglutaryl production of hydroxyl radicals and coenzyme A (HMG-CoA) reductase mes- increased lipid peroxidation. The activity COCOS NUCIFERA 125 was most significant for fresh samples and lowest level of malondialdehyde was ob- diminished significantly when heated or served in the coconut oil groupCN103. treated with acid, alkali, or dialysis. Matu- Antiviral activity. Crude extract of the rity of coconut drastically decreased the husk fiber and one of the fractions from ad- scavenging activity. Juice protected hemo- sorption chromatography rich in catechin globin from nitrite-induced oxidation when were active on acyclovir-resistant herpes- added before the autocatalytic stage of the simplex virus type 1CN070. oxidation. Acid, alkali, or heat-treated or Anti-yeast activity. Tincture of the dried dialyzed juice showed a decreased ability in fruit, on agar plate at a concentration of 30 protecting hemoglobin from oxidationCN069. PL/disc, was inactive on Candida albicans. Antiparasitic activity. Polyphenolic-rich Extract of 10 g plant material in 100 mL extract of the husk fiber, in cell culture at a ethanol was usedCN056. Ethanol (50%) concentration of 10 Pg/mL, produced a extract of the leaf, at a concentration of 25 reduction approx 44% of the association Pg/mL or more, was inactive on Candida index between peritoneal mouse macro- albicans and Cryptococcus neoformansCN058. phages and Leishmania amazonensis pro- Seed oil, on agar plate at a concentration of mastigotes. It inhibited the growth of 0.05 mL, was active on Candida albicansCN017. promastigote and amastigote developmental Apo B synthesis. Oil, administered to 1- stages after 60 minutes. There was a con- month-old calves fed on a conventional comitant increase of 182% in nitric oxide milk replacer containing coconut oil, pro- production by the infected macrophage in duced a twofold lower concentrations of to- comparison to nontreated macrophagesCN064. tal (35S) proteins, (35S) albumin, and (35S) Antiproteinemic effect. Hydrogenated oil apo B in liver cells than in beef tallow-fed was administered orally to rats fed a protein- calves. The total amount of proteins se- deficient diet at a dose of 200 g casein and creted (including albumin) was similar in 50 g coconut oil or 20 g casein and 50 g co- both groups. The amount of VLDL-(35S) apo conut oil for 28 days. The treatments pro- secreted was twofold lower in coconut oil- duced a low concentration of protein and fed groupCN169. Oil, administered to rabbits triacylglycerol (in serum VLDL, LDL–HDL at a dose of 14% of the diet for 4 weeks, pro- 1 and 2–3), of cholesterol (in LDL–HDL1), duced an increase in HDL-cholesterol (C) and of phospholipids (in VLDL) in the pro- level from 170 to 250% over chow-fed con- tein-deficient groups. Relative amounts of trol, with peak differences occurring at 1 linoleic and arachidonic acids in phospho- week. Plasma apo A-I levels were also in- lipids of VLDL and HDL 2–3 were also low- creased from 160 to 180%. After 4 weeks, ered in the 20 g casein and 50 g coconut oil there was no difference in plasma VLDL-C groupCN095. Coconut fat, administered to rats, or LDL-C levels in the both groups. Hepatic produced an increase in plasma esterase-1 level of apo A-I mRNA was increased in the activityCN102. Oil, administered to male coconut-fed groups. Treatment of cultured Wistar rats at doses of 20% casein and 5% rabbit liver cells and sera with various satu- coconut oil or 2% casein and 5% coconut rated fatty acids did not alter apo A-I oil for 28 days, produced low concentration mRNA levels as observed in vivoCN182. of protein, triacylglycerol, and VLDL in the Arrhythmogenic effect. Fruit juice, admin- plasma of 2% casein and 5% coconut oil istered by intravenous infusion to dogs at a group. Malondialdehyde content of the 2% dose of 3 mL/minute, was activeCN036. casein and 5% coconut oil group was signifi- Atherosclerotic influence. Oil was admin- cantly higher than of control group. The istered orally to rabbits fed a semipurified, 126 MEDICINAL PLANTS OF THE WORLD cholesterol-free atherogenic diet at a dose influenced by the amount of fat. Clofibrate of 14% fat: coconut oil (CNO), corn oil did not affect lower cholesterol concentra- (CO), palm kernel oil (PO), and cocoa but- tion in rats fed the low fat diet, but it coun- ter (CB). Serum cholesterol levels (mg/dL) teracted the rise in liver cholesterol seen in at 9 months were CO, 64; PO, 436; CB, 220; rats fed the high-fat diet. The high-fat diet and CNO, 474. HDL cholesterol (%) was produced slightly higher levels of butyryl CO, 37; PO, 8.6; CB, 25; and CNO, 7. av- cholinesterase in the small intestine but erage artherosclerosis (arch + thoracic/2) markedly raised intestinal esterase-1 activ- was CO, 0.15; PO, 1.28; CB, 0.53; and ityCN101. CNO, 1.60CN127. Oil, administered to British Carcinogenic activity. Coconut oil acid Halflop rabbits at a dose of 3% of the diet, diethanolamine condensate in ethanol was produced an increase of cholesterol, administered externally to 10 male and 10 triacylglycerol, apo B, apo C-III, and apo E female F344/N rats at doses of 25, 50, 100, as compared to chow-fed rabbits. The apo 200, or 400 mg/kg body weight five times A level did not differ from the chow-fed rab- per week for 14 weeks. All of the rats sur- bits. There was a decrease in the low frac- vived the study. Final mean body weights tional catabolic rate of LDL-CCN128. Oil, and body weight gains of the 200 and 400 administered with cholesterol (30 g/kg) to mg/kg males and females were significantly male golden Syrian hamsters at a dose of 150 less than those of the controls. Clinical find- g/kg of diet, developed lipid-rich lesions in ings included irritation of the skin at the site the ascending aorta and aortic arch after 4 of application in the 100, 200, and 400 mg/ weeks. The lesions continued to progress kg males and females. Cholesterol concen- throughout the next 8 weeks. Removal of trations were significantly decreased in 200 cholesterol from the diet halted this progres- and 400 mg/kg males. Histopathological sion. Oil, administered without supplemen- lesions of the skin at the site of application tal cholesterol in the same dose for 16 included epidermal hyperplasia, sebaceous weeks, doubled the size of lesions in the as- gland hyperplasia, chronic active inflamma- cending aorta and decreased linearly the le- tion, parakeratosis, and ulcer. The inci- sion size in the aortic archCN183. dences and severities of skin lesions Blood pressure effect. Fruit juice, admin- generally increased with increasing dose in istered intravenously by infusion to dogs at males and females. The incidences of renal a dose of 3 mL/minute for 100 minutes, was tube regeneration in the 100, 200, and 400 active. Initial effect was a decrease in blood mg/kg females were significantly greater pressureCN036. Oil, administered to male than the vehicle control incidence, and the weanling rats at a dose of 10% of diet for 5 severities in the 200 and 400 mg/kg females weeks, produced significantly higher blood were increased. Coconut oil acid diethanol- pressure than other groups. Systolic blood amine condensate in ethanol was adminis- pressure was found related to the dietary tered externally to 10 male and 10 female intakes of saturated and unsaturated fatty B6C3F1 mice at doses of the 50, 100, 200, acids. Prenatal exposure of the rats to a mat- 400, or 800 mg /kg body weight five times ernal low-protein diet abolished the hyper- per week for 14 weeks. All mice survived tensive effect of the coconut oil dietCN206. until the end of the study. Final mean body Butyryl cholinesterase activity. Oil was weights and body weight gains of dosed administered to rats at different doses with males and females were similar to those of or without clofibrate for 15 days. The the vehicle controls. The only treatment- hypolipidemic action of clofibrate was not related clinical finding was irritation of the COCOS NUCIFERA 127 skin at the site of application in males and mice at doses of 100 or 200 mg/kg body females administered the 800 mg/kg dose. weight five times a week for 104 to 105 Weights of the liver and kidney of 800 mg/ weeks. Survival of the mice was generally kg males and females, the liver of the 400 similar to that of the controls. Mean body mg/kg females, and the lung of the 800 mg/ weights of 100-mg/kg females from week 93 kg females were significantly increased and 200-mg/kg females from week 77 were compared to the controls. Epididymal sper- less than in the controls. The only clinical matozoal concentration was significantly finding attributed to treatment was irrita- increased in the 800-mg/kg males. Histo- tion of the skin at the site of application in pathological lesions of the skin at the site of males administered 200 mg/kg. The inci- application included epidermal hyperplasia, dences of hepatic neoplasms (hepatocellular sebaceous gland hyperplasia, chronic active adenoma, hepatocellular carcinoma, and inflammation, parakeratosis, and ulcer. The hepatoblastoma) were significantly in- incidences and severities of these skin le- creased in both sexes. Most of the inci- sions generally increased with increasing dences exceeded the historical control dose in males and females. Coconut oil acid ranges. The incidences of eosinophilic foci diethanolamine condensate in ethanol was in dosed groups of male mice were increased administered externally to 50 male and 50 relative to that in controls. The incidences female F344/N rats at doses of 50 or 100 mg/kg of renal tubule adenoma and renal tubule body weight five times a week for 104 weeks. adenoma or carcinoma (combined) were The survival rates of treated male and fe- significantly increased in the 200-mg/kg male rats were similar to those of the vehicle males. Several nonneoplastic lesions of the controls. The mean body weights of dosed skin at the site of application were consid- males and females were similar to those of ered treatment related. Incidence of epider- the vehicle controls throughout most of the mal hyperplasia, sebaceous gland study. The only chemical-related clinical hyperplasia, and hyperkeratosis were greater finding was irritation of the skin at the site in all dosed groups than in the controls. The of application in the 100-mg/kg females. incidence of ulcer in 200-mg/kg males and There were marginal increases in the inci- inflammation and parakeratosis in 200-mg/ dences of renal tubule adenoma or carci- kg females were greater than in the controls. noma (combined) in the 50-mg/kg females. The incidence of thyroid gland follicular The severity of nephropathy increased with cell hyperplasia in all of the dosed groups increasing dose in the female rats. Nonneo- was significantly greater than those in the plastic lesions of the skin at the site of ap- control groupsCN148. plication included epidermal hyperplasia, Cardiovascular effect. Coconut and coco- sebaceous gland hyperplasia, parakeratosis, nut oil, administered to 32 coronary heart and hyperkeratosis, and the incidences and disease patients in 16 age- and sex-matched severities of these lesions increased with in- healthy controls with no difference in the creasing dose. The incidence of chronic ac- fat, saturated fat, and cholesterol consump- tive inflammation, epithelial hyperplasia, tion, produced no effectCN086. Hydrogenated and epithelial ulcer of the forestomach in- oil, administered to young male Wistar rats, creased with dose in female rats and the in- at a dose of 10% of diet for 10 weeks, pro- creases were significant in the 100-mg/kg duced an increase in the risk of ventricular group. Coconut oil acid diethanolamine arrhythmias under conditions of both condensate in ethanol was administered ex- ischemia and reperfusion. The incidence of ternally to 50 male and 50 female B6C3F1 ventricular fibrillation was 67% in the oil- 128 MEDICINAL PLANTS OF THE WORLD fed group. The time until the first occur- decrease in 5'-nucleotidase, phosphodi- rence of extrasystole, the incidence of ven- esterase I and p-nitrophenylphosphatase tricular tachycardia, and the incidence of activity of cardiac sarcolemma. Sarcolemma reperfusion-induced ventricular fibrillation from coconut-fed rats contained a signifi- were influenced in a similar manner cantly lower concentration of total polyun- between groups. The fatty acid composition saturated fatty acids (PUFAs) and a higher of myocardial tissue, the ratio of n-3 to n-6 concentration of total monounsaturated fatty acids, and the double-bond index fatty acids than that from safflower-fed rats. were significantly affected by the various The fatty acid composition of the phos- dietsCN092. Oil was administered by gastric phatidylcholine exhibited the largest alter- intubation to male Sprague–Dawley rats at ations because of coconut oil feeding. No a dose of 86:14 w/w coconut oil/safflower oil dietary effect was observed in the sarco- for 10 days, containing either 0.8 mg Zn/kg lemma content of cholesterol and phos- or 111 mg Zn/kg. Zinc-deficient rats that pholipidsCN122. were fed coconut oil had higher concentra- Cholestatic liver disease. Medium-chain tions of triglycerides and total fatty acids in fat from the oil, administered to bile duct- the heart than the control rats. The con- ligated rats, resulted in a decrease of con- centrations of phospholipids and total sumption of the fat source compared to cholesterol were not different between zinc- control rats; however, carbohydrate and deficient and control rats. Concentrations protein intakes were not affected. Body of lauric acid, myristic acid, palmitic acid, weight gain was significantly greater in palmitoleic acid, and oleic acid were 65 to coconut-fed rats than in rats fed long-chain 192% higher in the hearts of zinc-deficient fat (Crisco vegetable shortening). Mortal- rats fed coconut diet than in the control ity was 44% in bile duct-ligated animals fed rats. The level of arachidonic acid in phos- the long-chain fat and 0% in those fed pholipids, which may represent desaturation medium-chain fatCN118. activity, was not different in the zinc-defi- Cholesterol metabolism. Hydrogenated cient rats and control ratsCN093. Oil was oil, administered orally to hamsters at a dose administered orally to rats fed a copper- of 20% of diet for 4 weeks, induced hyperc- deficient diet at doses of 10 g/100 g coconut holesterolemia. Oil feeding had no effect on oil or 10 g/100 g coconut oil with 1 g/100 g cholesterol synthesis but markedly inhibited cholesterol. Rats fed the diet with coconut cholesterol esterification in both the liver and cholesterol had left ventricular cham- and the intestine. The diet-induced hyper- ber volumes that were twofold larger than cholesterolemia was strongly correlated those of rats fed diet with coconut oil only. with an increase in acyl-CoA/cholesterol Copper deficiency reduced left ventricular acyltransferase activity. The hypercholes- chamber volume only in rats fed coconut oil terolemia increased aortic uptake of cho- and cholesterol. The results indicated that lesterol and hence acyl-CoA/cholesterol preload and contractility in the hearts of acyltransferase activityCN109. Coconut fat, coconut oil-fed rats were greater than car- administered orally to rabbits with partial diac response to cholesterol addition to the ileal bypass, produced a significant increase coconut oil diet. Hearts in copper-deficient of serum total cholesterol and phospholip- rats fed coconut oil and cholesterol exhib- ids concentrations. The effect on serum lip- ited eccentric hypertrophy and ventricular ids of the type of fat was similar in control dysfunctionCN099. Oil, administered orally to and partial ileal bypass rabbitsCN120. Coco- rats for 4 weeks, produced a significant nut—a main source of energy for two COCOS NUCIFERA 129

Polynesian groups, Tokelauans and Puka- in PLTP0/HL0 mice compared to PLTP0 pukans—was investigated. Tokelauans mice. Turnover studies indicated that coco- obtained a much higher percentage of nut oil was associated with delayed catabo- energy from coconut than the Pukapu- lism of phospholipids and phospholipids/ kans, 63% compared with 34%, so their free cholesterol-rich particles. Incubation of intake of saturated fat is higher. The serum these particles with hepatocytes of coconut- cholesterol levels are 35–40 mg higher in fed mice produced a reduced removal of Tokelauans than in Pukapukans. Analysis of phospholipids and free cholesterol by scav- a variety of food samples and human fat enger receptor BI , even though scavenger biopsies showed a high lauric (12:0) and receptor BI protein expression levels were myristic (14:0) acids content. Vascular dis- unchangedCN158. ease is uncommon in both populations, and Coagglutination activity. Oil was admin- there is no evidence of the high saturated istered to females at doses of a high-satu- fat intake having a harmful effect in these rated fatty acids diet (HSAFA diet; 38.4% populationsCN129. Oil, administered orally to of energy from fat, polyunsaturated/satu- growing male Sprague–Dawley rats fed a rated [P/S] fatty acid ratio 0.14) or low- satu- diet containing unoxidized or oxidized cho- rated fatty acids diet (LSAFA; 19.7% of lesterol (5 g/kg) with coconut or salmon oil energy from fat, P/S ratio 0.17). The post- (100 g/kg) for 5 weeks, produced an effect prandial plasma concentration of tissue independent of the dietary fatCN132. Hydro- plasminogen activator (t-PA) antigen was genated coconut oil was administered to decreased in the HSAFA-fed group. Plasma F(1)B Golden Syrian hamsters at a dose of t-PA antigen was correlated with plas- 20 g/100 g for 10 weeks. The hamsters were minogen activator inhibitor type 1 (PAI-1) ranked according to their plasma VLDL and activity when the participants consumed LDL cholesterol as a low or medium group. the HSAFA and LSAFA diet, although the Low-coconut oil group had significantly diets did not affect the PAI-1 levels. There higher aortic total and esterified cholesterol were no significant differences in postpran- concentrations than the low-cholesterol-fed dial variations in t-PA activity, factor VII group. Hamsters in the low-cholesterol- coagulant activity, or fibrinogen levels as a fed group had significantly higher aortic result of the diets. Serum-fasting Lp(a) lev- TNF-D concentrations than hamsters in the els were lower in the HSAFA group and low-coconut oil group. Hamsters in the were lower in the LSAFA group. Serum med-coconut oil group had significantly Lp(a) concentrations did not differ when higher aortic IL-1-E concentrations than the women consumed the HSAFA and hamsters in the med-cholesterol group. LSAFA dietsCN139. Hamsters in both cholesterol fed groups had Cytotoxic activity. Oil, in cell culture at a significantly lower plasma total cholesterol concentration of 300 Pg/mL, was active on concentrations than hamsters in the low- Ca-colon-HT29CN034. Coir fiber, adminis- coconut oil groupCN136. tered intratracheally to guinea pigs, resolved Cholesterolemic effect. Oil, administered the granulomas. Coir fiber and ash, in cell to phospholipids transfer protein knockout culture, produced a hemolytic activity and (PLTP0)-deficient mice, produced an macrophage cytotoxicity more marked with increase of phospholipids and free choles- ash compared with the fiber aloneCN126. terol in the VLDL-LDL region of PLTP0 Extract of the husk fiber, in cell culture at a mice. Accumulation of phospholipids and concentration of 10 Pg/mL, inhibited the free cholesterol was dramatically increased growth of promastigote and amastigote 130 MEDICINAL PLANTS OF THE WORLD developmental stages of Leishmania amazon- extract of the leaf, administered intraperi- ensis after 60 minutesCN064. Extract of the toneally to saline-loaded male rats at a dose fiber husk (rich in catechins), in erythroleu- of 0.185 mg/kg, was active. Urine was col- kemia cell line (K562) and normal human lected for 4 hours after treatmentCN058. peripheral blood lymphocytes activated by Epstein–Barr virus activation. Seed oil, in phytohemagglutinin or phorbol ester, pro- cell culture at a concentration of 50 Pg/mL, duced a dose-dependent effect. For phyto- was inactive on virus-transformed lympho- hemagglutinin, this effect was irreversible, blastsCN048. being already established on the first hours Erythrocytic effect. Hydrogenated coco- of cultureCN066. Oil, administered to C57B16 nut oil, administered orally to healthy rats mice at a dose of 21% fat by weight, pro- for 10 weeks, produced a significant effect duced a significant decrease in macrophage- on five of the six classes of erythrocytes mediated death of P815 cells by nitric oxide identified. The proportion of cells in each and did not alter the death of L929 cell by class was dependent on the diet. There was macrophages. Liposaccharide-stimulated no significant effect of diet on erythrocyte TNF-D production by macrophages decreased filterability index and no statistical correla- with increasing unsaturated fatty acid content tion between erythrocyte filterability index of the diet: fish oil < safflower oil < olive oil and morphologyCN088. < coconut oil < low-fat dietCN185. Estrogenic effect. Seed oil, administered to Denture stomatitis. Coconut soap, associ- female mice at a dose of 10% of diet, was ated with 05% sodium hypochlorite, used by activeCN007. patients for 15 days, significantly reduced Exocrine pancreatic secretion. Oil, clinical signs of denture stomatitis and was administered to piglets at a dose of 10 g/100 g effective in controlling denture biofilmCN131. of diet, did not affect the output of car- Desensitization effect. Saline extract of boxylester hydrolase. Protein, chymot- the dried pollen, administered subcutane- rypsin, carboxypeptidase A, elastase, and ously to 96 allergic adults at variable doses, amylase outputs were not different among produced a clinical improvement and the dietary treatment groups. The outputs decreased IgE levelsCN020. of trypsin and colipase were higher in the Dietary macronutrient distribution influ- coconut-fed groupCN167. Oil, administered to ence. Oil, administered to diet-induced three barrows at a dose of 15 g fat/100 g diet, overweight rats fed an energy-restricted diet produced a significant increase of chymot- with 60% of coconut oil, produced no dif- rypsin secretionCN207. ference between control and fat-fed group Fat digestibility. Fat, administered to male in weight loss and serum parameters. The rats at a dose of 8% of diet for 2 weeks, pro- coconut-fed group produced a greater reduc- duced no differential effect on growth. Glu- tion in the subcutaneous fat depot and of cose significantly depressed apparent lipid total body fat. Hepatic glycogen and glyco- digestibility in coconut fat-fed ratsCN176. genic amino acid were altered in coconut- Fatty acid composition influence. Oil was fed ratsCN163. administered orally to mice bearing the Diuretic activity. Decoction of the dried L1210 murine leukemia cells at a dose of fruit, administered nasogastrically to rats at 16% of diet. A microsome-rich fraction pre- a dose 1 g/kg, was activeCN053. Fruit juice, pared from the L1210 cells produced more administered intravenously by infusion to monoenoic fatty acids (37% vs 12%) com- dogs at a dose of 3 mL/minute for 100 min- pared to mice fed the sunflower oilCN124. Oil, utes, produced weak activityCN036. Ethanol administered to chicken at concentrations COCOS NUCIFERA 131 of 10 and 20% of diet, produced changes in in liver slices of coconut oil-fed than beef- fatty acid composition of free fatty acid and tallow-fed calves. Fatty acid esterification as triglyceride fractions of chick plasma paral- neutral lipids was 2.6- to 3.1-fold higher in lel to that of the experimental diet. Plasma liver slices of coconut oil-fed group. The phospholipids incorporated low levels of increase in neutral lipid production did not 12:0 and 14:0 acids, whereas 18:0, the main stimulate VLDL secretion by the hepato- saturated fatty acid of this fraction, cytes, leading to a triacylglycerol accumula- increased after coconut oil feeding. The per- tion in the cytosol of the calves fed coconut centage of 18:2 acid significantly increased oilCN178. Oil, administered to preruminant after coconut oil feedingCN154. Oil, adminis- calves fed a milk replacer containing coco- tered to rats at a dose of 15% of diet for 4 nut oil for 19 days, produced no significant weeks, produced an increase of total choles- difference in weight of the total body and terol in the liver and the decrease of total tissue between the treated groups. Plasma liver phospholipidsCN157. Coconut/soy oil, glucose and insulin concentrations were administered by infusion into the duode- lower in the coconut oil-fed group. Feeding num of rats, produced the proportion of on the coconut oil diet induced an 18-fold capric and lauric acids in the lymphatic increase in the hepatic concentration of triacylglycerol, reflecting the fatty acid com- triacylglycerol. The perixomal oxidation position in the diet. Results indicated that rate of oleate was 1.5-fold higher in the more than 50% of the capric and lauric acids hearts of calves fed coconut oil. The cyto- could have been absorbed from the intestine chrome C oxidase/citrate synthase activity as sn-monoacylglycerolsCN213. Hydrogenated ratio was lower in the liver of the coconut coconut oil was administered to rats at a oil-fed animalsCN184. Oil, administered as a dose of 7% of the diet (essential fatty acids ratio 7:1 w/w coconut oil/safflower oil by deficient in both n-6 and n-3) for 28 weeks gastric intubation to zinc-deficient rats, (1 week gestation, 3 weeks lactation, and 24 reduced G-desaturase activity in liver weeks thereafter). The fatty acid composi- microsomes of rats fed coconut oil. Zinc- tional changes indicative of an essential deficient rats on the coconut oil diet had fatty acid deficiency, such as the decreases unchanged G-6-desaturase activity with in the levels of 18:2 n-6 along with an accu- linoleic acid as substrate and lowered activ- mulation of 20:3 n-9 were observed in all the ity with D-linolenic acid as substrateCN197. salivary glands. In the submandibular Food intake suppression. Oil, adminis- glands, the proportions of 16:1, 18:1 n-9 and tered intragastrically to devazepide-treated 18:1 n-7 were higher in hydrogenated coco- rats at a dose of 1 g/4 mL 30 minutes before nut oil-fed group than in the other groups. feeding, produced a decrease of devazepide Some differences in the fatty acid composi- effectCN144. tion of the three glands were foundCN085. Gastrin inhibition. Hydrogenated oil, Fatty acid metabolism. Oil was adminis- administered to adult rats, produced a sig- tered to preruminant Holstein Friesian male nificant reduction in antral and plasma calves fed a conventional milk diet contain- gastrin concentrationsCN171. ing coconut oil for 19 days. Fatty acid oxi- Gastrointestinal effect. Oil, administered dation was determined by measuring the to rats, induced the secretion of surfactant- CN160 production of CO2 (total oxidation) and like particles in the small intestine . acid-soluble products (partial oxidation). Genotoxic activity. Coconut oil acid

Production of CO2 was 1.7–3.6-fold lower diethanolamine condensate with or without and acid soluble products tend to be lower S9 activation enzyme, in cell culture, pro- 132 MEDICINAL PLANTS OF THE WORLD duced no effect on Salmonella typhimurium. Glucose metabolism. Hydrogenated oil, The treatment did not produce an increase administered to prediabetic weanling BHE in mutant L5178Y mouse lymphoma cell rats fed a 6% fat and 64% sucrose diet, pro- colonies, and no increased in the frequen- duced an increase of the fractional irrevers- cies of sister chromatid exchanges or chro- ible glucose turnover rates, fractional mosomal aberrations in Chinese hamster glucose carbon recycling, hepatic fatty acid ovary cells. In a peripheral blood micro- synthesis rates, adipose fatty acid synthesis nucleus test in male and female mice from rate, lower muscle glycogen, and lower rates the 14-week test, positive results were of incorporation of glucose into muscle gly- obtainedCN148. cogen than corn oil-fed rats. The diet had Genotype and diet effect. Coconut oil was no effect on glucose mass and space, hepatic administered to female Zucker rats through- glycogen, or blood glucose levelsCN113. Oil, out mating and lactation. Homozygous lean administered to male Wistar rats at a dose male and female rats, obese male, and lean of 25% by weight for 26 days, produced a heterozygous female rats were bred. Addi- significant increase in serum total choles- tional male rats were maintained on the terol, LDLs, liver cholesterol, and liver same diet as their mothers until 11–12 days weight. There was a decrease in serum of age. Obese sucking rats had higher body HDLs, triacylglycerol levels, and abdominal weights than lean pups. Inguinal fat pad fat weight; an increase in 3-hydroxy-3- weights and pad-to-body weight ratios fol- methylglutaryl-CoA reductase activity in lowed the pattern of obese greater than lean the liver; reduction in plasma lecithin-cho- (FA/fa genes) pups that were greater than lesterol acyltransferase activity; lower level lean (FA/FA) pups. A similar relation- of serum insulin; and liver glycogen in the ship was found for adipose tissue lipogenic coconut oil-fed rats. Glucose use was altered enzyme activities. At 11–12 weeks of age, because lower glucose-6-phosphatase and measurements followed the general pattern increased glucokinase activities in the liver of obese rats having greater value than lean of coconut oil-fed rats were foundCN190. rats (i.e., FA/fa = FA/FA). Coconut oil-fed Coconut palm wine was administered to rats fa/fa rats had lower hepatic lipogenic at a dose of 24.5 mL/kg body weight/d for enzyme activities and lower fat cell numbers 15 days before conception and throughout than safflower-fed fa/fa rats. High-fat diet gestation. On the 19th day of gestation, did not result in a heterozygous effect in hypoglycemia was observed in both wine- young adult lean male ratsCN079. Hydroge- and ethanol-treated groups. Synthesis of nated coconut oil, corn oil, or menhaden oil glycogen was elevated on exposure to etha- were administered to diabetes-prone BHE/ nol/wine, but its degradation was enhanced cdb and normal Sprague–Dawley rats. Both only in ethanol-exposed rats. Key enzymes fat source and strain affected the tempera- of the citric acid cycle and gluconeogenesis ture dependence of succinate-supported res- were inhibited on administration in both piration. The transition temperature was groups. The activities of glycolytic enzymes greater in BHE/cdb rats than in the were increasedCN204. Hydrogenated oil (6%), Sprague–Dawley rats. The efficiency of administered to BHE rats at a dose of 5% of adenosine triphosphatase synthesis as diet, produced no influence on glucose. reflected by the adenosine diphosphatase / Hepatocytes isolated from rats fed coconut O ratio was decreased in the BHE/cdb rats oil had a significantly lower affinity for in- compared to Sprague–Dawley ratsCN084. sulin than menhaden oil-treated ratsCN104. COCOS NUCIFERA 133

Glucose-6-phosphate dehydrogenase of 10% of diet for 9 weeks, produced no sig- activity. Oil, administered to rats, reduced nificant alteration of hepatic 5-, 6-, and 9- the G-6-PDH activity of lymphocytes by desaturase activity. Addition of oil to the 16% and the activity of G-6-PDH in liver diet, simultaneously with lowering of the by 42%CN192. carbohydrate level, diminished the stimula- Glycemic index. The glycemic index of tory effect of dietary sucrose vs glucose on different commonly consumed products 9-desaturase activityCN121. supplemented with increasing levels of Hepatic lipid peroxidation. Oil, adminis- coconut flour was determined in 10 normal tered to apo E-deficient mice for 10 weeks, and 10 diabetic subjects. The test food with produced a significant increase in hepatic 200–250 g coconut flour/kg had signifi- lipid peroxidationCN172. cantly low, gastrointestinal (GI) (< 60); Hepatic mitochondrial effect. Oil, admin- with 150 g coconut flour/kg had GI ranging istered to chicken at a dose of 20% of the from 61.3 to 71.4. A very strong negative diet, produced a clear damage to the hepatic correlation (r –0.85, p < 0.005) was ob- mitochondria accompanied by an accumu- served between the GI and dietary fiber con- lation of glycogen and lipid droplets in the tent of foodCN067. Oil, administered to lean hepatocyte cytoplasm. Pharmaceutical Zucker rats at a dose of 5% of diet (87% coconut oil induced a high percentage of saturated fatty acids) for 2 weeks, produced cellular death when administered for 14 no differences in food intake, body weight, days. Fatty acid profiles in liver and hepatic tissue level of glucagons-like peptide-1, mitochondria changed during 24 hours after plasma insulin, and glucagons levels in co- pharmaceutical and cooking oils supple- conut oil- and olive oil-fed groupsCN174. mentation to the diet. The accumulation of Hair damage prevention. Coconut oil shorter chain fatty acids (12:0) and (14:0) application has a strong effect on hair as was higher after pharmaceutical than after compared to sunflower and mineral oils. cooking oil diet feeding. Mitochondrial Among the three oils investigated, coconut ratios of saturated/unsaturated and satu- oil was the only one that reduced the pro- rated fatty acids (SUFAs)/PUFAs rapidly tein loss remarkably for both damaged and changed in parallel to these ratios in both undamaged hair when used as a prewash and diets. Most of the mitochondrial parameters postwash grooming productCN146. measured recuperate to the control values Hemostatic effect. Coconut water, in when diets were supplied for 5–14 days. The citrated plasma of eight healthy volunteers, maintenance of these ratios after 14 days was observed. Replacement of up to 50% of pharmacological oil diet feeding was signifi- diluted plasma by water did not influence cantly higher than those in controlCN199. initiation of coagulation. Replacing 50% of Hydrogen peroxide release inhibition. citrated plasma by coconut water reduced Seed oil, administered to rats at a concen- maximum amplitude of thrombelastography tration of 8% of the diet, produced equivo- recording dose by 39%CN072. cal effect on macrophages. Capsaicin or Hemotoxic activity. Fruit juice, adminis- curcumin enhanced the effectCN021. tered by intravenous infusion to dogs at a Hyperalphalipoproteinemic activity. Oil, dose of 5 mL/minute for 60 minutes, was administered orally to rabbits fed commer- activeCN036. cial chow or chow plus 14% w/w coconut Hepatic activity. Hydrogenated oil, admin- oil, resulted in double increase the plasma istered orally to male weanling rats at a dose levels of HDL cholesterol, phospholipids, 134 MEDICINAL PLANTS OF THE WORLD and protein for up to 4 months without 0.17) for 3-week periods, produced no dif- affecting HDL lipid and apoprotein compo- ference in serum total cholesterol, LDL cho- sition. After 3 months also increased VLDL lesterol, and apo B concentrations between (107%) and LDL cholesterol (40%) levels, the diet periods. HDL cholesterol and apo but the absolute increases in each of these A-I were 15% and 11%, respectively, higher lipoprotein fractions was less than half of during HSAFA diet period than during that of HDL. Isotope kinetic studies of LSAFA diet period. The LDL/HDL-C and 125I-HDL protein indicated a double rate apo B/apo A-I ratios were higher during of production of HDL and no change in LSAFA diet periodCN152. the efficiency of removal of HDL from Hyperlipidemic activity. Palm wine was plasmaCN115. administered orally to female albino rats at Hypercholesterolemic activity. Seed oil, a dose of 24.5 mL/kg body weight/day for 15 administered by gastric intubation to dogs, days before conception and during preg- was active. Seed oil, administered orally to nancy. On days 13 and 19 of gestation, liver adults, was activeCN037. Oil, administered function and hyperlipidemia were seen in orally to rats at a dose of 79 g/day for 3 the fetuses. Hyperlipidemia was caused by weeks, produced a significant increase of the increased biosynthesis since the incorpora- final plasma cholesterol in groups that con- tion of 14C acetate into lipids and activity sumed yeast with coconut oil (91 mg/dL), of HMG-CoA reductase and lipogenic in comparison to group consuming soybean enzymes were elevatedCN080. Oil, adminis- protein with coconut oil (36 mg/dL)CN089. tered to miniature pigs fed a pig chow Coconut fat, administered to hyporespon- supplemented with 17.1% of coconut oil for sive and hyperresponsive inbred strains of 30 d, produced a significant increase of rabbits with high or low response of plasma cholesterol, triglyceride, HDL cholesterol cholesterol to dietary SUFAs vs PUFAs, and subfractions, LDL cholesterol and produced no influence on the efficiency of subfractions, and lipoprotein lipase activity cholesterol absorptionCN106. Fat, adminis- in both genders. For cholesterol, triglycer- tered orally to young normolipidemic males ide, HDL cholesterol (HDL-C and HDL[2]- at a dose of 30% of the diet with a polyun- C), LDL cholesterol (LDL-C, LDL[1 and saturated/saturated fat ratio of 4 or 0.25 for 2]-C), and hepatic lipase, the female 8 weeks, produced a significant increase of response to the diet was exaggerated com- total plasma cholesterol levelCN111. Oil, pared to the male responseCN153. administered to Mongolian gerbils, pro- Hyperthermic effect. Coconut oil, admin- duced a hypercholesterolemia associated istered orally to rats with human recombi- with elevations in VLDL, LDL, and HDL. nant TNF-D at a dose of 190 g/kg for 12 The type of dietary fat did not influence weeks, produced an antihypothermic effect lipoprotein composition and sizeCN130. Fresh and changes in serum albumin and Cu con- and thermally oxidized oil, administered to tent 8 hours after treatment and in muscle rats at a dose of 20% of diet, produced an and liver protein after 24 hours. The results increase of total cholesterol, LDL and indicated that changes in ecosanoid VLDL cholesterol, and triacylglycerol and metabolism may be involved in the modu- phospholipids levels and a decrease in HDL latory effect of the coconut oil-enriched cholesterolCN149. Oil, administered to 25 dietCN110. women at doses of 38.4% of energy from fat Hypertriglyceridemic activity. Coconut (HSAFA; PUFA/SUFA P/S ratio = 0.14) or oil, administered orally to rats at a dose of 19.7% energy from fat (LSAFA; P/S ratio 14%:0.5% oil/cholesterol diet, produced an COCOS NUCIFERA 135 increase of lipids and apo B in the VLDL air-dried plant material), produced weak and intermediate-density lipoprotein frac- activityCN043. The neutral detergent fiber tions. The particle diameters of lipoproteins from kernel, administered orally to rats at were similar in coconut oil- and olive oil- doses of 5%, 15%, and 30% of diet, resulted fed groups. The rates of triglyceride hydroly- in significant decrease in the level of blood sis of both groups’ VLDL by postheparin glucose and serum insulin, with increasing lipoprotein lipase in vitro were the same. in the intake of fiber. The increase of fecal The average fractional removal of apo B did excretion of Cu, Cr, Mn, Mg, Zn, and Ca not differ between diet groupsCN105. Oil, was presentCN075. Neutral detergent fiber administered to rabbits at a dose of 14%: from coconut kernel, administered to rats at 0.5% coconut oil/cholesterol of diet, pro- doses of 5, 15, and 30% of diet, produced an duced an increase of plasma triglycerides 15 increase of fecal excretion of Cu, Cr, Mn, times higher than basal level. Postprandial Mg, Zn, and CaCN180. triglyceride responses after the first high-fat/ Hypolipidemic activity. Protein, adminis- cholesterol meal were more prolonged in tered orally to hypercholesterolemic rats, coconut-fed rabbits than in olive-fed group. reduced total, LDL, and VLDL cholesterol; Postprandial triglyceride responses after triglycerides; and phospholipids levels in the chronic coconut oil/cholesterol feeding serum and increased the level of serum HDL were significantly greater compared to the cholesterol. The concentration of total cho- olive oil-fed group. One coconut oil/choles- lesterol, triglycerides, and phospholipids in terol meal was associated with a 40% the tissues was lower than in the control increase of postheparin plasma lipoprotein group. There was increased activity of lipase activity and changed little in chroni- superoxide desmutase and catalase. An cally fed coconut oil/cholesterol groupCN112. increase of hepatic cholesterogenesis, con- Hypocholesterolemic activity. Kernel version of cholesterol to bile acids and fecal protein, administered orally to rats on a excretion of bile acids, and excretion of coconut oil diet, lowered the levels of cho- urinary nitrate and an decrease of malonal- lesterol, phospholipids, and triglycerides in dehyde level in the heart were observedCN071. the serum and most tissues when com- The neutral detergent fiber of kernel pared to casein-fed animals. The increase of digested with cellulase and hemicellulase hepatic degradation of cholesterol to bile was administered orally to rats. Hemicellu- acids and hepatic cholesterol biosynthesis lose-rich fiber showed decreased concentra- and the decrease of esterification of free tion of total cholesterol and LDL and VLDL cholesterol were noted. In the intestine, cholesterol and increased HDL cholesterol. cholesterogenesis was decreased. The kernel Cellulose-rich fiber showed no significant proteins also decreased lipogenesis in the alteration. There was increased HMG-CoA liver and intestineCN077. reductase activity and increased incorpora- Hypoglycemic activity. Ethanol extract of tion of labeled acetate into free cholesterol. the leaf, administered orally to rats at a dose Rats fed hemicellulose-rich fiber produced of 250 mg/kg, produced less than a 30% drop lower concentration of triglycerides and in blood sugar levelCN058. Fruit juice, admin- phospholipids and a lower release of lipopro- istered intravenously by infusion to dogs at teins into circulation. There were an a dose of 3 mL/min for 100 min, was increased concentration of hepatic bile activeCN036. Hot water extract of the dried acids and increased excretion of fecal sterols shell, administered by gastric intubation to and bile acidsCN081. dogs at a dose of 200 mL/animal (20 g of 136 MEDICINAL PLANTS OF THE WORLD

Hypotensive activity. Fruit juice, adminis- in rats fed the low-fat diet, but it counter- tered by intravenous infusion to dogs at a acted the rise in liver cholesterol seen in rats dose of 10 mL/minute for 30 minutes, was fed the high-fat diet. The high-fat diet activeCN036. Water extract of the fresh leaf produced slightly higher levels of butyryl and stem, administered intravenously to cholinesterase in the small intestine but dogs at a dose of 0.1 mL/kg, was activeCN002. markedly raised intestinal esterase-1 acti- Hypothermic activity. Ethanol (50%) vityCN101. extract of the leaf, administered intraperi- Intestinal neoplasia. Oil was adminis- toneally to mice at a dose of 0.375 mg/kg, tered to 8-week-old male Fischer rats divi- was inactiveCN058. ded into two groups of 60 each (sedentary Ileal oleic acid uptake. Hydrogenated oil, and exposed to moderate exercise), at a dose administered to rats at a dose of 5 g/100 g of of 21% of diet for 38 weeks. The exercising diet, produced saturable kinetics in ileal and sedentary rats fed coconut oil were sig- brush border membrane vesicles: Vmax = 0.23 nificantly heavier than rats fed corn oil. In 03 mol/mg protein/5 minutes and K = r P m the rats fed coconut oil diet, nine carcino- 196 50.3 nmol for controls, and V = 04 r max r mas were recorded in the sedentary groups 01 mol/mg protein/5 minutes and K = 206 P m and five in the exercised rats, which devel- CN198 r 85.3 nmol for coconut oil-fed group . oped significantly fewer neoplasms than Coconut oil, adminis- Immune function. corn oil-fed groupCN173. tered to rats fed a fat-rich diet (corn oil) or a Intestinal transport. Coconut water in diet poor in linoleate (coconut oil) at high different stages of maturation, administered and low concentrations, completely abol- to rats, produced a jejunal water absorption ished the responses to Escherichia coli (17 r 0.45 PL/minutes/cm), sodium excre- endotoxinCN119. tion (–1694 r 296 PEq/minutes/cm), and Insulin secretion stimulation. Oil, admin- istered orally to young suckling rabbits, glucose absorption (5212.70 r 2098.47 Pg%/ CN137 quickened and strengthened the rise of minutes/cm) in all the stages studied . immunoreactive serum insulinCN123. Intravenous hydration. The use of coco- Intestinal brush border membrane. Oil, nut water as a short-term intravenous administered orally to rats at a dose of 10% hydration fluid for Solomon Island residents CN076 for 5 weeks, produced an increase in level of was investigated . Fresh young coconut saturated fatty acids in the brush border water, administered to eight healthy male membrane from coconut oil-fed animals. volunteers in three doses in separate trials Membrane fluidity was as follows: coconut representing 50, 40, and 30% of the 120% oil less than commercial pellet diet less than fluid loss at 30 and 60 minutes of the 2-hour corn oil less than fish oil. The membrane rehydration period. The percent of body hexose content was high in the coconut-fed weight loss than was regained (used as index rats. Hexamines were elevated in coconut- of percent rehydration) was 75 r 5%. The treated rat brush borders. The activities of rehydration index, which provided an indi- alkaline phosphatase, sucrase, and lactase cation of how much of what was actually were increasedCN209. ingested and used for body weight restora- Intestinal esterase activity. Oil was ad- tion, was 1.56 r 0.14. There was no differ- ministered to rats at different doses with or ence at any time in serum Na+ and Cl–, without clofibrate for 15 days. The hypo- serum osmolality, and net fluid balance lipidemic action of clofibrate was not influ- among the trials. Coconut water was signifi- enced by the amount of fat. Clofibrate did cantly sweeter, caused less nausea and more not affect lower cholesterol concentration fullness and no stomach upset, and was COCOS NUCIFERA 137 easier to consume in a larger amount com- lesterol concentrations compared to con- pared to carbohydrate-electrolyte beverage trols. The concentrations of total cholesterol, and plain waterCN161. Water, administered to free and esterified cholesterol, triglycerides, children with diarrhea, was inactive. The and TBARS were increased in the macro- results indicated that coconut water compo- phages of coconut-fed mice, whereas the sition, sodium and glucose concentrations, content of total phospholipids did not and osmolality values vary during matura- change. The phospholipids composition tion of the fruit. In no instance did the showed an increase of phosphatidylcholine coconut water contain sodium and glucose and a decrease of phosphatidylethanol- concentrations of value as an oral rehydra- amine. Incorporation of [3H]-cholesterol tion solutionCN215. into the macrophages and into the choles- Iron bioavailability. Oil, administered to terol ester fraction was increased. The suckling rats dosed with 59Fe-labeled diet, coconut oil diet did not affect [3H]-AA produced a higher percentage of 59Fe in the uptake, induced an increase in [3H]-AA blood than those fed other fat sources. release, and enhanced AA mobilization Administration to weanling rats produced a induced by lipopolysaccharideCN133. Oil, ad- significantly higher percentage of 59Fe reten- ministered to 28 persons with moderately tion than rats fed a formula-blend fat elevated cholesterol level, decreased total dietCN168. cholesterol and LDL cholesterol (6.4 r 0.8 Jejunal oleic acid uptake. Hydrogenated and 4.2 r 0.7 mmol/L), respectively, com- oil, administered to rats at a dose of 5 g/100 pared to butter diet (6.8 r 0.9 and 4.5 r 0.8 g of diet, produced saturable kinetics in mmol/L). Apos A-1 and B were significantly jejunal brush border membrane vesicles: higher on coconut oil and on butter than

Vmax = 0.15 r 01 Pmol/mg protein/5 minutes, on safflower oil. In the group as a whole, and Km= 136 r 29.1 nmol for controls, and HDL did not differ significantly in the three

Vmax = 03 r 01 Pmol/mg protein/5 minutes diets, whereas levels in women fed coconut and Km = 124.5 r 72.6 nmol for the coconut oil were significantly higher than in the saf- oil-fed groupCN198. flower oil group. Triacylglycerol level was Juvenile hormone activity. Acetone ex- lower in coconut oil group, but results were tract of the dried stem produced weak significant statistically only in womenCN212. activity on Dysdercus cingulatusCN012. Lipid peroxide formation stimulation. Lauric acid incorporation. Lauric acid Seed oil, administered to rats at a dose of (50%) from the oil, administered to rats for 15% of diet for 6 weeks, was inactive on rat 6 weeks, produced no significant difference liver microsomes. Malondialdehyde con- between the experimental distribution of centration was unchanged among animals triacylglycerol types and the random distri- given different oils. Vitamin E level bution, calculated from the total fatty acid decreased among those fed soybean oilCN018. compositionCN116. Lipogenetic effect. Kernel protein, admin- Lipid metabolism. Oil, administered orally istered orally to rats on a coconut oil diet, to female C57BL/6 mice weaned at 21 d of decreased lipogenesis in the liver and intes- age at a dose of 15% w/w for 6 weeks, tine. The kernel proteins also lowered the increased the total lipids, triglycerides, LDL levels of cholesterol, phospholipids, and and VLDL cholesterol, and thiobarbituric triglycerides in the serum and most tissues acid-reactive substances (TBARS) and when compared to casein-fed animals. reduced glutathione concentrations, with- There was an increase in hepatic degrada- out changes in phospholipids or total cho- tion of cholesterol to bile acids and hepatic 138 MEDICINAL PLANTS OF THE WORLD cholesterol biosynthesis and a decrease in dose of 24.5 mL/kg body weight/day) for 15 esterification of free cholesterol. In the in- days before conception and during preg- testine, cholesterogenesis was decreasedCN077. nancy. On days 13 and 19 of gestation, liver Lipoprotein composition. Oil, adminis- function and hyperlipidemia were seen in tered to newborn chicken at a dose of 20% the fetuses. Altered liver function was evi- for 2 weeks, increased cholesterol concen- denced by the increased activity of alcohol tration in all the lipoprotein fractions, dehydrogenase, aldehyde dehydrogenase, whereas 10% coconut oil only increased glutamic oxaloacetic transaminase (GOT) cholesterol in LDL and HDL, an increase (aspartate amino transferase), and glutamic that was significant after 1 week of treat- pyruvic transaminase (GPT) (alanine ment. Similar results were obtained for amino transferase)CN080. triacylglycerol concentration after 2 weeks Membrane fluidity and composition. Oil, of treatment. Changes in phospholipids and administered to male weanling Wistar rats total protein levels were less profound. Co- at a dose of 100 g fat/kg diet with 10% of the conut oil decreased LDL and fluidityCN208. fat provided as corn oil, produced a 61.5% Oil, administered with or without 0.5% of lipid that were free to diffuse in the cholesterol to 36 young male Syrian ham- plasma membraneCN203. sters for 6 weeks, produced higher plasma Myocardial infarction. Coconut oil, ad- total triglyceride and total cholesterol in ministered orally to rabbits with myocardial coconut oil without cholesterol supplemen- infarction induced by isoproterenol, pro- tation-fed group than in the fish oil-fed duced a higher level of phospholipids in the group. With cholesterol supplementation, heart and aorta. The concentrations of cho- there was no significant difference in plasma lesterol and triglycerides were lower in the total triglyceride level among the three di- safflower oil fed groupCN108. etary groups. The hepatic cholesteryl ester Nasal absorption. Sucrose ester of coconut content was higher, and there was lower fatty acid in aqueous ethanol solution (su- liver microsomal acyl-CoA/cholesterol crose cocoate SL-40) administered intrana- acyltransferase activity in the cholesterol- sally to anesthetized male Sprague–Dawley supplemented coconut oil group compared rats at a dose of 0.5% sucrose cocoate with to other groups. There was no significant insulin, produced a rapid and significant in- difference in the excretion of fecal neutral crease in plasma insulin level with a con- and acidic sterols among the three dietary comitant decrease in blood glucose levels. groupsCN211. Administration of a dose of 0.5% sucrose Lipoprotein lipase activity. Oil, adminis- cocoate with calcitonin produced a rapid tered to preruminant calves, produced no increase in plasma calcitonin levels and a effect on palmitate oxidation rate by whole concomitant decrease in plasma calcium homogenates and induced higher palmitate levelsCN150. oxidation by intermyofibrillar mitochon- Nephrotoxic activity. Fruit juice, adminis- dria. Carnitine palmitoyltransferase I activ- tered by intravenous infusion to dogs at a ity did not significantly differ between the dose of 3 mL/minute for 100 minutes, pro- groups. Heart and longissimus thoracis duced weak activity. Albuminuria was ob- muscle of calves fed coconut oil had higher served just before the end of infusion lipoprotein lipase activity but produced no administrationCN036. differences in fatty acid-binding protein Neutrophil functions. Oil, administered to content or activity of oxidative enzymesCN181. rats 21 days old at a dose of 15% final fat Liver function effect. Palm wine was ad- content of the diet for 6 weeks, produced a ministered orally to female albino rats at a reduction in spontaneous and phorbol COCOS NUCIFERA 139

myristate acetate-stimulated H2O2 genera- in male group equal to 954 r 367 pmol/kg/ tion in glycogen-elicited peritoneal neutro- 24 hours in the coconut oil fed group com- phils relative to neutrophils from rats fed pared to 403 r 150 pmol/kg/24 hours in the the control diet. The activity of superoxide control. Calculated per whole animal, the desmutase, glutathione peroxidase, and excretion was 328 r 128 pmol/24 hours in catalase did not change in animals fed the the coconut oil-fed rats and 137 r 51 pmol/ CN189 fat-rich diets. The initial rate of O2 genera- 24 hours in the control . tion in both resting neutrophils and phorbol Oxygen radical inhibition. Seed oil, ad- myristate acetate-stimulated cells was sig- ministered to rats at a concentration of 8% nificantly reduced when animals were fed of diet, produced equivocal effect on mac- coconut oilCN188. rophages. Capsaicin or curcumin enhanced Ophthalmic absorption. Sucrose ester of the effectCN021. coconut fatty acid in aqueous ethanol solu- Oxytocinase inhibition. Coconut oil, ad- tion (sucrose cocoate SL-40), administered ministered to mice, produced lower level of ophthalmically to anesthetized Sprague– oxytocinase activity in the testis of mice Dawley male rats at a dose of 0.5% sucrose compared to fish oilCN162. cocoate with insulin, produced an increase Pheromone (sex attractant). Ether extract in plasma insulin level and a decrease in of the stem, produced equivocal effect on blood glucose levelsCN150. Aspiculuris tetraptera, female and male Dacus Ornithine decarboxylase activity. Fixed dorsalis, male Mediterranean fruit flies, and oil (4.5%), Clupeidae brevortia tyrannus male and female melon fliesCN014. (4%), and Zea mays (1.5%); fixed oil Pheromone (signaling). Ether extract of (7.5%), Clupeidae brevortia tyrannus (1%), the stem, produced equivocal effect on and Zea mays (1.5%); fixed oil (8.5%) and Aspiculuris tetraptera, female and male Dacus Zea mays (1.5%), administered orally to dorsalis, male Mediterranean fruit flies, and mice for 1 year, were active vs benzoyl per- male and female melon fliesCN014. oxide-induced ornithine decarboxylase Phospholipidemic effect. Oil, adminis- activityCN035. Oil, administered to 30 ultra- tered to phospholipids transfer protein violet (UV)-irradiated Sencar and SKH-1 knockout (PLTP0)-deficient mice, pro- mice at doses of 1/14% (A diet), 7.9/7.1% duced an increase of phospholipids and free (B diet), and 15/0% (C diet) corn oil/coco- cholesterol in the VLDL–LDL region of nut oil for 6 weeks, produced no increase in PLTP0 mice. Accumulation of phospholip- enzyme activity. The level of ornithine de- ids and free cholesterol was dramatically in- carboxylase activity in the UV-irradiated creased in PLTP0/HL0 mice compared to mice fed diet A was significantly higher PLTP0 mice. Turnover studies indicated than in mice fed the B or C diet. In the that coconut oil was associated with delayed SKH-1 mice, ornithine decarboxylase activ- catabolism of phospholipids and phospho- ity was increased by 3 weeks and was signifi- lipids/free cholesterol-rich particles. Incu- cantly higher in mice fed diet C than in bation of these particles with hepatocytes of mice fed diet A. There was no significant coconut-fed mice produced a reduced re- effect of dietary fat on UV-induced skin tu- moval of phospholipids and free cholesterol mor incidenceCN210. by SRBI, even though SRBI protein expres- Oxidative DNA damages. Oil, adminis- sion levels were unchangedCN158. tered to Fischer F344 rats at a dose of 19.8% Plasma fatty acids. Oil, administered to coconut oil and 2% corn oil for 12–15 chicken at doses of 10% and 20% of the weeks, produced an excretion of 8-oxo- diet, produced an increase in the percent- 7,8dihydro-2'-deoxyguanosine (8-oxodG) ages of lauric and myristic acids in free fatty 140 MEDICINAL PLANTS OF THE WORLD acid and triacylglycerol fractions in chick Platelets aggregation stimulation. Fruit plasma, whereas these changes were less juice, administered intravenously by infu- pronounced in phospholipids and choles- sion to dogs at a dose of 5 mL/min, was ac- terol esters. The percentage of arachidonic tive. Total infusion was 300 mLCN036. Oil, acid was higher in plasma phospholipids administered orally to six New Zealand than in the other fractions and was drasti- white rabbits fed a commercial diet supple- cally decreased by coconut oil feeding. mented with 60 g/kg of coconut oil low in Linoleic acid, the main fatty acid of choles- all PUFA for 60 days, produced a platelets terol esters, was increasedCN156. Oil, adminis- aggregation induced by both thrombin and tered to 37 children 1 year of age in the form collagen significantly lower with either fish of full vegetable-fat milk (3.5 g fat/dL, 100% or linseed oil (n-3 PUFA), than with corn vegetable fat from palm, coconut, and soy- oil (n-6 PUFA) or the low PUFA coconut bean oils), produced higher amounts of oilCN125. plasma linoleic acid and a plasma D-toco- Proinflammatory mediator production. pherol concentrations than in the other Oil, administered to male C57B16 rats for 6 milks testedCN165. Oil, administered to male weeks, produced a decreased TNF-D level by Wistar rats at a dose of 40% of diet for 2 resident macrophages (M phis) than in the months, increased apo A-I concentration in fish oil-fed ratsCN177. plasma and did not change apo A-I mRNA Prostaglandin outflow. Oil was adminis- levelCN175. Oil, administered to 38 healthy tered to weanling male rats fed ad libitum a children in a form of full vegetable-fat milk semisynthetic diet supplemented with 10% (3.5 g fat/dL, 100% vegetable fat from palm, by weight of primrose oil, replaced partly or coconut, and soybean oils), produced a sig- completely (25, 50, 75, or 100%) by hydro- nificantly lower percentage of SUFAs in genated coconut oil for 8 weeks. The release plasma triglycerides than in children fed of prostanoids from the mesenteric vascula- standard-fat milk. Plasma PUFA levels were ture was significantly reduced in the animals significantly higher than in children fed on the diet with the oil replaced by coconut standard-fat milkCN179. Oil, administered to oilCN117. 41 healthy adults, produced a decrease of Protective effect of vitamin A. Vitamin A, plasma lathosterol concentration, the ratio 240,000 IU, predissolved in 11.7 g of coco- plasma lathosterol/cholesterol, LDL choles- nut oil and bolused directly into the rumen terol, and apo B. Plasma total cholesterol, of mature wethers along with 4 g of chromic HDL cholesterol, and apo A levels were not oxide or predissolved in 11.7, 23.4, or 35 g significantly different between butter and of coconut oil, produced significantly higher coconut dietsCN193. Oil, administered to male recoveries of vitamin A when dissolved in golden Syrian hamsters at a dose of 15% w/w coconut oil (55.6%) compared to safflower for 4 weeks, produced the highest triglycer- oil (35.5%). Recoveries in abomasal digesta ide levels of the diets studiedCN200. Oil, ad- increased linearly with the amount of car- ministered to male golden Syrian hamsters rier coconut oilCN195. at a dose of 4 g/kg of diet (12:0 and 14:0) for Pyretic activity. Fruit juice, administered 7 weeks, produced the highest plasma cho- intravenously to guinea pigs at a dose of 10 lesterol concentration compared to rapeseed mL/kg four times at 1-hour intervals, was and sunflower seed oil diets. Biliary lipids, activeCN036. lithogenic index, and bile acid profile of the Repellent activity. The lotions and creams gallbladder bile did not differ significantly containing coconut oil were efficient in pro- among the six dietsCN201. tecting against Simulium damnosum bitesCN068. COCOS NUCIFERA 141

Respiratory stimulant effect. Fruit juice, inactive on spermCN058. Fixed oil, adminis- administered by intravenous infusion to tered to male adults at a concentration of dogs at a dose of 5 mL/minute for 60 min- 1:10, was inactiveCN052. utes, was activeCN036. Subcellular membrane-bound enzymes Semen coagulation. Ethanol (50%) ex- activity. Oil, administered to male CFY tract of the leaf, administered to rat semen weanling rats at a dose of 20% for 16 weeks, at a concentration of 2%, was inactiveCN058. produced an increase of synaptosomal ace- Semen cryopreservation. Coconut water tylcholinesterase activity in the coconut oil- extender, administered with glycerol to the fed group. The Mg2+-adenosine triphosphate semen of six adult dogs at concentrations of (ATPase) activity was similar among all 4, 6, and 8%, produced satisfactory effect. groups in all the brain regionsCN196. There was no difference among groups in Superoxide production inhibition. Seed motility and vigor. A smaller percentage of oil, administered to rats at a concentration total and secondary abnormalities were of 8% of diet, produced equivocal effect on observed using 6% glycerolCN151. macrophages. Capsaicin or curcumin en- Sensitization (skin). Fruit juice, adminis- hanced effectCN021. tered subcutaneously to guinea pigs at a dose Tachycardiac activity. Fruit juice, admin- of 02 mg/animal, was active on skin. Edema istered by intravenous infusion to dogs at a occurred at the site of injection and recov- dose of 5 mL/minute for 60 minutes, was ered within 200 minutes.Fruit juice, admin- activeCN036. istered subcutaneously to adults at a dose of Toxicity assessment. Ethanol extract of 02 mg/person, was active on skin. Inflam- the leaf, administered intraperitoneally to CN058 mation occurred at the site of injection and mice, was active, LD50 0.75 g/kg . Etha- recovered within 90 minutesCN036. Aqueous nol extract of the fresh leaf and stem, ad- extract of the husk fiber, administered ex- ministered intraperitoneally to mice at the ternally to rabbits, produced no significant minimum toxic dose of 1 mL/animal, was dermic or ocular irritationCN063. active. Water extract of the fresh leaf and Shock prevention. Oil, administered to stem, administered intraperitoneally to rats injected with Escherichia coli endotoxin, mice at the minimum toxic dose of 1 mL/ produced a significant effectCN219. animal, was activeCN002. Aqueous extract of Sickness behavior. Hydrogenated oil, ad- the husk fiber, administered orally to mice, CN063 ministered to Swiss Webster mice at a dose was active, LD50 2.30 g/kg . of 17% w/w for 6 weeks, produced the bio- Tricarboxylate carrier influence. Oil, activity of plasma TNF-D equal to 32.6 r administered to rats at a dose of 15% of the 3.6 ng/mL in mice fed coconut oil diet com- diet for 3 weeks, produced a differential pared to mice fed fish oil (98.2 r 5.1 ng/ mitochondrial fatty acid composition and mL)CN202. no appreciable change in phospholipids Spasmogenic activity. Ethanol (95%) ex- composition and cholesterol level. Com- tract of the fresh leaf and stem, adminis- pared with coconut oil-fed rats, the mito- tered to guinea pigs at a dose of 0.5 mL/L, chondrial tricarboxylate carrier activity was was active on ileum. Water extract of the markedly decreased in liver mitochondria fresh leaf and stem, administered intraperi- from fish oil-fed rats. No difference in the toneally to guinea pigs at a dose of 0.5 mL/L, Arrhenius plot between the two groups was was active on ileumCN002. observedCN138. Spermicidal effect. Ethanol (50%) extract Tumor prevention. The effect of kernel fi- of the leaf, administered to male rats, was ber on metabolic activity of intestinal and 142 MEDICINAL PLANTS OF THE WORLD fecal E-glucuronidase activity during 1,2- brevortia tyrannus, and 1.5% Zea mays; and dimethylhydrazine (DMH)-induced colon 8.5% fixed and 1.5% Zea mays, administered carcinogenesis was studied. Inclusion of fi- to mice in the diet for 52 weeks, were active. ber supported lower specific activity and less Tumors were initiated with dimethylben- fecal output of E-glucuronidase than did the zanthracene and promoted with benzoyl fiber-free dietCN074. Kernel, administered to peroxide for 52 weeksCN035. Oil, administered animals treated with DMH, resulted in orally to female Sencar mice at doses of 5, higher average weight. A decrease of cho- 10, 15, and 20%, with addition of 5% corn lesterol and increase of phospholipids and oil for 1 week after initiation with 7,12- cholesterol/phospholipids ratio in most of dimethylbenzanthracene and 3 weeks tissues was found. HMG-CoA reductase ac- before the start of promotion with 12-0- tivity was decreased in most of the tissues of tetradecanoylphorbol-13-acetate, produced the kernel and DMH, kernel and chili, and no significant difference in latency or inci- kernel, chili, and DMH groups. Histopatho- dence of papillomas or carcinomas between logical studies showed that kernel-fed ani- the saturated fat diet groupsCN073. Oil, admin- mals had fewer papillae, less infiltration istered to 30 Sencar and SKH-1 mice at into the submucosa, and fewer changes in doses of 1:14% (A diet); 7.9%:7.1% (B diet) the cytoplasm with decreased mitotic and 15:0% (C diet) corn oil/coconut oil for figuresCN083. Oil, administered to rats for 4–8 3 weeks before UV irradiation, produced weeks, produced a small but statistically tumor incidence that reached a maximum insignificant reduction in TNF production. of 60, 60, and 53% for diets A, B, and C, After 8 weeks, coconut oil suppressed respectively, with an average one to two tu- production of the cytokine. Coconut oil mors per Sencar mouse. For the SKH-1 produced no modulatory effect on the mice, the diet groups reached 100% inci- interleukin productionCN094. Oil, adminis- dence by 29 weeks, with approx 12 tumors tered orally at a dose of 20% of diet to virgin per mouse. No significant effect of dietary female Balb/c mice treated with 7,12- fat was found for tumor latency, incidence, dimethylbenz[a]anthracene (DMBA), pro- or yield in either strainCN210. Oil (17%) with duced no effect on body weight, feed intake, 3% of sunflower seed oil, administered to or survival to 44 weeks of age and 36 weeks DMBA-treated female Sprague–Dawley rats after the six DMBA doses. Mammary tumor in the diet, produced twice as many tumors incidence was the same in the coconut oil as those fed 3% sunflower seed oil or 20% of or menhaden oil but significantly higher in either saturated fat alone. Tumor yields in the corn oil groupCN100. Oil was adminis- the rats fed these mixed-fat diets were com- tered to female Wistar rats before mating parable to rats fed a 20% lard diet, which and throughout pregnancy and gestation, provided about the same amount of linoleic and the male offspring were supplemented acidCN217. from weaning until 90 days of age. They Uncoupling protein expression. Oil, were inoculated subcutaneously with Walker administered to female Wistar rats fed ad 256 tumor cells. Supplementation of the libitum a high-fat diet with coconut oil for 7 diet with coconut oil did not change cancer weeks, promoted an increase in body fat cachexia, except for a small decrease in content, body weight, and uncoupling pro- serum triacylglycerol concentrationCN141. tein levels. At the completion of experi- Tumor-promoting effect. Fixed oil (4.5%) ment I, oil was administered to high-fat diet with 4% Clupeidae brevortia tyrannus and rats for 3 weeks. Adipose depots were 1.5% Zea mays; 7.5% fixed oil, 1% Clupeidae strongly reduced in the rats fed the high fat COCOS NUCIFERA 143 diet enriched with coconut oil. Specific nation of aluminium in soil and plant uncoupling protein was 3.4 times higher digest. J Sci Food Agr 1974; 25: 381. than in controlsCN191. CN012 Gopakumar, B., B. Ambka, and V. K. K. Prabhu. Juvenomimetic activity in Vascular permeability increased. Fixed some South Indian plants and the oil (4.5%), 4% Clupeidae brevortia tyrannus, probable cause of this activity in Morus and 1.5% Zea mays; 7.5% of fixed oil, 1% alba. Entomon 1977; 2: 259–261. Clupeidae brevortia tyrannus, and 1.5% Zea CN013 Jansz, E. R., E. E. Jeya, N. Pieris, and mays; 8.5% fixed oil and 1.5% Zea mays, D. J. Abeyratne. Cyanide liberation administered to mice in the diet for 52 from linamarin. J Natl Sci Counc Sri Lanka 1974; 2: 57–65. weeks, was active vs vascular permeability CN014 Keiser, I., E. J. Harris, D. H. Miyashita, induced by benzoyl peroxideCN035. M. Jacobson, and R. E. Perdue. Attrac- tion of ethyl ether extracts of 232 bota- REFERENCES nicals to oriental fruit flies, melon flies, CN001 Atakeuchi, K. Amino acids in the and Mediterranean fruit flies. LLoydia endosperm of some Amazonian Pal- 195; 38(2): 141–152. mae. Chiba Daigaku Buuri Gakuba CN015 Wong, W. Some folk medicinal plants Kiyo Shizen Kagku 1961; 3: 321–325. from Trinidad. 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Effects of dietary coconut oil, butter CN202 Kozak, W., D. Soszynski, K. Rudolph, and safflower oil on plasma lipids, C. A. Conn, and M. J. Kluger. Dietary lipoproteins and lathosterol levels. Eur n-3 fatty acids differentially affect sick- J Clin Nutr 1998; 52(9): 650–654. ness behavior in mice during local and CN194 Pumhirun, P., P. Towiwat, and P. systemic inflammation. Am J Physiol Mahakit. Aeroallergen sensitivity of 1997; 272(4 Pt. 2): 1298–1307. Thai patients with allergic rhinitis. CN203 Clamp, A. G., S. Ladha, D. C. Clark, Asian Pac J Allergy Immunol 1997; R. F. Grimble, and E. K. Lund. The 15(4): 183–185. influence of dietary lipids on the com- CN195 Fichter, S. A., and G. E. Mitchell Jr. position and membrane fluidity of rat Coconut oil as a protective carrier of hepatocyte plasma membrane. Lipids dietary vitamin A fed to ruminants. 1997; 32(2): 179–184. Int J Vitam Nutr Res 1997; 67(6): CN204 Lal, J. J., C. V. Kumar, M. V. Suresh, 403–406. M. Indira, and P. L. Vijayammal. Effect CN196 Srinivasarao, P., K. Narayanareddy, A. of coconut palm wine (Toddy) on car- Vajreswari, M. Rupalatha, P. S. bohydrate metabolism in pregnant rats Prakash, and P. Rao. Influence of and fetuses. Plant Foods Hum Nutr dietary fat on the activities of subcel- 1997; 50(1): 71–79. lular membrane-bound enzymes from CN205 Ju, H. R., H. Y. Wu, S. Nishizono, M. different regions of rat brain. Sakono, I. Ikeda, M. Sugano, and K. Neurochem Int 1997; 31(6): 789–794. Imaizumi. Effects of dietary fats and CN197 Eder, K., and M. Kirchgessner. Activi- curcumin on IgE-mediated degranula- ties of liver microsomal fatty acid tion of intestinal mast cells in brown desaturases in zinc-deficient rats force- Norway rats. Biosci Biotechnol fed diets with a coconut oil/safflower Biochem 1996; 60(11): 1856–1860. oil mixture of linseed oil. Biol Trace CN206 Langley-Evans, S. C., A. G. Clamp, R. Elem Res 1995; 48(3): 215–229. F. Grimble, and A. A. Jackson. Influ- CN198 Prieto, R. M., W. Stremmel, C. Sales, ence of dietary fats upon systolic blood and J. A. Tur. Effect of dietary fatty pressure in the rat. Int J Food Sci Nutr acids on jejunal and ileal oleic acid 1996; 47(5): 417–425. uptake by rat brush border membrane CN207 Gabert, V. M., M. S. Jensen, H. vesicles. Eur J Med Res 1996; 1(7): Jorgensen, R. M. Engberg, and S. K. 355–360. Jensen. Exocrine pancreatic secretions CN199 Gil–Villarino, A., M. I. Torres, M. F. in growing pigs fed diets containing Zafra, and E. Garcia–Peregrin. Supple- fish oil, rapeseed oil or coconut oil. J mentation of coconut oil from differ- Nutr 1996; 126(9): 2076–2082. ent sources to the diet induces cellular CN208 Castillo, M., J. H. Hortal, E. Garcia- damage and rapid changes in fatty acid Fuentes, M. F. Zafra, and E. Garcia- composition of chick liver and hepatic Peregrin. Coconut oil affects lipoprotein mitochondria. Comp Biochem Physiol composition and structure of neonatal C Pharmacol Toxicol Endocrinol chicks. J Biochem (Tokyo) 1996; 1997; 117(3): 243–250. 119(4): 610–616. CN200 Gonzalez, I., M. Escobar, and P. CN209 Kaur, M., J. Kaur, S. Ojha, and A. Olivera. Plasma lipids of golden Syrian Mahmood. Dietary fat effects on brush hamsters fed dietary rose hip, sun- border membrane composition and flower, olive and coconut oils. Rev Esp enzyme activities in rat intestine. Ann Fisiol 1997; 53(2): 199–204. Nutr Metab 1996; 40(5): 269–276. CN201 Trautwein, E. A., A. Kunath-Rau, J. CN210 Berton, T. R., S. M. Fischer, C. J. Dietrich, S. Drusch, and H. F. Conti, and M. F. Locniskar. Compari- Erbersdobler. Effect of dietary fats rich son of ultraviolet light-induced skin in lauric, myristic, palmitic, oleic or li- carcinogenesis and ornithine decar- noleic acid on plasma, hepatic and bil- boxylase activity in sencar and hairless iary lipids in cholesterol-fed hamsters. SKH-1 mice fed a constant level of Br J Nutr 1997; 77(4): 605–620. dietary lipid varying in corn and coco- 154 MEDICINAL PLANTS OF THE WORLD

nut oil. Nutr Cancer 1996; 26(3): gic contact dermatitis caused by coco- 353–363. nut diethanolamide, N-ethyl-4-toluene CN211 Lin, M. H., S. C. Lu, J. W. Hsieh, and sulfonamide, and 4-tolyldiethanol- P. C. Huang. Lipoprotein responses to amine. Acta Derm Venereol 1993; fish, coconut and soybean oil diets 73(2): 126–129. with and without cholesterol in the CN217 Hopkins, G. J., and K. K. Carroll. Syrian hamster. J Formos Med Assoc Relationship between amount and 1995; 94(12): 724–731. type of dietary fat in promotion of CN212 Cox, C., J. Mann, W. Sutherland, A. mammary carcinogenesis induced by Chisholm, and M. Skeaff. Effects of 7,12-dimethylbenz[a]anthracene. coconut oil, butter, and safflower oil on J Natl Cancer Inst 1979; 62(4): lipids and lipoproteins in persons with 1009–1012. moderately elevated cholesterol levels. CN218 Emmett, E. A., and R. C. Wright. Aller- J Lipid Res 1995; 36(8): 1787–1795. gic contact dermatitis from TEA-Coco CN213 Roche, M. E., and R. M. Clark. Lym- hydrolyzed protein. Arch Dermatol phatic fatty acids from rats fed human 1976; 112(7): 1008–1009. milk and formula containing coconut CN219 Lim–Navarro, P. R. T., R. Escobar, M. oil. Lipids. 1994; 29(6): 437–439. Fabros, and C. S. Dayrit. Protection CN214 Pinola, A., T. Estlander, R. Jolanki, K. effect of coconut oil against E. coli Tarvainen, and L. Kanerva. Occupa- endotoxin shock in rats. Coconut tional allergic contact dermatitis due Today 1994; 11: 90–91. to coconut diethanolamide (cocamide CN220 Stalcup, A. M., K. H. Ekborg, M. P. DEA). Contact Dermatitis 1993; Gasper, and D. W. Armstron. Enantio- 29(5): 262–265. meric separation of chiral components CN215 Fagundes Neto, U., L. Franco, K. reported to be in coffee, tea and cocoa. Tabacow, and N. L. Machado. Nega- J Agr Food Chem 1993; 41(10): 1684– tive findings for use of coconut water 1689. as an oral rehydration solution in CN221 Mourafe, J. A., W. H. Brown, F. M. childhood diarrhea. J Am Coll Nutr Whiting, and J. W. Stull. Unsaponi- 1993; 12(2): 190–193. fiable matter of crude and processed CN216 Kanerva, L., R. Jolanki, and T. coconut oil. J Sci Food Agr 1975; Estlander. Dentist’s occupational aller- 26: 523. COFFEA ARABICA 155

4 Coffea arabica L.

Common Names Akeita France Kafa Serbia Araabia kohvipuu Estonia Kafe Albania Bunna Ethiopia Kafe Bulgaria Ca-fae Thailand Kafe Czech Republic Café Africa Kafe Gambia Café Argentina Kafe Greece Café Bolivia Kafe Latin America Café Brazil Kafe Senegal Café Catalonia Ka-fei China Café Chile Kaffe Denmark Café Ecuador Kaffe Norway Café France Kaffe Sweden Café Peru Kaffee Germany Café Portugal Kaffeeplante Norway Café Spain Kaffeestrauch Germany Café Vietnam Kaffi Iceland Cafea Romania Kafija Latvia Caffe Finland Kahawa Africa Caffe Italy Kahioa Arabic countries Caife Ireland Kahva Bosnia Chai Georgia Kahve Turkey Coffee Guyana Kahvi Finland Coffee United Kingdom Kape Philippines Coffee United States Kava Croatia Ga feh China Kava Czech Republic Gafae Thailand Kava Lithuania Ghah’veh Iran Kava Slovakia Ikhofi Africa Kava Slovenia Ikofu South Africa Kava Ukraine Ka’fe Israel Kave Hungary Kaafi India Kave Israel Kaapi Central America Kawa Poland Kaapi Mexico Kofe Russia Kaawa Uganda Koffee India

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 155 156 MEDICINAL PLANTS OF THE WORLD

Koffi United Kingdom Kope Hawaii Koffie Netherlands Kopi Indonesia Koffie South Africa Kopi Malaysia Koffieboom Netherlands Ko-pi Sri Lanka Kofi Botswana Ko-pyi Korea Kofi South Africa Lee-cah fee United States Kofii India Qahve Azerbaijan Kofje Netherlands Qahve Yemen Kohv Estonia Qahwah Arabic countries Koohii Japan Sourdj Armenia

BOTANICAL DESCRIPTION At the end of the 17th century, the Dutch Coffee is a medium-size tree of RUBI- started to cultivate coffee on Jawa, Ceylon, ACEAE family. The plants can live up to and Surinam. In the 18th century, it was 25 years and grows to a height of 6–15 m; cultivated in Latin America and Brazil, then commercially are kept to the height of 175– in Kenya, Tanzania, Malawa, and Uganda. 185 cm. The leaf is developed from the axil Main producers currently are Brazil and and arranged in pairs. The leaves on the Columbia. main trunk develop in pairs and spirally, TRADITIONAL MEDICINAL USES whereas leaves from the branch develop in Brazil. Decoction of the seed is taken orally a fan-like manner. The size of the mature for influenzaCA183. leaf of Liberica coffee is approx 15–30 cm u Cuba. Hot water extract of the seed is taken 5–15 cm, with 7–10 veins. The dorsal sur- orally by males as an anaphrodisiacCA243. face is smooth and shiny. The mature leaf of Haiti. Decoction of the grilled fruit and leaf the Robusta coffee is about the same size, is taken orally for anemia, edema, asthenia, except that it has 8–13 veins, whereas the and rage. The fruit is taken orally for hepa- dorsal surface is shiny and wavy. The tree titis and liver troubles. The soaked fruit is starts flowering at the age of 18–36 months. used externally for nervous shock. For head- The flowers develop from the axil of the ache, the leaf decoction is taken orally or leaves in the form of several in a bunch. the leaf is applied to the headCA236. Coffee berries are green when immature and Mexico. The leaves are made into a poultice turn yellow and red at maturity and ripen- and used to treat feverCA168. Hot water extract ing. Usually, each berry will contain two of the roasted seed is taken orally by nursing cotyledon or beans. In the case of a single mothers to increase milk productionCA196. cotyledon, it is called peaberry. The time of Nicaragua. Leaves are used externally for maturity is approx 8–13 months for Liberica headache, and the hot water extract is taken and 9–10 months for Robusta. Fruits and orally for stomach painCA181. Decoction of beans are round, 0.8–1.5 cm (Robusta) and the seed is taken orally for fever and used 2–2.5 cm (Liberica), bean size 0.7–0.9 cm externally for cuts and hemorrhageCA184. (Robusta) and 1.3–1.5 cm (Liberica). Peru. Hot water extract of the dried fruit is ORIGIN AND DISTRIBUTION taken orally as a stimulant for sleepiness and Coffee originated from the tropical region drunkennessCA226. Infusion of the leaf is of the African continent. In the first centu- taken orally to induce labor, and the hot ries, it was cultivated in Arabic countries: water extract is taken orally as an antitus- Aden and Yemen, later in Iran and India. sive in flu and lung ailmentsCA200. COFFEA ARABICA 157

Thailand. Hot water extract of the dried Benzofuran, 2-methyl: Sd HuCA082 seed is taken orally as a cardiotonic and Benzofuran: Sd HuCA082 CA122 neurotonicCA245. Benzoic acid, 2-4-dihydroxy: Sd Benzoic acid, 3-4-dihydroxy: SdCA122 West Indies. Hot water extract of the seed Benzothiazole: Sd HuCA075 is taken orally for asthma. Root juice is Benzoxazole, 2-4-dimethyl: Sd HuCA076 CA226 taken orally for scorpion sting . Benzoxazole, 2-5-dimethyl: Sd HuCA076 CA076 CHEMICAL CONSTITUENTS Benzoxazole, 2-6-dimethyl: Sd Hu Benzoxazole, 2-methyl: Sd HuCA076 (ppm unless otherwise indicated) CA076 CA082 Benzoxazole, 4-methyl: Sd Hu Acetaldehyde, phenyl: Sd Hu CA082 CA094 Bifuryl, 2-2': Sd Hu Acetaldehyde: Sd But-2-en-1-4-olide, 2-3-4-trimethyl: Sd Acetic acid: SdCA063 (roasted)CA063 Acetoin: FrCA087 But-2-en-1-4-olide, 2-3-dimethyl: Sd Acetol: SdCA131 (roasted)CA063 Acetone: SdCA063 But-2-en-1-4-olide, 3-4-dimethyl: Sd Acetophenone, 2-hydroxy-5-methyl: Sd CA063 CA082 (roasted) Hu CA063 CA095 But-2-en-1-al, 2-methyl: Sd (roasted) Acetophenone, 3'-4'-dihydroxy: Sd CA063 CA063 But-2-en-1-ol, 3-methyl: Sd (roasted) Acrylic acid, 2-3-dimethyl: Sd (roasted) CA063 CA063 But-3-en-2-one, 4-(2'-furyl): Sd (roasted) Acrylic acid, 3-3-dimethyl: Sd (roasted) CA063 CA092 Butan-1-al, 2-methyl: Sd (roasted) Adenine, 7-glucosyl: Pl CA063 CA135 Butan-1-al, 3-methyl: Sd (roasted) Allantoic acid: Lf CA063 Allantoin: LfCA135 Butan-1-al: Sd (roasted) CA129 Butan-2-3-dione, 1-(2'-furyl): Sd Amine, dimethyl: Sd 4.0 CA063 Amine, ethyl-methyl: Sd 1.0CA129 (roasted) CA063 Amine, iso-butyl: Sd 1.0CA129 Butan-2-one, 1-acetoxy: Sd (roasted) CA063 Amine, iso-pentyl: Sd 1.0CA129 Butan-2-one, 4-(2'-furyl): Sd (roasted) Amine, N-pentyl: Sd 0.5-2.0CA129 Butan-2-one, 4-(2'-furyl-5'-methyl): Sd CA063 Amine, N-propyl: Sd 0.5CA129 (roasted) CA063 Arachidic acid: SdCA068 Butan-2-one: Sd (roasted) CA063 Arbutin: Sd 0.1CA096 Butan-3-one, 2-hydroxy: Sd (roasted) Atractyligenin, 2-O-(2-O-iso-valeryl-E-D- Butane-1-2-dione, 1-(2'-furyl): Sd glucopyranosyl): SdCA250 (roasted)CA063 CA063 Atractyligenin, 2-O-(3-O-E-D-glucopyranosyl- Butanedione: Sd (roasted) CA087 2-iso-valeryl-E-D-glucopyranosyl): SdCA250 Butyric acid, 2-methyl: Fr CA063 Atractyligenin, 2-O-(3-O-E-D-glucosyl2-O-iso- Butyric acid, iso: Sd (roasted) CA063 valeroyl-E-D-glucosyl): Sd 0.024%CA083 Butyric acid, N: Sd (roasted) CA063 Atractyligenin, 2-O-E-D-glucopyranosyl: Butyrolactone, J, D-methyl: Sd (roasted) SdCA250 Butyrolactone, J: Sd (roasted)CA063 CA062 CA136, CA132 Atractyligenin, 3'-O-(E-D-glucosyl)-2'-(O-iso- Cafesterol: Sd oil , Sd 0.3–5% CA130 valeroyl)-2-E-(2-deoxy), E-D-glucoside: Sd Cafestol palmitate: Sd 170-460CA117 Cafestol, 16-methoxy: SdCA065 Atractyligenin: Sd 10 (free)-400 (total)CA126 Cafestol, 16-O-methyl: Sd 140CA066, LfCA079 CA079 CA124 Atractyligenin-2-O-(2-O-iso-valeryl-E-D- Cafestol: Lf , Sd 1.2% glucoside: SdCA116 Cafestol-2-one-11-O-(E-D-glucoside): SdCA118 CA064,CA078 Atractyligenin-2-O-(E-D-glucoside): Sd 290- Caffeic acid: Sd 0.14–1.051% 340CA117 Caffeine: Sd 0.00004–3.98%CA121,CA103, CA088 CA099 Atractyligenin-2-O-E-D-glucoside: Sd 220CA083 Pl , Call Tiss 0.9–1 mg/mL , Fr, Avenasterol, 5-dehydro: SdCA107 LfCA077, PcCA111, Fr (unripe)CA120 Benzaldehyde, 3-4-dihydroxy: SdCA122 Caffeoyl-quinic acid, 3: SdCA090 Benzaldehyde: Sd HuCA082 Caffeoyl-quinic acid, 3-5-di-O: SdCA104 Benzofuran, 2-3-dihydro: Sd HuCA082 Caffeoyl-quinic acid, 4: SdCA090 158 MEDICINAL PLANTS OF THE WORLD

Caffeoyl-quinic acid, 5: SdCA090 Ferulic acid: Sd 0.84%CA078 Campesterol: SdCA107 Feruloyl-quinic acid: SdCA090 Candol B: SdCA070 Formate, ethyl: Sd (roasted)CA063 Carbon disulfide: Sd (roasted)CA063 Formate, methyl: Sd (roasted)CA063 Chlorogenic acid A, iso: SdCA112 Formic acid: Sd (roasted)CA063 Chlorogenic acid B, iso: SdCA104 Fucosterol: SdCA107 Chlorogenic acid C, iso: SdCA112 Furan, 2-3-5-trimethyl: Sd HuCA082 Chlorogenic acid, iso: Sd 0.05–1%CA127 Furan, 2-5-dimethyl: Sd (roasted)CA063 Chlorogenic acid, neo: Sd 0.17– Furan, 2-acetyl: Sd (roasted)CA063 0.395%CA127,CA064 Furan, 2-acetyl-5-methyl: Sd (roasted)CA063 Chlorogenic acid: Sd 0.26–9.9%CA134,CA114 Furan, 2-methyl: Sd (roasted)CA063 Chrysanthemin: Fr PuCA085 Furan, 2-methyl-5-(2'-furfuryl): Sd Cinnamic acid, 3-4-dimethoxy: Sd 560CA078 (roasted)CA063 Citric acid: SdCA081 Furan, 2-N-butyryl: Sd (roasted)CA063 Cofaryloside: Sd 40CA098 Furan, 2-propionyl: Sd (roasted)CA063 Coffea arabica sterol (MP 128–130): Sd oil Furan, 2-vinyl: Sd HuCA082 2.7%CA133 Furan, 3-5-dimethyl-2-vinyl: Sd HuCA082 Coffea arabica tryptamine derivative C-2: Fr Furan, 3-methyl-2-vinyl: Sd HuCA082 (unripe) 0.1CA120 Furan, 3-phenyl: Sd (roasted)CA063 Coumaric acid, ortho: Sd 0.2%CA078 Furan, 4-5-dimethyl-2-vinyl: Sd HuCA082 Coumaric acid, para: Sd 0.34%CA078 Furan, 4-methyl-2-vinyl: Sd HuCA082 Cresol, meta: Sd HuCA082 Furan, 5-methyl-2-acetyl: Sd HuCA082 Cresol, ortho: Sd (roasted)CA063 Furan, 5-methyl-2-vinyl: Sd HuCA082 Cresol, para: Sd HuCA082 Furan, tetrahydro, 2-methyl: Sd (roasted)CA063 Crotonic acid, cis: Sd (roasted)CA063 Furan, tetrahydro: Sd (roasted)CA063 Crotonic acid, trans: Sd (roasted)CA063 Furan: Sd (roasted)CA063 Cryptochlorogenic acid: Sd 0.4–2.63%CA127 Furan-2-ethyl: Sd HuCA082 Cyanidin-3-diglucoside: Fr PuCA085 Furan-2-iso-butenyl: Sd HuCA082 Cyclohex-2-en-1-one, 3-methyl: Sd HuCA082 Furan-2-iso-butyryl: Sd (roasted)CA063 Cyclohexan-1-2-dione, 3-methyl: Sd Furan-2-iso-propyl: Sd HuCA082 (roasted)CA063 Furan-2-methyl-5-iso-propyl: Sd HuCA082 Cyclohexylmethylketone: Sd HuCA082 Furan-2-methyl-5-N-propenyl: Sd HuCA082 Cyclopent-2-en-1-one, 2-3-dihydroxy: SdCA102 Furan-2-N-butyl: Sd HuCA082 Cyclopent-2-en-1-one, 2-3-dimethyl: Sd Furan-2-N-butyryl: Sd HuCA082 HuCA082 Furan-2-N-pentyl: Sd HuCA082 Cyclopent-2-en-1-one, 2-hydroxy-3-methyl: Furan-2-N-propenyl: Sd HuCA082 Sd HuCA082 Furan-2-N-propyl: Sd HuCA082 Cyclopentan-1-2-dione, 3-5-dimethyl: Sd Furan-2-propionyl: Sd HuCA082 (roasted)CA063 Furan-3-one, 2-(H), 2-5-dimethyl: Sd HuCA082 Cyclopentan-1-2-dione, 3-methyl: Sd Furan-3-one, tetrahydro, 2-methyl: FrCA087, Sd (roasted)CA063 (roasted)CA063 Cyclopentane-1-2-dione, 3-ethyl: Sd Furfural, 5-methyl: Sd (roasted)CA063 (roasted)CA063 Furfural: Sd (roasted)CA063 Cyclopentanone: Sd (roasted)CA063 Furfuryl mercaptan: Sd HuCA082 Dimethyl disulfide: Sd HuCA082 Furfuryl, 2, 2'-methyl-butyrate: Sd Dimethyl sulfide: Sd (roasted)CA063 (roasted)CA063 Ethan-1-al: Sd (roasted)CA063 Furfuryl, 2, acetate: Sd (roasted)CA063 Ethanethiol: Sd (roasted)CA063 Furfuryl, 2, alcohol: Sd (roasted)CA063 Ethanol: Sd (roasted)CA063 Furfuryl, 2, formate: Sd (roasted)CA063 Ethyl acetate: Sd (roasted)CA063 Furfuryl, 2, methyl ether: Sd (roasted)CA063 Ethylamine: Sd 2CA129 Furfuryl, 2, methyl sulfide: Sd HuCA082 Eugenol, iso: Sd HuCA082 Furfuryl, 2, propionate: Sd (roasted)CA063 COFFEA ARABICA 159

Furfuryl, 2-2'-di: Sd (roasted)CA063 Mascaroside: SdCA097 Furfuryl, 5-hydroxy-methyl: Sd HuCA082 Mesityl: Sd HuCA082 Furfuryl, 5-methyl: Sd HuCA082 Methacrylic acid: Sd (roasted)CA063 Furoate, ethyl: Sd HuCA082 Methanethiol: Sd (roasted)CA063 Furoate, methyl: Sd HuCA082 Methanol: Sd (roasted)CA063 Furyl, 2, (2'-methyl-5'-furyl-methane): Sd Methyl acetate: Sd (roasted)CA063 HuCA082 Methylamine: Sd 27CA129 Furyl, 2, acetone: Sd (roasted)CA063 Myricetin: Fr 0.5CA093 Furyl, 2-2'-di, methane: Sd (roasted)CA063 Myristic acid: SdCA068 CA089 CA129 Glycine: Sd NH3 inorganic: Sd 820 Glycolic acid: SdCA105 Nicotinic acid methyl ester: Sd (roasted)CA063 Glyoxal, methyl: SdCA131 Nicotinic acid: SdL04511 Glyoxal: SdCA131 Oleic acid: SdCA068 Guaiacol, 4-ethyl: Sd (roasted)CA063 Oxazole, 2-4-5-trimethyl: Sd HuCA076 Guaiacol, 4-vinyl: Sd (roasted)CA063 Oxazole, 2-4-dimethyl: Sd HuCA076 Guaiacol: Sd (roasted)CA063 Oxazole, 2-4-dimethyl-5-acetyl: Sd HuCA076 Heptan-2-ol: FrCA087 Oxazole, 2-4-dimethyl-5-ethyl: Sd HuCA076 Heptan-3-ol, FrCA087 Oxazole, 2-5-dimethyl: Sd HuCA076 Heptane-2-5-dione: Sd (roasted)CA063 Oxazole, 2-5-dimethyl-2-N-propyl: Sd HuCA076 Hexan-3-one: Sd (roasted)CA063 Oxazole, 2-5-dimethyl-4-ethyl: Sd HuCA076 Hexane-2-3-dione: Sd (roasted)CA063 Oxazole, 2-5-dimethyl-4-N-butyl: Sd HuCA076 Hexane-2-5-dione: Sd (roasted)CA063 Oxazole, 2-ethyl: Sd HuCA076 Histidine: LfCA135 Oxazole, 2-methyl-4-ethyl: Sd HuCA076 Hydrogen peroxide inorganic: SdCA089 Oxazole, 2-methyl-5-ethyl: Sd HuCA076 Hydrogen sulfide: Sd (roasted)CA063 Oxazole, 2-N-butyl: Sd HuCA076 Hydrolase, 7-methyl-N-nucleoside: FrCA119 Oxazole, 2-phenyl: Sd HuCA076 Hydrolase, nucleotide: Pl, Call TissCA123 Oxazole, 4-5-dimethyl: Sd HuCA076 Hydroquinone, 2-hydroxy: SdCA080 Oxazole, 4-5-dimethyl-2-ethyl: Sd HuCA076 Hydroquinone: Sd 2CA096 Oxazole, 4-ethyl: Sd HuCA076 Indole, 2-methyl: Sd HuCA076 Oxazole, 4-methyl-2-ethyl: Sd HuCA076 Indole: Sd HuCA076 Oxazole, 4-methyl-5-ethyl: Sd HuCA076 Iso-amyl acetate: SdCA063 Oxazole, 5-acetyl-2-methyl: Sd (roasted)CA063 Isoprene: SdCA063 Oxazole, 5-ethyl: Sd HuCA076 Isopropyl: SdCA063 Oxazole, 5-methyl-2-ethyl: Sd HuCA076 Kahweol eicosanoate: SdCA065 Oxazole, 5-methyl-2-N-propyl: Sd HuCA076 Kahweol linoleate: SdCA065 Oxazole, 5-methyl-4-ethyl: Sd HuCA076 Kahweol oleate: SdCA065 Oxindole, 3: Sd HuCA076 Kahweol palmitate: SdCA130 Palmitic acid: SdCA068 Kahweol stearate: SdCA065 Pectic acid: Mesocarp, EpicarpCA073 Kahweol: SdCA110, LfCA079 Pectin: Mesocarp, EpicarpCA071 Kauren-18-oic acid, 16-17-dihydroxy: SdCA067 Pentan-1-al: Sd HuCA063 Libertine, methyl: SdCA113 Pentan-2-one, 1-acetoxy: Sd (roasted)CA063 Libertine: SdCA113 Pentan-3-one, A-acetoxy: Sd (roasted)CA063 Ligustrazine: Sd (roasted)CA063 Pentane-2-3-dione: Sd (roasted)CA063 Limonene: FrCA087 Pent-trans-2-en-4-one: Sd (roasted)CA063 Linalool, cis: Sd (roasted)CA063 Phenethyl alcohol: Sd HuCA076 Linalool, trans: Sd (roasted)CA063 Phenethyl formate, E: Sd (roasted)CA063 Linalool: Sd (roasted)CA063 Phenol, 2-6-dimethyl: Sd (roasted)CA063 Linoleic acid: SdCA068 Phenol: Sd (roasted)CA063 Maleic anhydride, dimethyl: Sd (roasted)CA063 Phenylacetate, methyl: Sd (roasted)CA063 Maleic anhydride, methyl: Sd (roasted)CA063 Phenylethanol, 4-methyl: Sd HuCA076 Maltol: Sd HuCA082 Phosphoric acid inorganic: SdCA105 160 MEDICINAL PLANTS OF THE WORLD

Piceol: Sd (roasted)CA063 Pyrazine, 5-ethyl: SdCA069 Pipecolic acid: LfCA077, FrCA077 Pyrazine, 5-methyl-2-(2'-furyl-4'-5'-methyl): Piperidine: Sd 2CA129 Sd HuCA076 Polysaccharide: Mesocarp, EpicarpCA073 Pyrazine, 5-methyl-2-(2'-furyl-4'-5'-methyl): Praline, hydroxyl: Lf, FrCA077 Sd HuCA076 Prop-2-en-1-al, 3-(2'-furyl): Sd (roasted)CA063 Pyrazine, 5-methyl-2-(2'-furyl-4'-methyl): Propan-1-2-dione, 1-(2'-furyl): Sd Sd HuCA076 (roasted)CA063 Pyrazine, 5-methyl-2-(2'-furyl-5'-methyl): Propan-1-2-dione, 1-(2’-furyl-5'-methyl): Sd Sd HuCA076 (roasted)CA063 Pyrazine, 5-methyl-2-(2'-furyl-5'-methyl): Propan-1-al, 2-methyl: Sd (roasted)CA063 Sd HuCA076 Propan-1-al, 3-(2'-furyl): Sd (roasted)CA063 Pyrazine, 5-methyl-2-acetyl: Sd HuCA076 Propan-1-al: Sd (roasted)CA063 Pyrazine, 5-methyl-2-acetyl: Sd HuCA076 Propan-1-ol: Sd (roasted)CA063 Pyrazine, 6-methyl-2-(2'-furyl-4'-methyl): Propan-1-one, 1-(2'-furyl-5'-methyl): Sd Sd HuCA076 (roasted)CA063 Pyrazine, 6-methyl-2-(2'-furyl-5'-methyl): Propane, 1-hydroxy: Sd (roasted)CA063 Sd HuCA076 Propanethiol: Sd (roasted)CA063 Pyrazine, 6-methyl-2-acetyl: Sd HuCA076 Propanone, 1-acetoxy: Sd (roasted)CA063 Pyrazine, diethyl-dimethyl: Sd HuCA076 Propionate, methyl: Sd (roasted)CA063 Pyrazine, methyl: Sd (roasted)CA063 Propionic acid: Sd (roasted)CA063 Pyrazine, trimethyl: Sd (roasted)CA063 Protein: Sd Pu 11.9%CA072 Pyrazine: Sd (roasted)CA063 Pyrazine, 2-3-5-trimethyl: SdCA069 Pyridine, 2-acetyl: Sd HuCA076 Pyrazine, 2-3-diethyl: Sd (roasted)CA063 Pyridine, 2-acetyl-methyl: Sd HuCA076 Pyrazine, 2-3-diethyl-5-methyl: Sd Pyridine, 3-acetyl: Sd HuCA076 (roasted)CA063 Pyridine, 3-methyl: Sd (roasted)CA063 Pyrazine, 2-5-7-trimethyl: SdCA069 Pyridine: Sd (roasted)CA063 Pyrazine, 2-5-dimethyl: Sd (roasted)CA063 Pyroglutamic acid: Sd 0.05-0.15%CA106 Pyrazine, 2-6-dimethyl: Sd (roasted)CA063 Pyrrole, N-methyl: Sd (roasted)CA063 Pyrazine, 2-acetyl: Sd HuCA076 Pyrone, 3-hydroxy-2-methyl: Sd (roasted)CA063 Pyrazine, 2-ethyl-3-5-6-methyl: Sd Pyrrole, 1-5-dimethyl: Sd (roasted)CA063 (roasted)CA063 Pyrrole, 1-ethyl: Sd (roasted)CA063 Pyrazine, 2-ethyl-3-methyl: Sd (roasted)CA063 Pyrrole, 2, 5-methyl: Sd (roasted)CA063 Pyrazine, 2-ethyl-5-methyl: Sd (roasted)CA063 Pyrrole, 2, N-methyl: Sd (roasted)CA063 Pyrazine, 2-ethyl-6-methyl: Sd (roasted)CA063 Pyrrole, 2: Sd (roasted)CA063 Pyrazine, 3-5-dimethyl-2-(2'-furyl): Sd HuCA076 Pyrrole, 2-4-dimethyl: Sd HuCA076 Pyrazine, 3-5-dimethyl-2-acetyl: Sd HuCA076 Pyrrole, 2-4-dimethyl-3-ethyl: Sd HuCA076 Pyrazine, 3-6-dimethyl-2-(2'-furyl): Sd HuCA076 Pyrrole, 2-acetyl: Sd (roasted)CA063 Pyrazine, 3-6-dimethyl-2-acetyl: Sd HuCA076 Pyrrole, 2-acetyl-1-ethyl: Sd (roasted)CA063 Pyrazine, 3-ethyl-2-5-dimethyl: Sd Pyrrole, 2-acetyl-N-methyl: Sd (roasted)CA063 (roasted)CA063 Pyrrole, 2-carboxaldehyde: Sd HuCA082 Pyrazine, 3-ethyl-2-6-dimethyl: Sd (roasted)CA063 Pyrrole, 2-ethyl: Sd HuCA082 Pyrazine, 3-ethyl-2-methyl: Sd HuCA076 Pyrrole, 2-iso-butyl: Sd HuCA076 Pyrazine, 3-methyl-2-(2'-furyl-4'-methyl): Pyrrole, 2-methyl-N-acetyl: Sd HuCA082 Sd HuCA076 Pyrrole, 2-N-pentyl: Sd HuCA076 Pyrazine, 3-methyl-2-(2'-furyl-5'-methyl): Pyrrole, 2-propionyl: Sd HuCA082 Sd HuCA076 Pyrrole, 5-methyl-N-acetyl: Sd HuCA082 Pyrazine, 3-methyl-2-acetyl: Sd HuCA076 Pyrrole, N-(2'-furfuryl), 2-carboxaldehyde: Sd Pyrazine, 5-6-dimethyl-2-(2'-furyl): Sd HuCA082 HuCA076 Pyrrole, N-(2'-furfuryl): Sd HuCA082 Pyrazine, 5-6-dimethyl-2-acetyl: Sd HuCA076 Pyrrole, N-(2'-furfuryl-5'-methyl): Sd Pyrazine, 5-7-dimethyl: SdCA069 (roasted)CA063 COFFEA ARABICA 161

Pyrrole, N-(3-methyl-butyl): Sd HuCA082 Thiazole, 2-4-dimethyl-5-ethyl: Sd HuCA075 Pyrrole, N-acetyl: Sd HuCA082 Thiazole, 2-5-diethyl: Sd HuCA075 Pyrrole, N-ethyl, 2-carboxaldehyde: Sd HuCA082 Thiazole, 2-5-dimethyl: Sd HuCA075 Pyrrole, N-ethyl: Sd HuCA082 Thiazole, 2-5-dimethyl-4-ethyl: Sd HuCA075 Pyrrole, N-furfuryl-2-acetyl: Sd HuCA082 Thiazole, 2-ethyl: Sd HuCA075 Pyrrole, N-furfuryl-2-methyl: Sd HuCA082 Thiazole, 2-methyl: Sd HuCA076 Pyrrole, N-methyl, 2-carboxaldehyde: Thiazole, 2-methyl-4-ethyl: Sd HuCA075 Sd HuCA082 Thiazole, 2-methyl-5-ethyl: Sd HuCA075 Pyrrole, N-methyl: Sd HuCA082 Thiazole, 2-N-butyl: Sd HuCA075 Pyrrole, N-methyl-2-acetyl: Sd HuCA082 Thiazole, 2-N-propyl: Sd HuCA076 Pyrrole, N-N-pentyl: Sd HuCA082 Thiazole, 4-5-dimethyl: Sd HuCA075 Pyrrole, N-propionyl: Sd HuCA082 Thiazole, 4-5-dimethyl-2-ethyl: Sd HuCA075 Pyrrole: Sd (roasted)CA063 Thiazole, 4-ethyl: Sd HuCA075 Pyrrolidine: Sd 10CA129 Thiazole, 4-methyl: Sd HuCA075 Quercetin: Fr 0.5CA093 Thiazole, 4-methyl-2-acetyl: Sd HuCA075 Quercetin-3-O-D-L-glucoside: LfCA100 Thiazole, 4-methyl-2-ethyl: Sd HuCA075 Quinic acid, 4-5-dicaffeoyl: SdCA104 Thiazole, 4-methyl-5-ethyl: Sd HuCA075 Quinic acid, 5-O-feruloyl: SdCA104 Thiazole, 5-ethyl: Sd HuCA075 Quinic acid, dicaffeoyl: SdCA090 Thiazole, 5-ethyl-2-N-propyl: Sd HuCA076 Quinic acid: Sd 0.55%CA125, Sd Thiazole, 5-methyl: Sd HuCA075 (immature)CA109, SdCA089 Thiazole, 5-methyl-4-ethyl: Sd HuCA075 Quinide: Sd (immature)CA109 Thiazole: Sd HuCA076 Quinoline, 4-methyl: Sd HuCA076 Thiolan, 2-one: Sd (roasted)CA063 Quinoxaline, 2-3-dimethyl: SdCA069, Sd Thiophan-3-one, 2-methyl: Sd HuCA082 HuCA076 Thiophene, 2-acetyl: Sd (roasted)CA063 Quinoxaline, 2-5-dimethyl: Sd HuCA076 Thiophene, 2-acetyl: Sd HuCA082 Quinoxaline, 2-ethyl: SdCA069 Thiophene, 2-acetyl-3-methyl: Sd Quinoxaline, 2-methyl: Sd HuCA076 (roasted)CA063 Quinoxaline, 5-methyl: SdCA069 Thiophene, 2-acetyl-4-methyl: Sd HuCA082 Quinoxaline: Sd HuCA076 Thiophene, 2-acetyl-5-methyl: Sd Salicylic acid methyl ester: Sd (roasted)CA063 (roasted)CA063 Sitosterol, E: Sd oil 9.4%CA133, SdCA107 Thiophene, 2-aldehyde: Sd (roasted)CA063 Stearic acid: SdCA068 Thiophene, 2-methyl: Sd HuCA082 Stigmasterol: SdCA107 Thiophene, 2-N-butyl: Sd HuCA082 Styrene, 3-4-dihydroxy: SdCA122 Thiophene, 2-N-propyl: Sd HuCA082 Styrene, 3-4-dimethoxy: Sd HuCA082 Thiophene, 2-propionyl: Sd (roasted)CA063 Styrene, 4-hydroxy-3-methoxy: SdCA122 Thiophene, 3-acetyl: Sd (roasted)CA063 Succinimide, N-D-dimethyl: Sd (roasted)CA063 Thiophene, 3-methyl, 2-carboxaldehyde: Sucrose: SdCA089 Sd HuCA082 Sulfide, 2-furfuryl-methyl: Sd (roasted)CA063 Thiophene, 3-methyl: Sd HuCA082 Sulfide, methyl-ethyl: Sd (roasted)CA063 Thiophene, 5-methyl, 2-acetyl: Sd HuCA082 Tannic acid: SdCA091 Thiophene, 5-methyl, 2-carboxaldehyde: Tannins: AerCA128 Sd HuCA082 Terpineol, D: FrCA087 Thiophene: Sd (roasted)CA063 Theacrine: SdCA113 Tocopherol: Sd oil 0.02-0.05%CA133 Thenyl, 2-acetate: Sd (roasted)CA063 Toualdehyde, meta: Sd (roasted)CA063 Thenyl, 2-alcohol: Sd (roasted)CA063 Transferase, N-methyl: Pl, Call TissCA123, Theobromine: PlCA108, Sd, PcCA111 FrCA119, Theophylline: PcCA111 Trigonelline: SdCA101 Thiazole, 2-4-5-trimethyl: Sd HuCA075 Tryptamide, 5-hydroxy: SdCA074 Thiazole, 2-4-diethyl: Sd HuCA075 Tryptamine, 5-hydroxy, N-E-(20-hydroxy- Thiazole, 2-4-dimethyl: Sd HuCA075 arachidoyl): Fr (unripe) 0.5CA120 162 MEDICINAL PLANTS OF THE WORLD

Tryptamine, 5-hydroxy, N-E-(22-hydroxy- more per day: odds ratio 2.2. Among smok- behenoyl): Fr (unripe) 0.5CA120 ers, caffeine ingestion was not associated Tryptamine, 5-hydroxy, N-E-(arachidoyl): CA120 with an excess risk of spontaneous abortion. Fr (unripe) When the analysis was stratified according Tryptamine, 5-hydroxy, N-E-(behenoyl): Fr (unripe)CA120 to the results of karyotyping, the ingestion Tryptamine, 5-hydroxy, N-E-(indoleoyl): of moderate or high levels of caffeine was Fr (unripe)CA120 associated with an excess risk of spontane- Tryptamine, 5-hydroxy, N-E-(lignoceroyl): ous abortion when the fetus had a normal or Fr (unripe)CA120 unknown karyotype but not when the fetal CA194 CA084 Tryptamine, 5-hydroxy: Wax , Sd karyotype was abnormalCA021. CA086 Ursolic acid: Lf 0.05% Alanine aminotransaminase level in- Ut-2-en-1-4-olide, 2-3-4-trimethyl: Sd (roasted)CA063 crease. Roasted seed powder, administered Valeolactone, J: Sd (roasted)CA063 in unfiltered coffee to adults at a dose of 8 g/ Valeric acid, iso: Sd (roasted)CA063 day, was activeCA172. Vitamin D: Sd oilCA133 Allergenic activity. Ground coffee con- Vitamin K-1: Sd 0.2K18625 tains polyphenol haptens that activate Xanthine, 7-methyl: PlCA115 the factor XII (Hageman factor)-depen- CA113 Xanthine, para: Sd dent pathways of coagulation, fibrinolysis, PHARMACOLOGICAL ACTIVITIES and kinin generation in normal human AND CLINICAL TRIALS plasmaCA006. Extract of the dried aerial part, Abortifacient effect. In a population- administered by inhalation to female adult based, case-controlled study of early sponta- who developed rhinitis and conjunctivitus neous abortion in Sweden, 562 women who on exposure to coffee plant, was active. A had spontaneous abortion at 6–12 weeks of skin prick test and rhinoconjunctival provo- gestation and 953 women who did not have cation test to coffee leaf allergen extract abortion, indicated that the ingestion of caf- were positiveCA201. Seeds, administered by feine may increase the risk of an early spon- inhalation to adults at variable doses, were taneous abortion among nonsmoking active. A 37-year-old worker in a coffee- women carrying fetus with normal karyo- roasting facility developed rhinoconjunc- types. Information on the ingestion of caf- tivis as a result of exposure to the dust of feine was obtained from in-person interviews. green, unroasted coffee beanCA153. Extract of Plasma cotinine was measured as an indica- the dried seed, administered by inhalation tor of cigarette smoking, and fetal karyo- to female adults, was active. Extract of the types were determined from tissue samples. fresh seed, administered by inhalation to Multivariate analysis was used to estimate females with rhinitis and conjunctivitus, the relative risks associated with caffeine produced a positive skin prick test and ingestion after adjustment for smoking and rhinoconjunctival provocation test to cof- symptoms of pregnancy, such as nausea, fee leaf allergen extractCA201. vomiting, and tiredness. Among the non- D-Amylase inhibition. Powder of the dried smokers, more spontaneous abortions seed, administered intragastrically to mice occurred in women who ingested at least at a dose of 100 mg/kg, was active vs N-me- 100 mg of caffeine per day than in women thyl-N'-nitro-N-nitroso-guanidine-induced who ingested less than100 mg/day, with the mutagenesisCA191. increase in risk related to the amount Ambulatory blood pressure. The effect of ingested; 100–299 mg/day: odds ratio, 1.3; regular coffee drinking on 24-hour ambula- 300–499 mg/day: odds ratio 1.4; 500 mg or tory blood pressure in 22 men and women COFFEA ARABICA 163 who were normotensive and 26 men and active. Dialysis separation of roasted coffee women who were hypertensive with a mean components also showed that a coffee com- age of 72.1 years (range 54–89 years) was ponent fraction commonly considered as investigated. After 2 weeks of drinking caf- low-molecular weight coffee melanoidins feine-containing drinks or instant coffee may sensibly contribute to the roasted (five cups/day, equivalent to 300 mg caffeine coffee’s antiadhesive propertiesCA001. per day), changes in systolic blood pressure Anti-aging activity. Extract of the dried (SBP) and diastolic blood pressure (DBP) in seed, administered externally to adults at a the hypertensive group rise in mean SBP concentration of 0.5%, was active. The was greater by 4.8 (Standard error of the biological activity reported has been pa- mean, 1.3) mmHg (p = 0.031) and increase tentedCA151. in mean DBP was higher by 3 (1) mmHg (p Antibacterial activity. Extract of the dried = 0.010) in coffee drinkers than in abstain- seed, on agar plate at a concentration of 0.1 ers. There were no significant differences mL/plate, was inactive on Pseudomonas between coffee drinkers and abstainers in aeruginosa, Salmonella typhi, Salmonella the normotensive groupCA047. In the group of typhimurium, Shigella dysenteriae, Shigella 52 participants, the effect of coffee on blood flexneri 2A, Vibrio mimicus, Yersinia entero- pressure was estimated with the use of a ran- litica, and Escherichia coli. Enteroinvasive, dom-effects model. In 11 trials, median du- enterohemorrhagic, enteropathogenic and ration was 56 days (range 14–79 days) and enterotoxic Escherichia coli was usedCA211. median dose of coffee was five cups per day. Extract of the dried seed, on agar plate at SBP and DBP increased by 2.4 (range 1–3.7) a concentration of 0.1 mL/plate, produced mmHg and 1.2 (range 0.4–2.1) mmHg, re- weak activity on Enterobacter cloacae, Aero- spectively, with coffee treatment compared monas sobria, Clavibacter michiganense ssp. to controls. Multiple linear regression analy- nebraskense, Staphylococcus aureus, Staphylo- sis identified an independent, positive rela- coccus epidermidis, Vibro cholera 0-1 V86 EL tionship between coffee consumption and TOR, Vibro cholerae 0-1 569B classical changes in SBP. The effect on SBP and DBP strain, Vibro cholera non 0-1 strain, Vibrio was greater in trials with younger partici- fluvialis, and Vibrio parahaemolyticus. Ex- pantsCA050. tract of the dried seed, on agar plate at a Anemia-producing activity. Hot water concentration of 0.1 mL/plate, was active extract of the roasted coffee, administered on Plesiomonas shigelloidesCA211. Ethanol orally to adults of both sexes, was inac- (95%) extract of the dried seed, on agar tiveCA167. plate at a concentration of 1 mg/disc, was Anti-adhesive effect. Green and roasted active on Bacillus subtilisCA246. EtOAc extract coffee, used in a treatment mixture and as a of the roasted seed, on agar plate at a con- pretreatment on beads, inhibited the Strep- centration of 0.76 mg/mL, was active on tococcus mutans’ sucrose-independent ad- Streptococcus mutansCA204, and a concentra- sorption to saliva-coated hydroxyapatite tion of 0.84 mg/mL was active on Staphylo- beads. The inhibition of Salmonella mutans coccus aureus. Water extract of the roasted adsorption indicated that coffee-active mol- seed, on agar plate at a concentration of ecules may adsorb to a host surface, prevent- 12.7 mg/mL, was active on Streptococcus ing the tooth receptor from interacting with mutans, and a concentration of 13.5 mg/mL any bacterial adhesions. Among the known was active on Staphylococcus aureus. Infu- tested coffee components, trigonelline and sion of the roasted seed, on agar plate at a nicotinic and chlorogenic acids are very concentration of 1.56 mg/mL, was active on 164 MEDICINAL PLANTS OF THE WORLD

Streptococcus mutans and Staphylococcus administered orally to female adults at vari- aureusCA204. Decoction of the dark-roasted able doses, was active. There was a correla- seed, on agar plate at concentrations of 3 tion between heavy coffee drinking and and 6 mg/mL, was active on Staphylococcus difficulty in becoming pregnant in women aureus. Decoction of the medium-roasted in the United StatesCA242. Hot water extract seed, on agar plate at concentrations of 4, 6, of the roasted seed, administered in the 10, 11, and 34 mg/mL, were active on Sta- drinking water of male rats at variable doses phylococcus aureus. Decoction of the light- daily for 30 weeks, was inactiveCA228. roasted seed, on agar plate at concentrations Antigen modification. Pig-to-rhesus mon- of 6, 11, 12, 15, and 17 mg/mL, was active key vein transplants were studied to identify on Staphylococcus aureusCA204. the efficiency of green bean D-galactosidase Anticarcinogenic activity. The effects of in delaying hyperacute rejection. Biopsies coffee consumption on thyroid carcinomas were taken after occluding the grafts for and adenomas were investigated using a light microscopy (hematoxylin and eosin), standard questionnaire is a case–control scanning electron microscopy, and immu- study in southwestern Germany, a know nostaining with Griffonia simplicifolia IB4 iodine-deficient area. The protective role of lectin, and for immunoglobulin (Ig) M, IgG, coffee drinking and the consumption of and IgC3. Galactosidase is effective in cruciferous vegetables, such as broccoli, removing the terminal D-galactosidase and were confirmed for both genders. Treatment delays the onset of hyperacute rejection; for goiter and decaffeinated coffee consump- however, its effect is temporary and it pro- tion were associated with an increased risk longs the survival of pig organs transplanted for malignant tumors, but less so for into primatesCA056. adenomasCA028. Antihemolytic activity. Water extract of Anticlastogenic activity. Powder of the the dried seed, administered to rabbits’ red roasted seed, administered intragastrically blood cells at variable concentrations, was to mice and Microtus montanus at a dose of inactive vs Staphylococcus aureus D-toxin- 100 mg/kg, was active vs N-methyl-N'- induced hemolysis and produced weak nitro-N-nitroso-guanidine-induced muta- activity vs Vibrio parahaemolyticus-induced genesis. E-carotene, curcumin, ellagic acid, hemolysisCA213. and chlorogenic acid inhibited urethane- Anti-inflammatory activity. Extract of the induced micronuclei formation. E-carotene, green seed, administered externally to adult curcumin, and D-tocopherol inhibited mi- with skin inflammations by free radical cronuclei formation. Coffee potentiated the inhibition at a concentration of 1%, was effect. A combination of curcumin, chloro- activeCA177. genic acid, eugenol, anethole, and D-toco- Antimitogenic activity. Hot water extract pherol did not significantly inhibit of the fruit, administered orally to adults at micronuclei formation. Coffee did not alter variable doses, was active vs phytohemag- the activity. A mixture of pure compounds glutinin-, concanavalin A-, and pokeweed was usedCA145. mitogen-induced mitogenesisCA241. Antifertility effect. Decoction of the dried Antimutagenic activity. Extract of the seed, administered orally to female adults at seed, on agar plate at a concentration of 2.5 a dose of 0.96 L/day, was active. Coffee Pg/mL, was active on Salmonella typhimu- intake delayed the time to conception and rium TA100 and TA102 vs T-butyl perox- increased relative risk of failure to con- ide-induced mutagenesisCA169. Hot water ceiveCA152. Decoction of the dried seed, extract of the seed, on agar plate at a con- COFFEA ARABICA 165 centration of 3 mg/mL, was active on Sal- substances of coffee and its antioxidant monella typhimurium TA1535CA223. Infusion activity in vitro and in vivo as protective of the seed, on agar plate at a concentration activity against rat liver cell microsome lipid of 100 PL/disc, was inactive on Salmonella peroxidation measured as thiobarbituric typhimurium TA98 vs 2-amino-anthracene acid-reacting substances. Reducing sub- induced mutagenicity. Metabolic activation stances of Robusta samples were significantly was required for activityCA188. Lyophilized higher when compared to those of Arabica extract of the seed, on agar plate at a con- samples (p < 0.001). Antioxidant activity centration of 6.8 mg/mL, was active on Sal- for green coffee samples was slightly higher monella typhimurium TA1535 vs aflatoxin-2; than for the corresponding roasted samples 4-NQO-, MNNQ-, and ultraviolet light- (p < 0.001). Extraction with three different induced mutagenicityCA235. Lyophilized organic solvents (ethyl acetate, ethyl ether, extract of the seed, on agar plate at a con- and dichloromethane) showed that the centration of 15 mg/mL, was active on Sal- most protective compounds are extracted monella typhimurium TA100. Addition of from acidified dark-roasted coffee solutions catalase decreased the activityCA230. Decoc- with ethyl acetate. Analysis of acidic extract tion of the dried seed, at a concentration of by gel filtration chromatography produced 2% was active on Drosophila melanogaster vs five fractions. Higher molecular mass frac- cyclophosphamide-induced genotoxicity. A tions showed protective activity. The small concentration of 5% was active vs urethane- amounts of these acidic low-molecular-mass induced genotoxicity. Methylene chloride/ protective fractions isolated indicated that 2-propanol (1:1) extract, at a concentration they contain strong protective agentsCA007. of 2%, was active on Drosophila melanogaster Coffee and the sum of coffee and red wine on vs mitomycin C-induced genotoxicity CA185. healthy subjects showed detectable capacity Hot water extract of the roasted coffee, on to scavenge radical cations in the colonic agar plate at a concentration of 1%, was lumen, suggesting that antioxidant activity active on Salmonella typhimurium TA100 vs occurs in the colonic lumen. Fourteen sub- benzopyrene, AF-2, and 4NQO mutagenic- jects recorded their food intake three times ity. Hot water extract of the roasted coffee, for a period of 2–4 days, each time collect- on agar plate at a concentration of 1%, was ing all of the feces passed during the next active on Salmonella typhimurium TA98 vs 24 hours. Total antioxidant activity (6- TRP-P-2, Glu-P-1, 2-acetylaminofluorene, hydroxy-2,5,7,8-tetramethulchroman-2- and IQ mutagenicity. Hot water extract of carboxylic acid) of fecal suspension was the roasted coffee, on agar plate at a con- measured using the 2,2'-azinobis-(3-ethyl- centration of 1%, was inactive on Salmonella benzothiazoline)-6-sulfonic acid radical cat- typhimurium TA100 vs E-propiolactone and ion decolorization assay. The average total glycidol mutagenicity. Hot water extract of antioxidant activity of feces was 26.6 mmol/ the roasted coffee, on agar plate at a con- kg wet feces. The total amount of antioxi- centration of 1%, was inactive on Salmonella dant equivalents excreted over 24 hours, typhimurium TA100 vs acrolein mutagen- derived by multiplying the total antioxidant icityCA234. activity by the amount of feces passed dur- Antioxidant activity. Green and roasted ing 24 hours, was 3.24 mmol, and this was coffee beans were evaluated in relation to significantly correlated with the average 24- degree of roasting and species (Coffea hour intake of coffee and red wine, particu- arabica and Coffea robusta). The properties larly to the sum of coffee and red wineCA015. were evaluated by determining the reducing Hot water extract of the seed, produced an 166 MEDICINAL PLANTS OF THE WORLD inhibition of Fenton-catalyzed oxidation of Blood flow increase. Decoction of the 2'-deoxyguanosineCA169. seed, administered orally to adults, was Antispasmodic activity. Ethanol (50%) active. Result was the same for both regular extract of the aerial parts was active on the and decaffeinated coffee drinkersCA164. guinea pig ileum vs acetylcholine - and his- Bone mineral density. The association of tamine-induced spasmsCA139. caffeine consumption and bone mineral Anti-tumor activity. Water extract of the density has been investigated in 177 healthy dried seed, administered intraperitoneally to women, age 19–26 years. Average caffeine mice, was active on CA-755 cellsCA171. Hot intake was calculated from self-reports of water extract of the dried seed, administered the consumption of coffee, tea, colas, in the drinking water of mice at a concen- chocolate products, and selected medica- tration of 0.5%, was active on spontaneous tions during the previous 12 months. Mean mammary tumorsCA180. caffeine intake was 99.9 mg/day. Bone min- Antiviral activity. Hot water extract of the eral density at the femoral neck and the seed, in cell culture, produced weak activity lumbar spine was measured by dual-energy on poliovirus 1CA225. X-ray absorptiometry. After adjusting for Anti-yeast activity. Ethanol (100%) extract potential confounders, including height, of the seed, on agar plate at a concentration body mass index, age and menarche, cal- of 18.7 mg/mL, was active on Candida cium intake, protein consumption, alcohol albicans. Water extract of the seed, on agar consumption, and tobacco use, caffeine plate was inactive on Candida albicansCA205. consumption was not a significant predictor Arrhythmogenic effect. Hot water extract of bone mineral density. For every 100 mg of the dried seed, administered orally to of caffeine consumed, femoral neck bone adults with cardiac abnormalities at a dose mineral density decreased 6.9 mg/cm2 and of 200 mg/person, produced equivocal lumbar spine bone mineral density effectCA210. decreased 11.9 mg/cm2. No single source of Atherosclerotic effect. Hot water extract caffeine was significantly associated with a of the roasted coffee, administered orally to decrease in bone mineral density. Further- 85,747 female nurses, produced no correla- more, the association between caffeine tion between coffee consumption and coro- consumption and bone mineral density at nary heart diseaseCA179. either site did not differ significantly Birth-weight effect. Caffeinated coffee between those who consumed low levels of alone had an adjusted odds ratio of 1.3 (95% calcium (Յ836 mg/day) and those who confidence limits [CL] = 1.0, 1.7) for consumed high levels of calcium (>836 mg/ preterm delivery; mothers who consumed day)CA025 both caffeinated and decaffeinated coffee Bone mineral effect. Coffee, taken by 258 had an adjusted odds of 2.3 (95% CL = 1.3, healthy occupationally active men aged 40– 4), whereas those who consumed only 63 years, significantly reduced the trabecu- decaffeinated coffee showed no increased lar bone mineral content. The extent of odds of small-for-gestational age birth, low- alcohol intake did not differentiate bone birth-weight or preterm delivery. A reduc- mineral content values at the distal radius, tion in mean birth-weight of –3 g per cup whereas the significant detrimental effects per week (95% CL = –5.9, –0.6) for of both smoking and coffee drinking on tra- caffeinated coffee and an increase of +0.4 g becular (but not cortical and total) bone per cup per week (95% CL = 3.7, 4.5) for mineral content were revealed. Simulta- decaffeinated coffee was foundCA046. neously, smokers and ex-smokers, when COFFEA ARABICA 167 compared to lifelong nonsmokers, had lower inhibited mammary tumor development in trabecular bone mineral contentCA014. SHN virgin mice. Water-soluble fraction of Brain metabolic response. Changes in the dried fruit, administered to female mice brain lactate resulting from the combined at a dose of 0.25% of diet, inhibited mam- effects of caffeine’s stimulation of glycolysis mary glands in SHN virgin mice CA202. and reduction of cerebral blood flow were Decoction of the dried seed, administered determined by a rapid proton echoplanar in drinking water to rats at a concentration spectroscopic imaging technique in a group of 57.0 g/L, produced no effect on dime- of nine heavy caffeine users and nine caf- thylnitrosamine-induced glutathione S- feine-intolerant persons. They were studied transferase positive foci after subtotal at baseline and 1 hour after ingestion of caf- hepatectomyCA176. Decoction of the dried feine citrate (10 mg/kg). Five of the caffeine seed, administered intragastrically to preg- users were restudied after a 1- to 2-month nant rhesuses at a dose of 10 mL/kg for 90 caffeine holiday. Significant increases in minutes before dosing with cyclophos- global and regionally specific brain lactate phamide, N-nitrosodiethylamine, N-nitroso- and psychological and physiological distress N-ethylurea, or mitomycin, produced in response to caffeine ingestion were micronuclei and polychromatophilic nucle- observed only among the caffeine-intoler- ated erythrocytes in fetal liver, marrow, and ant persons. Reexposure of the regular cof- bloodCA182. Seeds, administered in ration of fee drinkers to caffeine after a caffeine high mammary tumor strain of SHN/MEI holiday resulted in little or no adverse clini- virgin female mice, were activeCA175. Hot cal reaction but did result in significant rises water extract of the dried seed, administered in brain lactate, which were of a magnitude in drinking water to rats at a dose of 6000 similar to that observed for the caffeine- ppm, was activeCA158. Hot water extract of intolerant groupCA051. the dried seed, administered orally to adults Caffeine intake, tolerance, and with- at variable doses, produced no effect on pan- drawal. Caffeine in the form of brewed and creatic cancerCA207. Hot water extract of the instant coffee, tea, and caffeinated drinks dried seed, administered orally to adults at was taken by 1934 individual twins from variable doses, was inactive. Patients with female–female pairs, including 486 monozy- newly diagnosed breast cancer (n = 818) gotic and 335 dizygotic pairs. The resem- were compared to surgical and neighbor- blance in twin pairs for total caffeine hood controls in a dietary case–control consumption, heavy caffeine use, caffeine study of the relationship of dietary intake of intoxication, tolerance, and withdrawal was coffee and total methylxanthine from cof- substantially greater in monozygotic than in fee, tea, chocolate, and cocoa drinks. A dizygotic twin pairs and could be ascribed nonsignificant negative association was solely to genetic factors, with estimated found between methylxanthine consump- broad heritabilities of between 35 and tion and breast cancer. This pattern was 77%CA052. stronger in patients with high-fat diets after Cancer-associated risk factor. Infusion of controlling several confounding hormonal the seed, administered orally to adults, pro- factors. A diminished risk was found when duced equivocal effect on urinary bladder consumption of methylxanthine of patients cancerCA156. with breast cancer is compared to that of pa- Carcinogenesis inhibition. Water-soluble tients with benign diseaseCA231. Decoction of fraction of the dried fruit, administered to the dried seed, administered to male rats at female mice at a dose of 0.25% of diet, a dose of 5% of diet, was active vs dimeth- 168 MEDICINAL PLANTS OF THE WORLD ylnitrosamine-induced carcinogenesisCA218. of dosing with cycasin orally (150 mg/kg) Lyophilized extract of the dried seed, ad- on day 121, produced five tumors. Hot wa- ministered intragastrically to mice at a dose ter extract of the roasted seed, adminis- of 50.0 g/kg of diet, was active. Animals tered orally to rats at a dose of 2%, was were exposed to coffee in utero, as mother’s inactive CA195. diet was 1% instant coffee. After weaning, Carcinogenic risk analysis. Pooled data of animals were given an instant coffee for 2 564 cases and 2929 hospitals or population years. Incidence of neoplasms decreased controls who had never smoked were en- from 70.6 to 34.8% in males and from 56.8 rolled in epidemiological studies to exam- to 36.2% in females. The incidence of be- ine the association of coffee with an excess nign tumor was 2.72 vs 0% for controlsCA216. bladder cancer risk. The data were evalu- Seed oil, administered to hamster at a con- ated from 10 studies conducted in Denmark, centration of 2.25% of diet, was active vs Germany, Greece, France, Italy, and Spain. 7,12-dimethylbenz[a]anthracene (DMBA)- Information on coffee consumption and induced oral tumors. Seed, administered to occupation was recoded following standard hamsters at a concentration of 15% of criteria. Unconditional logistic regression diet, was active vs DMBA-induced oral was applied adjusting for age, study center, tumorsCA173. Seed, administered to rats at a occupation, and gender. Seventy nine per- concentration of 20% of diet, was active vs cent of the study population reported hav- DMBA-induced carcinogenesisCA143. Decoc- ing consumed coffee, and 2.4% were heavy tion of the roasted coffee, administered drinkers, reporting having ingested on aver- orally to adults, was active on risk of colon age 10 or more cups per day. There was no or rectal cancer. Risk of colon cancer was excess risk in coffee drinkers compared to reduced in drinkers of four or more cups of nondrinkers. The risk did not increase coffee per day. There was no effect on rectal monotonically with dose, but a statistically cancerCA147. Methylene chloride/2-propanol significant risk was seen for subjects having (1:1) extract of the roasted coffee, adminis- ingested 10 or more cups per day. This tered in drinking water of male rats at a con- excess was seen in both males and females. centration of 10%, was inactive on urinary There was no evidence of an association of bladderCA154. Seed oil, administered to male the risk with duration or type of coffee con- rats at a dose of 0.10%, was active on the sumption. Nonsmokers who are heavy cof- colonCA170. fee drinkers may have a small excess risk of Carcinogenic activity. Decoction of the bladder cancer. Although these results can- seed, administered orally to adults, was in- not be attributed to confounding by smok- active. There was no association between ing, the possibility of bias in control colorectal adenomas and consumption of selection cannot be discarded. On the basis extractCA189. Roasted seed, administered to of the data, only a small proportion of can- male rats at a dose of 6% of diet for 2 years, cers of the bladder among nonsmokers could was inactive. Water extract of the roasted be attributed to coffee drinkingCA018. seed, administered to female rats at a dose Cardiac mechanoenergetics. Caffeine in of 6% of diet, was inactive. Regular and a concentration higher than 0.05 mM, cor- decaffeinated instant coffees were studied. responding to the maximum blood concen- Coffees with highest caffeine content tration after a healthy human subject showed lower tumor incidenceCA197. Hot wa- consumed a cup of coffee, depresses left ven- ter extract of the roasted seed, administered tricular systolic and diastolic functions and orally to 18 rats at a dose of 2% for 120 days decreases a measure of total mechanical COFFEA ARABICA 169 energy per beat in terms of SBP-volume area ated under caffeine); and increased over more severely in failing hearts at concentra- baselines during all cognitive activities tions lower than those in normal heartsCA060. (ranges 3.8–6.9%)CA042. Cardioexcitatory activity. Hot water Chemopreventive effect. Chlorogenic extract of the dried seed, administered orally acid had a regressive effect on induced aber- to adults, produced weak activity. There was rant crypt foci, as well as on development of no change in electrocardiogram pattern, but aberrant crypt foci in azoxymethane- some subjects showed sinus arrhythmia, induced colorectal carcinogenesis in rats. sinus tachycardia, and incomplete right Rice germs and J-aminobutyric acid- bundle branch block, premature ventricular enriched defatted rice germ inhibited azoxy- contraction, and premature atrial contrac- methane-induced aberrant crypt foci tionCA224. formation and colorectal carcinogenesis in Cardiovascular effects. Caffeinated coffee rats. Ferulic acid, also known to be con- was taken by 72 males and 72 females with a tained in coffee beans and rice, prevented mean age of 21 years. Ingestion of caffeine azoxymethane aberrant crypt foci formation had no effect on initial mood or working and intestinal carcinogenesis in ratsCA017. memory, but it improved encoding of new Cholesteryl ester transfer protein activ- information, counteracted the fatigue, and ity. French press or filtered coffee, con- increased blood pressure and pulse rateCA044. sumed by 46 healthy normolipidemic Cerebral blood flow. The possibility of subjects for 24 weeks, produced a long-term caffeine-mediated changes in blood flow increase in cholesteryl ester transfer protein, velocity in the middle cerebral artery in- as well as phospholipid transfer protein duced by tests of cerebrovascular respon- activity; the increase in cholesteryl ester siveness was examined by transcranial transfer protein activity may contribute to doppler sonography. Velocity in the middle the rise in low-density lipoprotein (LDL) cerebral artery measures were obtained as cholesterol. Relative to the baseline values, healthy college students hypoventilated, French-press coffee significantly increased hyperventilated, and performed cognitive average cholesteryl ester transfer protein activities (short-term remembering, gener- activity by 12% after 2 weeks, by 18% after ating an autobiographical image, and solv- 12 weeks, and by 9% after 24 weeks. Phos- ing problems), each in 31-second tests. The pholipid transfer protein activity was signifi- measures were obtained from the same per- cantly increased by 6% after 2 weeks and by sons, in separate testing sessions, when they 10% after 12 weeks. Lecithin/cholesterol were noncaffeinated and under two levels of acyltransferase activity was significantly caffeine (45 mg/12 oz and 117 mg/8 oz). decreased by 6% after 12 weeks and by 7% Compared with the no-caffeine control after 24 weeks. The increase in cholesteryl condition, a smaller amount of caffeine had ester transfer protein clearly preceded the no significant effects on global velocity in increase in LDL cholesterol, but not the the middle cerebral artery but a larger increase in total triglycerides (TGs). How- amount suppressed the velocity by 5.8%. ever, consumption of French-press coffee Time course analyses indicated that the produced a persistent rise in cholesteryl velocity followed a triphasic pattern to ester transfer protein activity, whereas the increase over baselines during hypoventi- rise in serum TGs was transientCA032. lation, regardless of caffeine condition; Water extract of the green seed, adminis- slowed below baselines during hyperventi- tered intravenously to male rats at a dose of lation (with the degree of slowing attenu- 70 mg/kg, was inactive. Water extract of the 170 MEDICINAL PLANTS OF THE WORLD roasted seed, administered intravenously tion component of the choice reaction time to male rats at a dose of 0.84 mg/kg, was task. There were significant differences activeCA155. between tea and coffee at 75 mg caffeine Chromosome aberration induced. Lyo- dose after the first drink. Compared to cof- philized extract of the roasted seed, in cell fee, tea produced a significant increase in culture at a concentration of 3.9 mg/mL, critical flicker fusion threshold between 30 was active on human lymphocytes. and 90 minutes postconsumption. After the Caffeinated and decaffeinated coffees with- second beverage, caffeinated coffee at 75 mg out S9 mix was tested. The extract produced dose significantly improved reaction time, weak activity with S9 mixCA233. Extract of compared with tea at the same dose, for the the roasted seed, in cell culture at variable recognition component of the choice reac- concentrations, was active on human lym- tion time task. Caffeinated beverages had a phocytes. Metabolic activation reduced the dose-dependent negative effect on sleep on- effectCA239. set, time, and quality. Day-long tea con- Central nervous system effects. Ethanol sumption produced similar alert effects as (60%) extract of the dried seed, adminis- coffee, despite lower caffeine levels, but it is tered orally to adults at a dose of 30 mL/per- less likely to disrupt sleepCA036. son, increased acuteness of hearingCA244. Colonic cancer risk. French-press coffee, Water extract of the roasted seed, adminis- consumed by men and women with mean tered orally to adults, produced an increase age of 43 r 11 years, did not influence the in work performanceCA141. colorectal mucosal proliferation rate but Cognitive and psychomotor perfor- may increase the detoxification capacity mance. Coffee and tea, consumed four and antimutagenic properties in the times during the day by 30 healthy volun- colorectal mucosa through an increase in teers, maintained aspects of cognitive and glutathione concentrationCA033. psychomotor performance throughout the Comutagenic activity. Hot water extract day and evening when caffeinated beverages of the roasted seed with methylglyoxal, DL- were administered repeatedly. Tea, coffee, glyceraldehyde, dihydroxyacetone, and or water was administered in a randomized autoxidized linoleic acid, on agar plate at a five-way crossover design. A psychometric concentration of 1%, were active on Salmo- battery consisting of critical flicker fusion, nella typhimurium TA100CA234. choice reaction time, and subjective seda- Coronary heart disease. In a study of 20 tion tests was administered predose and at randomly selected groups of 179 Finnish frequent time points postdose. The Leeds men and women aged 30–59 years, it was sleep evaluation questionnaire was com- determined that coffee drinking did not pleted each morning, and a wrist Actigraph increase the risk of coronary heart disease was worn for the duration of the study. or death. In men, the effects of smoking and Caffeinated beverages maintained critical a high serum cholesterol level largely flicker fusion threshold throughout the explain slightly increased mortality from whole day, independent of caffeine dose or coronary heart disease and all causes in beverage type. During the acute phase of the heavy coffee drinkers. Habitual coffee beverage ingestion, caffeine significantly drinking, health behavior, major known sustained performance compared with coronary heart disease risk factors, and water after the first beverage of critical medical history were assessed at the baseline flicker fusion and subjective sedation and examination. Each subject was followed up after the second beverage for the recogni- 10 years after the survey using the national COFFEA ARABICA 171 hospital discharge and death registers. Mul- Down syndrome effect. Data from a case– tivariate analyses were performed using the control study of 997 live-born infants or Cox proportional hazards model. In men, fetuses with Down syndrome and 1007 the risk of nonfatal myocardial infarction live-born controls with a birth defect indi- was not associated with coffee drinking. The cated that among nonsmoking mothers, highest coronary heart disease mortality was high coffee consumption is more likely to found among those who did not drink cof- reduce the viability of a Down syndrome fee at all. Also, in women, all-cause mortal- conceptus than that of a normal con- ity decreased by increasing coffee drinking. ceptusCA020. The prevalence of smoking and the mean Embryotoxic effect. Hot water extract of level of serum cholesterol increased with the Folger’s instant coffee, administered by increasing coffee drinking. Non-coffee gastric intubation to pregnant mice at a dose drinkers more often reported a history of of 1.28 mg/animal, was inactiveCA229. Hot various diseases and symptoms, and they water extract of the roasted seed, adminis- were also more frequently users of several tered in drinking water of pregnant rats at drugs compared with coffee drinkersCA023. A variable doses daily for 30 weeks, was risk of coronary events (death, nonfatal inactiveCA228. infarction, or coronary artery surgery) was Estrogenic effect. Unsaponifiable fraction estimated in a group of more than 11,000 of the seed oil, administered subcutaneously men and women aged 40–59 years by approx to immature female rats at a dose of 117 mg/ 7.7 years of study. Coffee and tea consump- animal, was inactiveCA138. Subcutaneous tion showed a strong inverse relation. Cof- administration to ovariectomized female fee showed a weak but beneficial gradient guinea pigs was activeCA248. with increasing consumption, associated Fatalities. Extract of the roasted seed, with beneficial effects for mortality and administered rectally to a 37-year-old coronary morbidity, although there was a woman with breast cancer after radical mas- residual benefit of coffee consumption in tectomy and chemotherapy at a dose of 0.95 avoiding heart disease among menCA058. L/person four times daily, was active. Death Decoction of the dried seed, administered was attributed to fluid and electrolyte im- to adults of both sexes at variable doses, pro- balance. Sodium and chloride could not be duced equivocal effect. In a 12-year cohort detected. Extract of the roasted seed, admin- study on the influence of coffee intake on istered rectally to a 46-year-old woman at a coronary heart disease in 38,500 subjects it dose of 10–12 coffee enemas, three to four was indicated that during the first 6 years a an hour, produced convulsive seizures and strong correlation between high coffee eventually deathCA219. Decoction of the dark- intake and coronary death was found. After roasted seed, on agar plate, was active on the first 6 years, the correlation was signifi- Staphylococcus aureus, with lethal dose50 of cantly decreasedCA140. 16 mg/mL. Concentrations of 23, 35, and Cytotoxic activity. Ethanol (50%) extract 40 mg/mL, were active on Escherichia coli. of the aerial parts, in cell culture, was inac- Decoction of the medium-roasted seed at tive on CA-9KB, effective dose50 greater concentrations of 29, 41, 50, and 52 mg/mL, than 20.0 Pg/mLCA139. were active on Escherichia coli. Decoction of Dermatitis-producing effect. Hot water the light-roasted seed at concentrations of extract and powder of the dried seed, 40, 46, 50, and 57 mg/mL, were active on administered externally to adults, were Escherichia coli. Decoction of the roasted activeCA212. seed, on agar plate at concentrations of 28 172 MEDICINAL PLANTS OF THE WORLD and 41 mg/mL, was active on Escherichia J-Glutamyltransferase effect. In a cross- coli. Decoction of the medium-roasted seed, sectional study involving 1353 males aged on agar plate at a concentration of 4 mg/mL, 35–59 years, it was concluded that coffee was active on Sarcina luteaCA178. consumption is inversely related to serum Fertilization inhibition. Hot water extract J-glutamyltransferase and that coffee may of the roasted seed, administered in the inhibit the inducing effects of aging and drinking water of female rats at variable possibly of smoking on serum J-glutamyl- doses daily for 30 weeks, was inactiveCA228. transferase in the liverCA030. Fibrinogen level increase. Hot water ex- Gastroesophageal reflux effect. Coffee, a tract of the dried seed, administered to known lower esophageal sphincter relaxant, adults at a dose of five cups/day, produced was tested in 185 and 258 cases of esoph- CA150 weak activity . ageal adenocarcinoma and gastric adenocar- Fungal activity. Coffee leaves, fruits, and cinoma, respectively, and 815 controls. soil were cultured and inoculated into mice. There was no association between lower A fungus isolated from the liver of a mouse esophageal sphincter-relaxing foods and inoculated with soil showed temperature- symptoms of chronic reflux. There was no dependent dimorphism and in vitro myce- association between dietary factors known lium and yeast phases characteristic of to cause lower esophageal relaxation and Paracoccidioides brasiliensis. Yeast cells of the the risk of adenocarcinoma of the esopha- fungus produced disseminated infection af- gus or gastric cardia. The results indicated ter intraperitoneal inoculation in Wistar that dietary factors associated with lower rats from which the fungus was reisolated. esophageal sphincter relaxation and tran- An antigen reacting with sera from patients sient gastroesophageal reflux are not associ- with paracoccidioidomycosis was obtained ated with any important risk of esophageal from this Paracoccidioides brasiliensis strain; CA012 antigen identity with strain 339 and with malignancy . four other Paracoccidioides brasiliensis strains Gastrointestinal effect. It was demon- was detected by gel immunodiffusion. How- strated that coffee promotes gastroesoph- ever, when the exoantigen was submitted to ageal reflux. It stimulated gastrin release and sodium dodecyl sulfate-polyacrylamide gel gastric acid secretion, but studies on the ef- electrophoresis, a low gp43 expression in fect on lower esophageal sphincter pressure the new strain, which was called IbiaCA002, yielded conflicting results. Coffee also pro- was observed. longed the adaptive relaxation of the proxi- Gallbladder diseases. The relation of ul- mal stomach, suggesting that it might slow trasound-documented gallbladder disease gastric emptying. However, other studies with coffee drinking in 13,938 adult partici- indicated that coffee does not affect gastric pants was examined between 1988 and emptying or small bowel transit. It induced 1994. The prevalence of total gallbladder cholecystokinin release and gallbladder disease was unrelated to coffee consumption contraction, which may explain why patients in either men or women. However, among with symptomatic gallstones often avoid women, a decreased prevalence of previ- drinking coffee. Coffee increased rectosig- ously diagnosed gallbladder disease was moid motor activity within 4 minutes after found with increased coffee drinking. These ingestion in some people. Their effects on findings do not support a protective effect the colon were comparable to those of a of coffee consumption on total gallbladder 1000-kcal meal. Because coffee contains no disease, although coffee may decrease the calories and its effects on the gastrointesti- risk of symptomatic gallstones in women CA022. nal tract cannot be ascribed to its volume COFFEA ARABICA 173 load, acidity, or osmolality; it must have teine in healthy individuals. Coffee increased pharmacological effects. Caffeine alone homocysteine concentrations in 24 of 26 could not account for these gastrointestinal individuals. Circulating concentrations of CA009 effects . vitamin B6, vitamin B12, and folate were Genotoxicity inhibition. Hot water extract unaffectedCA027. Infusion of the seed oil, of the fruit, administered intragastrically to administered orally to more than 15,000 mice at a dose of 500 mg/kg, was active vs adults of both sexes at variable doses, was adriamycin-, cyclophosphamine-, procarba- active on plasmaCA190. zine-, and mitomycin-induced genotoxicity. Hypercholesterolemic effect. Triacylgly- Genotoxicity was measured by the presence cerols has been determined to be the major of micronucleated polychromatic erythro- lipid constituents of the coffee oil, along cytes in bone marrow CA240. with sterol esters, sterols/triterpene alcohol, Glutathione-S-transferase induction. Seed hydrocarbons, and the hydrolyzed products oil, administered to hamsters at a concentra- of triacylglycerols as the minor components. tion of 2.25% of diet, was activeCA173. The Fatty acid composition of total oil, neutral seed, administered in ration of female mice, lipids, polar lipids, and pure triacylglycerols was activeCA221. showed the presence of fatty acids of C14, Hialuronidase inhibition. Hot water ex- C16, C18, and C20 carbon chains. Palmitic tract of the seed, at a concentration of and linoleic acids were the major fatty acids 0.01%, produced 53% inhibition, probably and comprise approx 38.7% and 35.9%, resulting from tanninsCA137. respectively. Pancreatic lipase hydrolysis Homocysteine effects. Elevated homo- revealed that the linoleoyl and palmityl cysteine concentration is considered an moieties are preferentially esterified at the independent risk factor for cardiovascular Sn-2 and Sn-1,3 positions of triacylgly- diseases and has been associated with neu- cerols, respectively. The presence of high ral tube defects. In a study of 290 young amounts of palmitic acid at Sn-1,3 position women aged 25–30 years and in 288 older in coffee oil may be partly responsible for its women aged 60–65 years total homocys- hypercholesterolemic effectsCA004. Coffee oil teine concentrations were measured. All of was administered orally to 11 healthy the participants completed questionnaires normolipemic volunteers at a dose of 2 g/ about factors, including lifestyle, health, day for 3 weeks. After a 2-week washout and use of vitamin supplements. Smoking period, the reverse treatments were applied status, coffee consumption, SBP, and body for another 3 weeks. Six subjects received mass index were positively associated, and oil supplying 72 mg/day of cafestol and 53 estrogen replacement therapy and tea con- mg/day of kahweol, and five received oil sumption were inversely associated with that provided 40 mg of cafestol, 19 mg of total homocysteine in some of the models. 16-O-methyl-cafestol, and 2 mg of kahweol/ According to the criteria used, between 1 day. The average cholesterol level increased and 36% of the women had suboptimal by 0.65 mmol/L (13%) on coffee oil. The folate intake. Folic acid is a strong predictor TG level increased by 0.49 mmol/L (61%). of total homocysteine concentration; how- No effects on serum lipids or lipoprotein ever, several dietary and other lifestyle fac- cholesterol levels were significantly differ- tors are important as wellCA026. Coffee, ent between variety Arabica or Robusta oils. consumed by 26 volunteers (18–53 years of The treatments elevated serum lipid levels; age) at a dose of 1 L/day for 4 weeks, raised therefore, cafestol must be involved and plasma concentrations of total homocys- kahweol cannot be the sole cholesterol-rais- 174 MEDICINAL PLANTS OF THE WORLD ing diterpeneCA005. Coffee total lipids, coffee tered in drinking water of hamster and rats nonsaponifiable matter, and coffee diter- at a concentration of 0.5 g/mL, was pene alcohols have been examined in adult inactiveCA187. Decoction of the dried seed, Syrian hamsters. The animals were fed administered orally to adults, produced either a commercial laboratory chow diet equivocal resultsCA157,CA163. Decoction of the containing 5% fat and low in saturated fat roasted coffee, administered orally to 20 (1.46 g/100 g diet) and cholesterol (0.03 g/ healthy volunteers at a dose of 600 mL/day 100 g diet) or a semisynthetic diet set in for 4 weeks, produced a significant increase gelatin, containing 10% fat and high in of LDL and TG levels, and LDL–HDL ratio. saturated fat (4 g/100 g diet) and cholesterol Decoction of the boiled coffee passed (90.5 g/100 g diet). The coffee lipid extracts through a conventional paper filter, admin- were dissolved in olive oil (concentration istered orally to 20 healthy volunteers at a either 5 mg of total lipid, 0.5 mg nonsa- dose of 600 mL/day for 4 weeks, produced ponifiable matter or 0.5 mg diterpene alco- no change in LDL and TG levels and LDL– hols for 250 PL olive oil) in study 1 and in HDL ratio. Filtering removed more than coconut oil (concentrations either 20 mg 80% of the lipid-soluble substances present total lipid, 2 mg nonsaponifiable matter, or in boiled coffeeCA161. Heartwood, adminis- 2 mg diterpene alcohols per 250 PL) in study tered orally to adults for 24 hours, produced 2. A dose of 250 PL of these solutions was an increase of cholesterol levelCA238. Hot administered daily by gavage. Control ani- water extract of the seed, administered mals received 250 PL vehicle only. For orally to 1629 middle-aged adults, pro- serum lipid analysis, blood samples were duced an increase of serum cholesterol obtained on days 0, 7, and 14 in study 1 and level and intake of fat. Hot water extract on days 0, 7, 14, and 21 in study 2. The of the seed, administered orally to 1625 results indicated a tendency of serum total middle-aged adults, produced equivocal cholesterol (TC) and high-density lipopro- effect. Consumers of filtered coffee had no tein (HDL) cholesterol to increase with ad- significant change in serum cholesterol ministration of coffee total lipid, level K12893. Powder of the seed, administered nonsaponifiable, and diterpene alcohols. In orally to adults at a dose of 8 g/day dosed contrast, in study 2 there were no signifi- daily in unfiltered coffee, was activeCA172. cant differences in serum lipids between Hexane-diethyl ether extract of the roasted control and coffee lipid-treated groups seed, administered intragastrically to ham- across time. The results support the concept sters at a dose of 2 mg/animal, was active. that coffee lipids may be hypercholester- Lipid fraction of the roasted seed, adminis- olemic and indicate that diterpene could be tered to hamsters at a dose of 20 mg/animal, the lipid component responsible for such was active. Nonsaponifiable fraction of the an effect. However, it appears that this roasted seed, administered to hamsters at a hypercholesterolemic effect is apparent only dose of 2 mg/animal, was active. The effect when the background diet is low in satu- was found only in diet low in saturated fat rated fat and cholesterol. A high-saturated and cholesterolCA174. Decoction of the dried fat/high-cholesterol diet may mask the hy- seed, administered orally to adults of both percholesterolemic effect of coffee lipidCA010. sexes at variable doses, decreased the level Hot water extract of the dried kernel, ad- of cholesterol. Decoction of the dried seed, ministered intragastrically to male hamsters, administered orally to adults at a dose of five was active vs feeding high-fat dietCA160. Hot cups per day, produced weak activity, and water extract of the boiled seed, adminis- when administered to new coffee drinkers COFFEA ARABICA 175 of both sexes at variable doses, decreased with a mutated tumor (mean of 14.5 cup/ cholesterol levelCA247. week vs 8.8 among patients with a wild-type Hypertiglyceridemic activity. Hot water tumor, p < 0.05). Regarding non-regular extract of the boiled seed, administered in drinkers, the odds ratio of a mutated tumor drinking water of hamster and rats at a con- adjusted by age, sex, smoking, and alcohol centration of 0.5 g/mL, was inactiveCA187. drinking was 3.26 for drinkers of 2–7 cups/ Hypoglycemic activity. Flower, green week, 5.77 for drinkers of 8–14 cups/week, seed, and leaf, administered by gastric intu- and 9.99 for drinkers of more than 15 cups/ bation to mice, were activeCA208. week (p = 0.01)CA057. Immunostimulant activity. Hot water ex- Leukocytosis activity. Hot water extract of tract of fruit, in the drinking water of mice the seed, administered orally to adults at a at a concentration of 0.5%, increased the dose of five cups per day, produced weak percentage of thymocytes expressing mature activityCA150. CD4 or CD8 markers and increased the pro- Lipid profile alteration. Hot water extract portion of peripheral lymphocytes express- of the seed, administered orally to adults at ing CD25, a marker of activationCA186. Hot a dose of five cups per day, produced weak water extract of the fruit, administered activity on apolipoprotein (apo) B HDL-C orally to adults at variable doses, was active and apo A-1CA150. on lymphocytes vs suppressor T-cells and Lipoprotein modification. Decoction of natural-killer cells and inactive vs helper T- the seed, administered orally to 22 adults at cellsCA241. Methanol extract of the dried peri- a dose of five to six strong cups for 1 day, carp, administered in drinking water of mice was active. Consumption of cafestol and at a concentration of 0.5%, was active on kahweol resulted in decreased lipoprotein A lymphocytes B. The extract enhanced li- levels. Filtering coffee removed the popolysaccharide-induced activationCA148. diterpenesCA146. Decoction of the dried stem Extract of the dried seed, administered in- bark, administered orally to 150 healthy tramuscularly to adult calves at a concen- adults of both sexes who consumed five or tration of 10 mL/animal, was activeCA203. more cups of boiled coffee and 159 filter cof- Insecticidal activity. Ethanol (50%) ex- fee consumers at a dose of 1.2 L/day, was tract of the aerial parts, at a concentration active on human serum. Median level of se- of 1%, was inactive on Musca domestica and rum lipoprotein was higher in the boiled Tribolium castaneumCA128. coffee drinkersCA144. K-ras gene mutagenesis. The relationship Liver dysfunction. In a 4-year study in between consumption of coffee and muta- 1221 liver dysfunction-free (serum aspartate tions in the K-ras gene in exocrine pancre- aminotransferase [AST] and alanine ami- atic cancer was investigated in 185 patients, notransferase [ALT] <39 IU/L and no medi- 121 for whom tissue was available. Muta- cal care for or no past history of liver tions in codon 12 of K-ras were detected by disease) males aged 35–56 years, was inves- the artificial restriction fragment-length tigated for the association of coffee con- polymorphism technique. Mutations were sumption with the development of increased found in tumors from 94 of 121 patients serum AST and/or ALT activities. From the (77.7%) and were more common among analysis using the Kaplan-Meier method, regular coffee drinkers than among non- the estimated incidence of serum AST and/ regular coffee drinkers (82% vs 55.6%, p = or ALT t 40 IU/L, t 50 IU/L, and t 60 IU/ 0.018, n = 107). The weekly intake of coffee L decreased with an increase in coffee con- was significantly higher among patients sumption. From the Cox proportional haz- 176 MEDICINAL PLANTS OF THE WORLD ards model, coffee drinking was indepen- adults at variable doses, was inactive on dently inversely associated with the devel- lymphocytes B vs B-cell proliferationCA241. opment of serum AST and/or ALT t 40 IU/ Molluscicidal activity. Water extract of L, t 50 IU/L, and t 60 IU/L, controlling for the roasted seed, was inactive on Biompha- age, body mass index, alcohol intake, and laria pfeifferiCA237. cigarette smokingCA041. Mood effects. In a full crossover design Maternal risks. Three-hundred six moth- study, the effect of coffee and tea on acute ers who gave birth to babies with cleft lip, physiological responses and mood indicated or palate, or both were matched with 306 that caffeinated beverages acutely stimulate mothers who gave birth to healthy babies in the autonomic nervous system and increase the same area during the same period. Sig- alertness. In the study, caffeine levels in tea nificantly more babies in the cleft palate were 37.5 and 75 mg and in coffee 75 and group had a family history of clefts (48/306 150 mg in one group. In another group caf- compared with 7/306) in the cases studied; feine, level was manipulated. SBP, DBP, combined cleft lip and palate was signifi- heart rate, skin temperature, skin conduc- cantly more common among boys (82/157 tance, and mood were monitored over each compared with 57/149) and cleft palate 3-hour study session. Tea and coffee pro- alone among girls (48/149 compared with duced mild autonomic stimulation and an 22/157). There was no difference between elevation on mood. There were no effects of the groups regarding dietary preferences, but tea vs coffee or caffeine dose, despite a four- during pregnancy the mothers who gave fold variation in the latter. In one study, birth to babies with defects tended to drink increasing beverage strength was associated less alcohol and less coffeeCA038. with greater increases in DBP and energetic Mean platelet volume increase. Hot arousal. In the other, caffeinated beverages water extract of the seed, administered increased DBP, SBP, and skin conductance orally to adults at a dose of five cups per day, and lower heart rate and skin temperature produced weak activityCA150. compared to water. Significant dose–re- Metabolism. Decoction of the seed, admin- sponse relationships to caffeine were seen istered orally to adults at variable doses, was only for SBP, heart rate, and skin tempera- active. Volunteers consumed food contain- ture. There were significant effects of caf- ing hydroquinone or glycopyranoside feine on energetic arousal but no consistent derivative (arbutin). Blood and urine levels dose–response effectsCA035. of the compounds and conjugates were Mutagenic activity. Freeze-dried roasted assayedCA150. and instant coffee, at a dose of 20 mg/plate, Miscellaneous effects. Decoction of the induced between 6 and 10 times the rever- dried seed, administered orally to 171 tants found in negative controls of Salmo- healthy nonsmoking adults of both sexes nella typhimurium. Green coffee beans had over the age of 50 years, indicated that cof- no mutagenic activity. Mutagenicity in- fee may decrease postprandial falls in SBP creased with roasting time to 4 minutes, and can increase DBP in untreated the time normally used roast coffee. The hypertensivesCA192. genotoxic compounds were quickly formed Mitogenic activity. Hot water extract of at temperature of 220qC. Mutagenic acti- the fruit, administered orally to adults at vity was independent of the roasting variable doses, was inactive on lymphocytes procedureCA011. Water extract of the dried vs T-lymphocyte proliferation. Hot water fruit, in cell culture at a concentration of 2 extract of the fruit, administered orally to mg/mL, was active on hamster lung cells COFFEA ARABICA 177 without microsomal activationCA206. Hot wa- concentration of 10 g/L, was active on Sal- ter extract of the seed, on agar plate at con- monella typhimurium TA98CA166. Hot water centration of 40 mg/plate, was active on extract of the roasted seed, on agar plate at Salmonella typhimurium TA102 and inactive a concentration of 14 mg, was active on Sal- on Salmonella typhimurium TA100 CA169. Hot monella typhimurium TA100. The activity water extract of the seed, on agar plate at shown was the result of caffeineCA227. concentration of 50 mg/plate, was active on Myocardial infarction. A group of 340 of Salmonella typhimurium TA100 and inactive age-, sex-, and community-matched indi- on Salmonella typhimurium TA1535, viduals drinking caffeinated and decaf- TA1537, TA1538, and TA98CA165. Hot wa- feinated coffee was investigated. The odds ter extract of the seed, administered ratio for drinking four or more cups per day intragastrically to mice at a dose of 6 g/ani- of caffeinated coffee was 0.84 (95 % confi- mal, was inactive on Escherichia coli K12 and dence interval [CI], 0.49–1.42) compared Salmonella typhimurium TA1530. The effect with drinking one cup or less per week, after was assayed on bacteria injected intrave- adjustment for coronary risk factors. The nously coincidentally with extract adminis- odds ratio for drinking more than one cup tration and harvested 1.5 hours laterCA165. per day of decaffeinated coffee vs nondrink- Ethanol (95%) and hot water extracts of the ers was 1.25 (95% CI, 0.76–2.04)CA053. solid residue of brewed coffee, on agar plate Neuron-sprouting stimulation. Chro- at a concentration of 12.5 mg/plate, were matographic fraction of the dried seed, in inactive on Salmonella typhimurium TA100 cell culture at a concentration of 1 Pg/mL, and TA98. Hot water extract of the distil- was active on SK-N-SH cellsCA249. lates of brewed coffee overheated to 150qC, Nuclear aberration reduction. Decoction on agar plate at a concentration of 5 mg/ of the seed, administered intragastrically plate, was inactive on Salmonella typhimu- with methylurea and sodium nitrite to mice rium TA100. Metabolic activation had no at a dose of 1 g/animal, was active. Decoc- effect on the results. MeCl2 extract of distil- tion of the seed, administered intragastri- lates of brewed coffee overheated to 300qC, cally with methylurea and sodium nitrite to on agar plate at a concentration of 100 Pg/ mice at a dose of 600 mg/animal, was active plate, was inactive on Salmonella typhimu- on colonCA214. rium TA100 and TA98. Extract was toxic Occupational respiratory allergy. There at higher doses. MeCl2 extract of distillates was a significant correlation between sensi- of brewed coffee overheated to 300qC, on tization to green coffee bean and work- agar plate at a concentration of 300 Pg/ related symptoms (asthma and/or rhinitis) plate, was active on Salmonella typhimurium (p < 0.01), common allergic symptoms (p < TA98. Metabolic activation was required 0.05), and atopy by prick test (p < 0.01)CA061. for activity. MeCl2 extracts of distillates and Ovarian cancer risk. In a study of 549 solid residue of brewed coffee, on agar plate women with newly diagnosed epithelial at a concentration of 5 mg/plate, were inac- ovarian cancer and 516 control women, it tive on Salmonella typhimurium TA100 and was concluded that coffee and caffeine con-

TA98. MeCl2 extract of distillates of brewed sumption may increase the risk of ovarian coffee overheated to 150qC, on agar plate at cancer among premenopausal women. Cof- a concentration of 750 Pg/plate, was active fee and alcohol consumption was assessed on Salmonella typhimurium TA98. Metabolic through a semiquantitative food-frequency activation was required for activityCA232. Hot questionnaire, and information on tobacco water extract of the seed, on agar plate at a smoking was collected through personal 178 MEDICINAL PLANTS OF THE WORLD interview. There was no risk for ovarian creasing amounts of coffee was also associ- cancer overall associated with tobacco or ated with lower risk of Parkinson’s disease alcohol use in either premenopausal or post- in men who were never, past, and current menopausal women. Association of border- smokers at baseline. Other nutrients in cof- line significance for tobacco and invasive fee, including niacin, were unrelated to serous cancers and alcohol and mucinous Parkinson’s disease incidence. The relation- cancers were observed but reduced after ship between caffeine and Parkinson’s dis- adjustment for coffee consumptionCA029. ease was unaltered by intake of milk and Ovulation inhibition effect. Hot water sugarCA037. extract of the roasted seed, administered in Peroxide formation stimulation. Hot drinking water of female rats at variable water extract of the seed was active. Poly- CA228 doses daily for 30 weeks, was inactive . phenolics catalyzed the oxidation of O2 to CA169 Pancreatic cancer risk. In a study of 583 H2O2 . individuals with histologically confirmed Pharmacokinetic interactions. The most pancreatic cancer and 4813 controls, it was serious coffee (caffeine)-related central ner- determined that consumption of total alco- vous system (CNS) effects include seizures hol, wine, liquor, beer, and coffee was not and delirium. Other symptoms affecting the associated with pancreatic cancerCA039. cardiovascular system range from moderate Parkinson’s disease. The association of increases in heart rate to more severe car- smoking, alcohol, and coffee consumption diac arrhythmia. Although tolerance devel- with Parkinson’s disease was investigated in ops to many of the pharmacological effects 196 subjects who developed Parkinson’s dis- of caffeine, tolerance may be overwhelmed ease from 1976 to 1995. Each incident case by the nonlinear accumulation of caffeine was matched by age (r 1 year) and sex to a when its metabolism becomes saturated. general population control subject. The This might occur with high levels of con- findings suggest an inverse association sumption or as the result of pharmacoki- between coffee drinking and Parkinson’s netic interaction between caffeine and disease; however, this association did not medications. The polycyclic aromatic hy- imply that coffee has a direct protective drocarbon-inducible cytochrome P450 IA2 effect against Parkinson’s diseaseCA024. In a participated in the metabolism of caffeine, study of 8004 Japanese-American men aged as well as of several clinically important 45–60 years, it was indicated that higher drugs. A number of drugs, including certain coffee intake is associated with a signifi- selective serotonin reuptake inhibitors (par- cantly lower incidence of Parkinson’s dis- ticularly fluvoxamine), antiarrhythmics ease. Data were analyzed from 30 years of (mexiletine), antipsychotics (clozapine), follow-up. During the follow-up, 102 men psoralens, idrocilamine and phenylpropano- were identified as having Parkinson’s dis- lamine, bronchodilators (furafylline and ease. Age-adjusted incidence of Parkinson’s theophylline), and quinolones (enoxacin), disease declined consistently with increased have been reported to be potent inhibitors amounts of coffee intake from 10.4 per of this isoenzyme. Thus, pharmacokinetic 10,000 person-years in men who drank cof- interactions at the cytochrome P450 IA2 fee to 1.9 per 10,000 person-years in men enzyme level may cause toxic effects during who drank at least 450 g/day. Similar concomitant administration of caffeine and relationships were observed with total certain drugs used for cardiovascular, CNS, caffeine intake and for caffeine from gastrointestinal, infectious, and respiratory noncoffee sources. Consumption of in- and skin disordersCA031. Decoction of the COFFEA ARABICA 179 dried seed was administered orally to nine with body temperature below physiological healthy patients of both sexes with ileosto- values; during the first period of diarrhea mies at a dose of 720 mL (one, two, or three (between days 4 and 6), there was a signifi- cups of French-press coffee with a standard- cantly lower tendency of diarrhea, and after ized breakfast) for three separate days in ran- the second period of diarrhea (day 9), a bet- dom order. Ileostomy effluent was collected ter and quicker recovery and a lower ten- for 14 hours and urine for 24 hours. Stabil- dency of exsiccation as the control calves. ity of cafestol and kahweol was assessed The average duration of illness was shorter under simulated gastrointestinal tract con- (4.7 instead of 7 days), and the average ditions. Corrected mean absorption of number of therapeutical interventions were diterpenes expressed as percentages of the less (3.1 instead of 4.5) than in control amount consumed and the amount entering calves. Within the four herds endemically the duodenum were 67% and 88%, respec- showing a high number of cases of diarrhea tively, for cafestol and 72% and 93%, re- in newborn calves, the morbidity could be spectively, for kahveol. There was a loss of dropped by 35% by the administration of diterpenes during incubation in vitro with one to three subcutaneous injections of 10 gastric juice (cafestol 24% and kahweol mL of the extractCA008. 32%), during storage with ileostomy efflu- Prostaglandin inhibition. Water extract of ent (cafestol 18% and kahweol 12%), and the dried seed, administered in drinking during freeze-drying (cafestol 26% and water of rats at a dose of 5%, was active. kahweol 32%). Mean excretion of Prostaglandin I-2 synthesis in the rat tho- glucuronidated plus sulphated conjugates in racic aorta was assayedCA217. urine was 1.2% of the ingested amount for Psychomotor performance. Coffee, taken cafestol and 0.4% of the ingested amount for by 17 introverts and 19 extroverts at doses kahweol. Approximately 70% of the in- of 2 and 4 mg caffeine/kg during the morn- gested cafestol and kahweol was absorbed in ing and evening, did not support the hy- ileostomy volunteers. Only a small part of pothesis that caffeine differentially affects the diterpenes was excreted as a conjugate extroverts and introverts. In this random- of glucuronic acid or sulphate in urineCA199. ized, double-blind, crossover study, the sub- Pheromone. Ether extract of the stem was jects drank coffee during the mornings and active on Aspiculuris tetraptera and male evenings. At 30-minute intervals for 180 Mediterranean fruit flies. Ether extract of minutes after drinking coffee, the partici- the stem produced equivocal effect on Dacus pants completed the Profile of Mood States, dorsalis and melon flies of both sexesCA142. a battery of self-report visual analog scales, Prophylactic effect. The therapeutical and the Digital Symbol Substitution Test. effect of a 30% extract from coffee beans has Caffeine affects on mood and task perfor- been investigated in newborn calves in mance did not significantly interact with herds that endemically showed a high pro- extroversion, except for nonsignificant portion of infections within the gastroen- trends for caffeine to increase happiness and teric and/or respiratory system in calves. vigor more among extroverts than intro- Fifty newborn calves were given a subcuta- verts. No three-way interactions of group, neous injection of 10 mL of the extract on time, and dose were found on any scales or the first and third days of life. Another 50 on the Digital Symbol Substitution Test calves received physiological saline as con- CA043. trol. On the first 2 days of life, the group Renin–angiotensin–aldosterone system treated with the extract had fewer animals activity. Plasma renin activity and enzyme- 180 MEDICINAL PLANTS OF THE WORLD converting angiotensin I to angiotensin II est for FEF50 and FEF25. Disodium cro- activity, serum concentration of aldoster- moglycate significantly diminished across- one, and catecholamines in patients with shift reductions for FEF50 and FEF25 in a hypertension and patients with low or nor- subgroup of the examined workersCA013. mal plasma renin activity, drinking one cup Rheumatoid arthritis risk. Coffee, con- of coffee were measured by radioimmunoas- sumed by 6809 subjects with no clinical say, and blood pressure was measured by arthritis, indicated that the amount of cof- ambulatory monitoring. Drinking one cup fee consumed was directly proportional to of coffee produced, after 1–2 hours, elevated the prevalence of rheumatoid factor positiv- SBP and after 1 hour DBP in patients with ity. The consumption of coffee was first low renin–angiotensin–aldosterone system studied for its association with rheumatoid activity who habitually drink coffee. factor (sensitized sheep cell agglutination Patients with normal renin–angiotensin– titer) in a cross-sectional survey and second aldosterone system activity had elevations for its prediction of rheumatoid in a cohort only in DBP from 1 to 2 hours after drink- of 18,981 men and women who had neither ing. Plasma catecholamines, aldosterone arthritis nor a history of it at the baseline con-centrations, blood renin activity, and examination. In the cross-sectional survey, enzyme-converting angiotensin I to angio- the amount of coffee consumes was directly tensin II activities were not elevatedCA055. proportional to the prevalence of rheuma- Respiratory effect. Respiratory conse- toid factor. Adjusted for age and sex, this quences of work in coffee processing were association was significant, but after further studied in 764 female workers exposed to adjustment for smoking, the linear trend dusts associated with the processing of green declined below significance. In the cohort and roasted coffee. A group of 387 females study, there was an association between cof- not exposed to respiratory irritants served as fee consumption and the risk of rheumatoid controls for the prevalence of acute and factor-positive rheumatoid arthritis that did chronic respiratory symptoms. A greater not result from age, sex, level of education, prevalence of all acute and chronic respira- smoking, alcohol intake, body mass index, tory symptoms was consistently found or serum cholesterol. After adjusting for among exposed workers than among control these potential confounders, the users of workers. The highest prevalence of chronic four or more cups a day still have a relative respiratory symptoms was recorded for risk of 2.2 (95% CI at 1.13–4.27) for devel- chronic cough (40%), followed by acute oping rheumatoid factor-positive rheuma- symptoms of dry cough (58.7%). Mean toid arthritis compared with those drinking acute reductions of lung function through- less. Coffee consumption did not predict the out the work shift were recorded in all of development of rheumatoid factor-negative the studied groups; the mean across-shift rheumatoid arthritisCA034. decrease as a percentage of preshift values RNA (messenger) polymerase inhibition. was particularly marked in forced expiratory Petroleum ether extract of the green seed, flow at 75% ([FEF25]; –26.7%), forced administered in ration of female mice at expiratory flow at 50% ([FEF50]; –20.6%), variable doses for 12 days, produced strong followed by forced expiratory volume in activityCA220. The seed, administered in 1 second (–9.9) and forced vital capacity ration of female mice at variable concentra- (–3.7%). The preshift (baseline) values of tions for 12 days, was activeCA220. ventilatory capacity were decreased in com- Serum homocysteine concentration. The parison to the predicted ones, and were low- influence of nutritional factors associated COFFEA ARABICA 181 with total homocysteine in 260 school Although the effect of caffeine cannot be teachers, 151 women, and 109 men with a distinguished from the effects of coffee and median age of 64 years was performed by green tea, consumption of caffeine-contain- observational analyses of baseline and 2–4 ing beverages favorably altered hormone months follow-up tests that designed to test levels associated with the risk of developing the feasibility of conducting a large-scale breast cancerCA149. clinical trial of vitamin supplements. In Sister chromatid exchange stimulation. multivariable linear regression and gener- Lyophilized extract of the essential oil, alized linear models, there was a positive, administered by gastric intubation to mice significant dose–response relationship at a dose of 50 mL/kg in two doses, was between coffee consumption and total inactiveCA209. Lyophilized extract of the homocysteine (p = 0.01)CA048. dried seed, administered by gastric intuba- Serum lipids and lipoproteins. Serum tion to hamsters at a dose of 2.5 g/kg, was concentrations of TC, TGs, and HDL cho- inactiveCA209. lesterol were measured in a group of 4587 Skin depigmentation effect. Extract of the males aged 48–56 years, drinking instant dried seed, administered externally to adults and brewed coffee. LDL cholesterol levels at a dose of 5%, was active. Skin-lightening were calculated from the values of TC, TG, cosmetics contained extract of Coffea and HDL cholesterol. The consumption of arabica seeds (containing chlorogenic acid) brewed coffee was unrelated to any param- as melanin-formation inhibitors. The ex- eter, and instant coffee consumption tract has been incorporated into cosmetics showed a highly significant positive associa- for skin-aging prevention or into hair prepa- tion with serum LDL cholesterol levels and rations for hair protection. Biological activ- an inverse association with serum TG lev- ity reported has been patentedCA193. els. For each cup of instant coffee a day, LDL Smooth muscle relaxant activity. The cholesterol levels were 0.82 mg/dL (95% CI, aqueous extracts of green and roasted coffees 0.29–1.35) higher, and TG levels in a natu- were assayed on isolated guinea pig tracheal ral log-scale were 0.014 mg/dL (95% CI, spirals. Contractile and relaxant activities 0.006–0.022) lower. A tendency for positive were compared with histamine and theo- association between instant coffee intake phylline, respectively. Green coffee extracts and serum TC levels (p = 0.09) was induced concentration dependent contrac- observed. HDL cholesterol levels were un- tion, but the maximal tension never ex- related to instant coffee consumptionCA049. ceeded 76.3% r 5.2 of a maximal histamine Sex hormone-binding globulin level contraction (0.69 r 0.07 g/mm2 vs 0.52 r increase. Water extract of the seed, admin- 0.05 g/mm2; p = 0.01). One gram of green istered to 50 premenopausal women at vari- coffee dust had a biological activity equiva- able doses daily, was active. Blood samples lent to 1.23 r 0.1 mg of histamine. The pD2 were obtained from each woman on days 11 value of histamine was –5.17 r 0.05. The and 22 of her menstrual cycle. High intakes potency of green coffee was unaffected by of caffeinated coffee, green tea, and total mepyramine maleate (1 Pg/mL, final bath caffeine were commonly correlated with concentration), whereas that of histamine increasing sex hormone-binding globulin on was reduced 500-fold. Tissues contracted days 11 and 22 of the cycle after controlling with histamine were not significantly re- for potential confounders. Green tea but not laxed by green coffee extracts. By contrast, caffeinated coffee intake was inversely cor- roasted coffee extracts induced concentra- related with estradiol on day 11 of the cycle. tion-dependent relaxation of uncontracted 182 MEDICINAL PLANTS OF THE WORLD and histamine contracted tissues. Tissues 50% of the men and 80% of the women did contracted with green coffee extracts were not use any of the psychoactive substances also completely relaxed by roasted coffee heavily. Every third man and every fifth extracts. The pD2 value of theophylline was woman used one substance heavily. The –4.10 r 0.03. The relaxant activity of 1 g of prevalence for those who exceeded criteria roasted coffee was equivalent to 1.95 r 0.16 for joint heavy use of two substances was 9% mg of theophylline. The potency of these for men and 1% for women. Joint-heavy extracts was significantly reduced after pro- use of all three substances was rare. The pranolol (1 Pg/L; dose ratio 1.56)CA159. adjusted risk of suicide increased linearly Stress relief. A survey of 261 house staff, with increasing level of joint heavy use of nurses, and medical oncologists in a cancer alcohol, cigarette, and coffee. Among sub- research hospital and oncologists in outside jects with heavy use of one substance, the clinical practices was carried out to measure risk was 1.55, with joint-heavy use of two burnout, physiological distress, and physical substances 2.22, and with joint-heavy use of symptoms. Each participant completed a all three substances 3.99 compared with no questionnaire that quantified life stressors, heavy useCA016. personality attributes, burnout, psychologi- Sunscreen effect. Seed oil, administered cal distress, physical symptoms, coping strat- externally to adults at a concentration of egies, and social support. The results 30%, was active. Biological activity re- indicated that house staff experienced the ported has been patentedCA222. greatest burnout. They also reported greater Symptomatic gallstone disease. In a 10- emotional exhaustion, a feeling of emo- year study, 46,008 men aged 40–75 years tional distance from patients, and a poorer without history of gall stone disease were sense of personal accomplishment. Nurses investigated for the association of coffee and reported more physical symptoms than caffeinated drink consumption with symp- house staff and oncologists. However, they tomatic gallstone disease or cholecystec- were less emotionally distant from patients. tomy, diagnosed by ultrasonography or Women reported a lower sense of accom- X-ray. After adjusting for other known or plishment and greater distress. The four suspected risk factors, compared with men most frequent methods of relaxing were who did not consume regular coffee, the ad- talking to friends, using humor, drinking justed relative risk (RR) for those who con- coffee or eating, and watching televis- sistently drank two to three cups of regular ionCA019. coffee per day was 0.60 (95% CI, 0.42– Suicidal risk. Data from 36,689 adult men 0.86); four or more cups per day the RR was and women (25–64 years of age) who par- 0.55 (95% CI, 0.33–0.92). The risk of gall ticipated in a population survey between stone disease declined with increasing caf- 1972 and 1992 indicated that clustering of feine intake. RR for men in the highest cat- the heavy use of alcohol, cigarettes, and cof- egory of caffeine intake (>800 mg/day) fee could serve as a new marker for increased compared with men in the lowest category risk of suicide. The mortality of the cohort (d25 mg/day) was 0.55 (95% CI, 0.35– was monitored for a mean of 14.4 years, 0.87). Decaffeinated coffee was not associ- which yielded 169 suicides. Criteria for ated with a decreased riskCA045. The effect of heavy use of each psychoactive substance coffee drinking in relation to alcohol drink- were defined as: alcohol more than 120 g/ ing, smoking, and obesity was investigated week, cigarettes more than 21/day, and cof- in the population of 7637 males, aged 48– fee more than 7 cups/day. Approximately 59 years; 1360 men with a possible patho- COFFEA ARABICA 183 logic condition influencing liver enzyme carrier in isolated mitochondria and thus levels, and 182 former alcohol drinkers; the blocks oxidative phosphorylation. This has effect of coffee on serum J-glutamyltrans- been assumed to explain changes in carbo- ferase (GGT) was examined by a multiple hydrate metabolism and the toxic effects in linear regression model and analysis of vari- liver and kidney. In vitro proximal tubular ance adjusting for alcohol drinking, smok- cells are selectively sensitive to atractylo- ing and body mass index. The adjusted side, whereas other renal cell types are quite percentage of difference in serum GGT resistant. There are also differences in the was –4.3 (95% CI, –5 to –3.5) per cup. The response of liver and renal tissue to atrac- inverse coffee–GGT relationship was most tyloside. Thus, not all of the clinical, bio- prominent among men drinking 30 mL or chemical, and morphological changes more of ethanol and smoking 15 or more caused by atractyloside can simply be cigarettes/day, and positive associations of explained on the basis of mitochondrial alcohol and smoking with GGT were phosphorylation. The relevance to a wider attenuated by coffee drinking, more clearly human risk is shown by the presence of among men with body mass index of 25 kg/ atractyloside analogues in dried roasted cof- m2 or greater. Adjusted percentages of dif- fee beans (17.5–32 mg/kg)CA003. Ethanol ference in serum GGT were –2.6% (p = (50%) extract of the aerial parts, adminis- 0.0003) per cup of brewed coffee and –5.1% tered intraperitoneally to mice, was active, CA054 CA139 (p = 0.0001) per cup of instant coffee . lethal dose50 of 1 g/kg . Water extract of Thymidylate synthetase inhibition. Hot the roasted seed, administered to female rats water extract of the dried seed, administered at a dose of 6% of diet for 2 years, was inac- in drinking water of mice at a concentra- tive. Both regular and decaffeinated instant tion of 0.5%, was activeCA180. coffees were testedCA198. Thyroid effect. Coffee oil, administered Urinary diterpenes excretion. Absorption orally to 11 healthy normolipemic volun- and excretion of the cholesterol-raising cof- teers at a dose of 2 g/day for 3 weeks, pro- fee diterpenes cafestol and kahweol were duced no effect on serum total and free observed in nine healthy patients with ileo- thyroxine, triiodothyronine, and thyroid- stomies. Ileostomy effluent was collected for stimulating hormone CA005. 14 hours, and urine was collected for 24 Toxicity. Atractyloside, a diterpenoid gly- hours. Approximately 70% of the ingested coside that occurs naturally in plants, may cafestol and kahweol was absorbed. Only be present at levels as high as 600 mg/kg of small part of the diterpene was excreted as a dried plant material. Consumption of plants conjugate of glucuronic acid or sulphate in containing atractyloside or carboxyatractyl- urine, mean excretion was 1.2% of the oside has caused fatal renal proximal tubule ingested amount for cafesterol and 0.4% for necrosis and/or centrilobular hepatic necro- kahweolCA059. sis in man and farm animals. Although Urinary hydrogen peroxide. Instant cof- pure atractyloside and crude plant extracts fee, taken by healthy human volunteers, disrupt carbohydrate homeostasis and indicated that coffee drinking is rapidly and induce similar pathophysiological lesions in reproducibly followed by increased levels of the kidney and liver, it is also possible that hydrogen peroxide detectable in the urine the toxicity of atractyloside may be con- for up to 2 hours after drinking coffee. The founded by the presence of other natural levels of hydrogen peroxide indicated that constituents in plants. Atractyloside com- exposure of human tissues to hydrogen per- petitively inhibits the adenine nucleoside oxide might be greater than is commonly 184 MEDICINAL PLANTS OF THE WORLD supposed. It is possible that hydrogen per- their effects on serum lipids in man. J oxide in urine could act as an antibacte- Int Med 1995; 237(6): 543–550. rial agent and that hydrogen peroxide is CA006 Becker, C. G., N. Van Hamont, and M. Wagner. Tobacco, cocoa, coffee involved in the regulation of glomerular and ragweed: cross-reacting allergens functionCA040. that activate factor-XII-dependent White blood cell-macrophage stimulant. pathways. Blood 1981; 58(5): 861–867. Water extract of the freeze-dried fruit, at a CA007 Daglia, M., A. Papetti, C. Gregotti, F. concentration of 2 mg/mL, was inactive on Berte, and G. Gazzani. In vitro antioxi- dant and ex vivo protective activities of macrophages. Nitrate formation was used as green and roasted coffee. 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activity of tea and coffee. Lett Appl rally occurring phenolics, coffee and Microbiol 1989; 9(2): 65–66. tea. Mutat Res 1982; 95: 119–128. CA214 Aeschbacher, H. U. and E. Jaccaud. CA224 Lilahut, N. and S. Tancharoen. Stud- Inhibition by coffee on nitrosourea- ies of the effect of coffee on EKG of mediated DNA damage in mice. Food non-coffee drinker. Undergraduate Chem Toxicol 1990; 28(9): 633–637. Special Project Report 19878; 22 pp. CA215 Miwa, M., Z. L. Kong, K. Shinohara, CA225 Konowalchuk, J. and J. I. Speirs. Anti- and M. Watanabe. Macrophage stimu- viral effect of commercial juices and lating activity of foods. Agr Biol Chem beverages. Appl Environ Microbiol 1990; 54(7): 1863–1866. 1978; 35: 1219. CA216 Stalder, R., A. Bexter, H. P. Wurzner, CA226 Ayensu, E. S. Medicinal plants of the and H. Luginbuhl. A carcinogenicity West Indies. Unpublished Manuscript study of instant coffee in Swiss mice. Ed 1978; 110 pp. Chem Toxicol 1990; 28(12): 829–837. CA227 Nagao, M., Y. Takahashi, H. Yama- CA217 El Tahir, K. E. H., E. A. Hamad, A. M. naka, and T. Sugimura. Mutagens in Ageel, M. A. Abu Nasif, and E. A. coffee and tea. Mutat Res 1979; 68: Gadkarim. Influence of tea, and coffee 101–106. beverages on prostacyclin synthesis CA228 Nolen, G. A. The effect of brewed and by the rat aorta. Prostaglandins instant coffee in reproduction and ter- Leukotrienes Essent Fatty Acids atogenesis in the rats. Toxicol Appl 1990; 40(1): 63–66. Pharmacol 1981; 58: 171–183. CA218 Li, Y., R. Q. Yan, G. Z. Tan, X. X. CA229 Murphy, S. J. and C. P. Benzamin. Duan, and L. L. Tan. Comparative The effects of coffee on mouse devel- study on the inhibitory effect of green opment. Microbiol Lett 1981; 17: tea, coffee,, and levamisole on the 91–99. hepatocacinogenetic action of dimeth- CA230 Fujita, F. Y., K. Wakabayashi, M. ylnitrosamine. Chung-Hua Chung Nagao, and T. Sugimura. Characteris- Liu Tsa Chin 1991; 13(3): 193–195. tics of major mutagenicity of instant CA219 Eisele, J. W. and D. T. Reay. Death re- coffee. Mutat Res 1985; 142(4): lated to coffee enemas. JAMA 1980; 145–148. 244: 1608–1609. CA231 Lubin, F., E. Ron, Y. Wax, and B. CA220 Lam, L. K. T., V. L. Sparnins, and L. Modan. Coffee and methylxanthines W. Wattenberg. Isolation and identi- and breast cancer: a case-control fication of kahweol palmitate and study. J Nat Cancer Inst 1985; 74(3): cafestol palmitate as active constitu- 569–573. ents of green coffee beans that enhance CA232 Blair, C. A. and T. Shibamoto. Ames glutathione S-transferase activity in mutagenicity tests of overheated the mouse. Cancer Res 1982; 42: brewed coffee. Food Chem Toxicol 1193–1198. 1984; 22(12): 971–975. CA221 Lam, L. K. T., V. L. Sparnins, and L. CA233 Aeschbacher, H. U., E. Ruch, H. W. Wattenberg. Isolation and identi- Meier, H. P. Wurzner, and R. Munoz- fication of kahweol palmitate and Box. Instant and brewed coffees in the cafestol palmitate as active constitu- in vitro human lymphocyte mutagenic- ents of green coffee beans that enhance ity test. Food Chem Toxicol 1985; glutathione (GSH) S-transferase ac- 23(8): 747–752. tivity. Proc Am Ass Cancer Res 1982; CA234 Yamaguchi, T. and M. Iki. Inhibitory 23: 88. effect of coffee extract against some CA222 Grollier, J. F. and S. Pessis. Use of cof- mutagens. Agr Biol Chem 1986; fee oil as a solar radiation filter on the 50(12): 2983–2988. skin. Patent-Fr Demande-2,479,688 CA235 Obana, H., S. I. Nakamura, and R. I. 1981; 3 pp. Tanaka. Suppressive effects of coffee CA223 Stich, H. F., M. P. Rosin and L. Bryson. on the SOS responses induced by UV Inhibition of the mutagenicity of a and chemical mutagens. Mutat Res model nitrosation reaction by natu- 1986; 175; 47–50. COFFEA ARABICA 195

CA236 Weniger, B., M. Rouzier, R. Daguilh, CA244 Coleman, D. E. S. The effect of certain D. Henrys, J. H. Henrys, and R. Anton. homeopathic remedies upon the hear- Popular medicine of the central pla- ing. J Am Inst Homeopathy 1922; 15: teau of Haiti. 2. Ethnopharmacological 279–281. inventory. J Ethnopharmacol 1986; CA245 Wasuwat, S. A list of Thai medicinal 17(1): 13–30. plants, ASRCT, Bangkok. Report no. CA237 Kloos, H., F. W. Thiongo, J. H. Ouma, 1 on Res. Project 17. Research Report, and A. E. Buttersworth. Preliminary A. S. R. C.T., No. 1 on Research evaluation of some wild and cultivated Project 17, 1967; 22 pp. plants for snail control in Machakos CA246 Nishina, A., F. Kajishima, M. district, Kenya. J Trop Med Hyg 1987; Matsunaga, H. Tezuka, H. Inatomi, 90(4): 197–204. and T. Osawa. Antimicrobial sub- CA238 Kark, J. D., Y. Friedlander, N. A. stance, 3’,4’-dihydroxyacetophenone, Kaufmann, and Y. Stein. Coffee, tea, in coffee residue. Biosci Biotech and plasma cholesterol: the Jerusalem Biochem 1994; 58(2): 293–296. lipid research clinic prevalence study. CA247 Wei, M., C. A. Macera, C. A. Br Med J 1985; 291(6497): 699–701. Horning, and S. N. Blair. The impact CA239 Aeschbacher, H. U., E. Ruch, H. of changes in coffee consumption on Meier, H. P. Wurzner, and R. Munoz- serum cholesterol. J Clin Epidemiol Box. Instant and brewed coffees in the 1995; 48(10): 1189–1196. in vitro human lymphocyte mutagenic- CA248 De G Paula, R. D. Investigation of ity test. Food Cosmet Toxicol 1985; coffee oil. Anail Assoc Brasil Quim 23(8): 747–752. 1943; 2: 57. CA240 Abraham, S. K. Inhibition of the in CA249 Tohda, C., N. Nakamura, K. Komatsu, vivo genotoxicity by coffee. Food and M. Hattori. Trigonelline-induced Chem Toxicol 1989; 27(12): 787–792. neurite outgrowth in human neuro- CA241 Melamed, I., J. D. Kark, and Z. Spirer. blastoma SK-N-SH cells. Biol Pharm Coffee and the immune system. Int J Bull 1999; 22(7): 679–682. Immunopharmacol 1990; 12(1): CA250 Fontana, G., G. Mantia, P. Vetri, F. 129–134. Venturella, V. Hopps, and G. Cascio. CA242 Christianson, R. E., F. W. Oechsli, and Effects on the carbohydrate metabo- B. J. Van Dert Berg. Caffeinated bev- lism of “coffee atractylosides”. Fitote- erages and decreased fertility. Lancet rapia 1994; 65(1): 29–33. 1989; 1989(8634): 378. CA251 Booth, S.L., H.T. Madabushi, K.W. CA243 Roig Y Mesa, J. T. Plantas medicinales, Davidson, and J.A. Sadowski. Tea and aromaticas o venenosas de Cuba, coffee brews are not dietary sources of Ministerion de Agricultura, Republica vitamin K-1 (phylloquinone). JAMA de Cuba, Havana. 1945; 872 pp. 1995; 95(1): 82–83. DAUCUS CAROTA 197

5 Daucus carota L.

Common Names Boktel Malaysia Gazar baladi India Bokti Indonesia Gazar India Bortol Sudan Gazur India Cairead Ireland Gelbe Rube Germany Caretysen Cornwall Gele peen Netherlands Carot Cambodia Gele Wortel Netherlands Carot Vietnam Gujjur India Carota Italy Gujjur-jo-beej India Carota salvatica Italy Gularot Faeroe Islands Carote Italy Gulerod Denmark Carotola Germany Gullerodder Denmark Carotte sauvage Mauritius Gulrot Norway Carotte France Have-gulerod Denmark Carradje The Isle of Man (Manx) Havijk Iran Carrot sauvage Belgium Havuc Turkey Carrot sauvage Canada Hong cai tou China Carrot sauvage France Hong da gen China Carrot sauvage Tunisia Hong lu fai China Carrot Guyana Hong luo bo China Carrot United Kingdom Hu lu fai China Carrot United States Hu luo bo China Cenoura brava Portugal Huang luo bo China Cenoura selvagem Brazil Hu-lo-po-tze China Cenoura Portugal Ikherothi Africa Curral Scotland Ilikherothi Africa Curran Scotland Jazar barri Iraq Dauco marino Italy Kaareti New Zealand Daucus carotte France Karot Australia Gaajara India Karot Cambodia Gahzar India Karot Netherlands Antilles Gaiweruam Germany Karot Philippines Gajar India Karote Albania Gajjarakkilangu India Karote Hawaii Gajor India Karoti Samoa

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 197 198 MEDICINAL PLANTS OF THE WORLD

Karoto Greece Ruokaporkana Finland Karotte Germany Sargarepa Croatia Karotten Germany Sargarepa Hungary Karotter Denmark Sargarepa Serbia Karuvathu kelengu India Segwere South Africa Kdyuir Turkmenistan Speisemohre Germany Khaerot Thailand Speisemohren Germany Lobak merah Malaysia Spisegulerod Denmark Marchew Poland Vild gulerod Benin Meacan dearg Ireland Vild gulerod Denmark Mohre Germany Viljelty porkkana Finland Mohrrube Germany Vill gulrot Norway Morkov Bulgaria Wild carrot Canada Morkov Macedonia Wild carrot England Morkov Romania Wild carrot New Zealand Morkov Russia Wild gulerod Denmark Morkva Ukraine Wilde mohre Germany Moronen Wales Wilde peen Belgium Morot Sweden Wilde peen Netherlands Mrkva Yugoslavia Wilde wortel Belgium Niistsikapa’s United States Wildmorot Sweden Nora-ninjij Japan Wortel Indonesia Pahari gajar India Wortel Netherlands Pastanaga Spain Wortel South Africa Pastenade France Yang hua luo bo China Pastenaga France Ye hu luo bo China Pastinaca selvatica Italy Zanahoria Silvestre Dominican Republic Peen Netherlands Zanahoria silvestre Chile Phakchi-daeng Thailand Zanahoria silvestre Peru Pitta gajur India Zanahoria silvestre Spain Porkkana Finland Zanahoria silvestre Venezuela Queen Anne’s lace Canada Zanahoria Puerto Rico Risch melna Switzerland Zanahoria Spain

BOTANICAL DESCRIPTION compound, more or less globose, to 7-cm- Carrot is an erect (30–120 cm high) annu- in-diameter umbels. Rays are numerous, al or biennial herb of the UMBELLI- bracts 1–2 pinnated, lobes linear, 7–10 FERAE family with branched stem arising bracteoles similar to bracts. Flowers are from a large, succulent, thick, fleshy 5–30 white or yellowish; the outer are usually the cm long tap root. The color of the root in largest. Sepals are minute or absent, there the cultivated varieties ranges from white, are five petals and stamens, ovary inferior with two cells and one ovule per cell, two yellow, orange, light purple, or deep red to styles. Fruits are oblong, with bristly hairs deep violet. The shape varies from short along ribs, 2–4 mm long. stumps to tapering cones. Leaves are finely dissected, twice or thrice-pinnate, segments ORIGIN AND DISTRIBUTION are linear to lanceolate, 0.5–3 cm long. Up- Cultivated carrot originated in Afghanistan per leaves are reduced, with a sheathing then spread to China in the 13–14th cen- petiole. Stem is striate or ridged, glabrous to tury and reached England in the 15th cen- hispid, up to 1 m tall. Flowers are borne in tury. It was introduced to North America by DAUCUS CAROTA 199 settlers and is grown widely in temperate Dried seeds are mixed with crude sugar and and tropical regions of the world. eaten to terminate early pregnancyDC188. Hot TRADITIONAL MEDICINAL USES water extract of the dried root is taken orally as a tonic, expectorant, diuretic, stomachic, Algeria. Hot water extract of the seed, and liver cleanserDC219. Hot water extract of mixed with Euphorbia species and a beetle, the leaf is taken orally as a uterine stimulant is taken orally to facilitate childbirthDC010. during parturitionDC020. Hot water extract of The dried seeds are used Arabic countries. the seed is taken orally as an abortifacient, as an abortifacient in the form of a pessary emmenagogue, and aphrodisiacDC008. The in Unani medicineDC191. dried seeds are used as a powerful aborti- Dried root is taken orally for Belgium. facientDC239. The root is taken orally as a hy- diabetesDC088. potensive medicationDC098. Water extract of the dried root is Brazil. Iran. Water extract of the fruit is taken taken orally as a nerve tonic and stimu- orally as an emmenagogueDC014. lantDC089. Italy. Decoction of the root is used as a Canary Islands. Infusion of the dried aerial gargle for loss of speechDC072. Root juice is DC208 parts is taken orally for cystitis . taken orally as an anthelmintic and cicatri- China. Decoction of the seed is taken orally zing agent, for leukorrhea, and to improve DC108 as an emmenagogue . Root juice is taken sightDC224. The fresh root is used externally orally for cancer of the stomach, bowel, and for dermatitis and burns. The fresh root DC108 uterus, and for ulcers . juice is taken orally for loss of voice and per- Egypt. Hot water extract of the fruit is taken sistent coughs, and the decoction is taken orally to facilitate pregnancy and as an em- orally for diuresisDC222. The root is taken menagogue, aphrodisiac, diuretic, and orally as a diuretic and a digestive and to DC151 antispasmodic . Hot water extract of the treat uricemia and constipationDC102. dried fruit is taken orally as a diuretic and Kuwait. The seeds are taken orally as an DC174 for urinary colic . emmenagogueDC113. England. Hot water extract of the root and Madeira. Infusion of the entire plant is seed are taken orally to induce the men- taken orally for jaundiceDC101. DC017 strual cycle . Mexico. Hot water extract of the fresh root Europe. Decoction of the dried leaf is taken is taken orally as a cardiotonicDC173. The orally for diabetes mellitusDC140. Hot water flowers or root, boiled together with Cassia extract of the root is taken orally as an fistula and “Rosa de Castilla,” are taken emmenagogueDC019 and anthelminticDC237. orally before breakfast to induce abortion. Hot water extract of the seed is taken orally To correct delayed menstruation, the liquid to induce menstruationDC011. is taken daily for 40 daysDC234. Fiji. Fresh leaf juice is used as a nose drop Morocco. The fruit is taken orally for uri- for headache. Fresh root is taken orally for nary tract infectionsDC253. heart diseasesDC207. New Caledonia. Infusion of the fruit is France. Hot water extract of the fruit is taken orally as an emmenagogueDC009. taken orally as an emmenagogueDC227. Pakistan. Hot water extracts of the leaf and Greece. Infusion of the dried flowers is seed are taken orally as stimulants of the taken orally as a tonic and to relieve uterus during parturitionDC003. sluggishnessDC083. Peru. Hot water extracts of the dried root India. Decoction of the fresh root is taken and dried aerial parts are taken orally as a orally for jaundice and inflammation, as an carminative, emmenagogue, and vermi- anthelmintic, and externally for leprosyDC118. fugeDC218. 200 MEDICINAL PLANTS OF THE WORLD

Philippines. Hot water extract of the leaf is Arginine: PlDC161 taken orally as a stimulant of the uterus dur- Asaraldehyde: Sd EODC023 DC090 ing parturitionDC001. Asarone, cis: Fr EO 4.10% trans DC090 Rodrigues Islands. Decoction of the entire Asarone, : Fr EO 40.325 Asarone: Sd EODC023, Fr EO 6.08%DC090 plant is taken orally for gout, jaundice, and Ascorbic acid, dehydro: RtDC244 DC100 mouth ulcers . Ascorbic acid: RtDC093 South Korea. Hot water extract of the dried Aspartic acid: PlDC161 fruit is taken orally as an abortifacient and Astragalin: SdDC177 emmenagogueDC206. Avenasterol, 7-dehydro: Fr EODC134 Tunisia. Dried leaf is used externally for Benzene, 4-methyl-iso-propenyl: SdDC149 DC246 chilblainsDC254. Benzoic acid, 4-hydroxy: Rt DC199 Turkey. The seed, ground with the seeds of Benzylamine, N-methyl: Rt 16.50 Benzylamine: Rt 2.80DC199 Brassica rapa and Raphanus sativus, is taken Bergapten: Rt 0.3DC175, Call Tiss 115DC076, DC099 orally as a tonic . FrDC142 United States. Hot water extract of the Betaine: Sh 0.3 Pmol/gDC181 fruit is taken orally to stimulate menstru- Bisabolene, E: Sd EODC171, Fr EO ationDC012. Hot water extract of the seed is 20.13%DC090, Sd EO 1.5%DC029 taken orally as an emmenagogueDC021. Seeds Bisabolene, J, trans: RtDC144 are taken orally as an emmenagogue, di- Bisabolene, J: RtDC067 DC023 DC064 uretic, and abortifacientDC182. The fresh root Bisabolene: Sd EO , Rt Borneol acetate: RtDC064 is taken orally for general nervousness, and Caffeic acid: Aer, RtDC245, LfDC248, Call the hot water extract is taken orally as a di- TissDC246 DC250 uretic in dropsy and as a tonic . Hot wa- Caffeoylquinic acid: RtDC111 ter extract of the dried root and seed is taken Calcium inorganic: RtDC153 orally as a carminative, diuretic, and Campesterol: LfDC172, Aer, RtDC198 stimulantDC249. Capric acid: Fr fixed oil 1.56%DC134 Car-3-ene monoterpene: Fr EO 1.27%DC090 CHEMICAL CONSTITUENTS Carota-1-4-E-oxide sesquiterpene: Sd EO (ppm unless otherwise indicated) 66DC131 Aesculetin coumarin: Lf, RtDC248 Carotene, D, all-trans: RtDC106 Alanine(DL): BdDC236 Carotene, D: RtDC157, LfDC030 Alanine: SdDC065, RtDC126,DC200 Carotene, E, 9-cis: RtDC135 Alcanols (C22–C30): Lf 305DC172 Carotene, E, all-trans: RtDC135 Aldolase: Call TissDC036 Carotene, E: RtDC078 Alkanes (C13–C58): RtDC126 Carotene,H: RtDC022 Alkanes (C15–C39): Lf 0.033DC172 Carotene, J: LfDC030, RtDC157 Amine, ethyl-methyl: Rt 7DC199 Carotene: RtDC243 Ammonia-lyase: PlDC194 Carotol: EODC042, SdDC146,Sd EODC033 Amylase: Call TissDC036 Caryophyllene, E: RtDC144 Amyrin, D: AerDC198 Caryophyllene: RtDC067 Amyrin, E: AerDC198 Chlorogenic acid, iso: RtDC159, LfDC248 Aniline, N-methyl: Rt 0.8DC199 Chlorogenic acid, trans: AerDC129 Aniline: Rt 30.9DC199 Chlorogenic acid: RtDC031, AerDC245, Call Anthocyanins: Call TissDC233, PlDC085 TissDC060, LfDC248 Apigenin: Lf DC087 Chlorophyll: Fr Ju 0.2DC197 Apigenin-4'-O-E-D-glucoside: SdDC177, FrDC170 Chloroplasts: RtDC143, Call TissDC063, LfDC030 Apigenin-7-galactomannoside: SdDC177 Cholesterol: LfDC172 Arabinoside: RtDC200 Choline, phosphatidyl: PlDC120 Arachic acid: Fr fixed oil 0.31%DC134 Choline: SdDC018 DAUCUS CAROTA 201

Chromone, 5-7-dihydroxy-2-methyl: RtDC024 Falcarindiol-1-acetate: RtDC069 Chrysanthemin: Call TissDC184 Falcarinol: Rt 10DC069 Chrysin: FrDC170 Farnesene, E, trans: Sd EO 2.5%DC029 Chrysoeriol: LfDC087 Ferulic acid: RtDC040, Call TissDC060, LfDC248 Cinnamic acid, trans; PlDC194 Fructokinase, phospho: RtDC150 Cinnamic acid: Call TissDC060 Fructose: RtDC228 Citric acid, iso: RtDC240 Fumarase: Call TissDC036 Citric acid: RtDC240 Fumaric acid: RtDC240 Coenzyme Q-10: PlDC058 Galactose: RtDC200 Cosmosiin: FrDC170 Galactosidase, E: PlDC161 Coumaric acid, para: RtDC040, Call TissDC246 Galacturonanase, exo-D: RtDC112 Coumarin, iso, 3-4-dihydro-8-hydroxy-6- Gentisic acid: Call TissDC246 mehoxy-3-methyl: RtDC041, Call TissDC037 Geraniol: Sd 300DC149 Coumarin, iso: RtDC159 Geranyl-2-methyl-butyrate: 0.05%DC149 Cpsmosiin: LfDC170 Glucose: RtDC228, BdDC236 Cryptoxanthin, E: RtDC122 Glucosidase, D: PlDC161 Cyanidin diglycoside: RtDC247 Glucosidase, E: PlDC161 Cyanidin-3-(sinapoyl-xylosyl-glucosyl-galacto- Glucuronidase, E: PlDC161 side): Pl, LfDC125 Glutamic acid: PlDC161, RtDC200 Cyanidin-3-0-galactoside: Call TissDC184 Glycerol, phosphatidyl: PlDC120 Cyanidin-3-5-digalactoside: Call TissDC184 Glycine: SdDC065, PlDC161, RtDC126, BdDC236 Cyanidin-3-glucogalactoside: Call TissDC184 Guaiacol, para-vinyl: Sd 0.4%DC149 Cymen-8-ol, para: Sd 0.9DC149 Hentraicontane, N: SdDC032 Cynaroside: FrDC170, AerDC129, LfDC170 Heptacosane, N: BdDC236, SdDC032 Cysteine: PlDC161 Heptadeca-2-9-diene-4-6-diyn-8-ol-acetoxy: Dauca-4-8-diene sesquiterpene: Sd EO RtDC069 4.1%DC029 Heraclenin: Rt, AerDC178 Daucarin: SdDC189 Histidine: PlDC161, RtDC200 Daucic acid: RtDC039 Hydroxylase, cinnamic acid-4: PlDC168 Daucol, dehydroxy: Sd EODC033 Indole, acetic acid: Call TissDC155 Daucol: Sd EODC033 Inosidol, phosphatidyl: PlDC196 Daucosterol: LfDC087 Invertase: PlDC231 Dauc-trans-8-en-4-E-ol sesquiterpene: Sd EO Ionone, E: Sd 0.03%DC149 4.1%DC029 Kaempherol: RtDC075, FrDC170 Daucus carota agglutinin: RtDC180 Lauric acid: Fr Fixed oil 2.08%DC134 Daucus carota alkaloid 2: SdDC018 Leucine, iso: PlDC161, RtDC200 Daucus carota exopolygalacturonase: RtDC027 Leucine: RtDC126, BdDC236, PlDC161, SdDC065 Daucus carota protein (75 kDa): PlDC028 Lignin: PlDC034 Daucus carota tertiary alkaloid: SdDC166 Limonene: RtDC064 Dehydrogenase, glutamic acid: PlDC168 Linoleic acid: Sd 12.2%DC195 Diosgenin: Call Tiss 0.6%DC121 Linolenic acid: Sd oilDC148 Elemicin: Sd 0.2%DC149 Lupeol: RtDC198 Esterase, pectin: RtDC119 Lutein: Rt 2.8 DC068 Ethanolamine, phosphatidyl: PlDC196 Luteolin: FrDC170, Rt 1.4DC073 Ethylamine: Rt 1DC199 Luteolin-7-O-(6''-O-malonyl)-E-D glucoside: Eugenin: Call TissDC037, RtDC156 AerDC129 Eugenol methyl ether phenylpropanoid: Fr EO Luteolin-7-O-E-D-glucoronide: AerDC129 1.23%DC090 Lyase, phenylalanine-ammonia: Call TissDC109, Eugenol phenylpropanoid: 0.70%DC149, Fr EO PlDC168 1.72%DC090 Lycopene: LfDC030, Call TissDC063, RtDC157 Extensil: RtDC055 Lysine: PlDC154, RtDC200 Falcarindiol monoacetate: RtDC057 Malic acid: RtDC240 202 MEDICINAL PLANTS OF THE WORLD

Malvidin-3-5-diglucoside: RtDC032 Ribonuclease: PlDC165 Mannose: RtDC200 RNase: Call TissDC036 Melatonin: Rt 55.3 pg/gDC084 Rutin: RtDC075 Mellein, 6-hydroxy, (-): RtDC024 Scopoletin: RtDC024, LfDC248 Mellein, 6-methoxy, (-): RtDC024 Serine: SdDC065, BdDC236, RtDC200 Mellein, 6-methoxy: PlDC124, RtDC193 Shikimic acid: RtDC240 Methionine: PlDC154 Sitosterol, E: SdDC035, RtDC057, BdDC236, Lf DC172, Methylamine: Rt 3.80DC199 AerDC198 Mevalonic acid: Rt 4DC232 Sterase: PlDC161 Myrcene: RtDC144 Stigmasterol: LfDC172, Aer, Lf DC198 Myricetin: Rt 1DC073 Suberin: RtDC046 Myristic acid: Sd oilDC148 Succinic acid: RtDC240 Myristicin: Rt 34.4DC179 Sucrose: RtDC228 Nerol acetate: EO 2.51%DC107 Syringic acid: RtDC246 Nerol: Fr EO 0.30%DC107 Taraxasterol: Aer, RtDC198 Neurosporene: RtDC157 Tartaric acid: RtDC240 DC199 DC064 NH3 inorganic: Rt 3970 Terpinen-4-ol: Rt Nonacosane, N: BdDC236, SdDC032 Terpinene, D: RtDC144 Nucleotidase, 3': PlDC165 Terpinene,J RtDC064 DC032 Octacosane, N: Sd Terpineol, D: PlDC257 Oleic acid: Sd oilDC136, Sd 11.6%DC195, Fr Terpinolene: RtDC144 Fixed oil 76.25%DC134 Threonine: RtDC200 Paeonol: Fr EO 1.33%DC090 Tiglic acid: Sd EODC023 Palmitic acid: Sd oilDC148, Fr fixed oil Toluidine: Rt 7.20DC199 3.25%DC134 Transaminase, glutamate-oxalacetate: Call DC114 Palmitoleic acid: Rt , Fr fixed oil TissDC036 DC134 0.31% Transaminase, glutamate-pyruvate: Call DC032 Peroxidase: Rt TissDC036 DC145 DC195 Petroselinic acid: Sd oil , Sd 71.2% Tryptophan: RtDC126, PlDC154 DC144 Phellandrene, D: Rt Tyrosine: BdDC236, SdDC065, PlDC161, RtDC200 DC199 Phenethylamine, N-methyl: Rt 2 Ubiquinone 10: Call Tiss 0.125DC062, Pl DC199 Phenetrhylamine: Rt 2 160DC061 DC200 Phenylalanine: Rt Umbelliferone: LfDC241 DC161 Phosphatase, acid: Pl Uronic acid: RtDC200 DC157 Phytofluene: Rt Valine: RtDC126, BdDC236, SdDC065, PlDC161 DC080 PIK-A49: Pl Vanillic acid: Call TissDC246 DC095 Pimpinellin, iso: Call Tiss Xanthotoxin: Pl, CrDC123, Rt 0.3DC175, Call DC146 DC064 DC029 Pinene, D: Sd , Rt , Sd EO 0.9% TissDC095, FrDC082 DC064 Pinene, E: Rt Xylitol: RtDC110 DC077 Polysaccharides: Pl Xylose: RtDC200 DC200 Proline, 4-hydroxy: Rt DC160 DC126 DC161 DC181 Zeatin, cis: Call Tiss Zeatin: Call Proline: Rt , Pl , Sh 0.1 Pmol/g TissDC160 Protein: PlDC038, Sd 30%DC229 Psoralen, 5-methoxy: Pl, CrDC123, FrDC082 PHARMACOLOGICAL ACTIVITIES Psoralen: Rt 0.3DC175,DC142 AND CLINICAL TRIALS Putrescine: Call TissDC152 DC064 Abortifacient effect. Ethanol (95%) ex- Pyrazine, 2-methoxy-3-sec-butyl: Rt tract of the dried seed, administered by gas- Qercitrin: FrDC170 Quercetin: RtDC075, FrDC170 tric intubation to pregnant mice at doses of Quinic acid: RtDC240 30 mg/animal and 40 mg/kg on days 4–6, Rhamnose: RtDC200 was inactiveDC238. Petroleum ether extract of Ribonuclease, deoxy: PlDC165 the dried seed, administered subcutaneously DAUCUS CAROTA 203 to pregnant rats beginning on day 7 of preg- the fresh root, on agar plate at a concentra- nancy, was activeDC127. Petroleum ether ex- tion of 500 Pg/plate, produced weak activ- tract of the dried seed, administered ity on Salmonella typhimurium TA100 vs subcutaneously to pregnant rats at a dose N-nitrosoamine-induced mutagenicityDC115. of 2 mL/kg, was active. The effect was Agglutinin activity. Water extract of the blocked by progesterone given on days 7–19 fresh root at variable concentrations was of pregnancyDC205. Seed essential oil, admin- active on Streptococcus mutansDC180. istered to pregnant mice at a dose of 5 mg/ AIDS therapeutic effects. Water extract of kg, was activeDC171. Acetone extract of the the dried rhizome taken orally by adults was fresh root, at a concentration of 1 Pg/mL, active. A pharmaceutical solution contain- produced weak activity and the propanol ing fruit bodies of Tremella fuciformis, extract was inactive on Salmonella typhimu- Daucus carota rhizome, Astragalus mongho- rium TA98 vs 2-amino-3-methylimidazo licus root, and Zizyphus jujuba fruits, honey, (4,5-F) quinoline-induced mutagenicityDC053. vitamin A palmitate, zinc sulfate, and vita- Fresh fruit juice, administered by gastric in- min C was useful for controlling acquired tubation to male mice at a dose of 0.5 mL/ immunodifficiency syndrome (AIDS), can- animal, was active on Schizosaccharomyces cer, and infectionsDC139. pombe. The animals were treated with the Anti-allergenic activity. Water extract of juice and nitrosation precursors, then yeast the fresh root, in cell culture at a con- cells were injected into the venous plexus centration of 100 PL/mL, was inactive on of the orbit. Four hours later, the animals Leuk-RBL 2H3 vs biotinylated anti-deoxy- were sacrificed and the livers removed, riboneucleoprotein immunoglobulin E /avi- plated with yeast and examined. Results din-induced E-hexosaminidase releaseDC086. were significant at p < 0.001 levelDC197. Infu- Anti-amoebic activity. Essential oil, in sion of the stem, on agar plate at a concen- broth culture at a concentration of 0.5 PL/ tration of 100 PL/disc, produced strong mL, was active on Entamoeba histolyticaDC091. activity on Salmonella typhimurium TA98 Antibacterial activity. Essential oil, on vs 2-amino-anthracene-induced mutagenic- agar plate at a concentration of 0.43 mg/mL, ity. Metabolic activation was not required produced weak activity on Streptococcus-E for activity. Weak activity was produced on hemolytic and Staphylococcus aureus, equivo- Salmonella typhimurium TA100 vs ethyl cal on Escherichia coli, minimal inhibitory methanesulfonate-induced mutagenicity. concentration (MIC) 1.74 mg/mL and in- Metabolic activation was not required for active on Proteus mirabilis, MIC 17.4 mg/ activityDC255. Methanol extract of the dried mL. Fruit essential oil on agar plate was ac- root, on agar plate at a concentration of 50 tive on Staphylococcus aureus, MIC 0.12 mg/ PL/disc, was inactive on Bacillus subtilis mL, and Streptococcus-E hemolytic, MIC 0.23 NIG-1125 His Met and Escherichia coli B/R- mg/mL, inactive on Proteus mirabilis, MIC WP2-TRPDC203. Root juice, on agar plate 18.5 mg/mL, and equivocal on Escherichia at a concentration of 500.0 PL/plate coli, MIC 9.25 mg/mLDC107. Ethanol (70%) produced weak activity on Salmonella extract of the fruit, on agar plate, was active typhimurium TA98 vs 2-nitrofluorine- and on Bacillus megaterium, Staphylococcus albus, 1-nitropyrene-induced mutagenesisDC056. Staphylococcus aureus, and Bacillus cereusDC190. Water extract of the fresh root, on agar plate Ethanol (95%) and water extracts of the en- plus S9 mix at a dose of 0.4 mL/plate, was tire plant, on agar plate, were inactive on active on Salmonella typhimurium TA 100 vs Escherichia coli and Staphylococcus aureusDC026. TRP-P-2 mutagenicityDC215. Water extract of Fresh root, macerated, in pieces and shred- 204 MEDICINAL PLANTS OF THE WORLD ded, was active on Listeria monocytogenesDC137. lium digitatum, Rhizopus nigrans, and Tri- Fresh shredded root dipped in chlorine and chophyton mentagrophytesDC212. Seed essential packaged under an atmosphere containing oil, in broth culture at variable concentra- 3% oxygen and 97% nitrogen, was active on tions, was active on Cladosporium wern- Listeria monocytogenes. Bacterial growth was eckiiDC192. The root, on agar plate, was active inhibited on shredded carrots more than on on Porphyromonas gingivalisDC048. whole carrots. There was no inhibition on Antigen expression inhibition. Fresh plant cooked carrotsDC132. The root, on agar plate, juice, in the ration of female mice, was ac- was active on Streptococcus mutansDC048. tive vs IgE antibody expression in ovalbu- Anticlastogenic activity. Plant juice, ad- min-sensitized miceDC116. ministered intragastrically to male mice at Antihalitosis effect. Dried root ingested by a dose of 1 mL/kg, produced weak activity adults was active. The biological activity on reticulocyte vs J-ray irradiationDC047. has been patentedDC050. Anticytotoxic activity. Ethanol (95%) Antihepatotoxic activity. Water extract of extract of the fresh root, at a concentra- the fresh root, administered intragastrically tion of 80 mg/mL in cell culture, was ac- to male rats at a dose of 20 mL/kg, was ac- tive on Vero cells vs N-nitrosopiperidine, tive vs lindane-induced hepatotoxictyDC118. N-nitrosodibutylamine, and N-nitrosodi- Supernatant of the fresh root, administered methylamine cytotoxicity. A dose of 20 mg/ intragastrically to male mice at a dose of 50 mL was inactive vs N-nitrosopiperidine, mL/kg, decreased serum bilirubin, urea, lac- nitrosodimethylamine, N-nitrosopyrroli- tic dehydrogenase, serum glutamic pyruvic dine, and N-nitrosodibutylamine cytotox- transaminase, and serum glutamic oxaloace- icityDC104. tic transaminase levels vs carbon tetrachlo- DC092 Anti-edema activity. Methanol extract of the ride (CCl4)-induced hepatoxicity . root, applied externally to mice at a dose of Antihyperglycemic activity. Decoction, 2 mg/ear, produced inhibition ratio of 37DC071. ethanol (80%),DC088 and waterDC103 extracts of Anti-estrogenic effect. Ethanol (95%) ex- the dried root, administered intragastrically tract of the dried seed, administered by gas- to mice at a dose of 25 g/kg, were active vs tric intubation of ovariectomized mice at a glucose-induced hyperglycemia. Dried leaf, dose of 40 mg/kg daily for 3 days, produced administered to male mice at a concentra- weak activityDC238. Petroleum ether extract tion of 6.25% of the diet for 28 days, was of the dried seed, at a dose of 10 mg/kg, was inactive vs streptozotocin-induced hyper- activeDC117. glycemiaDC140. Fresh root, taken orally by 15 Antifertility effect. Hot water extract of adults of both sexes with type II diabetes at the dried seed, administered by gastric intu- a dose of 280 g/person, was activeDC133. bation to female rats, was activeDC201. Anti-implantation effect. Chloroform– Antifungal activity. Acetone, water, and methanol (9:1) fraction of ethanol (95%) ethanol (95%) extracts of the dried fruit, on extract, a chloroform-soluble fraction and agar plate at a concentration of 50%, were an ethyl acetate-soluble fraction of a water inactive on Neurospora crassaDC252. The es- extract, methanol-soluble fraction of a pe- sential oil, at a concentration of 1000 ppm troleum ether extract and chloroform on agar plate, produced weak activity on soluble fraction of petroleum ether extract Aspergillus flavusDC068. Ethanol (50%) extract of the seed, administered orally to female of the dried root, on agar plate at a concen- rats at a dose of 50 mg/kg, were active vs tration of 500 mg/mL, was active on Botrytis foot shockDC230. Water and petroleum ether cinerea and inactive on Aspergillus fumigatus, extracts of the seed, administered orally to Aspergillus niger, Fusarium oxysporum, Penicil- female rats at doses of 100 and 20 mg/kg, DAUCUS CAROTA 205 respectively, were activeDC006. Petroleum Petroleum ether extract of the seed, admin- ether extract of the seed, administered istered subcutaneously to pregnant rats at a orally to female rats at a dose of 500 mg/kg, dose of 0.6 mL/animal, was activeDC223. was inactiveDC044. Ethanol (50%) extract of Antispasmodic activity. Petroleum ether the dried seed, administered orally to fraction chromatographed and fraction female rats at a dose of 500 mg/kg, was eluted with chloroform, at a concentration inactiveDC167. Ethanol (95%) extract of the of 0.50 mg/mL, was active on the guinea dried fruit, administered orally to pregnant pigileum vs histamine-induced contrac- rats at a dose of 500 mg/kg, produced 60% tionsDC226. Tertiary alkaloid fraction of the inhibition of implantationDC169. Petroleum dried seeds produced weak activity on the ether extract of the dried seed, administered dog trachea vs acetylcholine (ACh)- and subcutaneously to pregnant rats at a dose of KCl-induced contractions, and active on 6 mL/kg, was inactiveDC187. Seed essential oil, the guinea pig ileum. A concentration of 25 administered to pregnant mice at a dose of Pg/mL was active on the rat uterus vs ACh- 5 mg/kg, was activeDC171. and oxytocin-induced contractions, results Antimycobacterial activity. Ethanol (95%) significant at p < 0.02 levelDC166. Methanol and water extracts of the entire plant, on extract of the dried seed, at a concentra- agar plate, were inactive on Mycobacterium tion of 0.1 mg/mL, was active on the guinea tuberculosisDC026. Leaf juice, on agar plate, pig ileum vs histamine-induced contrac- produced weak activity on Mycobacterium tionsDC221. tuberculosis, MIC less than 1:20DC007. Anti-thyroid activity. Boiled root, taken Anti-nematodal activity. Methanol ex- orally by adults at a dose of 554 g/person, tract of the fruit, at a concentration of 1 mg/ produced weak activity on iodine uptake by mL, was active, and the water extract, at a the thyroid. The root, taken orally by adults, concentration of 10 mg/mL, produced weak at a dose of 352 g/person, produced slight to activity on Toxacara canisDC147. high iodine uptake by the thyroidDC251. Antioxidant activity. Plant juice, at a dose Anti-tumor activity. Petroleum ether ex- of 100 PL/kg, produced weak activity vs tract of the dried seed, administered intrap- Fenton’s reagent-induced lipid peroxida- eritoneally to male mice at a concentration tionDC047. The root, at a concentration of 1%, of 3 mg/kg, was active on Chinese hamster produced weak activity at 120q FDC096. Water cells-V79DC059. The root, administered in the extract of the fresh root, at a concentra- ration of female rats for 1 month before tion of 10 PM trolox equivalent per gram, 7,12-dimethybenz[a]anthracene treatment, produced weak activity vs oxygen radical reduced tumor size DC045. Water extract of the absorption capacity assay with hydroxyl and aerial parts, administered intraperitoneally peroxyl radical generators, and Cu2+ (reac- to mice at a dose of 400 mg/kg, was inactive tive species) activityDC052. Fresh root homo- on Leuk (Friend Virus-Solid) and Leuk- genate produced 31.8% inhibition of lipid L1210. A dose of 500 mg/kg was inactive on peroxidationDC093. Sarcoma 180 (ASC)DC235. Water extract of Antioxytocic effect. Methanol extract of the dried root taken orally by adults was ac- the dried seed, at a concentration of 0.5 mg/ tive. A pharmaceutical solution containing mL, was equivocal vs oxytocin-induced fruit bodies of Tremella fuciformis, Daucus contractionsDC221. carota root, Astragalus mongholicus root, and Antiprogesterone effect. Petroleum ether Zizyphus jujuba fruits, honey, vitamin A extract of the dried seed, administered sub- palmitate, zinc sulfate, and vitamin C was cutaneously to pregnant rats at doses of 2 useful for controlling AIDS, cancer, and mL/kg and 0.6 mL/animal, were activeDC205. infectionsDC139. Hot water extracts of the 206 MEDICINAL PLANTS OF THE WORLD fresh leaf and fresh root, in cell culture, pro- solution. Consumption of the saccharin duced strong activity on Raji cells vs solution 2 days after the test was used to esti- phorbol myristate acetate-promoting ex- mate aversiveness of the test substanceDC216. pression of Epstein-Barr virus (EBV) early Cytotoxic activity. Ethanol (50%) extract antigenDC070. Methanol extract of the fresh of the root, in cell culture, was inactive on root, at a concentration of 200 mg/mL, was CA-9KB, effective dose (ED)50 greater than inactive on Raji cells vs EBV activation in- 20 Pg/mLDC013. Methanol extract of the fresh duced by 12-O-hexadecanoylphorbol (40 root, in cell culture at a concentration of ng/mL)DC097. 200 Pg/mL, was inactive on macrophage cell Anti-yeast activity. Ethanol (50%) extract line RAW 264.7DC054. Water extract of the of the dried root, on agar plate at a concen- aerial parts, in cell culture, was inactive on DC235 tration of 500 mg/mL, was inactive on CA-9KB, ED50 greater than 0.1 mg/mL . Candida albicans and Saccharomyces pasto- Dermatitis-producing effect. Ether ex- rianusDC212. tract of the fresh entire plant, applied by Cardiotonic activity. Petroleum ether frac- patch at a concentration of 1%, was tion chromatographed and fraction eluted activeDC130. Fresh root, in a mixture contain- with chloroform, administered by perfusion ing Apium graveolens, Aromatica rusticana, at a concentration of 0.20 mg/mL, was inac- Solanum tuberosum, and Petroselinum cris- tive on the guinea pig heartDC226. pum, was activeDC220. Catalase inhibition. Water extract of the Desmutagenic activity. Fresh plant juice, fresh root, administered intragastrically to on agar plate at a concentration of 0.5 mL/ infant mice at a dose of 50 mL/kg, was ac- disc, was inactive on Salmonella typhimurium tive. The treatment was administered for TA98DC213. Homogenate of the fresh root, at seven successive days, followed by a single a concentration of 100 PL/disc on agar plate, dose of 20% v/v CCl4 in olive oil subcutane- was active on Salmonella typhimurium TA98 ously at 1 mL/kg on the last day 1 hour after and TA100 vs 1,4-dinitro-2-methyl pyrrole the administration of the carrot extractDC074. mutagenesisDC211. Chloroform–methanol (9:1) fraction of the Diuretic activity. Ethanol (70%) extract of ethanol (95%) extract, ethyl acetate frac- the dried fruit, administered intravenously to tion of the water extract, and chloroform- dogs at a dose of 150 mg/kg, increased diure- soluble fraction of the water extract of the sis 1.7-foldDC141. Ethanol (95%) extract of the seed were active on the nonpregnant rat seed, administered orally to rats at a dose of uterusDC225. 100 mg/kg, was inactiveDC020. Seed essential Central nervous system (CNS) depres- oil, administered intravenously to dogs at a sant activity. Ethanol (95%) extract of the concentration of 4 PL/kg, produced 2.4-fold seed, administered orally to mice and rats at increase in urine flow and an increase in K+, a dose of 50 mg/kg, was inactiveDC020. Na+, and Cl- excretion. Ethanol (70%) ex- CNS stimulant activity. Ethanol (95%) tract of the seed essential oil, administered extract of the seed, administered orally to intravenously to dogs at a dose of 20 mg/kg, mice and rats at a dose of 50 mg/kg, was produced 1.6-fold increase in urine flowDC141. inactiveDC020. Embryotoxic effect. Ethanol (95%) ex- Conditioned taste aversion. Frozen leaf tract of the dried seed, administered by gas- and stem, administered intragastrically to tric intubation to pregnant rats at a dose of rats at a dose of 562 mg/kg, was inactive. 40 mg/animal on days 4–6, was inactiveDC238. The test substance was temporarily paired A dose of 0.10 g/kg, administered by gastric with the introduction of sodium saccharin intubation to pregnant rats on days 1–10, DAUCUS CAROTA 207 was inactive, and a dose of 0.25 mg/kg on levelDC185. Ethanol (95%) extract of the root, days 1–10 was equivocal. Six of 10 animals administered subcutaneously to female were pregnant vs 10 of 10 in the control infant mice, was active DC015,DC016. Ethanol groupDC209. Ethanol (50%) extract of the (95%) extract of the root, administered sub- dried seed, administered by gastric intuba- cutaneously to female infant mice, was tion to pregnant rats at a dose 200 mg/kg, inactiveDC004. The seed essential oil was was equivocalT05679. The water extract, at a inactiveDC171. Root, in the ration of female dose of 0.5 g/kg on days 1–10, was infant mice, produced activity equivalent inactiveDC209. Petroleum ether extract, ad- to 2 Pg stilbestrol in 100 g carrot (dry ministered subcutaneously to pregnant rats weight)DC002. at a dose of 1 mL/kg, was inactive and a dose Estrous cycle disruption effect. Petroleum of 2 mL/kg was active. Results were signifi- ether extract of the dried seed, administered cant at p < 0.05 levelDC187. Powdered dried subcutaneously to rats at a dose of 2 mL/kg, seed, administered by gastric intubation to was active. Results were significant at p < pregnant rats at doses of 2–4.5 g/kg on days 0.001 levelDC186. 1–10, was inactiveDC209. Petroleum ether ex- Glutathione formation induction. Water tract of the seed chromatographed and frac- extract of the fresh root, administered tion eluted with chloroform, administered intragastrically to infant mice at a dose of orally to female rats at a dose of 20 mg/kg, 25 mL/kg, was active. The treatment was was activeDC256. Ethanol (95%) extract of the administered for seven successive days fol- seed, administered orally to female rats at a lowed by a single dose of 20% v/v CCl4 in dose of 50 mg/kg, was inactive. Chloroform- olive subcutaneously at 1 mL/kg on the last soluble and ethyl acetate-soluble fractions day, 1 hour after the administration of the of a water extract of the seed, administered carrot extractDC074. orally to female rats at a dose of 50 mg/kg, Glutathione peroxidase inhibition. Water were active vs foot shock. Chloroform- and extract of the fresh root, administered methanol-soluble fractions of the petroleum intragastrically to infant mice at a dose of ether extract of the seed, administered 50 mL/kg, was active. The treatment was orally to female rats at a dose of 50 mg/kg, administered for seven successive days fol- DC230 was inactive . Petroleum ether extract of lowed by a single dose of 20% v/v CCl4 in the seed, administered subcutaneously to olive subcutaneously at 1 mL/kg on the last pregnant rats at a dose of 0.6 mL/animal, day, 1 hour after the administration of the was activeDC223. Seed essential oil, adminis- carrot extractDC074. tered subcutaneously to pregnant rats on Glutathione reductase stimulation. Wa- days 1, 2, 7, and 8, was activeDC206. ter extract of the fresh root, administered Estrogenic effect. Ethanol (95%) extract intragastrically to infant mice at a dose of of the dried seed, administered by gastric in- 25 mL/kg, was active. The treatment was tubation to infant female mice at doses of administered for seven successive days fol-

20 and 40 mg/animal daily for 3 days, pro- lowed by a single dose of 20% v/v CCl4 in duced weak activityDC238. Doses of 50, 100, olive subcutaneously at 1 mL/kg on the last and 500 mg/kg, administered subcutane- day, 1 hour after the administration of the ously to ovariectomized rats, produced weak carrot extractDC074. activityDC214. Petroleum ether extract of the Glutathione S-transferase induction. Fresh dried seed, administered subcutaneously to leaf was inactive on Spodoptera frugiperdaDC210. ovariectomized rats at doses of 2 and 6 mL/ Glutathione S-transferase inhibition. kg, was active, results significant at p < 0.01 Water extract of the fresh root, adminis- 208 MEDICINAL PLANTS OF THE WORLD tered intragastrically to infant mice at a dose dose of 2–5 mg/kg, was inactiveDC221. Seed of 50 mL/kg, was active. The treatment was essential oil, administered intravenously administered for 7 successive days followed to dogs at a concentration of 4 PL/kg, was DC141 by a single dose of 20% v/v CCl4 in olive active . subcutaneously at 1 mL/kg on the last day, Immunostimulant activity. Fresh plant 1 hour after the administration of the carrot juice, in the ration of female mice, was extractDC074. active in ovalbumin-sensitized miceDC116. Goitrogenic activity. Fresh root, in the ra- Water extract of the dried root, taken orally tion of rats at a dose of 9 g/day for 26 days, by human adults, was active. A pharmaceu- was activeDC204. tical solution containing fruit bodies of Hemagglutinin activity. Saline extract of Tremella fuciformis, Daucus carota root, the dried seed, at a concentration of 10%, Astragalus mongholicus root and Zizyphus was active on the human red blood cellsDC202. jujuba fruits, honey, vitamin A palmitate, Hypocholestrolemic activity. Fresh root, zinc sulfate, and vitamin C is claimed useful taken orally by human adults at a dose of as an immunostimulant for controlling 200 g/person, was active. Daily ingestion at AIDS, cancer, and infectionsDC139. breakfast for 3 weeks decreased cholesterol Inotropic effect (negative). Ethanol in serum by 11%, increased fecal bile acid (80%) extract of the aerial parts, at a con- and fat excretion by 50%, and increased centration of 0.3 mg/mL, was active on the stool weight by 25%DC163. guinea pig atriumDC081. Hypoglycemic activity. Dried leaf, in the Inotropic effect (positive). Ethanol (95%) ration of male mice at a concentration of extract of the seed, at a concentration of 4 6.25% of the diet for 28 days, was inactive mg/mL, was active on the perfused frog vs streptozotocin-induced hyperglycemiaDC140. heartDC020. Ether extract of the fresh root, administered Insecticidal activity. Water extract of the subcutaneously to dogs, rabbits, and human dried root, at variable concentrations, was adults, was activeDC025. inactive on Blatella germanica and Onco- Hypotensive activity. Essential oil, ad- peltus fasciatus, and a dose of 40 mg/kg, ministered intravenously to dogs at a dose administered intravenously, was inactive on of 3 PL/kg, was active. The ethanol (70%) Periplaneta americanaDC242. extract, administered intravenously to dogs Interferon induction stimulation. Fresh at a dose of 75 mg/kg, was active. There was plant juice, in cell culture, was active on a dip followed by rise in blood pressureDC141. mice splenocytesDC116. Ethanol (80%) extract of the aerial parts, at Interleukin-4 release inhibition. Fresh a dose of 10 mg/kg, was not blocked by atro- plant juice, in cell culture, was active on pine. The extract did not inhibit pressor mice splenocytesDC116. response of norepinephrine eitherDC081. Etha- Lipid peroxidase inhibition. Water extract nol (95%) extract of the seed, administered of the fresh root, administered intragastri- intravenously to dogs at a dose of 10 mg/kg, cally to infant mice at a dose of 50 mL/kg, produced a transient effect that was blocked was active. The treatment was administered by atropineDC020. Petroleum ether fraction for 7 successive days followed by a single chromatographed and fraction eluted with dose of 20% v/v CCl4 in olive subcutane- chloroform, administered intravenously to ously at 1 mL/kg on the last day, 1 hour after rabbits at a dose of 0.80 mg/kg, was the administration of the carrot extractDC074. inactiveDC226. Methanol extract, adminis- Lipid peroxide formation inhibition. tered intravenously to dogs and rabbits at a Fresh fruit juice, taken orally by human DAUCUS CAROTA 209 adults at a dose of 16 mg of E carotene/per- Protein synthesis inhibition. Buffer of the DC094 son, was active . Hot water extract of the fresh root produced weak activity, IC50 158 fresh leaf produced strong activity vs t-butyl Pg protein/mLDC086. hydroperoxide/heme-induced luminol- Quinone reductase induction. Acetoni- enhanced chemiluminescenceDC070. Hot trile extract of the dried root, in cell culture water extract of the fresh root produced at a concentration of 7.9 mg/g, was active weak activity vs t-butylhydroperoxide/ on Hematoma-Mouse-ICIC7. The sample heme-induced luminol-enhanced chemi- was assayed for the induction of detoxifying luminescenceDC070. enzymes that may have anticarcinogenic Liver regeneration stimulation. Seed es- activityDC079. sential oil, administered subcutaneously to Sister chromatid exchange inhibition. partially hepatectomized male rats at a dose Fresh root juice, in the drinking water of rats of 100 mg/animal daily for 7 days, was at a dose of 300 mL animal, was active on DC176 inactive . Chinese hamster ovary cells. The plasma Luteal suppressant effect. Petroleum ether from the rats treated with carrot juice and extract of the dried seed, administered sub- cyclophoshamide reduced sister chromatid cutaneously to female rats at a dose of 0.6 exchange in DNA-repair-deficient and in DC164 mL/animal, was active . normal human lymphocytes in the Chinese Methanol extract Mutagenic activity. hamster ovary cells when compared to of the fresh root, on agar plate, was inact- cyclophoshamide treated onlyDC128. ive on Salmonella typhimurium TA98 and Skeletal muscle relaxant activity. Petro- TA100DC162. Root juice, on agar plate at a leum ether fraction chromatographed and dose of 200 PL/mL, produced weak activity fraction eluted with chloroform, at a con- on Salmonella typhimurium TA100 and a centration of 0.50 mg/mL, was inactive on dose of 400 PL/mL was inactive on Salmo- the frog rectus abdominus muscle vs ACh- nella typhimurium TA98DC051. induced contractionsDC226. Nematocidal activity. Water extract of the dried fruit, in cell culture at a concentration Skeletal muscle stimulant activity. Etha- of 10 mg/mL, and methanol extract at a con- nol (95%) extract of the seed, at a concen- centration of 1 mg/mL, were active on tration of 10 mg/mL, was inactive on frog DC020 Toxacara canisDC105. rectus abdominus muscle . Oviposition stimulation. Ethanol (95%) Smooth muscle relaxant activity. Alka- extract of the aerial parts was active on loid fraction (tertiary) of the dried seed, at a black swallowtail butterflyDC129. concentration of 25 Pg/mL was active on Ovulation inhibition effect. Water, etha- the rabbit and rat ileumDC166. nol (95%), and petroleum ether extracts of Spasmogenic activity. Ethanol (95%) ex- the seed, administered orally to rabbits at a tract of the seed, at a concentration of 1.5 dose of 100 mg/kg, were inactiveDC005. mg/mL, was active on the dog tracheal Pheromone effect (sex attractant). Wa- chain. The extract, at a concentration of 1 ter extract of the root was active on mg/mL, was active on the guinea pig, rab- Costelytra zealandicaDC043. bit, and rat ileum. The activity was equal to Progesterone synthesis inhibition. Fresh approx 0.1 Pg/mL of acetylcholine. The ac- root, on the perfused ovaries of rabbits fed a tion was blocked by atropineDC020. carrot-rich diet, was active DC049. Spasmolytic activity. Ethanol (80%) ex- Pro-oxidant activity. The root, at a con- tract of the aerial parts, at a concentration centration of 1%, was active at 120q F on of 3 mg/mL, was active on the rabbit aorta peanut oilDC096. vs K+-induced contractionsDC081. 210 MEDICINAL PLANTS OF THE WORLD

Toxicity assessment. Ethanol (50%) extract DC002 Ferrando, R., M. M. Guilleux, and A. of the root, administered intraperitoneally Guerrillot-Venet. Oestrogen content of plants as a function of conditions of to mice, produced LD 500 mg/kgDC013. 50 culture. Nature 1961; 192: 1205. Tumor promotion inhibition. Methanol DC003 Ahmad, Y. S. A note of the plants of extract of the dried leaf, in cell culture at a the medicinal value found in Pakistan. concentration of 200 Pg/disc, was inactive Govt of Pakistan Press, Karachi 1957. on EBV vs 12-O-hexadecanoylphorbol-13- DC004 Walker, B. S., and J. C. Janney. acetate-induced EBV activationDC217. Estrogenic substances. II. An analy- Alkaloid frac- sis of plant sources. Endocrinology Uterine relaxation effect. 1930; 389. tion of the dried seed, at a concentration of DC005 Kapoor, M., S. K. Garg, and V. S. 25 Pg/mL, was active on the rat uterusDC166. Mathur. Antiovulatory activity of five Methanol extract of the dried seed, at a con- indigenous plants in rabbits. Indian J centration of 0.5 mg/mL, was equivocalDC221. Med Res 1974; 62: 1225–1227. Petroleum ether fraction of the seed, DC006 Garg, S. K., and V. S. Mathur. Effects of chromatographic fractions of Daucus chromatographed and fraction eluted with carota (seeds) on fertility in female chloroform, at a concentration of 0.50 mg/ albino rats. J Reprod Fertil 1972; mL, was active on the nonpregnant rat 31: 143. uterus vs oxytocin-induced contractionsDC226. DC007 Fitzpatrick, F. K. Plant substances Uterine stimulant effect. Petroleum ether active against Mycobacterium tubercu- fraction of the seed, chromatographed and losis. Antibiot Chemother 1954; 4: 528. DC008 Saha, J. C., E. C. Savini, and S. fraction eluted with chloroform, at a con- Kasinathan. Ecbolic properties of centration of 0.5 mg/mL, was active on the Indian medicinal plants. Part I. Indian nonpregnant rat uterus vs oxytocin-induced J Med Res 1961; 49: 130–151. contractionsDC226. Ethanol (95%) extract of DC009 Rageau, J. Les plantes medicinales de the seed, at a concentration of 1 mg/mL, was la Nouvelle Caledonie. Trav & Doc de inactive on the rat uterus. The amplitude Lorstom No 23, Paris 1973. DC020 DC010 Hilton-Simpson, M. W. Arab medi- was diminished but not the tone . cine and surgery. Oxford Univ Press, Vasodilator activity. Alkaloid fraction Humphrey Milford, London, 1922. (tertiary) of the dried seed, administered to DC011 Jochle, W. Menses-inducing drugs: frog by perfusion at a dose of 2.5 mg/kg, was their role in Antique, Medieval and active vs barium chloride-induced vasocon- Rennaissance gynecology and birth control. Contraception 1974; 10: strictionDC166. 425–439. White blood cell stimulant. Root juice, DC012 Krochmal, A., and C. Krochmal. Me- administered intraperitoneally to mice at a dicinal plants of the United States. dose of 0.2 mL/animal, increased neutrophil Quadrangle, the New York Times accumulation by 71%DC066. Book Co., New York 1973. White blood cell-macrophage stimulant. DC013 Bhakuni, D. S., M. L. Dhar, B. N. Dhawan, B. Gupta, and R. C. Srimali. Water extract of the freeze-dried root, at a Screening of Indian plants for biologi- concentration of 2 Pg/mL, was inactive. Ni- cal activity. Part III. Indian J Exp Biol trite formation was used as an index of the 1971; 9: 91. macrophage stimulating activityDC138. DC014 Hooper, D., and H. Field. Useful plants and drugs of Iran and Iraq. Field Mus REFERENCES Hist Publ Bot Ser 1937; 9(3): 73. DC001 Quisumbing, E. Medicinal plants of DC015 Ferrando, R., M. M. Guilleux, and A. the Philippines. Department of Agri- Guerillot-Vinet. Estrogen content of culture and Natural Resources Tech wheat, carrots and grass hay. C R Se- Bull 16, Manila; 1951. ances Soc Biol Ses Fil 1963; 157: 1024. DAUCUS CAROTA 211

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Institute of Latin American Studies, DC247 Krishnamoorthy, V., and T. R. University of Texas Press, Austin, Seshadri. Survey of anthocyanins from Texas 1965; 1–166. Indian sources: Part III. J Sci Ind Res- DC235 Abbott, B. J. J. Leiter, J. L. Hartwell, et B 1962; 21: 591–593. al. Screening data from the cancer che- DC248 Herrmann, K. Oxidative enzymes and motherapy national service center phenolic substrate in vegetables and screening laboratories. XXXIV. Plant fruit. I. Hydroxycinnamic acids. Z extracts. Cancer Res 1966; 26: Lebensm-Unters Forsch 1957; 106: 761–935. 341–348. DC236 Behari, M., and C. K., Andhiwal. DC249 Anon. The Herbalist. Hammond Book Chemical investigation of the seeds of Company, Hammond Indiana 1931; Daucus carota nantes. Indian J Chem 400 pp. 1975; 13A: 639. DC250 Liebstein, A. M. Therapeutic effects of DC237 Dragendorff, G. Die heilpflanzen der various food articles. Amer Med 1927; verschiedenen volker und zeiten. F. 33: 33–38. Enke, Stuttgart 1898; 885 pp. DC251 Greer, M. A., and E. B. Astwood. DC238 Sharma, M. M., G. Lal, and D. Jacob. The antithyroid effect of certain foods Estrogenic and pregnancy interceptory in man as determined with radioac- effects of carrot, Daucus carota seeds. tive iodine. Endocrinology 1948; 43: Indian J Exp Biol 1976; 506–508. 105–119. DC239 Nayar, S.L. Poisonous seeds of India. DC252 Kubas, J. Investigations on known or Part I. J Bombay Nat Hist Soc 1954; potential antitumoral plants by means 52(1): 1–18. of microbiological tests. Part III. Bio- DC240 Schramm, R. Paper chromatography of logical activity of some cultivated organic acids in storage roots of some plant species in Neurospora crassa test. Umbelliferae. Acta Soc Bot Pol 1961; Acta Biol Cracov Ser Bot 1972; 15: 30: 285–292. 87–100. DC241 Crowden, R. K., J. B. Harborne, and V. DC253 Bellakhdar, J., R. Claisse, J. Fleurentin, H. Heywood. Chemosystematics of the and C. Younos. Repertory of standard Umbelliferae - a general survey. Phy- herbal drugs in the Moroccan tochemistry 1969; 8: 1963–1984. Pharmacopoea. J Ethnopharmacol DC242 Heal, R. E., E. F. Rogers, R. T. 1991; 35(2): 123–143. Wallace, and O. Starnes. A survey of DC254 Boukef, K., H. R. Souissi, and G. plants for insecticidal activity. Lloydia Balansard. Contribution to the study 1950; 13(1): 89–162. on plants used in traditional medicine DC243 Pospisilova, J., V. Toul, and R. Dupal. in Tunisia. Plant Med Phytother Rapid modification of the method of 1982; 16(4): 260–278. determining provitamin A in plants. DC255 Badria, F. A. Is man helpless against Sbornik Ceskoslov Akad Zemedel cancer? An environmental approach: Ved 1959; 5: 583–594. Antimutagenic agents from Egyptian DC244 Tipson, R. S. A qualitative test for food and medicinal preparations. Can- dehydroascorbic acid. J Amer Pharm cer Lett 1994; 84(1): 1–5. Ass 1945; 34: 190–192. DC256 Garg, S. K., V. S. Mathur, and R. R. DC245 Herrmann, K. On the occurrence of Chaudhury. Screening of Indian plants caffeic acid and chlorogenic acid in for antifertility activity. Indian J Exp fruits and vegetables. Naturwissen- Biol 1978; (16): 1077–1079. schaften 1956; 43: 109. DC257 Burbott, A. J., R. Croteau, W. E. DC246 Netien, G., and J. Combet. Phenolic Shine, and W. D. Loomis. Biosynthe- acids present in in vitro plant tissue sis of cyclic monoterpenes by cell freee cultures compared to the original extracts of Mentha piperita. Int Congr plant. C R Acad Sci Ser D 1971; 272: Essent Oils (PAP) 6th Allured Publ 2491–2494. Corp Oak Park, Ill 1974; 17: 1. FERULA ASSAFOETIDA 223

6 Ferula assafoetida L.

Common Names Anjadana Pakistan Hing Bangladesh Asafetida England Hing India Asafetida Croatia Hingu India Asafetida Finland Ingu India Asafetida Germany Inguva India Asafetida Guyana Kama I anguza Afghanistan Asafetida Iceland Kama I anguza Pakistan Asafetida Lithuania Kayam India Asafetida Netherlands Ma ha hing Laos Asafetida Poland Merde du diable France Asafetida Russia Mvuje Mozambique Asafetida Spain Mvuje Tanzania Asafetida Sweden Mvuje Zaire Asafetida United States Ordoggyoker Hungary Asafetide France Perungayam India Asafootida Estonia Perunkaya India Asafotida Germany Perunkayan Sri Lanka Asant Germany Pirunpaska Finland Assa Foetida France Pirunpihka Finland Assafetida Italy Raamathan India A-wei China Rechina fena Iran Aza Greece Sagapeen Netherlands Devil’s dung United States Setan bokosu Turkey Djoflatao Iceland Seytan tersi Turkey Driveldrikis Latvia Sheingho Myanmar Duivelsdrek Netherlands Shing-kun Tibet Dyvelsdrak Denmark Stinkasant Germany Dyvelsdrekk Norway Stinking gum United States Dyvelstrack Sweden Teufelsdreck Germany Ferule persique France Velna suds Latvia Godenvoedsel Netherlands Zapaliczka cuchnaca Poland Hajupihka Finland Zaz Iran Hengu India

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 223 224 MEDICINAL PLANTS OF THE WORLD

BOTANICAL DESCRIPTION pasmodic, a diuretic, a vermifuge, and an Ferula assafoetida is an herbaceous, mono- analgesicFA072. ecious, perennial plant of the UMBEL- Fiji. Paste made from the dried resin is LIFERAE family. It grows to 2 m high with applied to the chest for whooping cough. a circular mass of leaves. Flowering stems Fried Ferula is taken with Allium sativum and are 2.5–3 m high and 10 cm thick, with a sugar to cleanse the new mother. Fried number of schizogenous ducts in the cortex Ferula, Piper nigrum, and Cinnamonum containing the resinous gum. Stem leaves camphora is taken orally for headache and have wide sheathing petioles. Compound toothache. Hot water extract of the dried large umbels arise from large sheaths. Flow- resin is taken orally for upset stomachFA056. ers are pale greenish yellow. Fruits are oval, India. Extract of dried Ferula assafoetida flat, thin, reddish brown and have a milky with Brassica alba and rock salt is diluted juice. Roots are thick, massive, and pulpy. with vinegar and taken orally as an It yields a resin similar to that of the stems. abortifacientFA057. Hot water extract of the All parts of the plant have the distinctive dried gum is taken orally as a carminative, fetid smell. an antispasmodic, and an expectorant in chronic bronchitis. Mixed with cayenne ORIGIN AND DISTRIBUTION pepper and sweet flag, it is used as a remedy Asafoetida is native to central Asia, eastern for choleraFA070. Exudate of the dried gum Iran to Afghanistan, where it grows from resin is eaten to prevent guinea worm 600 to 1200 m above the sea level. Al- diseaseFA046. Gum resin with salt and the bark though not native to India, it has been used juice of Moringa pterygosperma is used exter- in Indian medicine and cookery for ages. nally for stomachachesFA052. A dry Lampyris Today it is grown chiefly in Iran and Af- noctiluca without head is mixed with 200– ghanistan, from where it is exported to the 300 mg of Ferula and taken mornings and rest of the world. evenings for gallstones and kidney stones. TRADITIONAL MEDICINAL USES For old stones, potassium nitrate is added to Afghanistan. Hot water extract of the dried the mixtureFA054. Hot water extract of the gum is taken orally for hysteria and whoop- dried resin is taken orally as an emmena- ing cough and to treat ulcersFA071. gogueFA061. Brazil. Hot water extract of the dried leaf Malaysia. Gum is chewed by females for and stem is taken orally by males as an aph- amenorrheaFA028. rodisiac. Extract is taken orally as nerve and Morocco. Gum is chewed as an antiepi- general tonicsFA035. Oleoresin powder, lepticFA037. crushed with the fingertips, is used as a Nepal. Water extract of the resin is taken condimentFA041. orally as an anthelminticFA036. China. Decoction of the plant is taken Saudi Arabia. Dried gum is used medici- orally as a vermifugeFA038. nally for whooping cough, asthma, and Egypt. Dried gum is applied vaginally as a bronchitisFA068. contraceptive before or after coitus. Fifty- United States. Fluid extract of the resin is two percent of the women interviewed prac- taken orally as an emmenagogue, a stimu- ticed this method, and 48% of them lating expectorant, an anthelmintic, an depended on indigenous methods and/or aphrodisiac, and a stimulant to the brain prolonged lactationFA064. Hot water extract and nerves. It is claimed to be a powerful of the dried root is taken orally as an antis- antispasmodicFA029. FERULA ASSAFOETIDA 225

CHEMICAL CONSTITUENTS [4,8-dimethyl-3(E),7-nonadie nyl]-furo]3,2- FA082 (ppm unless otherwise indicated) c]coumarin: Rt 3,4,5-Trimethyl-2- (E)-3-Methylsulfinyl-2-propenyl sec-butyl (methylsulfinyloxymethyl)thiophene: disulfide: PlFA077 PlFA077 (E)-3-Methylsulfinyloxy-2-propenyl sec-butyl 3,4,5-Trimethyl-2-thiophenecarboxylic acid: disulfide: PlFA077 PlFA077 (Z)-3-Methylsulfinyloxy-2-propenyl sec-butyl FA024 FA077 Arabinose, L: Gum resin disulfide: Pl FA008 2,3-Dihydro-7-hydroxy-2R*,3R*-dimethyl-2- Arabinose: Gum Asacoumarin A: Resin 29.6FA002 [4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2- FA002 FA080 Asacoumarin B: Resin 61.6 C]coumarin: Rt FA024 2,3-Dihydro-7-hydroxy-2R*,3R*-dimethyl-2- Asadisulphide: Resin 46.7 Assafoetidnol A: RtFA079 [4-methyl-5- (4-methyl-2-furyl)-3(E)- FA079 FA080 Assafoetidnol B: Rt pentenyl]-furo[3,2-C]coumarin: Rt FA024 2,3-Dihydro-7-hydroxy-2R*,3R*-dimethyl-2- Asaresinotannoid A: Gum resin Asaresinotannoid B: Gum resinFA024 [4-methyl-5-(4-methyl-2-furyl)-3(E),7- FA008 FA078 Asaresinotannol A: Gum pentenyl]-furo[2,3-B]chromone: Rt FA008 2,3-Dihydro-7-hydroxy-2R*,3R*-dimethyl-3- Asaresinotannol B: Gum FA001 [4,8-dimethyl-3(E),7-nonadie nyl]-furo[3,2- Assafoetidin: Gum resin FA019 C]coumarin: RtFA082 Badrakemin acetate: Gum resin 1500 FA019 2,3-Dihydro-7-hydroxy-2S*,3R*-dimethyl-2- Badrakemin: Gum resin 1750 [4,8-dimethyl-3(E),7-nonadien-6-onyl]- Bis(3-methylthio-2E-propenyl) disulfide: FA077 furo[3,2-C]coumarin: RtFA080 Pl FA013 2,3-Dihydro-7-hydroxy-2S*,3R*-dimethyl-2- Borneol acetate: Sd EO 9.33% [4,8-dimethyl-3(E),7-nonadienyl]-furo[2,3- Butyl-propenyl-disulfide, secondary: Sd EO FA013 B]chromone: RtFA078 35.12% FA019 2,3-Dihydro-7-hydroxy-2S*,3R*-dimethyl-2- Coladonin: Gum resin 1250 FA005 [4-methyl-5-(4-methyl-2-furyl)-3(E)- Conferol: Rt 10 FA006 pentenyl]-furo[3,2-C]coumarin: RtFA080 Cynaroside: Fr FA010 2,3-Dihydro-7-hydroxy-2S*,3R*-dimethyl-2- Diallyl disulfide: EO FA010 [4-methyl-5-(4-methyl-2-furyl)-3(E),7- Diallyl sulfate: EO FA010 pentenyl]-furo[2,3-B]chromone: RtFA078 Diallyl sulfide: EO 2,3-Dihydro-7-hydroxy-2S*,3R*-dimethyl-3- Dimethyl trisulfide: EOFA015 [4,8-dimethyl-3(E),7-nonadie nyl]-furo[3,2- Disulfide, 1-(1-methyl-thio-propyl)-1-prope- C]coumarin: RtFA082 nyl: GumFA016 2,3-Dihydro-7-hydroxy-2S*,3R*-dimethyl-3- Disulfide, 2-butyl-3-methyl-thio-allyl: [4-methyl-5-(4-methyl-2-furyl)- 3(E)- GumFA016 pentenyl]-furo[3,2-C]coumarin: RtFA082 Disulfide, 2-butyl-methyl: EOFA015 2,3-Dihydro-7-methoxy-2R*,3R*-dimethyl-2- Disulfide, 2-butyl-propenyl: GumFA016 [4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2- Disulfide, di-2-butyl: EOFA015 C]coumarin: RtFA0780 Farnesiferol A: Gum resinFA022 2,3-Dihydro-7-methoxy-2S*,3R*-dimethyl-2- Farnesiferol B: Rt 19.2FA009, Gum resinFA022 [4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2- Farnesiferol BC: Rt 200FA009, Gum resinFA023, C]coumarin: RtFA080 Gum 1.67%FA004 2,3-Dihydro-7-methoxy-2S*,3R*-dimethyl-2- Ferocolicin: Gum resinFA001 [4,8-dimethyl-3(E),7-nonadien-6-onyl]- Feruginin: Rh 90FA011 furo-[3,2-C]coumarin: RtFA080 Ferula assafoetida polysaccharide: Gum 2,3-Dihydro-7-methoxy-2S*,3R*-dimethyl-2- resinFA020 [4-methyl-5-(4-methyl-2-furyl)-3(E)- Ferulic acid: Gum resinFA024, GumFA008, pentenyl]-furo[3,2-C]coumarin: RtFA080 EOFA010 2,3-Dihydro-7-methoxy-2S*,3R*-dimethyl-3- Foetidin: Rt 500FA018, PlFA017 226 MEDICINAL PLANTS OF THE WORLD

Foetisulfide A: PlFA077 Umbelliferone: Gum resinFA021, GumFA008, Foetisulfide B: PlFA077 EOFA010 Foetisulfide C: PlFA077 Umbelliprenin, 5-hydroxy: Gum 362.5FA004 Foetisulfide D: PlFA077 Umbelliprenin: Rt 23FA005 Foetithiophene A: PlFA077 Umbelliprenin8-acetoxy-5-hydroxy: Gum Foetithiophene B: PlFA077 175FA004 Foliferidin: Gum resin 500FA019 Umbelliprenin8-hydroxy: Gum 1550FA004 Galactose: GumFA008, Gum resinFA024 Umbelliprenin9-hydroxy: Gum 387.5FA004 Galbanic acid: Gum 2.06%FA004 Undecyl sufonyl acetic acid: Gum EO Geraniol acetate: EOFA010, Sd EO 7.71%FA013 18.8%FA012 Glucose: GumFA008,FA024 Glucuronic acid: Gum resinFA024 PHARMACOLOGICAL ACTIVITIES Gummosin: Gum resin 1500FA019, AND CLINICAL TRIALS Rt 769.2FA005 Allergenic activity. Oleoresin powder, ad- Jaeschkeanadiol, 5-D-(3-4-diacetoxy-benzoyl- ministered externally to adults, was active. 9-E-angeloxy: Rh 190FA011 Reactions to patch test occurred most com- Jaeschkeanadiol, 5-D-(3-methoxy-4-hydroxy- FA011 monly in patients who were regularly ex- benzoyl): Rh 1200 posed to the substance, or who already had Jaeschkeanadiol, 5-D-(4-hydroxy-benzoyl)-9- E-angeloxy: Rh 260FA011 dermatitis on the fingertips. Previously un- Jaeschkeanadiol, 5-D-(para-hydroxy-benzoyl): exposed patients had few reactions (i.e., no Rh 1500FA011 irritant reactions)FA041. Jaeschkeanadiol, 9-E-hydroxy: Rh 470FA011 Antibacterial activity. Dried gum resin, on Jaeschkeanadiol: Rh 6100FA011 agar plate, was active on Clostridium perfrin- Kamolonol: Gum resinFA003 gens and Clostridium sporogenesFA030. Karatavicinol: Gum resin 3000FA019 FA014 Anticarcinogenic activity. Dried resin, Linoleic acid: Sd 12.8% administered orally to Sprague–Dawley rats Lucuronic acid: GumFA008 Luteolin: FrFA006 at doses of 1.25 and 2.5% w/w of the diet, Mogoltadone: Gum resinFA003 produced a significant reduction in the mul- Myristic acid: Sd EO 21.23%FA013 tiplicity and size of palpable N-methyl-N- Oleic acid: Sd 5.3%FA014 nitrosourea-induced mammary tumors, and Petroselinic acid: Sd 76.5%FA013 a delay in mean latency period of tumor Phellandrene, D: EOFA010 appearanceFA076. Oral administration to mice FA013 Phellandrene: Sd EO 5.48% , Gum EO increased the percentage of life span by FA012 6.4% 52.9%. Intraperitoneal administration did Pinene, : EOFA010 D not produce any significant reduction in Pinene, E: EOFA010 Polyanthin: Gum resinFA003 tumor growth. The extract also inhibited a Polyanthinin: Gum resinFA003 two-stage chemical carcinogenesis induced Prop-cis-2-enyl, 2-butyl, disulfide (R): EOFA007 by 7,12-dimethylbenzathracene and croton Propenyl disulfide, sec-butyl: Gum EO oil on mice skin with significant reduction 51.9%FA012 in papilloma formationFA085. FA007 Prop-trans-2-enyl, 2-butyl, disulfide: EO Anticholesterolemic activity. Resin, ad- FA008,FA024 Rhamnose: Gum ministered to rats fed an atherogenic diet, Samarcandin acetate: Gum resin 4000FA019 FA005 at a dose of 1.5%, failed to reduce the serum Samarcandin, epi: Rt 9.2 FA092 Sodium ferulate: PlFA073 cholesterol levels . Terpineol, D: Sd EO 12.71%FA013 Anticoagulant activity. Water extract of Tetrasulfide, di-2-butyl: EOFA015 the gum, administered intravenously to Trisulfide, 2-butyl-methyl: EOFA015 dogs and rats at variable doses, was Trisulfide, di-2-butyl: EOFA015 activeFA065. FERULA ASSAFOETIDA 227

Antifertility effect. A mixture of Embella tion of 1% of diet, was inactiveFA050. A hot ribes fruit, Piper longum fruit, borax, Ferula mixture of Nigella sativa, Commiphora myr- dried gum, Piper betle, Polianthes tuberosa, rha, Ferula assafoetida, Aloe vera, and and Abrus precatorius, administered orally to Boswellia serrata, administered by gastric female adults at a dose of 0.28 g/person start- intubation to rats at a dose of 0.5 g/kg for 7 ing from the second day of menstruation days, was active vs streptozotocin-induced twice daily for 20 days, without sexual hyperglycemiaFA042. intercourse during the dosing period, pro- Antihyperglycemic activity. Hot water ex- duced the effect for 4 months. The biologi- tract of the dried gum, Nigella sativa, Myrrhis cal activity reported has been patentedFA049. odorata, and Aloe sp. in equal parts, admin- Gum, administered by gastric intubation istered by gastric intubation to rats at a dose to male mice at a dose of 5 mg/kg for 32 of 10 mL/kg for 7 days, was active vs days, was activeFA069. Methanol extract of the streptozotocin-induced hyperglycemia. Re- resin, administered orally to Sprague– sults were significant at p < 0.05 levelFA058. Dawley rats at a dose of 400 mg/kg daily for Hot water extract of the dried gum, admin- 10 days, prevented pregnancy in 80% of the istered by gastric intubation to rats at a dose rats. When administered as a polyvinylpyr- of 10 mL/kg for 7 days, was inactiveFA047. A rolidone 1:2 complex, 100% pregnancy in- hot mixture of Nigella sativa, Commiphora hibition was observed at this dose. Lower myrrha, Ferula assafoetida, Aloe vera, and doses of the extract produced a marked re- Boswellia serrata, administered by gastric duction in the mean number of implanta- intubation to rats at a dose of 0.5 g/kg for tions. Significant activity was observed in 7 days, was active vs streptozotocin-induced the hexane and chloroform eluents of sul- hyperglycemiaFA042. fur-containing extract in an immature rat Antihypertensive effect. Water extract bioassay, the methanol extract was devoid of the dried gum resin, administered intra- of any estrogenic activityFA093. venously to dogs at variable doses, was Antifungal activity. Ethanol (95%) extract activeFA067. of the dried gum on agar plate was activeFA039. Anti-implantation effect. A powdered Essential oil of rhizome, on agar plate at a mixture of Ferula assafoetida, Piper longum, concentration of 400 ppm, was active on Embella ribes, and borax, administered orally Microsporum gypseum and Trichophyton to female adults, was active. Biological ac- rubrum, and produced weak activity on Tri- tivity reported has been patentedFA027. chophyton equinumFA055. Extract of asafetida, Anti-inflammatory effect. Ethanol (95%) on agar plate at concentrations of 5–10 mg/ extract of the resin, administered orally mL, inhibited Aspergillus parasiticus afla- to two groups of 50 patients with irritable toxin productionFA083. colon, was active. Results were significant Antihepatotoxic activity. A mixture of the at p < 0.001 levelFA048. methanol-insoluble fraction of the dried Antimutagenic activity. Water extract of resin, fresh garlic, curcumin, ellagic acid, the dried gum, on agar plate at a concentra- butylated hydroxytoluene, and butylated tion of 2 mg/plate, was inactive on Salmo- hydroxyanisole, administered by gastric in- nella typhimurium TA100 vs aflatoxin tubation to ducklings at a dose of 10 mg/ani- B1-induced mutagenesis and a concentra- mal, was active vs aflatoxin B1-induced tion of 10 mg/plate, was inactive on Salmo- hepatotoxicityFA034. nella typhimurium TA98FA032. Asafoetida, on Antihypercholesterolemic activity. Gum, agar plate at a dose of 0.5 Pg/plate was ac- administered to female rats at a concentra- tive on Salmonella typhimurium TA98 and 228 MEDICINAL PLANTS OF THE WORLD

TA100 vs aflatoxin B1-induced muta- Apoptosis effect. Sodium ferulate, admin- genesisFA088. Asafoetida, on agar plate, was istered to human lymphocytes cell culture, active on Salmonella typhimurium TA100 induced apoptosisFA073. and TA1535 microsomal activation-depen- Carcinogenesis inhibition. Gum, adminis- dent mutagenicity of 2-acetamidofluo- tered to mice at a dose of 40 mg/g of diet, reneFA090. was active. The dose was inactive vs 3'-me- Antioxidant activity. Asafetida, adminis- thyl-4-dimethylaminoazobenzene-induced tered orally to Sprague–Dawley rats at doses carcinogenesisFA033. of 1.25% and 2.5% w/w, significantly Cardiac depressant activity. Tincture of restored the level of antioxidant system, the gland, administered by perfusion to depleted by N-methyl-N-nitrosourea treat- rabbits, produced weak activity on the ment. There was a significant inhibition in heartFA025. lipid peroxidation as measured by thiobar- Chemomodulatory influence. Asafetida, bituric acid-reactive substances in the liver administered orally to Sprague–Dawley rats of ratsFA076. at doses of 1.25% and 2.5% w/w in diet, pro- Antiparasitic activity. Oleo-gum resin duced an increase in the development and from roots and stems was active on Tri- differentiation of ducts/ductules and lobules chomonas vaginalisFA074. and a decrease in terminal end buds as com- Antispasmodic activity. Gum extract, ad- pared to both normal and N-methyl-N- ministered to isolated guinea pig ileum at a nitrosourea-treated control animals. dose of 3 mg/mL, produced a decrease of Asafetida treatment significantly reduced spontaneous contraction to 54 r 7% of con- the levels of cytochrome P450 and b5. trol. Exposure of precontracted ileum by There was an enhancement in the activities acetylcholine, histamine, and KCl to Ferula of glutathione-S-transferase, deoxythymi- gum extract produced a concentration-de- dine-diaphorase, superoxide desmutase, pendent relaxation. Preincubation with in- catalase, and reduced glutathioneFA076. domethacin, propanolol, atropine, and Central nervous (CNS) effects. Ethanol chlorpheniramine before exposure to the extract of the dried gum, administered orally gum, did not produce any relaxationFA075. to adults at a dose of 20 mL/person, was Antitumor activity. Water extract of the activeFA066. dried oleoresin, administered by gastric Cytotoxic activity. Ethanol (90%) extract intubation to mice at a dose of 50 mg/ani- of the dried plant, in cell culture adminis- mal daily for 5 days, was active on CA- tered at a concentration 0.25 mg/mL, was Ehrlich ascites, 53% increase in life span active on human lymphocytes. The extract (ILS)FA044. Water extract administered intra- was active on Vero cells, effective dose peritoneally was inactive on Dalton’s lym- (ED50 0.15 mg/mL; Chinese hamster ovary phoma, 4.8% ILS, and CA-Ehrlich ascites, (CHO) cells, ED50 0.575 mg/mL; and FA044 FA040 5.5% ILS . Dalton’s lymphoma, ED50 0.6 mg/mL . Antiulcerogenic activity. Colloidal solu- Water extract of the dried gum, in cell tion, administered orally to rats at a dose of culture at a concentration of 500 Pg/mL, 50 mg/kg, 60 minutes before experiment, produced weak activity on CA-mammary- produced significant protection against gas- microalveolar cellsFA045. tric ulcers induced by 2 hours cold restraint Digestive enzyme inhibition. Asafoetida, stress, aspirin, and 4 hours pylorus administered orally to rats at a dose of 2500 ligationFA081. mg% for 8 weeks, decreased the levels of FERULA ASSAFOETIDA 229 phosphatases and sucrase in the small Hypotensive activity. Tincture of the intestineFA089. gland, administered intravenously to rab- DNA synthesis inhibition. Ethanol (90%) bits, was activeFA025. Water extract of the extract of the dried entire plant at a con- dried gum resin, administered intravenously centration of 0.25 mg/mL, was activeFA040. to dogs at variable doses, was activeFA067. Fibrinolytic activity. Ether extracts of the Gum extract, administered to anaesthetized dried gum and gum resin, administered rats at doses of 0.3–2.2 mg/100 g body orally to 10 healthy subjects fed 100 g of weight, significantly reduced the mean butter to produce alimentary hyperlipemia, arterial blood pressureFA075. were activeFA031. Mutagenic activity. Ethanol (95%) extract Gastric mucosal exfoliant activity. Pow- of the dried resin, on agar plate at a concen- der of the dried entire plant, administered tration of 15 mg/plate, produced weak by gastric intubation to adults at a dose of activity on streptomycin-dependent strains 0.2 g for 1 hour, was activeFA059. of Salmonella typhimurium TA98. Metabolic Hepatic mixed function oxidase inhibi- activation has no effect on the resultFA060. tion. Oleoresin, administered to rats at a Resin, on agar plate at a concentration of dose of 250 mg%, was activeFA043. 200 Pg/plate, was active on Salmonella Hypocholesterolemic activity. A hot typhimurium TA1537 and inactive on Sal- mixture of Nigella sativa, Commiphora monella typhimurium TA1538 and Salmonella myrrha, Ferula assafoetida, Aloe vera, and typhimurium TA98FA062. Boswellia serrata, administered by gastric in- Olfactory status influence. Asafoetida tubation to rats at a dose of 0.5 g/kg for 7 extract, administered to allergic (group I) days, was active vs streptozotocin-induced and nonallergic rhinitis (group II) patients hyperglycemiaFA042. at a dose of 10% aqueous solution, produced Hypoglycemic activity. Hot water extract an elevation of olfactory thresholds by of the dried gum, Nigella sativa, Myrrhis 55.8% in group I and 66.8% for both odorata, and Aloe sp. in equal parts, admin- groupsFA086. istered by gastric intubation to rats at a Pancreatic digestive enzymes effect. dose of 10 mL/kg for 7 days, was active. Re- Asafetida, administered orally to albino rats sults were significant at p < 0.001 levelFA058. at a dose of 250 mg% for 8 weeks, enhanced Hot water extract of the dried gum, admin- pancreatic lipase activity, stimulated pancre- istered by gastric intubation to rats at a dose atic amylase and chymotrypsin. The stimula- of 10 mL/kg for 7 days, was inactiveFA047. A tory influence was not observed when their hot mixture of Nigella sativa, Commiphora intake was restricted to a single oral doseFA087. myrrha, Ferula assafoetida, Aloe vera, and Protein digestibility. Asafetida did not Boswellia serrata, administered by gastric affect the digestibility of protein in sor- intubation to rats at a dose of 0.5 g/kg for ghumFA084. 7 days, was active vs streptozotocin-induced Sister chromatid exchange stimulation. hyperglycemiaFA042. Gum, administered by gastric intubation to Hypolipemic activity. A hot mixture of mice at a dose of 1 g/kg, was active. The Nigella sativa, Commiphora myrrha, Ferula results were significant at p less than 0.01 assafoetida, Aloe vera and Boswellia serrata, level. A dose of 0.5 g/kg, produced weak administered by gastric intubation to rats at activityFA051. Asafoetida, administered orally a dose of 0.5 g/kg for 7 days, was active vs to mice, produced weak activity in sperma- streptozotocin-induced hyperglycemiaFA042. togoniaFA091. 230 MEDICINAL PLANTS OF THE WORLD

Smooth muscle relaxant activity. Tinc- FA006 Pangarova, T. T., and G. G. Zapes- ture of the gland, administered to rabbits, ochnaya. Flavonoids of Ferula assafoe- tida. Chem Nat Comp 1973; 9(6): 768. was active on the bladder and intestineFA025. FA007 Kjaer, A., M. Sponholtz, K. O. Abra- Toxic effect. Gum, administered orally to ham, M. L. Shankaranarayana, M. L. adults, was active. A case of methemoglo- Raghavan, and C. P. Natarajan. 2-bu- binemia occurred in a 5-week-old male tyl propenyl disulfides from asafetida: infant, after administration of asafetida separation, characterization and abso- preparation to alleviate colic. Treatment lute configuration. Acta Chem Scand Ser B 1976; 30: 137. was with intravenous methylene blue and FA008 Mahram, G. H., T. S. M. A. El-Alfy, FA053 the infant recovered . and H. A. Ansary. A phytochemical Tumor-promoting activity. Water extract study of the gum and resin of Afghan- of the dried oleoresin, administered exter- ian assafoetida. Bull Fac Pharm Cairo nally to mice at a dose of 200 PL/animal, Univ 1975; 12: 119. was active vs 7,12-dimethylbenz[a]anthra- FA009 Nassar, M. I. Spectral study of farnesi- FA044 ferol B from Ferula assafoetida L. cene and croton oil treatment . Pharmazie 1994; 49(7): 542–543. Uterine stimulant effect. Hot water ex- FA010 Mahran, G. H., T. S. M. A. El Alfy, tract of the plant, administered to female and S. M. A. Ansari. A phytochemical rats, was inactive on estrogen of uterus. Ex- study of volatile oil of Afghanian asa- tract administered to pregnant rats, was foetida. Bull Fac Pharm Cairo Univ inactive on uterusFA026. 1973; 12(2): 101–117. FA011 Singh, M. M., A. Agnihotri, S. N. Vasodilator activity. Water extract of the Garg, S. Agarwal, D. N. Gupta, G. dried gum resin, administered to frogs, was Keshri, and V. P. Kamboj. Antifertil- active on the veinFA067. ity and hormonal properties of certain carotene sesquiterpenes of Ferula REFERENCES jaeschkeana. Planta Med 1988; 54(6): FA001 Banerji, A., B. Mallick, A. Chatterjee, 492–494. H. Budzikiewicz, and M. Breuer. FA012 Ashraf, M., R. Ahmad, S. Mahood, Assafoetidin and ferocolicin, two and M. K. Bhatty. Studies of the essen- sesquiterpenoid coumarins from Ferula tial oils of the Pakistani species of the assafoetida Regel. Tetrahedron 1988; family Umbelliferae. XLV. Ferula assa- 29(13): 1557–1560. foetida, Linn (Herra Hing) gum oil. FA002 Kajimoto, T., K. Yahiro, and T. Pak J Sci Ind Res 1980; 23: 68–69. Nohara. Sesquiterpenoid and disul- FA013 Ashraf, M., R. Ahmad, S. Mahood, phide derivatives from Ferula assa- and M. K. Bhatty. Studies of the essen- foetida. Phytochemistry 189; 28(6): tial oils of the Pakistani species of the 1761–1763. family Umbelliferae. Part XXXV. Ferula FA003 Hofer, O., M. Widhalm, and H. assafoetida, Linn (Hing) seed oil. Pak J Greger. Circular dichroism of ses- Sci Ind Res 1979; 22(6): 308–310. quiterpene-umbelliferone ethers and FA014 Kleiman, R., and G. F. Spencer. Search structure elucidation of a new deriva- for new industrial oils: 16. Umbelliflorae- tive isolated from the gum resin ’asa- seed oils rich in petroselinic acid. J fetida’. Monatsh Chem 1984; 115(10): Amer Oil Chem Soc 1982; 59: 29–32. 1207–1218. FA015 Rajanikanth, B., B. Ravindranath, and FA004 Appendino, G., S. Taglipietra, G. M. M. L. Shankaranarayana. Volatile Nano, and J. Jakupovic. Sesquiterpene polysulphides of asafoetida. Phy- coumarin ethers from asafetida. Phy- tochemistry 1984; 23(4): 899–900. tochemistry 1994; 35(1): 183–186. FA016 Shankaranarayana, M. L., B. Ragha- FA005 Nassar, M. I., E. A. Abu-Mustafa, and van, and C. P. Natarajan. Odorous A. A. Ahmed. Sesquiterpene cou- compounds of asafetida. VII. Isolation marins from Ferula assafoetida L. Phar- and identification. Indian Food Pack mazie 1995; 50(11): 766–767. 1982; 36(5): 65–76. FERULA ASSAFOETIDA 231

FA017 Abu-Mustafa, E. A., A. Khattab, S. FA028 Gimlette, J. D. A dictionary of Ma- Meshaal, et al. Foetidin, a new layan medicine, Oxford University sesquiterpenoid coumarin from Ferula Press, New York, USA, 1939. assafoetida. Abstr Internat Res Congr FA029 Anon. Lilly’s handbook of pharmacy Nat Prod Coll Pharm Univ N Caro- and therapeutics, 5th rev, Eli Lilly and lina Chapel Hill NC July 7-12 1985; Co, Indianapolis 1898. 1985: Abstr-42. FA030 Garg, D. K., A. C. Banerjea, and J. FA018 Buddrus, J., H. Bauer, E. A. Abu- Verma. The role of intestinal Clostridia Mustafa, A. Khattab, S. Meshaal, E. A. and the effect of asafetida (Hing) and M. El-Khrisy, J., and M. Lincheid. alcohol in flatulence. Indian J Foetidin, a sesquiterpenoid coumarin Microbiol 1980; 20(3): 194–197. from Ferula assa-foetida. Phytochemis- FA031 Bordia, A., and S. K. Arora. The effect try 1985; 24(4): 869–870. of essential oil (active principle) of FA019 Hofer, O., M. Widhalm, and H. asafetida on alimentary lipemia. In- Greger. Circular dichroism of sesquit- dian J Med Res 1975; 63(5): 707–711. erpene-umbelliferone ethers and struc- FA032 Soni, K. B., M. Lahiri, P. Chakcradeo, ture elucidation of a new derivative S. V. Bhide, and R. Kuttan. Protective isolated from the gum resin “asa effect of food additives on aflatoxin- foetida.” Monatsh Chem 1984; induced mutagenicity and hepatocar- 115(10): 1207–1218. cinogenicity. Chem Lett 1997; 115(2): FA020 Guarnieri, A., and M. Amorosa. The 129–133. structure of gum polysaccharide from FA033 Aruna, K., and V. M. Sivaramakrish- gum-resin ammoniac. II. Smith degra- nan. Anticarcinogenic effect of some dation. Ann Chim (Rome) 1970; Indian plant products. Food Chem 60(2): 108–115. Toxicol 1992; 30(11): 953–956. FA021 Fujita, M., T. Furuya, and H. Itokawa. FA034 Soni, K. B., A. Rajan, and R. Kuttan. Crude drugs containing coumarins and Inhibition of aflatoxin-induced liver their derivatives. III. Chromatographic damage in ducklings by food additives. separation and determination of Mycotoxin Res 1993; 9(1): 22–27. umbelliferone and its homologs. FA035 Elisabetsky, E., W. Figueiredo, and G. Yakugaku Zasshi 1958; 78: 395–398. Oliveria. Traditional Amazonian FA022 Caglioti, L., H. Naef, D. Arigoni, and nerve tonics as antidepressant agents: O. Jeger. Sesquiterpenes and azulenes. Chaunochiton kappleri: a case study. J CXXVII. The constituents of asa- Herbs Spices Med Plants 1992; 1(1/ fetida. II. Farnesiferol B and C. Helv 2): 125–162. Chim Acta 1959; 42: 2557–2570. FA036 Bhattarai, N. K. Folk Anthelmintic FA023 Caglioti, L., H. Naef, D. Arigoni, and drugs of central Nepal. Int J Pharma- O. Jeger. Sesquiterpenes and azu- col 1992; 30(2): 145–150. lenes.126. The constituents of asafoe- FA037 Bellakhdar, J., R. Claisse, J. Fleuretin, tida. I. Farnesiferol A. Helv Chim and C. Younos. Repertory of standard Acta 1958; 41: 2278–2292. herbal drugs in the Moroccan Pharma- FA024 Mahran, G. H., T. S. M. A. El-Alfy, copoeia. J Ethnopharmacol 1991; and H. A. Ansary. A phytochemical 35(2): 123–143. study of the gum and resin of Afghan- FA038 Duke, J. A., and E. S. Ayensu. Medici- ian asafoetida. Bull Fac Pharm 1975; nal plants of China. Reference publi- 12(2): 119–132. cations, Inc. Algonac, Michigan 1985 FA025 Boyd, L. J. The pharmacology of the 1(4): 52–361. homeopathic drugs. I. J Amer Inst FA039 Thyagaraja, N., and A. Hosono. Effect Homeopathy 1928; 21: 7. of spice extract on fungal inhibition. FA026 Misra, M. B., S. S. Mishra, and R. K. Food Sci Technol (London) 1996; Misra. Screening of a few indigenous 29(3): 286–288. abortifacients. J Indian Med Ass 1969; FA040 Unnikrishn, M. C., and R. Kuttan. 52: 535. Cytotoxicity of extracts of spices to FA027 Das, P. C. Oral contraceptive. Patent- cultured cells. Nutr Cancer 1988; Brit-1,025,372 1966. 11(4): 251–257. 232 MEDICINAL PLANTS OF THE WORLD

FA041 Seetharam, K. A., and J. S. Pasricha. an infant treated with the folk remedy Condiments and contact dermatitis of glycerited asafetida. Pediatrics 1984; the finger-tips. Indian J Dermatol 73(5): 717–719. Venerol Leprol 1987; 53(6): 325–328. FA054 Tiwar, K. C., R. Majumder, and S. FA042 Al-Awadi, F., and M. Shoukry. The Bhattacharjee. Folklore medicines lipid lowering effect of an anti-diabetic from Assam and Arunachal Pradesh plant extract. Acta Diabetol 1988; (district Tirap). Int J Crude Drug Res 25(1): 1–5. 1979; 17(2): 61–67. FA043 Sambaiah, K., and K. Srinivasan. In- FA055 Dikshi, A., and A. Husain. Antifungal fluence of spices and spice principles action of some essential oils against on hepatic mixed function oxygenase animal pathogens. Fitoterapia 1984; system in rats. Indian J Biochem 55(3): 171–176. Biophys 1989; 26(4): 254–258. FA056 Singh, Y. N. Traditional medicine in FA044 Unnikrishn, M. C., and R. Kuttan. Fiji: some herbal folk cures used by Fiji Tumour reducing and anticarcino- Indians. J Ethnopharmacol 1986; genic activity of selected spices. Can- 15(1): 57–88. cer Lett 1990; 51(1): 85–89. FA057 Venkataraghavan, S., and T. P. Sun- FA045 Sato, A. Studies on anti-tumor activ- dareesan. A short note on contracep- ity of crude drugs. I. The effects of tive in Ayurveda. J Sci Res Pl Med aqueous extracts of some crude drugs 1981; 2(1/2): 39. in short-term screening test. Yaku- FA058 Al-Awadi, F. M., M. A. Khattar, and gaku Zasshi 1989; 109(6): 407–423. K. A. Gumaa. On the mechanism of FA046 Joshi, P. Herbal drugs used in Guinea the hypoglycaemic effect of a plant worm disease by the tribals of southern extract. Diabetologia 1985; 28(7): Rajasthan (India). Int J Pharmacog 432–434. 1991; 29(1): 33–38. FA059 Desai, H. G., and R. H. Kalro. Effect of FA047 Al-Awadi, F. M., and K. A. Gumaa. black pepper & asafetida on the DNA Studies on the activity of individual content of gastric aspirates. Indian J plants of an antidiabetic plant mixture. Med Res 1985; 81: 325–329. Acta Dabetol 1987; 24(1): 37–41. FA060 Shashikanth, K. N., and A. Hosono. In FA048 Rahlfs, V. W., and P. Mossinger. Asa vitro mutagenicity of tropical spices to foetida in the treatment of the irritable streptomycin dependent strains of Sal- colon. A double blind study. Dtsch monella typhimurium TA98. Agr Biol Med Wochenschr 1979; 104: 140–143. Chem 1986; 50(11): 2947–2948. FA049 Das, P. C. Oral contraceptive (long- FA061 Kamboj, V. P. A review of Indian acting). Patent-Brit-1,445,599 1976; medicinal plants with interceptive ac- 11 pp. tivity. Indian J Med Res 1988; FA050 Kamanna, V. S., and N. Chandra- 1988(4): 336–355. sekhara. Effect of garlic (Allium sativum FA062 Siwaswamy, S. N., B. Balachandran, S. Linn.) on serum lipoproteins and lipo- Balanehru, and V. M. Sivaramakrish- protein cholesterol levels in albino rats nan. Mutagenic activity of south In- rendered hypercholesterolemic by dian food items. Indian J Exp Biol feeding cholesterol. Lipids 1982; 1991; 29(8): 730–737. 17(7): 483–488. FA063 Self, P. A., F. D. Horowitz, and L. Y. FA051 Abraham, S. K., and P. C. Kesavan. Paden. Olfactions in newborn infants. Genotoxicity of garlic, turmeric and Dev Psychol 1972; 7(3): 349–363. asafetida in mice. Mutat Res 1984; FA064 El-Dean Mahmoud, A. A. G. Study of 136(1): 85–88. indigenous (folk ways) birth control FA052 John, D. One hundred useful raw drugs methods in Alexandria. Thesis-Uni- of the Kani tribes of Trivandrum forest versity of Alexandria-Higher Institute division, Kerala, India. Int J Crude of Nursing 1972. Drug Res 1984; 22(1): 17–39. FA065 Mansurov, M. M. Effect of Ferula asa- FA053 Kelly, K. J., J. Nue, B. M. Camitta, and fetida on the blood coagulability. Med G. R. Honig. Methemoglobinemia in Zh Uzb 1967; 1967(6): 46–49. FERULA ASSAFOETIDA 233

FA066 Coleman, D. E. S. The effect of certain FA077 Duan, H., Y. Takaishi, M. Tori, S. homeopathic remedies upon the hear- Takaoka, G. Honda, M. Ito, Y. ing. J Amer Inst Homeopathy 1922; Takeda, O. K. Kodzhimatov, K. 15: 279–281. Kodzhimatov, and O. Ashurmetov. FA067 Sarkis’yan, R. G. Effect of Ferula on Polysulfide derivatives from Ferula arterial pressure. Med Zh Uzb 1969; foetida. J Nat Prod 2002; 65(11): 1969(9): 23–24. 1667–1669. FA068 Seabrook, W. B. Adventures in Arabia FA078 Nagatsu, A., K. Isaka, K. Kojima, et al. among the Bedouins, Druses, whirling New sesquiterpenes from Ferula dervishes & Yezidee devil worshipers. ferulaeoides (Steud.) Korovin. VI. Iso- Blue Ribbon Book, New York 1927; lation and identification of three new 99–105. dihydrofuro[2,3-B]chromones. Chem FA069 Walia, K. Effects of asafetida (7-hy- Pharm Bull (Tokyo) 2002; 50(5): droxycoumarin) on mouse spermato- 675–677. cytes. Cytologia 1973; 38: 19–724. FA079 Abd El-Razek, M.H., S. Ohta, A. A. FA070 Subrahmanyan, V., L. V. L. Sastry, and Ahmed, and T. Hirata. Sesquiterpene M. Srinivasan. Asafoetida. J Sci Ind coumarins from the roots of Ferula Res B 1954; 13: 382–386. assa-foetida. Phytochemistry 2001; FA071 Mahran, G. H., T. S. M. A. El Alfy, 58(8): 1289–1295. and S. M. A. Ansari. A phytochemical FA080 Isaka, K., A. Nagatsu, P. Ondognii, O. study of volatile oil of Afghanian asa- Zevgeegiin, P. Gombosurengyin , K. fetida. Bull Fac Pharm Cairo Univ Davgiin, K. Kojima, and Y. Ogihara. 1973; 12(2): 101–107. Sesquiterpenoid derivatives from FA072 Buddrus, J., H. Bauer, E. Abu-Mustafa, Ferula ferulaeoides. V. Chem Pharm A. Khattab, S. Mishaal, E. A. M. El- Bull (Tokyo) 2001; 49(9): 1072–1076. Khrisy, and M. Linscheid. Foetidin, a FA081 Agrawal, A.K., C. V. Rao, K. Sairam, sesquiterpenoid coumarin from Ferula V. K. Joshi, and R. K. Goel. Effect of assa-foetida. Phytochemistry 1985; Piper longum Linn, Zingiber officinalis 24(4): 869–870. Linn and Ferula species on gastric FA073 Lu, Y., C. Xu, Y. Yang, and H. Pan. ulceration and secretion in rats. Indian The effect of antioxidant sodium J Exp Biol 2000; 38(10): 994–998. ferulate on human lymphocytes FA082 Kojima, K., K. Isaka, P. Ondognii, Oet apoptosis induced by H2O2. Zhongguo al. Sesquiterpenoid derivatives from Yi Xue Ke Xue Yuan Xue Bao 1998; Ferula ferulaeoides. IV. Chem Pharm 20(1): 44–48. Bull (Tokyo) 2000; 48(3): 353–356. FA074 Ramadan, N.I., and F. M. Al Kha- FA083 Soni, K.B., A. Rajan, and R. Kuttan. drawy. The in vitro effect of Assafoe- Reversal of aflatoxin induced liver tida on Trichomonas vaginalis. J Egypt damage by turmeric and curcumin. Soc Parasitol 2003; 33(2): 615–630. Cancer Lett 1992; 66(2): 115–121. FA075 Fatehi, M., F. Farifteh, and Z. Fatehi- FA084 Pradeep, K.U., P. Geervani, and B. O. Hassanabad. Antispasmodic and hy- Eggum. Influence of spices on utiliza- potensive effects of Ferula asafoetida tion of sorghum and chickpea protein. gum extract. J Ethnopharmacol 2004; Plant Foods Hum Nutr 199; 41(3): 91(2–3): 321–324. 269–276. FA076 Mallikarjuna, G.U., S. Dhanalak- FA085 Unnikrishnan, M.C., and R. Kuttan. shmi, S. Raisuddin, and A. R. Rao. Tumour reducing and anticarcino- Chemomodulatory influence of Ferula genic activity of selected spices. Can- asafoetida on mammary epithelial cer Lett 1990; 51(1): 85–89. differentiation, hepatic drug metabo- FA086 Mann, S.S., S. Maini, K. S. lizing enzymes, antioxidant profiles Nageswari, H. Mohan, and A. Handa. and N-methyl-N-nitrosourea-induced Assessment of olfactory status in al- mammary carcinogenesis in rats. lergic and non-allergic rhinitis pa- Breast Cancer Res Treat 2003; tients. Indian J Physiol Pharmacol 81(1): 1–10. 2002; 46(2): 186–194. 234 MEDICINAL PLANTS OF THE WORLD

FA087 Platel, K., and K. Srinivasan. Influence selected spices. Indian J Physiol of dietary spices and their active prin- Pharmacol 1995; 39(4): 347–353. ciples on pancreatic digestive enzymes in FA091 Abraham, S. K., and P. C. Kesavan. albino rats. Nahrung 2000; 44(1): 42–46. Genotoxicity of garlic, turmeric and FA088 Soni, K. B., M. Lahiri, P. Chackradeo, asafoetida in mice. Mutat Res 1984; S. V. Bhide, and R. Kuttan. Protective 136(1): 85–88. effect of food additives on aflatoxin- FA092 Kamanna, V.S., and N. Chandra- induced mutagenicity and hepato- sekhara. Effect of garlic (Allium sativum carcinogenicity. Cancer Lett 1997; Linn) on serum lipoproteins and lipo- 115(2): 129–133. protein cholesterol levels in albino rats FA089 Platel, K., and K. Srinivasan. Influence rendered hypercholesteremic by feed- of dietary spices or their active prin- ing cholesterol. Lipids 1982; 17(7): ciples on digestive enzymes of small 483–488. intestinal mucosa in rats. Int J Food FA093 Keshri, G., V. Lakshmi, M. M. Singh, Sci Nutr 1996; 47(1): 55–59. and V. P. Kamboj. Post-coital antifer- FA090 Soudamini, K. K., M. C. Unnikrishnan, tility actiivty of Ferula assafoetida K. Sukumaran, and R. Kuttan. Muta- extract in female rats. Pharmac Biol genicity and anti-mutagenicity of 1999; 37(4): 273–278. HORDEUM VULGARE 235

7 Hordeum vulgare L.

Common Names Almindelig Denmark Jecam Serbia Arlysen Cornwall Jeczmien Poland Arpa Hungary Jeemen Czech Republic Arpa Turkey Koarn Netherlands Arpa Turkmenistan Korn Sweden Barley Guyana Mach'ca Ecuador Barley United Kingdom Mehrzeilige Gerste Germany Barley United States Mitmerealine oder Estonia Barlysyn Wales Monitahoohra Finland Byg Denmark Oarn The Isle of Man (Manx) Bygg Faeroe Islands Ohra Finland Bygg Iceland Orge France Bygg Norway Orz Romania Cebada Spain Orzo Italy Cevada Portugal Paare(i) New Zealand Echemik Bulgaria Saat-Gerste Germany Elb Albania Sechszeilige Gerste Gemany Eorna Scotland Sibada Hawaii Garase South Africa Sibada Pacific Islands Gerst Netherlands Too moo China Gerste Germany Usurp China Gewone gerst Netherlands Yachmen Russia Haidd Wales Yachmin Ukraine Jecam Croatia

BOTANICAL DESCRIPTION heads in early summer. Winter varieties Hordeum vulgare is grass that may be ei- form branched stems or tillers at the base, ther a winter or a spring annual of the so several stems rise from a single plant. The POACEAE (GRAMINAE) family. It forms stems of both winter and spring varieties a rosette type of growth in fall and winter, may vary in length from 30 to 120 cm, de- developing elongated stems and flower pending on variety and growing conditions.

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 235 236 MEDICINAL PLANTS OF THE WORLD

Stems are round, hollow between nodes, beer are found in the earliest Egyptian and and develop five to seven nodes below the Sumerian writings. The origin of barley is head. At each node, a clasping leaf devel- still not known. There are differing views ops. In most varieties, the leaves are coated among researchers regarding whether the with a waxy chalk-like deposit. Shape and original wild forms were indigenous to East- size of leaves vary with variety, growing con- ern Asia, particularly Tibet, or to the Near ditions, and position on the plant. The spike East, Eastern Mediterranean area, or both. contains the flowers and consists of spike- Varieties are constantly changing as new lets attached to the central stem or rachis. ones are developed and tested while others Stem intervals between spikelets are 2 mm pass out of cultivation. or less in dense-headed varieties and up to TRADITIONAL MEDICINAL USES 4–5 mm in lax or open-headed kinds. Three Afghanistan. Flowers are taken orally by spikelets develop at each node on the rachis. females for contraceptionHV127. Hordeum vulgare is six-row variety, where all Argentina. Decoction of the dried fruit is three of the spikelets at each node develop taken orally for diarrhea and to treat respi- a seed. Each spikelet has two linear to lan- ratory and urinary tract infectionsHV063. ceolate glumes rising from near the base and China. Decoction of the dried fruit is taken flat and terminates in an awn. The glumes, orally for diabetesHV033. minus the awn, are approximately half the Egypt. Dried fruits are smoked as a treat- length of the kernel in most varieties, but ment for schistosomiasisHV109. The fruit is this varies from less than half to equal to the used intravaginally as a contraceptive be- kernel in length. Glumes may be covered fore and after coitus. Fifty-three percent of with hairs, weakly haired, or hairless. The 1200 puerperal women interviewed prac- awns on the glumes may be shorter than the ticed this method, of whom 47% depended gume, equal in length, or longer. The barley on indigenous method and/or prolonged kernel consists of the caryopsis, or internal lactationHV130. seed, the lemma, and palea. In most barley Guatemala. Hot water extract of the dried varieties, the lemma and palea adhere to the seed is taken orally for renal inflammation caryopsis and are a part of the grain follow- and kidney diseaseHV120. Hot water extract of ing threshing. The lemmas in barley are usu- the dried seed is used externally for derma- ally awned. Awns vary in length from very titis, inflammations, erysipelas, and skin short up to as much as 12 in. Edges of awns eruptionsHV122. may be rough or “barbed” (bearded) or India. Powdered flowers of Calotropis nearly smooth. Awnless varieties are also procera, fruits of Piper nigrum, seed ash of known. In six-row barley, awns are usually Hordeum vulgare, and rose water are taken more developed on the central spikelets orally for choleraHV115. than on the lateral ones. The barley ker- Iran. Flour is used as a food. A decoction of nel is generally spindle shaped. In com- the dried seed is used externally as an emol- mercial varieties, the length ranges from lient and applied on hemorrhoids and in- 7 to 12 mm. fected ulcers. A decoction of the dried seed ORIGIN AND DISTRIBUTION is taken orally as a diuretic and antipyretic Grains found in pits and pyramids in Egypt and used for hepatitis, diarrhea, scorbutism, indicated that barley was cultivated there nephritis, bladder inflammation, gout, en- more than 5000 years ago. The most ancient ema, and its tonic effect. Decoction of the glyph or pictograph found for barley is dated dried seed is applied to the nose to reduce approx 3000 BC. References to barley and internasal inflammationHV019. HORDEUM VULGARE 237

Italy. Seeds are eaten as a urinary anti- Benzoquinone, 1-4: Call Tiss, Rt, LfHV023 septicHV049. Compresses of boiled seeds are Benzoxazin-3(4H)-one, 1-4, (2H), 2-4- HV036 used to soothe rheumatic and joint painsHV123. dihydroxy: Seedling Benzoxazin-3-one, 1-4, 2-4-dihydroxy-7- Infusion of the dried seed is used as a HV101 HV039 methoxy: Aer galactogogue . Benzoxazolinone, 6-methoxy: SeedlingHV036 Korea. Hot water extract of the dried entire Betaine: Sh 15 Pmol/g, Rt 2 Pmol/gHV110 plant is taken orally for beriberi, coughs, Butyronitrile, 3-E-D-glucopyranosyloxy-3- influenza, measles, syphilis, nephritis, jaun- methyl: EpidermisHV013 dice, dysentery, and ancylostomiasis; for Butyronitrile, 4-E-D-glucopyranosyloxy-3- thrush in infants; and as a diuretic. Extract hydroxy-methyl: EpidermisHV013 HV029 of the dried entire plant is used externally Caffeic acid: Fr HV105 HV081 for prickly heatHV113. Calmodulin: Sh , Cotyledon Carnitine: Lf 0.83–3.6 nmol/gHV125 Peru. Hot water extract of dried fruits is Catechin-(4-D-8)-catechin-(4-D-8)-catechin: used externally for measles and as an emol- FrHV054 HV121 lient and taken orally as a diuretic . Catechin-(4-D-8)-gallocatechin-(4-D-8)- South Korea. Hot water extracts of the fruit catechin: FrHV054 and dried seeds are taken orally by pregnant Catechin, (+): SdHV106 women to induce abortionHV126,HV116. Hot Chlorogenic acid: FrHV029 water extracts of the fruits taken orally by Chlorophyll, proto: LfHV021 HV004 females as a contraceptiveHV126. Choline: Sd 1.08 mg/g Chrysoeriol-7-galactoside: LfHV107 Turkey. Decoction of the fruit is taken D HV107 HV074 Chrysoeriol-7-O-E- -glucoside: Lf orally for common colds . Corydine, (+): RtHV001 United States. Infusion of the dried seed is Coumaric acid, para, cis: Cell wallHV088 taken orally for dysentery, diarrhea, and Coumaric acid, para, trans: Cell wallHV088 colic and for digestive and gastrointestinal Coumaric acid, para: FrHV029 disordersHV099. Cramine: Lf 0.04–1.18%HV060 Cryptopine, allo, D: RtHV001 CHEMICAL CONSTITUENTS Cyclohexanamine, N-cyclohexyl: LfHV078 (ppm unless otherwise indicated) Cynaroside: LfHV107 Abscisic acid: SdHV034 Cystathionine: Seedling 0.07HV132 Aconitic acid: RtHV026 Delphinidin, pro: FrHV054 Aesculetin: ProtoplastHV091 Dicentrine: RtHV001 Aesculin: ProtoplastHV091 Docos-1-ene: LfHV078 Agmatine, para-coumaroyl: Sh 2.5HV002 Eicos-trans-3-ene: LfHV078 Alkyl resorcinol (C17:0): SdHV103 Eicos-trans-5-ene: LfHV078 Alkyl resorcinol (C19:0): SdHV103 Eicos-trans-9-ene: LfHV078 Alkyl resorcinol (C19:1): SdHV103 Ethanolamine, phosphatidyl: LfHV124 Alkyl resorcinol (C21:0): SdHV103 Ethylamine: Sd 3.4HV111 Alkyl resorcinol (C23:0): SdHV103 Ferulic acid, trans, 5-hydroxy: Cell wallHV088 Alkyl resorcinol (C25:0): SdHV103 Ferulic acid, trans: Cell wallHV088 Amine, diethyl: Sd 5.7HV111 Ferulic acid: SdHV037 Amine, dimethyl: Sd 1.6HV111 Flavone, 5-7-dihydroxy-3'-4'-5'-trimethoxy: AMP, cyclic: Sd, SeedlingHV022 St/LfHV087 HV025 Apigenin-7-O-E-D-diglucoside: LfHV107 Fucosterol, 28-iso: Em Arabinitol, 2-carboxy: Lf 814 nmol/gHV071 Fusariotoxin T-2: PlHV160 Azidoalanine: PlHV205 Gallocatechin-(4-D-8)-catechin-(4-D-8)- Barwin: Sd 6HV011 catechin: FrHV054 Benzaldehyde, 2-5-dihydroxy: LfHV078 Gallocatechin-(4-D-8)-gallocatechin-(4-D-8)- Benzene-1-3-diol, 5-pentadecyl: LfHV078 catechin: FrHV054 238 MEDICINAL PLANTS OF THE WORLD

Gallocatechin-(4-D-8)-gallocatechin-(4-D-8)- Mugineic acid, 3-hydroxy: RtHV133 catechin: FrHV054 Mugineic acid: RtHV133 Gallocatechin-(4-D-8)-gallocatechin-(4-D-8)- Naphthal-2-en-amine, N-phenyl: LfHV078 HV054 HV111 gallocatechin: Fr NH3 inorganic: Sd Gallocatechin, (+):FrHV054 Nucellain: EndospermHV018 J-3 hordein: SdHV180 Octadec-1-ene: LfHV078 Gibberellin A-1: SeedlingHV027 Octadeca-cis-9-cis-12-cis-15-trienoic acid Gibberellin A-3: SeedlingHV027 methyl ester: LfHV078 Gibberellin: SdHV034 Octadeca-cis-9-cis-15-dienoic acid methyl Glaucentrine: RtHV001 ester: LfHV078 Glaucine, (+): RtHV001 Oleic acid: LfHV083 Glucan, E: SdHV057,HV190 Orientin, iso, 3'-methyl ether: LfHV107 Glycine-betaine: LfHV031 Orientin, iso, 7-(ferulyl-glucoside): LfHV107 Glycoprotein D-1-G-1: LfHV119 Orientin, iso, 7-arabinosyl-glucoside: LfHV107 Gramine: SeedlingHV024, AerHV055, Protoplast, Orientin, iso, 7-O-E-D-glucoside: LfHV107 LfHV090, RtHV067 Orientin, iso, 7-rhamnoglucoside: LfHV107 Heptadecane, N: LfHV078 Orientin, iso: LfHV107 Heterodendrin, epi: EpidermisHV013 Palmitic acid: LfHV083 Hexadecanoic acid methyl ester: LfHV078 Palmitoleic acid: LfHV083 Hor v 9: PlHV164 Phytic acid: SdHV057 Hordein B: CaryopsisHV035 Phytol, iso: LfHV078 Hordenine: RtHV067, Seedling 63HV094 Phytol: LfHV078 Hordeum protein 26kDa: Sd 80HV095 Piperidine, 2-2-6-6-tetramethyl: LfHV078 Hordeum protein 30kDa: Sd 80HV095 Piperidine: Sd 1HV111 Hordeum protein 32kDa: Sd 3.0HV095 Plastohydroquinone 9: Call Tiss, Rt, LfHV023 Hordeum thaumatin-like protein R: SdHV009 Plastoquinone 9: Call Tiss, Rt, LfHV023, Hordeum thaumatin-like protein S: SdHV009 SeedlingHV129 Hordeum vulgare protease inhibitor: FrHV008 Polysaccharide (Hordeum vulgare): SdHV089 Hordeum vulgare protein MW 28000: Sd w/o Procyanidin B-3: SdHV106 seedcoatHV085 Prodelphinidin B-3 dimer: SdHV106 Hordeum vulgare protein MW 30000: Sd w/o Prodelphinidin B-3: SdHV106 seedcoatHV085 Prodelphinidin T-1: SdHV188 Hordeumin: SdHV072 Prodelphinidin T-2: SdHV188 Hordothionin, Z: SdHV015 Prodelphinidin T-3: SdHV188 Hydroxamic acid: Lf, ProtoplastHV090 Proline: Sh 0.4 Pmol/g, Rt 1.9 μmol/gHV110 Indole: LfHV078 Propane, diamino: SeedlingHV086 Indole-3-acetic acid: KernelHV043 Propelargonidin dimer: SdHV106 Indole-3-carboxylic acid: SeedlingHV006 Propene, 1-cyano-3-E-D-glucopyranosyl-oxy-2- Jasmonic acid: Sh, FrHV082 methyl: EpidermisHV013 Linoleic acid, 15(R)-hydroxy: Sd <1.0HV016 Protein Z(4): SdHV179 Linoleic acid: LfHV083 Protein: Rt, LfHV028 Linolenic acid: LfHV083 Putrescine: SeedlingHV086 Lipid transfer protein 1: SdHV179 Pyrazine, 2-5-diethyl: LfHV078 Lipid transfer protein CW-18: LfHV012 Pyrrolidine: Sd 0.9HV111 Lipid transfer protein CW-21: LfHV012 Pyrrolinium, 1-(3-amino-propyl): Lunasin: PlHV163 SeedlingHV086 Lutonarin: ShHV053 Quinic acid, feruloyl: LfHV097 Lutonarin-3'-methyl ether: ShHV053 Roquefortine C: SdHV102 Mannitol: RtHV007 Salazosulfapyridine: PlHV140 Melatonin: Sd 378.1 pg/gHV069 Salicylic acid: Sh 1HV066 Methylamine: Sd 4.5HV111 Salipurposide, iso: LfHV032 Methyl-D-glucopyranoside: LfHV078 Saponarin, 6''-feruloyl: Lf 11HV017 Mugineic acid, 2'-deoxy: RtHV133 Saponarin, 6''-sinapoyl, 4'-glucoside: Lf 6HV017 HORDEUM VULGARE 239

Saponarin, 6''-sinapoyl: Lf 22HV017 drome (AIDS) four to five doses/week for Saponarin: ShHV053 a year for the purpose of in clearing heat HV014 Satiomem: Sd and detoxifying the blood, produced an Scopoletin: ProtoplastHV091 improvement in the patient’s healthHV093. Shikimic acid, feruloyl: LfHV097 Sinapic acid, trans: Cell wallHV088 Allergenic activity. Extract of the dried Sitosterol, E: EmHV025 seed, administered externally to male adults Starch: SdHV020 at a concentration of 10%, was activeHV044. Stearic acid: LfHV083 Allergens, administered by ingestion or Stigmasterol: EmHV025 inhalation to 40 children aged 3–6 months Sutherlandin: EpidermisHV013 who suffered from diarrhea, vomiting, ecze- HV129 Tocopherol, D: Seedling , Call Tiss, Rt, ma, or weight loss after the introduction of LfHV023 the cereal in the diet and to 18 food-allergic Tocoquinone, D: Call Tiss, Rt, LfHV023 Trichothecene: PlHV160 adults and eight patients with Baker’s asth- Tricin: Lf/StHV087 ma, produced strong effect in childrenHV172. Tricin-7-O-E-D-glucoside: LfHV107 Protein Z(4), administered to four pa- Trigonelline: Sd 8.9HV118 tients with beer allergy, provoked weak Tryptamine: Lf 3HV065 positive response to skin testing in two of HV006 Tryptophan: Seedling the patients and was recognized by the four HV048 Tyramine, N-methyl: Fr , Seedling individual sera tested. Lipid transfer protein 48HV094, RtHV001 Tyramine: Seedling 26HV094 1 showed reactivity with three of four indi- Umbelliferone: FrHV029 vidual sera and induced strong positive skin Vanillic acid: FrHV029 prick test responses in all four of the pa- Vitamin B-1: Sd 4.47HV005 tients testedHV179. Two cases of severe sys- Vitamin B-2: Sd 1.28HV005 temic reactions resulted from beer ingestion: Vitamin K-1: Call Tiss, Rt, LfHV023 one case of anaphylaxis requiring emer- Vitexin-7-O-E-D-diglucoside: LfHV107 HV010 gency care and one of generalized urticaria Vitexin, iso, 2'' (3'')-O-glucosyl: Lf 590.9 and angioedema were reported. Barley was Vitexin, iso, 2''-O-diglucoside: LfHV080 Vitexin, iso, 2''-O-glucoside: LfHV041 recognized as the specific ingredient respon- HV183 Vitexin, iso, 2''-O-glucosyl: LfHV064 sible for the observed allergic reaction . Vitexin, iso, 4'-7-diglucoside: Lf 7HV017 Beer and malt allergens were found in three Vitexin, iso, 7-diglucoside: LfHV107 patients with urticaria. Urticaria from beer Vitexin, iso, 7-O-E-D-diglucoside: LfHV107 was an immunoglobulin E (IgE)-mediated Vitexin, iso, 7-rhamnosyl-glucoside: Lf 13HV017 hypersensitivity reaction induced by a pro- HV040 Vitexin, iso: 2''-O-glucosyl: Lf tein component of approx 10 kDa deriving Vitexin, iso: LfHV058 from barleyHV184. A 50-year-old man, who Vitexin-7-rhamnoglucoside: LfHV107 developed bronchial asthma after exposure PHARMACOLOGICAL ACTIVITIES to barley flour, was confirmed by skin prick AND CLINICAL TRIALS test and serum-specific IgE. Bronchial chal- 5-Hydroxytryptamine inhibition. Ethanol lenge test with every allergen showed no re- (80%) extract of the dried stem bark, in cell sponse, except for an immediate response to culture at a dose of 10 Pg/mL, inhibited the barley flour. The most relevant clinical fea- uptake of serotonin (5HT) in rat brainstem ture was an immediate asthmatic response neuronsHV046. developed after oral provocation with either Acquired immune deficiency syndrome barley-made beer or barley flour itself that therapeutic effect. Hot water extract of indicated IgE-mediated food-induced bron- the dried fruit, administered orally to pa- chial asthmaHV195. A 32-year-old storeman tients with acquired immuodeficiency syn- developed occupational asthma resulting 240 MEDICINAL PLANTS OF THE WORLD from barley grain dust in the packaging of Tincture of the dried seed, on agar plate at a flour, barley, and peanuts. He developed concentration of 30 PL/disc, was inactive on immediate symptoms of sneezing, cough, Escherichia coli, Pseudomonas aeruginosa, and and dyspnea on exposure to barley only. Staphylococcus aureus. Extract of 10 g plant Bronchial provocation test to the barley material in 100 mL ethanol was usedHV122. confirmed the diagnosisHV197. Anticoagulation activity. Serpin BSZx (an Ameliatory effect. Decoction of the grain, inhibitor of trypsin and chemotrypsin) at a dose of 250 mL, produced a decrease in inhibited thrombin, plasma kallikrein, fac- the passage time of whole blood with a tor VIIa/tissue factor, and factor Xa at hep- microchannel array flow analyzerHV173. arin-independent association rates. Only Anti-allergenic activity. Alcohol-soluble factor Xa turned a significant fraction of prolamines, administered to patients with BSZx over as substrate. Activated protein C gluten-sensitive enteropathy and dermatitis and leukocyte elastase were slowly inhibited herpetiformis, produced monoclonal anti- by BSZx, whereas factor XIIa, urokinase and bodies and serum reactionHV165. tissue type plasminogen activator, plasmin Anti-amoebic activity. Ethanol (50%) ex- and pancreas kallikrein, and elastase were tract of the seed, in broth culture at a con- not or only weakly affected. Trypsin from centration of 125 Pg/mL, was active on Fusarium was not inhibited, while interac- Entamoeba histolyticaHV001. tion with subtilisin Carlsberg and Novo was Anti-atherogenic activity. E-Glucan in rapid, but most BSZx was cleaved as a barley cellulose, administered to Syrian substrateHV192. golden F(1)B hamsters at doses of 2, 4, or 8 Antidiabetic activity. The plant, adminis- g/100 g in a semipurified hypercholester- tered to diabetic rats, produced a decrease olemic diet of 0.15 g/g cholesterol, 20 g/100 of blood glucose concentration, water con- g of hydrogenated coconut oil and 15 g/100 sumption, and weight loss. No differences g of cellulose, produced cholesterol-lower- were found in healthy animalsHV157. ing effect. Compared with control hamsters, Antidiarrheal activity. Extract of the ger- dose-dependent decreases that were similar minating seeds, administered in the ration in magnitude in plasma total and low-den- of male rats, was active vs cecocolectomy- sity lipoprotein (LDL) cholesterol concen- induced diarrheaHV045. Germinated barley trations were observed in hamsters fed the and scutellum fraction of germinated barley, E-glucan diet at weeks 3, 6, and 9. Liver administered to rats, prevented diarrhea cholesterol concentrations were also re- caused by cecocolectomy and increased the duced significantly in hamsters consuming protein content and sucrose activity of small 8 g/100 g E-glucanHV210. intestinal mucosaHV150. The aleurone and Antibacterial activity. Decoction of the scutellum fractions of barley grains before dried fruit, on agar plate, was inactive on and after germination, administered to rats Pseudomonas aeruginosaHV063. Ethanol (95%) with diarrhea, were active. The addition of and water extracts of the dried fruit, on agar fractions of germinated barley and not bar- plate at a concentration of 50 PL/plate, were ley collected before germination increased inactive on Staphylococcus aureusHV073. Wa- the fecal output and jejunal mucosal protein ter extract of the dried fruit, on agar plate, content. The effect of malted barley was at a concentration of 1 mg/mL, was inactive similar to that of germinated barley on Salmonella typhiHV030. Hot water extract of foodstuffHV151. the dried fruit, on agar plate at a concentra- Antifungal activity. Dried stem, on agar tion of 62.5 mg/mL, was inactive on Escheri- plate, was active on Sphacelia segetumHV131. chia coli and Staphylococcus aureusHV056. Hot water extract of the dried fruit, on agar HORDEUM VULGARE 241 plate at a concentration of 62.5 mg/mL, was administered to 20 men with hypercholes- inactive on Aspergillus nigerHV056. Water ex- terolemia aged 41 r 5 years, resulted in sig- tract of the seed, on agar plate at a concen- nificant fall in serum total cholesterol, LDL tration of 5 mg/mL, was inactive on cholesterol, and phospholipids, and LDL Helicobacter pyloriHV076. Protein fraction of and very low-density lipoprotein (VLDL). the seed without seed coat, on agar plate at A dose of 50/50 w/w mix with rice, adminis- a concentration of 2 Pg/disc, was active on tered to seven women with mild hypercho- Neurospora crassa and Trichoderma sp.HV085. lesterolemia aged 56 r 7 years twice daily Protein fraction of the seed without seed for 2–4 weeks, produced a significant im- coat, on agar plate at a concentration of 2 provement of serum lipid profiles. In the Pg/disc, was active on Neurospora crassaHV085. normolipemic subjects, serum lipids were Antihepatotoxic activity. Methanol ex- unaffectedHV193. Bran flour and oil extract, tract of the dried fruit, administered by gas- administered to 79 patients with hypercho- tric intubation to rabbits at a dose of 0.5 g/ lesterolemia, aged 48.2 years at a dose of 3 g kg, was active vs CCl4-induced hepatotox- oil extract or 30 g flour for 30 days, signifi- icity. A mixture of Machilus sp., Alisma sp., cantly decreased total serum cholesterol. Amomum xanthioides, Bulboschoenus mariti- LDL cholesterol was decreased 6.5% with mus, Artemisia iwaymogis, Atractylodes addition of bran flour and 9.2% with oil. japonica, Crataegus cuneata, Hordeum vul- High-density lipoprotein (HDL) cholesterol gare, Citrus sinensis, Polyporus umbellatus, decreased significantly in the bran flour Agastache rugosa, Raphanus sativus, Poncirus group but not in the oil groupHV059. Fiber trifoliatus, Curcuma zeodaria, Citrus auran- (nonstarch polysaccharides), administered tium, Saussurea lappa, Glycyrrhiza glabra, and to 21 men with mild hypercholesterolemia Zingiber officinale was usedHV112. aged 30–59 years for 4 weeks, produced a sig- Antihypercholesterolemic activity. Dried nificant fall in plasma total cholesterol and bran, administered in ration of male rats, LDL cholesterol. The triglyceride and glu- was activeHV068. Methanol extract of the cose concentrations did not change dried fruit, administered by gastric intuba- significantlyHV204. tion to rabbits at a dose of 500 mg/kg, was Antihyperglycemic activity. Dried seeds, active vs CCl4-induced hepatotoxicity. A administered orally to six patients with mixture of Machilus sp., Alisma sp., Amo- noninsulin-dependent diabetes mellitus mum xanthioides, Bulboschoenus maritimus, at a dose of 50 g/person, was active. A Artemisia iwaymogis, Atractylodes japonica, single dose resulted in a glycemic index of C. cuneata, Hordeum vulgare, Citrus sinensis, 53.4HV047. Water extract of the dried fruit, Polyporus umbellatus, Agastache rugosa, administered intragastrically to rats at a Raphanus sativus, Poncirus trifoliatus, Cur- dose of 150 mg/kg, produced weak activity cuma zeodaria, Citrus aurantium, Saussurea on blood vs streptozotocin-induced hyper- lappa, Glycyrrhiza glabra, and Zingiber glycemiaHV033. Dried seeds, administered officinale was used. Results were significant orally to eight adults with normal glucose at p < 0.01 levelHV112. Gum, administered tolerance at a dose of 50 g/person, were orally to male rats for 4 weeks, was active. activeHV052. Flour, administered in the ration Biological activity reported had been of male rats, was active vs streptozotocin- patentedHV104. Chromatographic fraction of induced hyperglycemiaHV062. Barley gum, the green leaf juice, administered to rats at administered to 4-week-old male Sprague– a dose of 1% of diet, was active vs choles- Dawley rats as a 2% dietary supplement for terol-loaded animals. The results were sig- 14 days, lowered serum cholesterol concen- nificant at p < 0.005 levelHV117. Seeds, tration and suppressed the elevation of 242 MEDICINAL PLANTS OF THE WORLD serum and liver triglyceride concentra- concentration of 50 PL/disc, was inactive on tionsHV154. Thick and thin rolled oat made Bacillus subtilis NIG-1125 HIS MET and from raw or preheated kernel, administered Escherichia coli B/R-WP2-TRPHV114. to healthy subjects, produced high glucose, Antioxidant activity. Water extract of the insulin, and metabolic responsesHV181. Barley roasted seed, at a concentration of 1 mg/mL, flour naturally high in E-glucan and E- produced strong activity vs a liposome model glucan-enriched flour, administered to 11 system. A concentration of 25 mg/mL was healthy men, resulted in a decrease of the active vs 2,2-diphenyl-1-picryl-hydrazyl- insulin response. Plasma glucose and insu- hydrate-induced radical. A concentration of lin concentrations increased significantly. 5 mg/mL was inactive vs linoleic acid sys- Cholesterol concentration dropped below temHV079. Ethanol (80%) extract of the freeze- the fasting concentration 4 hours after the dried leaf, at a concentration of 60 Pg/mL, meal and was significantly lower than was active vs oxidation of ethyl linoleate by after low-fiber meal. The cholecystokinin Fenton’s reagentHV010. Young leaf extract, remained elevated for a long time after administered orally to 36 patients with type the barley-containing mealsHV185. Boiled 2 diabetes at a dose of 15 g daily for 4 weeks, intact and milled kernels with different enhanced the scavenging of oxygen free amylase-amylopectin ratios, administered radicals, saved the LDL-vitamin E content, to healthy subjects, produced lower meta- and inhibited LDL oxidationHV177. Purified bolic responses and higher satiety scores green barley extract, in human mono- when compared to white wheat bread. The nuclear culture of cells isolated from per- boiled flours produced higher glucose and ithelial blood and synovial fluid of patients insulin responses than did the correspond- with rheumatoid arthritis, was activeHV178. ing boiled kernels. The impact of amylase Leaf essence, administered to atheroscle- to amylopectin on the metabolic responses rotic New Zealand White male rabbits at a was marginalHV198. The intact kernels, dose of 1% of diet, produced a decrease of administered to healthy subjects at concen- plasma total cholesterol, triacylglycerol, trations of 40 and 80% (SCB-40 and SCB- lucigenin-chemiluminescence, and lumi- 80), produced the glycemic and insulinemic nal-chemiluminescence levels. The value of indices 39 and 33 for SCB-80, compared to T50 of red blood cell hemolysis and the lag pumpernickel bread 69 and 61, respectively. phase of LDL oxidation increased in barley- The glycemic index for SCB-40 was 66HV199. treated group compared with the control. Anti-inflammatory activity. Germinated Ninety percent of the intimal surface of the barley foodstuff, administered to mice with thoracic aorta was covered with atheroscle- DSS-induced colitis, prevented disease rotic lesions in the control group, but only activity and loss of body weight after 60% of the surface was covered in the bar- induction of colitis. Serum interleukin (IL)- ley group. This inhibition was associated 6 level, mucosal STAT3 expression, necro- with a decrease in plasma lipids and an sis factor-NB activity, and mucosal damages increase in antioxidative abilitiesHV003. were decreased and cecal butyrate content Anti-tumor activity. Commercial barley increased. The germinated barley foodstuff- bran (13% dietary fiber) from the aleurone/ fed mice had lower bile acid concentration subaleurone layer; outer-layer barley bran, than the control groupHV161. Green barley including the germ (25.5% dietary fiber); extract, in LPS-activated human monocytes and spent barley grain bran (product of the cell line culture (THP-1), was activeHV178. brewery including the hull) (47.7% dietary Antimutagenic activity. Methanol extract fiber) were administered to male Sprague– of the dried fruit and leaf, on agar plate at a Dawley rats as a 5% dietary supplement for HORDEUM VULGARE 243

7 months. Commercial barley bran was mation with an increase in cecal butyrate most effective in reducing tumor incidence levelsHV139. Fiber and protein factions of ger- and burden. Tumor burden and tumor mass minated barley foodstuff, administered to index were reduced significantly by outer- dextran sodium sulfate-induced colitis layer barley bran and spent barley grain Sprague–Dawley rats, significantly attenu- bran. Commercial barley bran and spent ated the clinical signs of colitis and de- barley grain bran, administered to rats with creased serum D1-acid glycoprotein levels, 1,2-dimethylhydrazine-induced intestinal with an increase in cecal butyrate produc- tumor, produced a higher incidence and tion, whereas germinated barley foodstuff- burden of tumorHV153. Fiber was administered protein did not. Germinated barley foodstuff to 4-week-old male Sprague–Dawley rats with or without salazosulfapyridine, admin- with dimethylhydrazine-induced tumors at istered to rats after the onset of colitis, ac- a dose of 5% of diet. The insoluble fiber-rich celerated colonic epithelial repair and fraction (spent barley grain) was signifi- improved clinical signsHV140. Germinated cantly more effective at preventing induced barley foodstuff, administered orally to pa- tumors than the soluble commercial barley tients with mild to moderate active ulcer- bran. The incidence of rats affected, tumor ative colitis at a dose of 30 g/person daily for mass index, and plasma cholesterol concen- 4 weeks, produced a significant clinical and tration were reduced by spent barley grain. endoscopic improvement independent of Outer-layer barley bran was moderately disease extent. The improvement was asso- effective in cancer preventionHV155. The ciated with an increase in stool butyrate crude and partially purified lunasin, in sta- concentrations and in luminal Bifidobac- bly ras-transfected mouse fibroblast cell cul- terium and Eubacterium levels. After the end ture, suppressed colony formation induced of treatment, the patients had an exacerba- with isopropylthiogalactoside. This fraction tion of the diseaseHV141. Germinated barley also inhibited histone acetylation in mouse foodstuff with or without Clostridium butyri- fibroblast (NIH 3T3) and human breast cum, administered to 3% dextran sodium (MCF-7) cells in the presence of the histone sulfate-induced colitis in Sprague–Dawley deacetylase inhibitor sodium butyrateHV163. rats for 8 days, prevented bloody diarrhea Anti-ulcer activity. Water extract of the and mucosal damage and increased the fe- green leaf juice, administered by gastric in- cal short-chain fatty acid levelsHV143. Germi- tubation to rats at a dose of 500 mg/kg, was nated barley foodstuff, administered to active vs stress-induced (restraint) ulcers. Sprague–Dawley rats for 5 days, prevented The results were significant at p < 0.001 bloody diarrhea and mucosal damage, level. Water extract was active vs acetic elevated fecal acetic acid and N-butyric acid acid-induced and aspirin-induced ulcers. levels, and tended to increase the number The results were significant at p < 0.01 and of Eubacteria and Bifidobacteria. The number p < 0.005 levels, respectively. Water extract of Enterobacteriaceae, the total number of was inactive vs pylorus ligation-induced aerobes and Bacteroidaceae, were lowered by ulcersHV116. Extract of the dried seedling, ad- germinated barley foodstuff treatmentHV144. ministered orally to adults at a dose of 30 g/ Germinated barley foodstuff, administered person, was activeHV077. Germinated barley to HLA-B27 transgenic rats for 13 weeks, foodstuff, administered orally to male produced an increase of bacterial butyrate Sprague–Dawley rats on day 6 after initia- production and the decrease of cecal occult tion of colitis, was active vs dextran sodium blood, colonic mucosal hyperplasia, colonic sulfate-induced colitis. Germinated barley mucosal necrosis factor-NB-DNA binding foodstuff treatment reduced colonic inflam- activity, and the production of IL-8HV145. Bu- 244 MEDICINAL PLANTS OF THE WORLD tyrate from germinated barley foodstuff, ad- Extract of 10 g plant material in 100 mL ministered orally or intracecally to Sprague– ethanol was usedHV122. Dawley rats, produced reduction of mucosal Cardiovascular activity. E-glucan, admin- damage only by intrathecal administration. istered to 18 men with mild hypercholester- Bacterial butyrate production and reduction olemia with a mean body weight index of of mucosal damage depended on the dose of 27.4 r 4.6 at a dose of 8.1–11.9 g E-glucan germinated barley foodstuff in the dietHV146. per day, produced no significant change in Germinated barley foodstuff and scutellum total, LDL and HDL cholesterol, triacyl- fraction of germinated barley, administered glycerol, fasting glucose, and postprandial to Sprague–Dawley rats with colitis induced glucoseHV169. by 3% dextran sodium sulfate, prevented Cholesterol biosynthesis inhibition. The bloody diarrhea and mucosal damage in inhibitor I from oily nonpolar fraction of colitis. The germinated samples did not pro- flour, administered to chicken at a dose of duce a protective effect. Germinated barley 2.5–20 ppm, produced a significant decrease foodstuff increased mucosal protein and in hepatic cholesterogenesis and serum total RNA content in the colitis modelHV149. Ger- and LDL cholesterol and an increase in minated barley foodstuff, administered to 18 lipogenic activityHV158. patients with mildly to moderately active Cholesterol-7-D-hydroxylase inhibition. ulcerative colitis at a dose of 20–30 g germi- Petroleum ether extract of the fresh fruit, nated barley foodstuff daily for 4 weeks, pro- administered to pigs at a concentration of duced a significant decrease in clinical 3.5 g/kg of diet for 29 days, produced 40% activity index scores compared to the con- inhibition of the hepatic enzyme activ- trol group. No side effects related to germi- ityHV092. nated barley foodstuff were observed. Citrate lyase inhibition. Petroleum ether Germinated barley foodstuff therapy extract of the fresh fruit, administered to increased fecal concentrations of Bifido- pigs at a concentration of 3.5 g/kg of diet bacterium and Eubacterium limosumHV170. Ger- for 29 days, was active on the hepatic minated barley foodstuff, administered to enzymesHV092. patients with mild to moderate active ulcer- Cyclo-oxygenase inhibition. Methanol ative colitis, irresponsible to or intolerant of extract of the ether-insoluble fraction of the standard treatment at a dose of 20–30 g ger- fresh seed, administered to rats at a dose of minated barley foodstuff daily for 4 weeks, 100 Pg/mL, inhibited platelets by 46%. resulted in a significant clinical and endo- Methanol extract of ether-soluble fraction scopic improvement associated with an in- inhibited platelets by 29%HV051. crease in stool butyrate concentrationsHV174. Cytotoxic activity. Water extract of the Antiviral activity. Ethanol (50%) extract dried fruit, in cell culture at a concentration of the seed, in cell culture at a concentra- of 500 Pg/mL, produced weak activity on tion of 50 Pg/mL, produced weak activity on CA-mammary-microalveolarHV098. Ethanol Ranikhet virusHV001. Decoction of the dried (50%) extract of the seed, in cell culture, seed, in cell culture, produced weak activity was inactive on CA-9KB, ED50 greater than on WA-rotavirusHV042. Protein fraction of 20 Pg/mLHV001. Methanol extract of the dried the seed without seed coat, on agar plate at seed, in cell culture, was inactive on SNU-1 a concentration of 2 Pg/disc, was active on human cells, IC50 greater than 0.3 mg/mL, HV085 CA-Ehrlich ascites . and on SNU-C4 human cells, IC50 greater Anti-yeast activity. Tincture of the dried than 0.3 mg/mLHV061. Protein fraction of the seed, on agar plate at a concentration of 30 seed without seed coat, in cell culture at a PL/disc, was inactive on Candida albicans. concentration of 2 Pg/disc, was active on HORDEUM VULGARE 245

CA-Ehrlich ascitesHV085. Methanol extract of feeding periodHV138. Germinated barley food- the aerial parts, in cell culture at a concen- stuff, administered to Sprague–Dawley rats tration of 50 mg/mL, was equivocal on CA- fed on various diets with the same protein 9KBHV075. and dietary fiber levels, produced an in- Diuretic activity. Decoction of the dried crease fecal output compared with commer- seed, administered nasogastrically to rats at cial water-soluble and insoluble dietary a dose of 1 g/kg, produced strong activ- fibers. The dietary fiber from germinated ityHV120. barley foodstuff increased the fecal output Estrogenic effect. Ethanol (95%) extract of and mucosal protein content. The protein the aerial parts, administered subcutane- fraction of germinated barley foodstuff ously to infant mice, was activeHV128. degraded to the peptide form did not Fatty acid synthase inhibition. Petroleum increase the fecal output or mucosal protein ether extract of the fresh fruit, adminis- contentHV152. Germinated barley foodstuff tered to pigs at a concentration of 3.5 g/kg from aleurone and scutellum fractions of of diet for 29 days, was active on hepatic germinated barley, administrated to healthy enzymesHV092. volunteers at a dose of 9 g daily for 14 Gastrointestinal activity. Water extract of days, significantly increased fecal butyrate the green leaf juice, administered by gastric content and fecal Bifidobacterium and Eu- intubation to rats at a dose of 500 mg/kg, bacterium. Ten anaerobic microorganisms was inactive vs pylorus ligation-induced selected from intestinal microflora were cul- ulcersHV116. Fiber, administered orally to tured in vitro in germinated barley foodstuff young male Wistar rats at a dose of 500 g medium. After 3 days of incubation, seven extrudates/kg of diet for 6 weeks, produced strains (Bifidobacterium breve, Bifidobacte- a higher concentration of neutral sterols in rium longum, Lactobacillus acidophilus, Lac- the intestinal content of the barley-fed tobacillus casei ssp. casei, Bacteroides ovatus, group than in the control group (p < 0.005) Clostridium butyricum, and Eubacterium and affected indirectly the amount of limosum) lowered the medium pH produc- formed secondary bile acidsHV134. Fiber, ad- ing short-chain fatty acid. Germinated bar- ministered orally to young male Wistar rats ley foodstuff changed the intestinal at a dose of 50 g/100 g extrudates or mix- microflora and increased probiotics such as tures for 6 weeks, produced greater food in- Bifidobacterium. Butyrate was produced by take in the last 2 weeks and increased ceca the mutual action of Eubacterium and and colon masses, cecal and colon contents, BifidobacteriumHV186. Germinated barley concentration of resistant starch in cecal, foodstuff from aleurone layer, scutellum, most of colon contents, and E-glucan level and germ, administered to 10 healthy vol- in the small intestine, cecum, and colon. unteers at a dose of 30 g/day/person for 28 The numbers of coliforms and Bacteroides days, produced an increased fecal butyrate were lower and those of Lactobacillus were content, fecal weight, and water content. higher than in the control group. The dose There were no significant changes in body increased weight gain in the sixth week. weight and major abnormalities in hemato- Short-chain fatty acids were higher in the logic and urinary analysisHV187. Fiber, admin- cecal, colon, and feces content of the test istered to nine patients with ileostomies at group. The proportion of secondary bile ac- a dose of 35 g/day, increased the ileal excre- ids was lower and the amount of neutral ste- tion of starchHV191. Flaked and finely milled rol was higher in feces of fiber-treated barley, eaten by patients with ileostomies, animals. The concentrations of excreted showed that only 2 r 1% of starch remained bile acids increased up to 30% during the undigested after the consumption of finely 246 MEDICINAL PLANTS OF THE WORLD milled barley and 17 r 1% resisted diges- ministered to Sprague–Dawley rats with tion, partly as oligosaccharides but largely constipation induced by loperamide, pro- as intact unpitted starch granules bound by duced an increase of bowel movements, fe- intact cell walls. The energy excretion from cal water content, and concentration of the stoma was three times higher after short-chain fatty acids in cecal content, es- flaked that after milled barley. Nonstarch pecially butyrateHV148. polysaccharide, starch, and fat made almost Glucose tolerance effect. Fiber, adminis- equal contributions to the higher energy tered orally to type 2 diabetic Goto– excretionHV196. Bran flour, administered to Kakizaki male rats for 9 months, improved 44 volunteers at a dose of 30 g/day, de- the area under the plasma glucose concen- creased the transit time by 8.02 hours from tration time curves, lowered the fasting baseline and increased daily fecal weight by plasma glucose and glycosylated hemoglo- 48.6 gHV201. Groats were administered to vol- bin levels, and decreased plasma total cho- unteers at a dose of 1 g carbohydrate/kg body lesterol, triglycerides, and free fatty acid weight, three times or at three different levelsHV135. Fiber, administered orally to 8- doses of 0.75, 1, and 1.5 g carbohydrate/kg week-old male Goto–Kakizaki strain rats, at body weight. After consumption of 1 g car- a dose of 1.79 g/day/rat for 3 months, im- bohydrate/kg body weight, produced a mean proved glucose tolerance and lowered the mouth to cecum transit time of 8.4 r 0.4 plasma cholesterol and triglyceride levels. hour. After consumption of the high dose, a The fasting plasma glucose level was signifi- mean mouth-to-cecum transit time of 9.0 r cantly lower in comparison to rice and corn 0.5 hours was produced. Particle size did not starch-fed ratsHV136. High barley (high-fiber significantly affect the mouth-to-caecum diet), administered to 10 women (20.4 r 1.3 transit timeHV206. Germinated barley food- year-old, 19.2 r 2 kg/m2) for 4 weeks with a stuff, administered to Sprague–Dawley rats, 1-month interval, resulted in lowering prevented diarrhea and mucosal damages; plasma total and LDL cholesterol concen- increased mucosal protein, DNA, and RNA trations and reduced plasma triacylglycerol content; and depressed bacterial transloca- concentration. The barley diet increased tion and elevation of myeloperoxidase ac- stool volume. There was no significant dif- tivity induced by methotrexateHV147. ference in glucose tolerance between diet E-glucan-rich barley fraction, administered regimensHV168. Barley bread containing lac- to ileostomy subjects at a dose of 13.0 g E- tic acid and reference barley bread, admin- glucan/day for 2 days, increased the choles- istered in the morning to 10 healthy men terol excretion higher than with the oat and women, produced a significant lower- bran with E-glucanase and wheat flour di- ing of the incremental glycemic area and of ets. Bile acid excretion was 755 (133–1187) the glucose response at 95 minutes after in- mg/dayHV194. Carbohydrates, administered to gestion of the bread with lactic acid. At 45 healthy subjects at a dose of 90 g for dinner minutes after the meal, the insulin level was in random order 1 week apart, significantly significantly lower after the lactic acid increased the breath hydrogen and im- bread, compared with reference barley proved glucose tolerance. No difference in breadHV176. the rates of glucose disappearance or gut glu- Glucose-6-phosphate dehydrogenase cose absorption was observed. Serum-free inhibition. Petroleum ether extract of the fatty acid concentrations were significantly fresh fruit, administered to pigs at a concen- reduced the morning after the barley tration of 3.5 g/kg of diet for 29 days, was mealHV202. Germinated barley foodstuff, ad- active on hepatic enzymesHV092. HORDEUM VULGARE 247

Glutamate–oxaloacetate–transaminase Hypocholesterolemic activity. Fixed oil inhibition. Methanol extract of the dried of the bran, administered orally to adults of fruit, administered by gastric intubation to both sexes at a dose of 30 mg/day, was ac- rabbits at a dose of 500 mg/kg, was active vs tive. Flour bran, administered orally to HV059 CCl4-induced hepatotoxicity. A mixture of adults at a dose of 3 g/day, was active . Machilus sp., Alisma sp., Amomum xanthio- Dried bran, administered in the ration of ides, Bulboschoenus maritimus, Artemisia male rats, was activeHV068. Petroleum ether iwaymogis, Atractylodes japonica, Crataegus extract of the fresh fruit, administered to cuneata, Hordeum vulgare, Citrus sinensis, pigs at a concentration of 3.5 g/kg of diet, Polyporus umbellatus, Agastache rugosa, produced a decrease of serum total choles- Raphanus sativus, Poncirus trifoliatus, Cur- terol, LDL cholesterol, and HDL cholesterol cuma zeodaria, Citrus aurantium, Saussurea after 29 days of feedingHV092. Flour, adminis- lappa, Glycyrrhiza glabra, and Zingiber tered orally to adults with hypercholester- officinale was used. Results were significant olemia at a dose of 44 g/day, produced a at p < 0.01 levelHV112. decrease of total and LDL cholesterol Glutamate–pyruvate–transaminase inhi- levelsHV100. bition. Methanol extract of the dried fruit, Hypoglycemic activity. Water extract of administered by gastric intubation to rabbits the fermented root, administered intrave- at a dose of 500 mg/kg, was active vs carbon nously to rabbits, was activeHV007. The dried tetrachloride (CCl4)-induced hepatotoxic- seed, administered orally to eight healthy ity. A mixture of Machilus sp., Alisma sp., volunteers at a dose of 50 g/person, was ac- Amomum xanthioides, Bulboschoenus mariti- tive. A single dose resulted in a glycemic mus, Artemisia iwaymogis, Atractylodes index of 68.7 and an insulinemic index of japonica, Crataegus cuneata, Hordeum vul- 71.1HV047. gare, Citrus sinensis, Polyporus umbellatus, Hypolipemic activity. Fiber, administered Agastache rugosa, Raphanus sativus, Poncirus orally to nine adults with ileostomies at a trifoliatus, Curcuma zeodaria, Citrus auran- dose of 13 g/day, increased the excretion of tium, Saussurea lappa, Glycyrrhiza glabra, and cholesterolHV072. Petroleum ether extract of Zingiber officinale was used. Result was sig- the fresh fruit, administered to pigs at a nificant at p < 0.01 levelHV112. concentration of 3.5 g/kg of diet, was Growth inhibition. Germinated barley inactiveHV092. Purified green barley extract, foodstuff, administered orally to 4-week-old in human mononuclear culture of cells iso- female ICR mice at a dose of 10% for 24 lated from perithelial blood and synovial weeks, produced no effect on the growth fluid of patients with rheumatoid arthritis, rate of miceHV142. was activeHV178. Leaf essence, administered to Hair growth influence. Purified procyan- atherosclerotic New Zealand White male idin B-3, in hair epithelial cell culture, pro- rabbits at a dose of 1% of diet, produced a duced high hair-growing activity and in vivo decrease of plasma total cholesterol, anagen-inducing activity. (+)-Catechin pro- triacylglycerol, lucigenin–chemilumines- duced no hair-growing activityHV162. cence, and luminal–chemiluminescence

3-Hydroxy-3-methylglutaryl coenzyme levels. The value of T50 of red blood cell A reductase inhibition. Petroleum ether hemolysis and the lag phase of LDL oxida- extract of the fresh fruit, administered to tion increased in barley-treated group com- pigs at a concentration of 3.5 g/kg of diet for pared with the control. Ninety percent of 29 days, produced 40% inhibition of the the intimal surface of the thoracic aorta was hepatic enzyme activityHV092. covered with atherosclerotic lesions in the 248 MEDICINAL PLANTS OF THE WORLD control group, but only 60% of the surface that lasted for less than 24 hoursHV209. Sixty- was covered in the barley group. This inhi- nine of 80 dockworkers handling grains re- bition was associated with a decrease in ported evening feverish episodes/ symptoms plasma lipids and an increase in antioxi- not related to smoking or atopic status. dative abilitiesHV003. No gross deficits in lung function were Hypotriglyceridemic activity. Fixed oil of detectedHV200. the bran, administered orally to adults of Malic enzyme inhibition. Petroleum ether both sexes at a dose of 30 mg/day, was ac- extract of the fresh fruit, administered to tive. Flour bran, administered orally to pigs at a concentration of 3.5 g/kg of diet for adults at a dose of 3 g/day, was inactiveHV059. 29 days, was active on hepatic enzymesHV092. Laxative effect. Powdered dried bran, ad- Mineral utilization. Germinated barley ministered orally to 44 adults at a dose of 30 foodstuff, administered orally to 5-week-old g/person, was active on gastrointestinal mo- Sprague–Dawley rats for 14 days, promoted tility. Transit time decreased by 8 hours, and the absorption of calcium (Ca) and magne- fecal mass increased by 48.6 g/dayHV050. sium (Mg) by the gastrointestinal tract. The Lipid metabolism. Fiber, administered absorption of iron and potassium was not orally to male type 2 diabetic Goto– attenuated and mineral absorption was not Kakizaki rats for 9 months, improved the inhibitedHV142. Barley husk, administered to area under the plasma glucose concentra- 5- and 9-week-old rats at different doses, tion time curves, lowered the fasting plasma produced a lowering of zinc (Zn) and Ca glucose and glycosylated hemoglobin levels, absorption already at dose 20 g dietary fiber/ and decreased plasma total cholesterol, trig- kg dry matter and had a small negative ef- lycerides and free fatty acid levelsHV135. fect on potassium absorption. Phytate did Lipolytic effect. Ethanol (95%) extract of not appear as a major factor affecting min- the dried entire plant in combination with eral absorption in barley husk. All of the Rhizoma zingiberis, Ligustrum chuanxiong, diets containing barley husk had very low Lilium brownii, Nephelium longa, and Polygo- molar ratios (phytate:Zn was 4)HV159. Pro- num multiflorum, administered in drinking cessed or unprocessed barley was adminis- water to C57BL/6J obese mice at a concen- tered to healthy subjects in two single meals tration of 5%, was activeHV070. containing porridge or breakfast (60 g) ce- Lipoxygenase inhibition. Methanol ex- reals for 2 months. Zn absorption from hy- tract of ether-insoluble and ether-soluble drothermally-treated barley porridge was fractions of the fresh seed, administered to significantly higher than from the control rats at a dose of 100 Pg/mL, was inactive on porridge; Ca absorption did not differ. Zn plateletsHV051. absorption from breakfast cereals of malted Lung function. Exposure of six men to bar- barley with phytase activity was signifi- ley dust for 2 days decreased ventilatory ca- cantly higher than from flakes of barley pacity. Five volunteers not previously without phytase activity; Ca absorption was exposed to barley dust, when exposed to the not significantly differentHV167. Standard bar- dust for 2 hours, decreased the ventilatory ley and E-glucan-enriched barley dehulled capacity ranging from 200 mL to 800 mL, grains was administered to 10 healthy hy- with recovery taking up to 72 hours. All of drogen-producing adults at a dose of 35 g. the subjects had decreases in flow at 50% The percentage of the 13C dose oxidized was vital capacity but little or no change in flow greater after standard barley than after en- at 75% vital capacity. In three subjects, riched barley consumption. The area under there was a drop in specific conductance the curve for H2 was greater after enriched HORDEUM VULGARE 249 barley intake. There was no difference in intubation to rats at a dose of 500 mg/kg, HV171 CO2 production . Hull fiber extract, in was inactive vs pylorus ligation-induced Caco-2 cell culture, produced no effect on ulcersHV116. the rate of transepithelial 45Ca transport Periodontal effect. Fiber, administered to across Caco-2 cell monolayers and the male Alpk:APfSD rats for 107 weeks with uptake of 45Ca into Caco-2 cellsHV182. A low- sacrifices at 26, 53, and 77 weeks, produced phytate barley-fiber concentrate was admin- oronasal fistulation and severe periodon- istered to young women at a dose of 15 g titisHV156. barley fiber (high-fiber, high-protein diet) Phosphogluconate dehydrogenase inhi- and 15 g barley fiber (high-fiber, low-pro- bition. Petroleum ether extract of the fresh tein diet). The mean daily intake of the cat- fruit, administered to pigs at a concentra- ions was 25.4 and 22.9 mmol Ca, 10.1 and tion of 3.5 g/kg of diet for 29 days, was active 10 mmol Mg, 166.8 and 119.3 Pmol Zn, and on hepatic enzymesHV092. 186.2 and 154 Pmol Fe, respectively. Mean Protein synthesis inhibition. Chromato- balances were 1.9 and –0.8 mmol Ca, –0.2 graphic fraction of the dried seed, in cell and –0.5 mmol Mg, –4.6, and –18.4 Pmol culture, was active on reticulocyte lysate of

Zn, respectively. The mean apparent iron rabbits, inhibitory concentration50 15.25 ng/ absorption was 5.4 and –23.2 PmolHV203. mLHV084. Monocytic differentiation. Prodelphini- Proteinemic effect. Methanol extract of din B-3, T1, T2, and T3 from bran polyphe- the dried fruit, administered by gastric intu- nol extract, in HL60 human myeloid bation to rabbits at a dose of 500 mg/kg, pro- leukemia cell culture, induced 26–40% duced an increase in serum albumin and nitro blue tetrazolium positive cells and 22– protein content vs CCl4-induced hepato- 32% D-naphthyl-butyrate esterase-positive toxicity. A mixture of Machilus sp., Alisma cells. Proanthocyanidins potentiated all- sp., Amomum xanthioides, Bulboschoenus trans-retinoic acid-induced granulocytic maritimus, Artemisia iwaymogis, Atractylodes and sodium butyrate-induced monocytic japonica, Crataegus cuneata, Hordeum vul- differentiation in HL60 cellsHV188. gare, Citrus sinensis, Polyporus umbellatus, Mutagenic activity. Ethanol (70%) extract Agastache rugosa, Raphanus sativus, Poncirus of the dried seed, on agar plate at a con- trifoliatus, Curcuma zeodaria, Citrus auran- centration of 50 mg/mL, was inactive on tium, Saussurea lappa, Glycyrrhiza glabra, and Escherichia coli PQ 37. The water and chlo- Zingiber officinale was used. Results were sig- roform extracts of the ethanol (70%) ex- nificant at p< 0.01 levelHV112. tract were inactive. Metabolic activation Respiratory effect. Barley ear inhaled by a had no effect on the resultsHV096. 2.5-year-old child produced fever, dyspnea, Oxidative effect. Ethanol (95%) extract of right paracardiac infiltrate with pleural re- the dried entire plant, administered in action on X-rays, and normal bronchoscopy drinking water to C57BL/6J obese mice at a after 8 days. On day 11, extensive right concentration of 5%, increased glucose oxi- pneumothorax, and on day 20, right axillary dation in epididymal fat pads. Extract of inflammatory lesion were observed. On day mixture of following plants: Hordeum 28, the ear of barley was expulsed and there vulgare, Rhizoma zingiberis, Ligustrum was complete recoveryHV207. Barley spike, in- chuanxiong, Lilium brownii, Nephelium longa, haled into the tracheobronchial tree of 18 and Polygonum multiflorum was usedHV070. children under the age of 5 years, produced Pepsin inhibition. Water extract of the coughing and choking in 14 of the children. green leaf juice, administered by gastric The spikes were removed by laryngoscopy 250 MEDICINAL PLANTS OF THE WORLD in 12 patients and by rigid bronchoscopy Toxicity assessment. Ethanol (50%) ex- in two. Four patients with history of cough, tract of the seed, administered intraperito- dyspnea, fever, and serious respiratory dis- neally to mice, produced a maximum eases, such as pneumothorax, lobar pneu- tolerated dose of 1 g/kgHV001. Hexane extract monia, and pleural empyema, required of the green leaf juice, administered in ra- surgical intervention. All of the children tion of rats, produced lethal dose50 greater made satisfactory recoveriesHV189. Dust ex- than 10 g/kgHV117. tract of barley, in cell culture on nonsensi- Tyrosinase inhibition. Methanol (80%) tized guinea pig tracheal smooth muscle extract of the dried seedling, in cell culture pretreated with drugs, produced constrictor at a concentration of 100 Pg/mL, was effect that was significantly inhibited by inactiveHV038. atropine indicating an interaction of the Urease inhibition. Water extract of the extracts with parasympathetic nerves. Inhi- seed, in cell culture at a concentration of bition of contraction of other mediators was 0.3 mg/mL, was inactiveHV076. less effective and varied with the dust Weight gain inhibition. Ethanol (95%) ex- extractHV208. tract of the dried entire plant, administered Toxic effect. E-glucan-enriched soluble in drinking water to C57BL/6J obese mice barley fiber, administered orally to Wistar at a concentration of 5%, was active. The rats at concentrations of 0.7, 3.5, and 7.0% extract also contained Rhizoma zingiberis, E-glucan for 28 days, increased the number Ligustrum chuangxiong, Lilium brownii, of circulating lymphocytes in males. The Nephelium longa, and Polygonum multiflo- increase was not dose-dependent and was rumHV070. not observed in females. A dose-dependent increase in full and empty cecum weight was REFERENCES observed. There were no adverse effects on HV001 Dhar, M. L., M. M. Dhar, B. N. general condition and behavior, growth, Dhawan, B. N. Mehrotha, and C. Ray. Screening of Indian plants for biologi- feed and water consumption, feed conver- cal activity. Part I. Indian J Exp Biol sion efficiency, red blood cell and clotting 1968; 6: 232–247. potential parameters, clinical chemistry HV002 Stoessl, A. The antifungal factors in values, and organ weight. Necropsy and barley—3. Isolation of P-coumaroy- histopathology findings revealed no treat- lagmatine. 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HV115 Sahu, T. R., Less known uses of weeds HV124 Chetal, S., D. S. Wagle, and H. S. as medicinal plants. Ancient Sci Life Nainawatee. Phosphatidylethanola- 1984; 3(4): 245–249. mine in wheat and barley leaves under HV116 Ohtake, H., H. Yuasa, C. Komura, T. water stress. Phytochemistry 1982; Miyauchi, Y. Hagiwara, and K. Kubota. 21(6): 1432–1433. Studies on the constituents of green HV125 Ariffin, A., P. H. Mc Neil, R. J. Cooke, juice from young barley leaves. Antiul- C. Wood, and D. R. Thomas. Car- cer activity of fractions from barley nitine content of greening barley juice. Yakugaku Zasshi 1985; 105(11): leaves. Phytochemistry 1982; 21(6): 1046–1051. 1431–1432. HV116 Woo, W. S., E. B. Lee, K. H. Shin, S. HV126 Lee, E. B., H. S. Yun, and W. S. Woo. S. Kang, and H. J. Chi. A review of Plants and animals used for fertility research on plants for fertility regula- regulation in Korea. Korean J Pharma- tion in Korea. Korean J Pharmacog cog 1977; 8: 81–87. 1981; 12(3): 153–170. HV127 Hunte, P., M. Safi, A. Macey, and G. HV117 Ohtake, H., S. Nonaka, Y. Sawada, Y. B. Kerr. Indigenous methods of volun- Hagiwara, H. Hagiwara, and K. Kubo- tary fertility regulation in Afghanistan. ta. Studies on the constituents of green Natl Demographic Family Guidance juice from young barley leaves. Effect Survey of Settled Population Afghan- on dietary induced hypercholester- istan 1975; 4: 1. olemia in rats. Yakugaku Zasshi 1985; HV128 Kapoor, P. D., and A. K. Pal. Estro- 105(11): 1052–1057. genic activity of pasture plants used as HV118 Evans, L. S., and W. A. Tramontano. cattle feed. Indian J Exp Biol 1965; 3: Trigonelline and promotion of cell 61–63. arrest in G2 of various legumes. Phy- HV129 Peake, I. R., P. J. Dunphy, and J. F. tochemistry 1984; 23(9): 1837–1840. Pennock. The chemical diversity of HV119 Matsuoka, Y., H. Seki, K. Kubota, H. the plastochromanols. Phytochemis- Ohtake, and Y. Hagiwara. Anti-in- try 1970; 9: 1345. flammatory effect of glycoprotein, D 1- HV130 El-Dean Mahmoud, A. A. G. Study of G1, isolated from barley leaves. Ensho indigenous (folk ways) birth control 1983; 3(4): 602–604. methods in Alexandria. Thesis-MS- HV120 Caceres, A., L. M. Giron, and A. M. University of Alexandria-Higher Martinez. Diuretic activity of plants Institute of Nursing 1972. used for the treatment of urinary ail- HV131 Celayeta, F. D. Action of the tissues of ments in Guatemala. J Ethnopharma- various plants on the growth of Spha- col 1987; 19(3): 233–245. celia segetum. Farmacognosia (Madrid) HV121 Ramiez, V. R., L. J. Mostacero, A. E. 1960; 20: 91–101. Garcia, et al. Vegetales empleados en HV132 Datko, A. H., S. H. Mudd, and J. medicina traditional Norperuana. Giovaneli. A sensitive and specific as- Banco Agrario Del Peru & NACL say for cystathione: cystathione con- Univ Trujillo, Trujillo, Peru, June, tent of several plant tissues. Ann 1988; 54 pp. Biochem 1974; 62(2): 531–545. HV122 Caceres, A., L. M. Giron, S. R. HV133 Kawai, S., Y. Sato, S. I. Takagi, and K. Alvarado, and M. F. Torres. Screen- Nomoto. Separation and determination ing of antimicrobial activity of plants of mugineic acid and its analogues by popularly used in Guatemala for the high-performance liquid chromatogra- treatment of dermatomucosal dis- phy. J Chromatogr 1987; 391: 325–327. eases. J Ethnopharmacol 1987; 20(3): HV134 Dongowski G, M. Huth, and E. 223–237. Gebhardt. Steroids in the intestinal HV123 Leporatti, M. L., and A. Pavesi. New tract of rats are affected by dietary- or uncommon uses of several medici- fibre-rich barley-based diets. Br J Nutr nal plants in some areas of central 2003; 90(5): 895–906. Italy. J Ethnopharmacol 1990; 29(2): HV135 Li J., T. Kaneko, L. Q. Qin, J. Wang, 213–223. Y. Wang, and A. Sato. Long-term HORDEUM VULGARE 257

effects of high dietary fiber intake on Effects of germinated barley foodstuff glucose tolerance and lipid metabolism on microflora and short chain fatty in GK rats: comparison among barley, acid production in dextran sulfate so- rice, and cornstarch. Metabolism dium-induced colitis in rats. Biosci 2003; 52(9): 1206–1210. Biotechnol Biochem 2000; 64(9): HV136 Li J., T. Kaneko, Y. Wang, L. Q. Qin, 1794–1800. and A. Sato. Effects of dietary fiber on HV145 Kanauchi O., A. Andoh, T. Iwanaga, the glucose tolerance in spontaneously et al. Germinated barley foodstuffs at- diabetic rats–comparison among bar- tenuate colonic mucosal damage and ley, rice, and corn starch. Nippon mucosal nuclear factor kappa B activ- Eiseigaku Zasshi 2003; 58(2): 281–286. ity in a spontaneous colitis model. J HV137 Delaney B., T. Carlson, S. Frazer, et al. Gastroenterol Hepatol 1999; 14(12): Evaluation of the toxicity of concen- 1173–1179. trated barley beta-glucan in a 28-day HV146 Kanauchi O., T. Iwanaga, K. Mitsu- feeding study in Wistar rats. Food yama, et al. Butyrate from bacterial Chem Toxicol 2003; 41(4): 477–487. fermentation of germinated barley HV138 Dongowski G., M. Huth, E. Gebhardt, foodstuff preserves intestinal barrier and W. Flamme. Dietary fiber-rich bar- function in experimental colitis in the ley products beneficially affect the rat model. J Gastroenterol Hepatol intestinal tract of rats. J Nutr 2002; 1999;14(9): 880–888. 132(12): 3704–3714. HV147 Kanauchi O., K. Mitsuyama, T. Saiki, HV139 Fukuda M., O. Kanauchi, Y. Araki, et K. Agata, T. Nakamura, and T. Iwa- al. Prebiotic treatment of experimen- naga. Preventive effects of germinated tal colitis with germinated barley food- barley foodstuff on methotrexate-in- stuff: a comparison with probiotic or duced enteritis in rats. Int J Mol Med antibiotic treatment. Int J Mol Med 1998;1(6): 961–966. 2002; 9(1): 65–70. HV148 Kanauchi O., Y. Hitomi, K. Agata, T. HV140 Kanauchi O., T. Iwanaga, A. Andoh, Nakamura, and T. Fushiki. Germi- et al. Dietary fiber fraction of germi- nated barley foodstuff improves consti- nated barley foodstuff attenuated mu- pation induced by loperamide in rats. cosal damage and diarrhea, and Biosci Biotechnol Biochem 1998; accelerated the repair of the colonic 62(9): 1788–1790. mucosa in an experimental colitis. J HV149 Kanauchi O., K. Mitsuyama, T. Saiki, Gastroenteol Hepatol 2001; 16(2): K. Agata, T. Nakamura, and T. Iwa- 160–168. naga. Effects of germinated barley HV141 Kanauchi O, T. Iwanaga, and K. foodstuff on dextran sulfate sodium- Mitsuyama. Germinated barley food- induced colitis in rats. J Gastroenterol stuff feeding. A novel neutraceutical 1998; 33(2): 179–188. therapeutic strategy for ulcerative coli- HV150 Kanauchi O., T. Nakamura, K. Agata, tis. Digestion 2001; 63 Suppl 1: 60–67. T. Fushiki, and H. Hara. Effects of HV142 Kanauchi O., Y. Araki, A. Andoh, et germinated barley foodstuff in prevent- al. Effect of germinated barley foodstuff ing diarrhea and forming normal feces administration on mineral utilization in ceco-colectomized rats. Biosci Bio- in rodents. J Gastroenterol 2000; technol Biochem 1998; 62(2): 366–368. 35(3): 188–194. HV151 Kanauchi O., T. Nakamura, K. Agata, HV143 Araki Y., Y. Fujiyama, A. Andoh, S. and T. Fushiki. Preventive effect of Koyama, O. Kanauchi, and T. Bamba. germinated barley foodstuff on diar- The dietary combination of germi- rhea induced by water-soluble dietary nated barley foodstuff plus Clostridium fiber in rats. Biosci Biotechnol butyricum suppresses the dextran sul- Biochem 1997; 61(3): 449–354. fate sodium-induced experimental HV152 Kanauchi O., T. K. Agata, and T. colitis in rats. Scand J Gastroenterol Fushiki. Mechanism for the increased 2000;35(10): 1060–1067. defecation and jejunum mucosal HV144 Araki Y., A. Andoh, S. Koyama, Y. protein content in rats by feeding Fujiyama, O. Kanauchi, and T. Bamba. germinated barley foodstuff. Biosci 258 MEDICINAL PLANTS OF THE WORLD

Biotechnol Biochem 1997; 61(3): lant, has the potential to counteract 443–448. inhibitory regulation by TGF-beta1. HV153 McIntosh G. H., R. K. Le Leu, P. J. Exp Dermatol 2002;11(6): 532–541. Royle, and G. P. Young. A compara- HV163 Jeong H. J., Y. Lam, and B. O. de tive study of the influence of differing Lumen. Barley lunasin suppresses ras- barley brans on DMH-induced intesti- induced colony formation and inhibits nal tumours in male Sprague-Dawley core histone acetylation in mammalian rats. J Gastroenterol Hepatol 1996; cells. J Agric Food Chem 2002; 11(2): 113–119. 50(21): 5903–5908. HV154 Oda T, S. Aoe, S. Imanishi, Y. Kana- HV164 Astwood J.D., and R. D. Hill. Molecu- zawa, H. Sanada and Y. Ayano. Effects lar characterization of Hor v 9. Con- of dietary oat, barley, and guar gums on servation of a T-cell epitope among serum and liver lipid concentrations in group IX pollen allergens and human diet-induced hypertriglyceridemic rats. VCAM and CD2. Adv Exp Med Biol J Nutr Sci Vitaminol (Tokyo) 1994; 1996; 409: 269–277. 40(2): 213–217. HV165 Vainio E., and E. Varjonen. Antibody HV155 McIntosh G. H., L. Jorgensen, and P. response against wheat, rye, barley, oats Royle. The potential of an insoluble and corn: comparison between gluten- dietary fiber-rich source from barley to sensitive patients and monoclonal protect from DMH-induced intestinal antigliadin antibodies. Int Arch Al- tumors in rats. Nutr Cancer 1993; lergy Immunol 1995; 106(2): 134–138. 19(2): 213–221. HV166 Delaney B., T. Carlson, G. H. Zheng, HV156 Robinson M., D. Hart, and G. H. et al. Repeated dose oral toxicological Pigott.The effects of diet on the inci- evaluation of concentrated barley dence of periodontitis in rats. Lab beta-glucan in CD-1 mice including a Anim 1991; 25(3): 247–253. recovery phase. Food Chem Toxicol HV157 Naismith D. J., G. S. Mahdi, and N. 2003 ; 41(8): 1089–1102. N. Shakir. Therapeutic value of barley HV167 Fredlund K., E. L. Bergman, L. in the management of diabetes. Ann Rossander-Hulthen, M. Isaksson, A. Nutr Metab 1991; 35(2): 61–64. Almgren, and A. S. Sandberg. Hydro- HV158 Qureshi A. A., W. C. Burger, D. M. thermal treatment and malting of bar- Peterson, and C. E. Elson. The struc- ley improved zinc absorption but not ture of an inhibitor of cholesterol bio- calcium absorption in humans. Eur J synthesis isolated from barley. J Biol Clin Nutr 2003; 57(12): 1507–1513. Chem 1986; 261(23): 10544–10550. HV168 Li J., T. Kaneko, L. Q. Qin, J. Wang, HV159 Donangelo C. M., and B. O. Eggum. and Y. Wang. Effects of barley intake Comparative effects of wheat bran and on glucose tolerance, lipid metabolism, barley husk on nutrient utilization in and bowel function in women. Nutri- rats. 2. Zinc, calcium and phosphorus. tion 2003; 19(11-12): 926–929. Br J Nutr 1986; 56(1): 269–280. HV169 Keogh G. F., G. J. Cooper, T. B. HV160 Puls R., and J. A. Greenway. Fusario- Mulvey, et al. Randomized controlled toxicosis from barley in British Co- crossover study of the effect of a highly lumbia. II. Analysis and toxicity of beta-glucan-enriched barley on cardio- syspected barley. Can J Comp Med vascular disease risk factors in mildly 1976; 40(1): 16–19. hypercholesterolemic men. Am J Clin HV161 Kanauchi O., I. Serizawa, Y. Araki, et Nutr 2003; 78(4): 711–718. al. Germinated barley foodstuff, a pre- HV170 Kanauchi O., T. Suga, M. Tochihara, biotic product, ameliorates inflamma- et al. Treatment of ulcerative colitis by tion of colitis through modulation of feeding with germinated barley food- the enteric environment. J Gastro- stuff: first report of a multicenter open enterol 2003; 38(2): 134–141. control trial. J Gastroenterol 2002; 37 HV162 Kamimura A., and T. Takahashi. Suppl 14: 67–72. Procyanidin B-3, isolated from barley HV171 Lifschitz C. H., M. A. Grusak, and N. and identified as a hair-growth stimu- F. Butte. Carbohydrate digestion in HORDEUM VULGARE 259

humans from a beta-glucan-enriched barley gamma-3 hordein cross-react barley is reduced. J Nutr 2002; 132(9): with omega-5 gliadin, a major allergen 2593–2596. in wheat-dependent, exercise-induced HV172 Armentia A., R. Rodriguez, A. Callejo, anaphylaxis. Clin Exp Allergy 2001; et al. Allergy after ingestion or inhala- 31(3): 466–473. tion of cereals involves similar aller- HV181 Granfeldt Y., A. C. Eliasson, and L. gens in different ages. Clin Exp Bjorck. An examination of the possi- Allergy 2002; 32(8): 1216–1222. bility of lowering the glycemic index HV173 Suganuma H., T. Inakuma, and Y. of oat and barley flakes by minimal Kikuchi. Amelioratory effect of barley processing. J Nutr 2000; 130(9): tea drinking on blood fluidity. J Nutr 2207–2214. Sci Vitaminol (Tokyo) 2002; 48(2): HV182 Kennefick S., and K. D. Cashman. 165–168. Inhibitory effect of wheat fibre extract HV174 Bamba T., O. Kanauchi, A. Andoh, on calcium absorption in Caco-2 cells: and Y. Fujiyama. A new prebiotic from evidence for a role of associated germinated barley for nutraceutical phytate rather than fibre per se. Eur J treatment of ulcerative colitis. J Nutr 2000; 39(1): 12–17. Gastroenterol Hepatol 2002; 17(8): HV183 Bonadonna P., M. Crivellaro, A. 818–824. Dama, G. E. Senna, G. Mistrello, and HV175 Kaplan R.J., and C. E. Greenwood. In- G. Passalacqua. Beer-induced anaphy- fluence of dietary carbohydrates and laxis due to barley sensitization: two glycaemic response on subjective appe- case reports. J Invest Allerg Clin tite and food intake in healthy elderly Immunol 1999; 9(4): 268–270. persons. Int J Food Sci Nutr 2002; HV184 Curioni A., B. Santucci, A. Cristaudo, 53(4): 305–316. et al. Urticaria from beer: an immedi- HV176 Ostman E. M., H. G. Liljeberg ate hypersensitivity reaction due to a Elmstahl, and I. M. Bjorck. Barley 10-kDa protein derived from barley. bread containing lactic acid improves Clin Exp Allergy 1999; 29(3): 407– glucose tolerance at a subsequent meal 413. in healthy men and women. J Nutr HV185 Bourdon I., W. Yokoyama, P. Davis, et 2002; 132(6): 1173–1175. al. Postprandial lipid, glucose, insulin, HV177 Yu Y. M., W. C. Chang, C. T. Chang, and cholecystokinin responses in men C. L. Hsieh, and C. E. Tsai. Effects of fed barley pasta enriched with beta- young barley leaf extract and glucan. Am J Clin Nutr 1999; 69(1): antioxidative vitamins on LDL oxida- 55–63. tion and free radical scavenging activi- HV186 Kanauchi O., Y. Fujiyama, K. Mitsu- ties in type 2 diabetes. Diabetes Metab yama, et al. Increased growth of 2002; 28(2): 107–114. Bifidobacterium and Eubacterium by HV178 Cremer L., A. Herold, D. Avram, and germinated barley foodstuff, accompa- G. Szegli. A purified green barley ex- nied by enhanced butyrate production tract with modulatory properties upon in healthy volunteers. Int J Mol Med TNF alpha and ROS released by hu- 1999; 3(2): 175–179. man specialised cells isolated from RA HV187 Kanauchi O., K. Mitsuyama, T. Saiki, patients. Roum Arch Microbiol T. Fushikia, and T. Iwanaga. Germi- Immunol 1998; 57(3–4): 231–242. nated barley foodstuff increases fecal HV179 Garcia-Casado G., J. F. Crespo, J. volume and butyrate production in Rodriguez, and G. Salcedo. Isolation humans. Int J Mol Med 1998; 1(6): and characterization of barley lipid 937–941. transfer protein and protein Z as beer HV188 Tamagawa K., S. Fukushima, M. allergens. J Allergy Clin Immunol Kobori, H. Shinmoto, and T. Tsushida. 2001; 108(4): 647–649. Proanthocyanidins from barley bran HV180 Palosuo K., H. Alenius, E. Varjonen, potentiate retinoic acid-induced N. Kalkkinen, and T. Reunala. Rye granulocytic and sodium butyrate- gamma-70 and gamma-35 secalins and induced monocytic differentiation of 260 MEDICINAL PLANTS OF THE WORLD

HL60 cells. Biosci Biotechnol Bio- ucts: influence of food structure and chem 1998; 62(8): 1483-1487. amylose-amylopectin ratio. Am J Clin HV189 Ammari, F. F., K. T. Faris, and T. M. Nutr 1994; 59(5): 1075–1082. Mahafza. Inhalation of wild barley into HV199 Liljeberg H., and I. Bjorck. Bioavail- the airways: two different outcomes. ability of starch in bread products. Saudi Med J 2000; 21(5): 468–470. Postprandial glucose and insulin re- HV190 Robertson J. A., G. Majsak-Newman, sponses in healthy subjects and in vitro and S. G. Ring. Release of mixed link- resistant starch content. Eur J Clin age (1o3),(1o4) beta-D-glucans Nutr 1994; 48(3): 151–163. from barley by protease activity and HV200 Cockcroft A. E., M. McDermott, J. H. effects on ileal effluent. Int J Biol Edwards, and P. McCarthy. Grain Macromol 1997; 21(1–2): 57–60. exposure—symptoms and lung function. HV191 Lia A., B. Sundberg, P. Aman, A. S. Eur J Respir Dis 1983; 64(3): 189–196. Sandberg, G. Hallmans, and H HV201 Lupton J. R., J. L. Morin, and M. C. Andersson. Substrates available for co- Robinson. Barley bran flour accelerates lonic fermentation from oat, barley gastrointestinal transit time. JAm and wheat bread diets. A study in ileo- Diet Assoc 1993; 93(8): 881–885. stomy subjects. Br J Nutr 1996; 76(6): HV202 Thorburn A., J. Muir J, and J. Proietto. 797–808. Carbohydrate fermentation decreases HV192 Dahl S. W., S. K. Rasmussen, L. C. hepatic glucose output in healthy Petersen, and J. Hejgaard. Inhibition subjects. Metabolism 1993; 42(6): of coagulation factors by recombinant 780–785. barley serpin BSZx. FEBS Lett 1996; HV203 Wisker E, R. Nagel, T. K. Tanudjaja, 394(2): 165–168. and W. Feldheim. Calcium, magne- HV193 Ikegami S., M. Tomita, S. Honda, et sium, zinc, and iron balances in young al. Effect of boiled barley-rice-feeding women: effects of a low-phytate barley- in hypercholesterolemic and normoli- fiber concentrate. Am J Clin Nutr pemic subjects. Plant Foods Hum 1991; 54(3): 553–559. Nutr 1996; 49(4): 317–328. HV204 McIntosh G. H., J. Whyte, R. HV194 Lia A., G. Hallmans, A. S. Sandberg, McArthur, and P. J. Nestel. Barley and B. Sundberg, P. Aman, and H. Anders- wheat foods: influence on plasma cho- son. Oat beta-glucan increases bile lesterol concentrations in hypercholes- acid excretion and a fiber-rich barley terolemic men. Am J Clin Nutr 1991; fraction increases cholesterol excre- 53(5): 1205–1209. tion in ileostomy subjects. Am J Clin HV205 Arenaz P., and L. Hallberg. Nutr 1995; 62(6): 1245–1251. Genotoxicity of azidoalanine in mam- HV195 Vidal C., and A. Gonzalez-Quintela. malian cells. Environ Mol Mutagen Food-induced and occupational asth- 1989; 13(3): 263–270. ma due to barley flour. Ann Allergy HV206 De Vries J. J., T. Collin, C. M. Asthma Immunol 1995; 75(2): 121–124. Bijleveld, J. H. Kleibeuker, and R. J. HV196 Livesey G., J. A. Wilkinson, M. Roe, Vonk. The use of complex carbohy- et al. Influence of the physical form of drates in barley groats for determina- barley grain on the digestion of its tion of the mouth-to-caecum transit starch in the human small intestine time. Scand J Gastroenterol 1988; and implications for health. Am J Clin 23(8): 905–912. Nutr 1995; 61(1): 75–81. HV207 Paillard S., P. Cochat, and L. David. A HV197 Yap J.C., C. C. Chan, Y. T. Wang, S. migrating ear of barley: a curious story C. Poh, H. S. Lee, and K. T. Tan. A of an intrabronchial foreign body. case of occupational asthma due to bar- Pediatrie 1987; 42(6): 447–449. ley grain dust. Ann Acad Med HV208 Zuskin E., J. Mustajbegovic, and V. Singapore 1994; 23(5): 734–736 Sitar-Srebocan. Pharmacologic study HV198 Granfeldt Y., H. Liljeberg, A. Drews, of the effects of the components of beer R. Newman, and I. Bjorck. Glucose in vitro. Lijec Vjesn 1997; 119(3-4): and insulin responses to barley prod- 103–105. HORDEUM VULGARE 261

HV209 McCarthy P. E., A. E. Cockcroft, and Zheng, R. Hess, K. Ostergren, J. M. McDermott. Lung function after Haworth and N. Knutson. Beta-glucan exposure to barley dust. Br J Ind Med franctions from barley and oats are 1985; 42(2): 106–110. similarly antiatherogenic in hypercho- HV210 Delaney, B., R. J. Nicolosi, T. A. Wil- lesterolemic Syrian golden hamsters. J son, T. Carlson, S. Frazer, G. H. Nutr 2003; 133(2): 468–475. LARREA TRIDENTATA 263

8 Larrea tridentata (D. C.) Cov.

Common Names Black bush United States Gobernadora United States Chaparral England Grease bush United States Chaparral United States Greasewood United States Creosote bush England Guamis Spain Creosote bush United States Hediondilla Spain Creosotum United States Jarilla Spain Dwarf Evergreen Oak United States Kreosotestrauch Germany Gobernadora England Paloondo Spain Gobernadora Spain

BOTANICAL DESCRIPTION some of leaves during extreme drought. Yel- low flowers are solitary and axillary, numer- Larrea tridentata is a member of the caltrop ous, up to 2 cm wide, mostly bloom from family ZYGOPHYLLACEAE. It is a native, February to August, some individuals main- drought-tolerant, evergreen shrub slowly tain flowers year-round. Fruits are small, growing to 2–4 m tall and 1.8 m wide, with reddish-white, globose, consisting of five numerous flexible stems projecting at an united, indehiscent, one-seeded carpels that angle from its base. The bush is a group of may or may not break apart after maturing. four to 12 plants that shoot up from one Each carpel is densely covered by long, gray plant in all directions. The root system con- or white trichomes. sists of a shallow taproot and several lateral secondary roots, each approx 3 m in length ORIGIN AND DISTRIBUTION and 20–35 cm deep. The taproot extends to Larrea tridentata occurs throughout the Mo- a depth of approx 80 cm. The leaves are jave, Sonoran, and Chihuahuan Deserts. Its thick, waxy, resinous, 12–25 mm long, al- distribution extends from southern Califor- ternate leaves with two leaflets, pointed, nia northeast through southern Nevada to yellow-green in color, covered with a var- the southwest corner of Utah and southeast nish; darker and aromatic after rainfall. through southern Arizona and New Mexico These leaves grow directly from the to western Texas and north-central Mexico. branches of the bush. The bush may lose It is known to attain ages of several thou-

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 263 264 MEDICINAL PLANTS OF THE WORLD sand years; some clones may be the earth’s (+)-3,3'-Didemethoxyverucosin: PlLT048 oldest living organisms. The age of the larg- Acetophenone: EOLT027 Agarofuran, D: EOLT027 est clone in Johnson Valley, California, is LT027 estimated at 9400 years; one estimated the Anisic acid methyl ester, ortho: EO Ayanin: LfLT027 average longevity to be 1250 years at a study Benzaldehyde: EOLT027 site in Dateland, CA, and 625 years at a San Benzoic acid ethyl ester: EOLT027 Luis site. Larrea tridentata commonly grows Benzoic acid hex-3-enyl ester: EOLT027 on gentle well-drained slopes, plains, valley Benzoic acid N-hexyl ester: EOLT027 floors, and sand dunes and in arroyos at el- Benzyl acetate: EOLT027 evations up to 1515 m and occurs on calcar- Bergamotene, D: EOLT027 LT027 eous, sandy, and alluvial soils with a layer of Borneol acetate: EO Borneol: EOLT027 caliche. It can survive without any added Butan-1-al, 3-methyl: EOLT027 water. Often the most abundant shrub, even Butanoic acid benzyl ester: EOLT027 forming pure stands. Butanoic acid, 2-methyl: EOLT027 LT027 TRADITIONAL MEDICINAL USES Butyric acid, iso: EO Calamenene: EOLT027 Mexico. Decoction of the bark and dried Camphene: EOLT027 branches is taken orally as an abortive and Camphor: EOLT027 for diabetes. Decoction of the dried root is Car-3-ene: EOLT027 taken orally by pregnant humans as an abor- Chrysoeriol-6-8-di-C-E-D-glucoside: LfLT023 tive and for diabetesLT034. Infusion of the Cineol 1-8: EOLT027 shade-dried entire plant is taken orally to Cinnamic acid ethyl ester, hydro: EOLT027 LT027 treat infectious diseasesLT011. Decoction of Copanene: EO Curcumene, : EOLT027 the dried leaf is taken orally for treatment of D Cymene, para: EOLT027 diabetes. Hot water extract of the dried leaf Edulane: EOLT027 is taken orally as a blood purifier; to treat Erythrodiol, 3-E-(3-4-dihydroxy-cinnamoyl): kidney problems, urinary tract infections, St 0.073–8LT035, LT028 and frigidity; for gallstones, rheumatism and Eudesmol, E: EOLT027 arthritis, diabetes, wounds, and skin inju- Eudesmol, J: EOLT027 LT027 ries, displacement of the womb, and paraly- Farnesol: EO LT027 sis; and to dissolve tumorsLT032. Fenchene, D: EO Furan, tetrahydro, 3-4-dimethyl: EOLT027 United States. Hot water extract of the Gossypetin, 3-3'-7-tri-O-methyl: LfJ05600 dried leaf is taken orally as a stimulating ex- Gossypetin, 3-7-di-O-methyl: LfLT008 pectorant and tonic, for tuberculosis, and is Gossypetin-3-3'-7-8-tetramethyl ether: LfLT030 drank by Indians of the Southwest for bowel Guaiacin, didehydro, 3'-3'-demethoxy-6-O- cramps, as a diuretic, and for venereal dis- demethyl: Lf/Tw 2.8LT005 ease. Hot water extract of the dried leaf is Guaiacin, iso, nor, 3'-demethoxy, triacetate: LT025 LT038 Lf/Tw used externally for wound healing . Hot LT031 water extract of the dried plant is taken Guaiacin, iso, nor, 3'-demethoxy: Pl , Lf/ Tw 53, St 1.49LT035 orally for cancer. Effects described are from Guaiacin, iso, nor: St 1.4LT035 LT029 multicomponent reaction . Guaiacin, iso: 3'-6-di-O-demethyl: Lf/Tw LT005 CHEMICAL CONSTITUENTS 32.6 Guaiacin, iso: 3'-demethoxy-6-O-demethyl: St (ppm unless otherwise indicated) LT006 LT005 LT048 0.2 , Lf/Tw 3.5 (–)-3,3'-Didemethoxyverucosin: Pl Guaiacin, iso: St 0.2LT006 (–)-8'-Epi-larreatricin: Pl LT048 LT048 Guaiaretic acid, nor-dihydro, 3'-O-methyl: (–)-Larreatricin: Pl PlLT018, LfLT007 LARREA TRIDENTATA 265

Guaiaretic acid, nor-dihydro, 4-O-methyl: Pentadecanoic acid ethyl ester: EOLT027 LfLT012 Pinene, D: EOLT027 Guaiaretic acid, nor-dihydro: Lf/TwLT003, Pinene, E: EOLT027 LfLT012, PlJ15279, Lf & StLT038, Pyran-5-ol, tetrahydro, 2-6-6-trimethyl-2- OleoresinLT024, Aer 0.696%LT049, St vinyl, cis: EOLT027 26.9LT035 Rossal-2-ene: EOLT027 Guaiazulene: EOLT027 Rossalene, 2: EOLT027 Hept-1-en3-one: EOLT027 Santalene, E: EOLT027 Heptan-2-one: EOLT027 Sitosterol, E: St 2-3.5LT028,LT035 Herbacetin, 3-7-di-O-methyl: LfLT009 Sucrose: Lf/TwLT003, Lf & StLT038 Herbacetin-3-7-8-trimethyl ether: LfLT030 Terpineol, D: EOLT027 Hex-1-en-3-one: EOLT027 Tetradecan-2-one: EOLT027 Hex-3-enyl acetate: EOLT027 Tetradecane, N: EOLT027 Hexan-1-al: EOLT027 Tricosane, N: EOLT027 Hexan-3-ol: EOLT027 Tridecan-2-one: EOLT027 Hexan-3-one: EOLT027 Tridecane, N: EOLT027 Larrea divaricata flavonoid: Lf, StLT038 Undecan-2-one: EOLT027 Larrea divaricata sterol (MP126-128): Lf, Vicenin 2: Lf LT023 StLT038 Larrea lignan 1-B: LfLT007 PHARMACOLOGICAL ACTIVITIES Larrea lignan 1-C: LfLT007 AND CLINICAL TRIALS Larrea lignan 1-D: LfLT007 Alkaline phosphatase stimulation. Ex- Larrea lignan 1-E: LfLT007 tract of the leaf, administered orally to Larrea lignan 1-F: LfLT007 adults, was active. Patients with subacute LT007 Larrea lignan 1-H: Lf hepatic necrosis had negative workup, Larrea lignan 1-I: LfLT007 LT007 except for consumption of 15 tablets of the Larrea lignan 2-D: Lf LT017 Larreantin: RtLT033 herbal extract per day for 4 months . Larreatricin, 3-3'’-dimethoxy: St 1.9LT006 Anthelmintic activity. Water and petro- Larreatricin, 3-4-dehydro: St 0.087– leum ether extracts of the dried oleoresin 1.2LT035,LT006 were active on Eimeria tenella in chickenLT024. Larreatricin, 4-epi, 3''-hydroxy: Lf & Tw Anti-amoebic activity. The resin of Larrea 7.4LT006 produced inhibitory activity at a concentra- Larreatricin, 4-epi: St, Lf & Tw 3LT006 tion of 1 ppm on Entamoeba invadens PZ Larreatricin: St 9.6LT006 LT035,LT006 axenic cultures. The nordihydroguaiaretic Larreatridenticin: St 0.8 –6 –8 LT027 acid activity was observed at 10 to 10 Limonene: EO LT047 Linalool, cis, oxide: EOLT027 concentrations . Linalool, trans, oxide: EOLT027 Antibacterial activity. Methylene chloride Linalool: EOLT027 extract of the dried aerial parts of the plants, Meso-3,3'-didemethoxynectandrin B: PlLT048 on agar plate at a concentration of 1 g/mL, Muurolene, D: EOLT027 was active on Bacillus subtilisLT016. Methanol Myrcene: EOLT027 extract of the shade-dried plant, on agar Naphthalene, 1-2-dihydro, 1-5-5-trimethyl: plate at a concentration of 0.6 mg/mL, was EOLT027 LT027 inactive on Staphylococcus aureus. A con- Naphthalene, methyl: EO centration of 10 mg/mL was inactive on Nonan-2-one: EOLT027 Nordihydroguaiaretic acid: Lf, TwLT040 Escherichia coli and Pseudomonas aureugi- LT011 Ocimene, E: EOLT027 nosa . Oct-1-en-3-one: EOLT027 Antidiabetic activity. Masoprocol, a com- Palmitic acid ethyl ester: EOLT027 pound derived from Larrea, administered Pentadecan-2-one: EOLT027 orally to streptozotocin-induced diabetic 266 MEDICINAL PLANTS OF THE WORLD rats at a dose of 0.83 mmol/kg body weight masoprocol decreased serum triglyceride twice daily for 4 days, lowered glucose without an apparent reduction in hepatic concentrations an average of 35% com- triglyceride secretion. The adipose tissue pared with vehicle (14.2 r 1.1 vs 21.7 r hormone-sensitive lipase was decreased, 1.0 mmol/L, p < 0.001). The animals were while adipose tissue lipoprotein lipase activ- fed a 20% fat diet for 2 weeks before iv in- ity was increased in masoprocol-treated jection with streptozotocin (STZ, 0.19 ratsLT044. mmol/kg). Diabetic animals (glucose 16–33 Anti-implantation effect. Chloroform ex- mmol/L) were treated with vehicle, metformin tracts of the dried leaf, twig, and stem, ad- (0.83 mmol/kg), or masoprocol. Masoprocol ministered intragastrically to pregnant rats decreased triglyceride level 80% compared at a dose of 0.58 g/kg for 10 days, were ac- with vehicle; nonesterified fatty acids and tive. The phenolic fraction, at a dose of 0.52 glycerol concentration by approx 65%, in g/kg and methanol extract at a dose of 0.70 comparison to vehicle. Adipocytes isolated g/kg, were active. Water extract, at a dose from normal animals, treated with of 1 g/kg and petroleum ether extract at a masoprocol (30 Pmol/L) had higher basal dose of 0.38 g/kg, were inactiveLT035. and insulin-stimulated glucose clearance Anti-tumor activity. Water extract of the than adipocytes treated with vehicle (p < dried root, administered intraperitoneally to 0.05)LT045. Oral administration of masopro- mice at a dose of 400 mg/kg, was inactive on col to two mouse models for type 2 diabetes Leuk (friend virus-solid) and Leuk-L1210. reduced plasma glucose concentration A dose of 500 mg/kg was inactive on sar- approx 8 mmol/L in male C57BL/ks-db/db coma 180(ASC)LT036. or C57BL/6J-ob/ob mice. The decline in Antiviral activity. Chloroform/methanol plasma glucose concentration after maso- extract (1:1) of the dried leaf, in cell cul- procol treatment in the mice was achieved ture, was active on HIV-1 virus. TAT without any change in plasma insulin con- transactivation was inhibitedLT007. Ethanol centration. Oral glucose tolerance im- acetate soluble fraction of the dried leaf, in proved, and the ability of insulin to lower cell culture at a concentration of 0.75 Pg/ plasma glucose concentrations was accentu- mL, was active on HIV virus vs HIV cyto- ated in masoprocol-treated db/db miceLT013. pathic effectLT022. Antifungal activity. Ethanol and methanol Anti-yeast activity. Methanol extract of (41.5–100%) extracts prepared from 6 g of the shade-dried plant, on agar plate at a con- dried leaf and stem powders were active on centration of 1.25 mg/mL, was inactive on Aspergillus flavus, Aspergillus niger, Penicil- Candida albicansLT011. lium chrysogenum, Penicillium expansum, Cytotoxic activity. Water extract of the Fusarium poae, and Fusarium moniliformeLT039. dried root, in cell culture, was inactive on LT036 Antihypertriglyceridemic activity. Maso- CA-9KB, ED50 greater than 0.1 Pg/mL . procol (nordihydroguaiaretic acid), admin- The methanol extract was active on Leuk- LT004 istered orally to rodent models of type 2 P388, ED50 0.57 Pg/mL . diabetes at a dose range of 10 to 80 mg/kg Detoxification activity. Phenolic resin, in twice daily for 4 to 8 days, decreased serum increasing levels, was mixed with alfalfa pel- glucose and triglyceride levels. Masoprocol, lets and fed to wood rats. Three detoxifica- at a dose of 40 or 80 mg/kg twice daily, sig- tion pathways and urine pH, which are nificantly reduced hepatic triglyceride se- related to detoxification of allelochemicals, cretion (p < 0.01) and liver triglyceride were measured. The excretion rate of two- content (p < 0.001), whereas lower doses of phase II detoxification conjugates, glucu- LARREA TRIDENTATA 267 ronides, and sulfides increased with increas- topical use was prescribed. None of the pa- ing resin intake, whereas excretion of hip- tients had history of liver disease. In all of puric acid was independent of resin intake. the cases, Larrea tridentata was given as ei- Urine pH declined with increasing resin in- ther part of a complex herbal formula indi- gestion. The results indicated that a wood vidualized for each patient containing less rat’s tolerance to resin intake is related to than 10% Larrea tridentata tincture or an the capacity for amination, sulfation, or pH extract in castor oil for topical use. The four regulationLT042. patients with complete before and after Gene expression inhibition. Chloroform/ blood chemistry panels and complete blood methanol extract (1:1) of the dried leaf, in counts had no indication of liver damage cell culture, was active on hepatoma-Cos-7, from use of Larrea tridentata. This included

IC50 600.0 Pg/mL vs TAT-dependent acti- one patient who was taking medications vation of HIV promoter bioassayLT022. with significant potential for hepatotoxic- Hepatotoxic activity. The leaf, taken ity. No patient showed any sign of organ orally by a female adult, was activeLT021. A damage during the follow-up periodLT043. patient consumed 15 tablets of the leaf per Nordihydroguaiaretic acid is a lignan found day for 4 months. Approximately 1 year af- in high amounts (up to 10% by dry weight) ter stopping consumption, liver enzymes re- in the leaves and twigs of Larrea tridentata. turned to normal and fatigue was no longer It has been shown to reduce cystic nephr- a complaintLT017. Infusion of the dried leaf, opathy in the rats, but no reports have been taken orally by a female adult at variable made concerning the hepatotoxic potential doses, was active. The 60-year-old woman of the compound. Larrea-containing medi- who took Larrea tridentata for 10 months cations induce hepatotoxicity and nephro- developed severe hepatitis for which no toxicity in humans. Intraperitoneal other cause could be found. Despite aggres- administration of nordihydroguaiaretic acid sive supportive therapy, the patient’s condi- produced LD50 75 mg/kg. Administration is tion deteriorated and required orthotropic associated with a time- and dose-dependent liver transplantationLT019. Dried leaves, ad- increase in serum alanine aminotrans- ministered orally to adults at variable doses, ferase levels, which suggest liver damage. were active. A public warning has been is- Freshly isolated mouse hepatocytes are sued by the US Centers for Disease Control more sensitive to nordihydroguaiaretic based on reports of liver toxicity after use of acid than human melanoma cells. Glucur- Larrea tridentata teaLT015. Dried leaves, ad- onidation was identified as a potential ministered orally to adults of both sexes at detoxification mechanism for nordihydro- variable doses, were activeLT010. The plant, guaiaretic acidLT040. administered orally to adults at variable Insecticide activity. Acetone extracts of doses, was activeLT020. Dried leaves, adminis- the dried leaf, dried root, and dried stem, at tered orally to adults at variable doses, were a low concentration, were inactive on Culex active. One case of hepatotoxicity induced quinquefasciatusLT002. Water extract of the by Larrea tridentata taken as a nutritional dried leaf, administered intravenously, supplement was reportedLT014. Thirteen pa- produced weak activity on Periplaneta ameri- tients were identified for whom Larrea canaLT037. tridentata tincture for internal use was pre- Pigmented cholelithiasis prophylaxis. scribed. Additionally, 20 female and three Powdered hydroalcoholic extract of the leaf male patients were identified from whom an was administered to Syrian golden hamster extract of Larrea tridentata in castor oil for (ChCM). The extract was added to the 268 MEDICINAL PLANTS OF THE WORLD lithogenic diet (basic diet plus 25 000 IU of REFERENCES vitamin A) at the 4% level for 70 days. The LT001 Bennett, E. L., and J. Nbonner. Isola- results indicated that the Larrea-fed group tion of plant growth inhibitors from did not develop pigment cholelithiasis, Thamnosma montana. Amer J Bot whereas the group that received the 1953; 40: 29. LT002 Hartzell, A., and F. Wilcoxon. A sur- lithogenic diet alone developed cholelithi- vey of plant products for insecticidal asis in 63% of the cases. It is suggested that properties. Contrib Boyce Thompson the active principle present in the leaves of Inst 1941; 12: 127–141. Larrea, are responsible for the prevention is LT003 Waller, C. W., and O. Gisvold. A phy- nordihydroguaiaretic acid, a potent antioxi- tochemical investigation of Larrea dant. However, the hamsters that received divaricata Cav. J Amer Pharm Ass 1945; 34: 78–81. the diet containing Larrea showed serious LT004 Luo, Z. Y., D. Meksuriyen, C. A. J. signs of toxicity and pathological changes, Erdelmeier, H. H. S. Fong, and G. A. such as marked reduction of growth, pro- Cordell. Larreantin, a novel, cytotoxic nounced irritability and aggressiveness, and naphthoquinone from Larrea triden- a marked hypoplasia of testicular and acces- tata. J Org Chem 1988; 53(10): 2183– sory sex glandsLT046. 2185. LT005 Konno, C., H. Z. Xue, Z. Z. Lu, et al. 1- Plant growth inhibitor. Water extract of ARYL tetralin lignans from Larrea the aerial parts, administered externally, tridentata. J Nat Prod 1989; 52(5): was toxic to tomato plant seedlingsLT001. 1113–1117. Prothrombin time increased. Extract of LT006 Konno, C., Z. Z. Lu, H. Z. Xue, et al. the leaf, administered orally to adults, was Furanoid lignans from Larrea triden- active. Patients with subacute hepatic ne- tata. J Nat Prod 1990; 53(2): 396–406. LT007 Gnabre, J., R. Chih, C. Huang, et al. crosis had negative workups, except for their Characterization of anti-HIV lignans consumption of 15 tablets of the herbal ex- from Larrea tridentata. Tetrahedron tract daily for 4 monthsLT017. 1995; 51(45): 12203–12210. Skin cancer chemoprevention. Topically LT008 Sakakibara, M., and T. J. Mabry. A applied nordihydroguaiaretic acid pre- new 8-hydroxyflavonol from Larrea vented phorbol ester promotion of tumors tridentata. Phytochemistry 1975; 14: 2097–2098. in mouse skin, indicating that nordihydro- LT009 Sakakibara, M., B. N. Timmermann, guaiaretic acid may be a candidate drug for N. Nakatani, H. Waldrum, and T. J. the chemoprevention of skin cancer. Mabry. New 8-hydroxyflavonol from Nordihydroguaiaretic acid, investigated as a Larrea tridentata. Phytochemistry potential inhibitory agent for ultraviolet-B 1975; 14: 849–851. (UVB)-induced signaling pathways in the LT010 Sheikh, N. M., R. M. Philen, and L. A. Love. Chaparral-associated hepatotox- human keratinocyte cell line HaCaT, sig- icity. Arch Inter Med 1997; 157(8): nificantly inhibited UVB-induced c-fos and 813–919. activator protein-1 transactivation. It also LT011 Navarro, V., M. L. Villarreal, G. Rojas, inhibited the activity of phosphatidylinosi- and X. Lozoy. Antimicrobial evalua- tol 3-kinase, a UVB-inducible enzyme that tion of some plants used in Mexican traditional medicine for the treatment contributes c-fos expression and activator of infectious diseases. J Ethnopharma- protein-1 transactivation by inhibiting the col 1996; 53(3): 143–147. phosphatidylinositol 3-kinase signaling LT012 Ma, Y., L. Qi, J. N. Gnabre, R. C. C. pathwayLT041. Huang, F. E. Chou, and Y. Ito. Purifi- LARREA TRIDENTATA 269

cation of anti-HIV lignans from Larrea LT023 Sakakibara, M., T. J. Mabry, M. L. tridentata by pH-zone-refining coun- Bouillant, and J. Chopin. 6,8-Di-C- tercurrent chromatography. J Liq glucosylflavones from Larrea tridentata Chromatogr 1998; 21(1/2): 171–181. (Zygophyllaceae). Phytochemistry LT013 Luo, J., T. Chuang, J. Cheung, et al. 1977; 16: 1113–1114. Masoprocol (nordihydroguaiaretic LT024 Zamora, J. M., and E. C. Mora. Cyto- acid): a new antihyperglycemic agent toxic, antimicrobial and phytochemi- isolated from the creosote bush (Larrea cal properties of Larrea tridentata tridentata). Eur J Pharmacol 1998; Cav. Diss Abstr Int B 1985; 45(12): 346(1): 77–79. 3809–3810. LT014 Clark, F., and D. R. Reed. Chaparral- LT025 Fronczek, F. R., P. Caballero, N. H. induced toxic hepatitis. California and Fischer, S. Fernandez, E. Hernandez, Texas, 1992. MMWR Morbid Mortal and L. M. Hurtado. The molecular Wkly Rep 1992; 41(43): 812–814. structure of 3’-demethoxynorisoguai- LT015 Anon. From the Food and Drug Ad- acin triacetate from creosote bush ministration. Public Warning about (Larrea tridentata). J Nat Prod 1987; herbal product “Chaparral”. J Amer 50(3): 497–499. Med Ass 1993; 269(3): 328. LT026 Gonzalez-Coloma, A., C. S. Wisdom, LT016 Dentali, S. J., and J. J. Hoffmann. Po- and P. W. Rundel. Ozone impact on tential anti-infective agents from the antioxidant nordihydroguaiaretic Eriodictyon angustifolium and Salvia acid content in the external leaf resin apiana. Int J Pharmacog 1992; 30(3): of Larrea tridentata. Biochem Syst Ecol 223–231. 1988; 16(1): 59–64. LT017 Katz, M., and F. Saibil. Herbal LT027 Bohnstedt, C. F., and T. J. Mabry. The hepatitis: Subacute hepatitis necrosis volatile constituents of the genus secondary to Chaparral leaf. J Clin Larrea (Zygophyllaceae). Rev Latino- Gastroenterol 1990; 12(2): 203–206. amer Quim 1979; 10: 128–131. LT018 Gnabre, J. N., J. N. Brady, D. J. LT028 Xue, H. Z., Z. Z. Lu, C. Konno, et al. 3- Clanton, et al. Inhibition of human Beta-(3,4-dihydroxycinnamoyl) immunodeficiency virus type 1 tran- erythrodiol and 3-beta-(-4-hydroxy- scription and replication by DNA cinnamoyl) erythrodiol from Larrea sequence-selective plant lignans. Proc tridentata. Phytochemistry 1988; Natl Acad Sci 1995; 92(24): 11239– 27(1): 233–235. 11243. LT029 Nebelkopf, E. Herbs and cancer. Part LT019 Gordon, D. W., G. Rosental, J. Hart, II. Herbalist 1981; 6(1): 26–39. R. Sirota, and A. L. Baker. The broad- LT030 Bernhard, H. O., and K. Thiele. Addi- ening spectrum of liver injury caused tional flavonoids from the leaves of by herbal medication. JAMA 1995; Larrea tridentata. Planta Med 1981; 41: 273(5): 489–501. 100–103. LT020 Koff, R. S. Herbal hepatotoxicity revis- LT031 Nuzzo, N. A., A. M. Martin, C. Konno, iting a dangerous alternative. JAMA C. D. Fakroddin, H. H. S. Fong, and 1995; 273(5): 502. D. P. Waller. Effect of nor-3’- LT021 Smith, B. C., and P. V. Desmond. demethoxyisoguaiacin (NDI) on fertil- Acute hepatitis induced by ingestion ity in female rats. Biol Reprod 1987; of the herbal medication Chaparral. 36(1): Abstr-301. Aust N Z J Med 1993; 23(5): 526. LT032 Winkelman, M. Frequently used medi- LT022 Gnabre, J. N., Y. Ito, Y. Ma, and R. C. cinal plants in Baja California Norte. J Huang. Isolation of anti-HIV-1 lignans Ethnopharmacol 1986; 18(2): 109–131. from Larrea tridentata by counter-cur- LT033 Luo, Z. Y., D. Meksuriyen, C. A. J. rent chromatography. J Chromatogr A Erdelmeier, H. H. S. Fong, and G. A. 1996; 719(2): 353–364. Cordell. Larreantin, a novel, cytotoxic 270 MEDICINAL PLANTS OF THE WORLD

naphthoquinone from Larrea trident- LT042 Mangione, A. M., D. Dearing, and W. ata. Abstr International Congress on Karasow. Detoxification in relation to Natural Products, Research Park City, toxin tolerance in desert woodrats eat- UT. July 17-21 1988; 1988: Abstr-013. ing creosote bush. J Chem Ecol 2001; LT034 Dimayuga, R. E., R. F. Murillo, and M. 27(12): 559–2578. L. Pantoja. Traditional medicine of LT043 Heosn, S., and E. Yarnell. The safety Baja California sur Mexico II. J Ethno- of low-dose Larrea tridentata (DC) pharmacol 1987; 20(3): 209–222. Coville (creosote bush or chapar- LT035 Konno, C., A. M. Martin, B. X. Ma, et ral): A retrospective clinical study. J al. Search for fertility regulating agents Alt Complement Med 2001; 7(2): from Larrea tridentata. Proc First Prin- 175–185. cess Chulabhorn Science Congress LT044 Scribner, K. A., T. M. Gadbois, M. Bangkok 1989; 1989: 328–337. Gowri, S. Azhar, and G. M. Reaven. LT036 Abbott, B. J., J. Leiter, J. L. Hartwell, Masoprocol decreases serum triglyc- et al. Screening data from the cancer eride concentrations in rats with chemotherapy National Service Cen- fructose-induced hypertriglyceride- ter Screening Laboratories. XXXIV. mia. Metabolism 2000; 49(9): 1106– Plant extracts. Cancer Res 1966; 26: 1110. 761–935. LT045 Reed, M.J., K. Meszaros, L. J. Entes, et LT037 Jacobson, M. Insecticides from plants. al. Effect of masoprocol on carbohy- A review of the literature, 1941-1953. drate and lipid metabolism in a rat Agr Handbook No.154, USDA 1958: model of type II diabetes. Diabetologia 299 pp. 1999; 42(1): 102–106. LT038 Waller, C. W., and O. Gisvold. A phy- LT046 Granados, H., and R. Cardenas. Biliary tochemical investigation of Larrea calculi in the golden hamster. XXXVII. divaricata Cav. J Amer Pharm Ass Sci The prophylactic action of the creosote Ed 1945; 34: 78–81. bush (Larrea tridentata) in pigmented LT039 Tequila-Meneses, M., M. Cortez- cholelithiasis produced by vitamin A. Rocha, E. E. Rosas-Burgos, S. Lopez- Rev Gastroenterol Mex 1994; 59(1): Sandoval, and C. Corrales-Maldonado. 31–35. Effect of alcoholic extracts of wild LT047 Segura, J. J. Effects of nordihydro- plants on the inhibition of growth of guaiaretic acid and ethanol on the Aspergillus flavus, Aspergillus niger, Peni- growth of Entamoeba invadens. Arch cillium chrysogenum, Penicillium expan- Invest Med (Mex) 1978; 1: 157–162. sum, Fusarium moniliforme and Fusarium LT048 Moinuddin, S. G., S. Hishiyama, M. H. poae moulds. Rev Iberoam Microl Cho, L. B. Davin, and N. G. Lewis. 2002; 19(2): 84–88. Synthesis and chiral HPLC analysis of LT040 Lambert, J. D., D. Zhao, R. O. Meyers, the dibenzyltetrahydrofuran lignans, R. K. Kuester, B. N. Timmermann, and larreatricins, 8’-epi-larreatricins, 3,3’- R. T. Dorr. Nordihydroguaiaretic acid: didemethoxyverrucosins and meso- hepatotoxicity and detoxification in 3,3’-didemethoxynectandrin B in the the mouse. Toxicon 2002; 40(12): creosote bush (Larrea tridentata): evi- 1701–1708. dence for regiospecific control of cou- LT041 Gonzalles, M., and G. T. Bowden. pling. Org Biomol Chem 2003; 1(13): Nordihydroguaiaretic acid-mediated 2307–2313. inhibition of ultraviolet B-induced ac- LT049 Page. J. O. Determination of nord- tivator protein-1 activation in human hydroxyguaiaretic acid in creosote keratinocytes. Mol Carcin 2002; bush. Anal Chem 1955; 27: 1266– 34(2): 102–111. 1268. ALOE VERA 1

Plate 1. Camellia sinensis (see full dis- cussion in Chapter 1).

Plate 3. Cocos nucifera (see full discus- sion in Chapter 3).

Plate 2. Cannabis sativa (see full discus- sion in Chapter 2).

Plate 4. Coffea arabica (see full discus- sion in Chapter 4). 2 MEDICINAL PLANTS OF THE WORLD

Plate 5. Daucus carota (see full discus- sion in Chapter 5).

Plate 7. Hordeum vulgare (see full dis- cussion in Chapter 7).

Plate 6. Ferula assafoetida (see full dis- cussion in Chapter 6).

Plate 8. Larrea tridentata (see full dis- cussion in Chapter 8). ALOE VERA 3

Plate 9. Nicotiana tabacum (see full discussion in Chapter 9).

Plate 11. Oryza sativa (see full discus- sion in Chapter 11).

Plate 10. Olea europaea (see full dis- cussion in Chapter 10).

Plate 12. Plantago ovata (see full dis- cussion in Chapter 12). 4 MEDICINAL PLANTS OF THE WORLD

Plate 13. Saccharum officinarum (see full discussion in Chapter 13).

Plate 15. Sesamum indicum (see full discussion in Chapter 15).

Plate 14. Serenoa repens (see full dis- cussion in Chapter 14).

Plate 16. Zingiber officinale (see full discussion in Chapter 16). NICOTIANA TABACUM 271

9 Nicotiana tabacum L.

Common Names A´-li Colombia Tabacco Virginia Italy Aco Wales Tabacni izdelki Slovenia Baco Wales Tabaco Brazil Dé-oo-wé Colombia Tabaco Mexico Dohány Hungary Tabaco Portugal Duhan Albania Tabaco Spain Duhan Croatia Tabaco Venezuela Duvan Serbia Tabák Czech Republic Duvn Serbia Tabak Germany Dybaco Wales Tabak Netherlands E´-li Colombia Tabak South Africa Echter tabak Germany Tabak Russia Faco Wales Tabaka Surinam Fyglys Wales Tabako France Grand tabac France Tabako Netherlands Antilles Hogesoppu India Tabako Philippines Kanvoc Greece Tabako Spain Kapva Greece Tabaku Netherlands Antilles Kherm´-ba Ecuador Tabat France Lukux-ri Colombia Tamaku India Maco Wales Tambaku India Mahora Romania Tamrakatu India Mu-lu´ Colombia Tembakau Indonesia Myglys Wales Tembakau Malaysia Navadni tobak Slovenia Temmdki Turkmenistan Nhybaco Wales Thybaco Wales Nicotiane France Tobac Ireland Pagári-mulé Colombia Tobacco Australia Petun Brazil Tobacco Guyana Pogaku India Tobacco Iceland Pokala India Tobacco Italy Pugaiyilai India Tobacco Kenya Tabac France Tobacco New Zealand Tabac Spain Tobacco United Kingdom

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 271 272 MEDICINAL PLANTS OF THE WORLD

Tobacco United States Tütün Turkey Tobacco West Indies Twak South Africa Tobak Denmark Tybaco Wales Tobak Sweden Tyton szlachetny Poland Tobaken Sweden Tyutyun Bulgaria Tobakk Norway Tyutyun Ukraine Tobakken Denmark Ugwayi Botswana Tombaca Scotland Ugwayi South Africa Tombagey The Isle of Man (Manx) Vaaristubukas Estonia Toombak Sudan Virginiantupakka Finland Tubbak Faeroe Islands Virginiatobak Sweden Tumbako Mozambique Virginiatobakk Norway Tumbako Tanzania Virginischer tabak Germany Tumbako Zaire Virginsk tobak Denmark Tupakka Finland Ye´-ma Brazil Tutun Romania

BOTANICAL DESCRIPTION Theobroma subircanum or other Theobroma Nicotiana tabacum is a stout annual of the species to make an intoxicating snuff. Snuff TOMENTOSAE family, approx 1–3 m is not a hallucinogenic, but it does produce high. The stem is erect with few branches. inebriationNT617. The Tukanoan peoples of Leaves are ovate, elliptic, or lanceolate, up the Vaupes rub a decoction of the leaf to 100 cm or more in length, usually sessile briskly over sprains and bruises. The leaf or sometimes petiolate with frilled wing or juice is taken orally to induce vomiting and auricle. The inflorescence is a panicle with narcosisNT619. distinct rachis and several compounds Colombia. The Witotos and Boras used the branches. Flowers are light red, light pink, fresh leaf as poultice over boils and infected or white. The fruit is a capsule approx 15– wounds. The Tikuna men mix the crushed 20 mm long, narrowly elliptic ovoid or or- leaves with oil from palms and used as a hair bicular. Seeds spherical or broadly elliptic, treatment to prevent baldness. The juice is 0.5 mm long, brown, with fluted ridges. taken orally by the Tukanos to induce vom- iting and narcosisNT619. ORIGIN AND DISTRIBUTION Cuba. Extract of the leaf is taken orally to Nicotiana tabacum originated from the bor- treat dysmenorrheaNT614. ders of Argentina and Bolivia. It has been East Africa. Dried leaves of Nicotiana cultivated in pre-Columbian times in the tabacum and Securinega virosa are mixed in a West Indies, Mexico, Central America, and paste and used externally to destroy worms the northern region of South America. It is in soresNT592. now found worldwide as a cultivated crop. Ecuador. The Jivaros use the leaf juice for TRADITIONAL MEDICINAL USES indisposition, chills, and snake bites and to Argentina. Leaves are smoked by adults treat pulmonary ailments. The Aguarunas in ayahuasca mixture during healing rit- apply leaf juice by clyster, alone or mixed ualsNT481. with ayahuasca, to induce vomiting before Brazil. Dried leaf is used as an insecti- tobacco-ayahuasca enema. The Kulina cus- cideNT609. Leaves are heated and the juice is tomarily smoke all night when taking squeezed out, mixed with ash from bark of ayahuascaNT619. NICOTIANA TABACUM 273

Fiji. Fresh root is taken orally for asthma Nigeria. Hot water extract of the fresh leaf and indigestion. Fresh root juice is applied is taken orally as a sedativeNT580. ophthalmically as drops for bloodshot eyes Papua New Guinea. Dried plant, mixed and other problems. Seed is taken orally for with the bark of Galbulima belgraveana and rheumatism and to treat hoarsenessNT594. Zingiber officinale is taken orally for head Guatemala. Leaves are applied exter- liceNT611. Young leaf tip is chewed to relieve nally by adults for myasis, headache, and stomachache. Decoction of the young leaf woundsNT464. A mixture of the leaf with men- is taken orally to treat gonorrheaNT455. thol VapoRub is applied externally for chil- Paraguay. Extract of the plant is adminis- dren for coughNT470. Hot water extract of the tered orally to cows as an insecticide and dried leaf is applied externally for ring- insect repellentNT456. Smoked or chewed worms, fungal diseases of the skinNT516, dried leaf will spoil the milk of nursing wounds, ulcers, bruises, sores, mouth lesions, mothers. Dried resin accumulated in the stomatitis, and mucosaNT607. The leaf is taken stem of a smoking pipe is applied exter- orally for kidney diseasesNT605. nally against botfly larvae and severe Haiti. Decoction of the dried leaf is taken pediculosisNT600. orally for bronchitis and pneumoniaNT598. Peru. Decoction of the leaf with ayahuasca India. Juice of Securinega leucopyrus is mixed beverage (Banisteriopsis caapi and Psychotria with the dried leaf and applied externally for viridis) is taken orally for hallucinating parasitesNT517. Fresh leaf is mixed with corn- effect during shamanic training. A diet of cob or Amorphophallus paeonifolium to treat cooked plantain and smoked fish follows asthmaNT467. each useNT585. Hot water extract of the dried Iran. Infusion of the dried leaf is applied flower and leaf is used externally for snake externally as an insect repellent. Ointments and spider bitesNT606. The Witotos and Boras made from crushed leaves are used for bald- used the fresh leaves as poultice over boils ness, dermatitis, and infectious ulcerations and infected wounds. The Tikuna men mix and as a pediculicide. Juice is applied exter- the crushed leaves with oil from palms as a nally as an insect repellentNT358. Leaf is added hair dressing to prevent baldness. The to the betel quid and used as a mild stimu- Jivaros use the tobacco juice for indisposi- lantNT329. tion, cold, chills, and snake bites and to Kenya. Water extract of the dried leaf is treat pulmonary ailmentsNT619 applied ophthalmically for corneal opacities Sierra Leone. Leaf is chewed and rubbed on and conjunctivitisNT466. area to dress umbilical stumpNT586. Malaysia. Infusion of the dried leaf is taken Tanzania. Leaves are placed in the vagina orally as a sedativeNT414. to stimulate laborNT618. Mexico. Extract of the plant, massaged on Turkey. Powdered leaf is applied externally the abdomen with saliva, is used to facili- for woundsNT459. tate expulsion of placentaNT438. Exudate from United States. Extract of the plant is taken the leaf and stem is used as a dentifrice for orally to treat tiredness, ward off diseases, gum inflammationNT469. and quiet fearNT364. Nepal. Leaf juice is applied externally to CHEMICAL CONSTITUENTS NT463 treat scabies . (ppm unless otherwise indicated) Nicaragua. Leaves are chewed for 2,3,6-Trimethyl-1,4-naphthoquinone: PlNT037 NT465 toothache and applied externally for 2-Methylquinone: Lf smokeNT160 aches, pains, bites, stings, and skin 2-Naphthylamine: LfNT038 rashesNT468. 3-(Nitrosomethyloamino)propionic acid: PlNT107 274 MEDICINAL PLANTS OF THE WORLD

3-Hydroxypyridine: Lf smokeNT188 Anatabine, N'-methyl: Lf 1NT565 3-Hydroxypyridine: Lf smokeNT188 Anatabine: AnNT391,LfN5T01, PlNT437, LfNT543, 4-(Methylnitrosamino)-1-(3-pirydyl)-1-butanol: RtNT508 LfNT011 Anatalline: Rt 10.4NT321, PlNT562 4-(Methylnitrosamino)-1-(3-pirydyl)-1- Anethole: Lf, Rt, St, Bk, TwNT428 butanone: LfNT005 Aniline-HCl: Lf smokeNT160 4-(Methylnitrosamino)-4-(3-pyridyl)butyric Antheraxanthin: LfNT363 acid: LfNT087 Anthralin: SmokeNT183 4-(Nitrosomethyloamino)-1-(3-pirydyl)butyric Arachidic acid: LfNT544 acid: PlNT106 Areginine: SdNT515 4-(Nitrosomethyloamino)butyric acid: PlNT107 Arginine: PlNT562 4-(N-nitrosomethyloamino)-4-(3- Aristolochene, 5-epi: PlNT510 pirydyl)butyric acid: Pl 0.01-0.95NT107 Aspartic acid: SdNT515 4-Aminobiphenyl: Lf smokeNT160 ATP: StNT397 6-Methyl-3-hydroxypyridine: Lf smokeNT188 Avenasterol, 7-dehydro: SdNT515 Abienol, cis: PlNT424 Azetidine-2-carboxylic acid: PlNT377 Abscisic acid, β-D-glucopyraoside: StigmaNT596 Basm-4-en-6-one, 7-8-epoxy: LfNT561 Abscisic acid, cis-2-trans-4: PetioleNT581 Basman-6-one, 1(R)-3(R)-3(R)-epoxy-4(S)- Abscisic acid, methyl ester: StigmaNT596 8(S)-dihydroxy, (2S-8S-11R-12S): FlNT356 Abscisic acid: Petal, Cy, Ovary, Style, Stamen, Basman-6-one, 1(R)-3(R)-epoxy-4(S)-8(R)- An, StigmaNT596 dihydroxy, (2S-7R-11S-12S): FlNT356 Acetaldehyde: LfNT599 Benzaldehyde, 3-4-dimethoxy: Lf, Rt, St, Bk, Acetamide: LfNT543 TwNT428 Acetic acid: AnNT391, LfNT440 Benzaldehyde: Lf, Rt, St, Bk, TwNT428 Acetonitrile: StNT376 Benzene, 1-2-4-trihydroxy: LfNT448 Acetophenone, 3-4-dimethoxy: Lf, Rt, St, Bk, Benzene, allyl: Lx (St)NT376 TwNT428 Benzene, N-propyl: Lx (St)NT376 Acetophenone: Lf, Rt, St, Bk, TwNT428 Benzene, tert-butyl: Lx (St)NT376 Acrolein: LfNT599 Benzo-(A)-anthracene: Lf 2.6 μg/100 CigNT434 Acrylonitrile: LfNT022 Benzo-(A)-fluorene: Lf 4.9 μg/100 CigNT434 Actinidiolide, dihydro: Lf, Rt, St, Bk, TwNT428 Benzo-(A)-pyrene: Lf 1.7 μg/100 CigNT434 Actinidol, 3-oxo: Lf, Rt, St, Bk, TwNT428 Benzo-(F)-fluoranthene: Lf 2.1 μg/100 Adenine, 6-benzyl: Call TissNT518 CigNT434 Aesculetin: LfNT448 Benzo-(G-H-I)-perylene: Lf 0.3 μg/100 Agropine: St 7%NT538 CigNT434 Alainine: SdNT515 Benzo-(K)-fluoranthene: Lf 1.2 μg/100 Alanine, phenyl: SdNT515 CigNT434 Albumin: cured LfNT359 Benzo[e]pyrene: SmokeNT183 Alkyl-2-cyclopenten-2-ol-1-one: Lf Benzofuran, octahydro, 6-hydroxy-4-4-7-(A)- smokeNT188 trimethyl: Lf, Rt, St, Bk, TwNT428 Alkyl-2-hydroxy-2-cyclopenten-1-one: Lf Benzoic acid: Lf 36NT498 smokeNT171 Benzonitrile: LfNT472 Amine, N-nitroso-diethanol: LfNT599 Benzopyrene: LfNT599 Amine, N-nitroso-dimethyl: LfNT599 Benzoquinone, 1-4: Call Tiss, Rt, LfNT379 Amyrin, β: LfNT540, Sd oilNT491, SdNT480 Benzyl acetate: Lf, Rt, St, Bk, TwNT428 Anabasine, N'-formyl: Lf 4.3–8.6NT565 Benzyl alcohol: Lf, Rt, St, Bk, TwNT428 Anabasine, N'-methyl, (2'S): PlNT562 Bicycle-(4-4-O)-decan-9-one, 1-3-7-7- Anabasine, N'-nitroso: LfNT599 tetramethyl-2-oxa: Lf, Rt, St, Bk, TwNT428 Anabasine, N-methyl: LfNT472 Bicyclo-(4-4-O)-dec-5-en-9-oe, 1-3-7-7- Anabasine, N-nitroso: LfNT599 tetramethyl-2-oxa: Lf, Rt, St, Bk, TwNT428 Anabasine: AnNT391, Lf, PlNT437, Cx, RtNT508 Bicyclo(5.4.0)-undecan-3-one, 4-oxa-7(R)-11- Anatabine, N'-formyl: LfNT506 11-trimethyl, (1S): Lf 0.016NT349 NICOTIANA TABACUM 275

Bicyclodamascenone A: Lf EONT430 Carotene: LfNT363 Bicyclodamascenone B: Lf EONT430 Carvone: Lf, Rt, St, Bk, TwNT428 Biphenyl methane: Lf, Rt, St, Bk, TwNT428 Caryophyllene, β: Lf, Rt, St, Bk, TwNT428 Bipyridine, 2-3': PlNT562 Catechol: LfNT022 Bipyridyl, 2-3', 5-methyl: Lf 0.9NT565 Cedrene, α: Lf, Rt, St, Bk, TwNT428 Bipyridyl, 2-3': LfNT506 Cedrol: Lf, Rt, St, Bk, TwNT428 Bipyridyl, 2-3'-5-methyl: Lf 11NT565 Cembr-2-en-12-one, 4-6-dihydroxy-7-8-epoxy- Blumenol A β-D-glucopyranoside: LfNT548 20-nor, (1S-2-trans-4S-6R-7R-8R): FlNT335 Blumenol C: Lf 0.23NT572 Cembra-2-6-12-(20)-triene-4-8-diol, 11- Brassicasterol: SdNT515 hydroperoxy: Lf 0.1NT330 But-2-en-4-olide, 3-(4-methyl-1-pentyl): Cembra-2-7-11-trien-6-one, 4(R)-hydroxy, Lf 0.002NT349 (1S-2-trans-4R-6R-7-trans-11-trans): FlNT451 But-3-en-2-one, 3-methyl: Lx (St)NT376 Cembra-2-7-11-trien-6-one, 4(S)-hydroxy, Butan-1-ol, 4-(methyl-nitrosamino)-4-(3- (1S-2-trans-4S-6R-7-trans-11-trans): FlNT451 pyridyl): LfNT599 Cembra-2-7-11-triene-4-6-diol, (1S-2-trans- Butan-1-one, 4-(N-methyl-N-nitrosamino)-1- 4R-6R-7-trans-11-trans): FlNT451 (3-pyridyl): LfNT599 Cembra-2-7-11-triene-4-6-diol, (1S-2-trans- Butan-4-olide, 4-ethyl: Lf, Rt, St, Bk, TwNT428 4S-6R-7-trans-11-trans): FlNT451 Butane-2-3-dione: Lx (St)NT376 Cembra-2-7-11-triene-4-6-diol, α: LfNT460 Buten-2-al: Lx (St)NT376 Cembra-2-7-12 (20-triene-4-6-11-triol), But-trans-2-en-1-one, 1-(2-3-6-trimethyl- (1S-2-trans-4S-6R-7-trans): FlNT451 phenyl): LfNT535 Cembra-2-7-dien-12-one, 4-6-dihydroxy-20- Butyraldehyde: LfNT022 nor, (1S-2-trans-4S-6R-7-trans): FlNT335 Butyric acid, N, caffeoyl-4-amino: PlNT350 Cembra-2-7-diene-4-6-diol, 11-12-epoxy, Butyric acid, N, N-caffeoyl-4-amino: BdNT350 (1S-2-trans-4R-6R-7-trans-11-trans): FlNT451 Butyric acid: LfNT440, AnNT391 Cembra-2-7-diene-4-6-diol, 11-12-epoxy, Butyronitrile, 1: Lx (St)NT376 (1S-2-trans-4S-6R-7-trans-11-trans): FlNT451 Cadinene, Δ: LfNT565 Cembra-3-7-11-15-tetraen-6-ol: GumNT567 Cadinenol: Lf, Rt, St, Bk, TwNT428 Cembra-trans-2-12(20)-dien-6-one, 4(S)-8(R)- Caffeic acid: LfNT591, Sd oilNT491 11(S)-trihydroxy, 1(S): FlNT341 Calamanene: Lf, Rt, St, Bk, TwNT428 Cembra-trans-2-12(20)-dien-6-one, 4(S)-8(S)- Campest-7-en-ol: SdNT515 11(S)-trihydroxy, 1(S): FlNT341 Campestanol: SdNT515 Cembra-trans-2-12(20)-dien-6-one, 8(R)- Campesterol acyl glycoside: LfNT368 11(S)-epoxy-4(S)-hydroxy, 1(S): FlNT328 Campesterol ester: LfNT368 Cembra-trans-2-12(20)-diene-4(S)-6(R)-7(S)- Campesterol glycoside: LfNT368 triol, 8(R)-11(S)-epi-dioxy: FlNT337 Camphor: Lf, Rt, St, Bk, TwNT428 Cembra-trans-2-12(20)-diene-4(S)-6(R)-7(S)- Capnos-11-ene-2-10-dione, 4-6-8-trihydroxy: triol, 8(R)-11(S)-epoxy, (1S): FlNT337 FlNT345 Cembra-trans-2-8(19)-12(20)-triene-4(S)- Capnos-12(20)-en-2-one, 8(R)-11(S)-epoxy- 6(R)-7(R)-11(S)-tetraol, (1S): FlNT341 4(S)-6(R)-dihydroxy, (1S-3R-7R): FlNT356 Cembra-trans-2-8(19)-12(20)-triene-4(S)- Capnos-12(20)-ene, 4(S)-6(R)-diol, 2(R)- 6(R)-7(S)-11(S)-tetraol, (1S): FlNT341 11(R), 8(R)-11(R)-diepoxy, (1S-3S): Cembra-trans-2-en-6-one, 8(R)-11(S)-epoxy- FlNT356 4(S)-12(R)-dihydroxy, 1(S): FlNT328 Capric acid: LfNT413 Cembra-trans-2-trans-11-diene-4-(S)-6(R)- Caproic acid: LfNT440 diol, 7(R)-8(R)-epoxy. 1(S): LfNT333 Capronic acid, iso: AnNT391 Cembra-trans-2-trans-11-diene-4(S)-6(R)-diol, Capsidiol: PlNT454 7(S)-8(S)-epoxy, 1(S): FlNT333 Capsidol: RtNT457 Cembra-trans-2-trans-12-dien-6-one, 8(R)- Carboxylase, ribulose-diphosphate: PlNT371 11(S)-epoxy-4(S)-hydroxy, 1(S): FlNT328 Cardinene, γ: LfNT565 Cembra-trans-2-trans-6-12(20)-trien-4-ol, Carotene, β: Call TissNT411 8-11-epoxy, (1S-4R-11S): Lf 0.05NT546 276 MEDICINAL PLANTS OF THE WORLD

Cembra-trans-2-trans-6-12(20)-triene-4(R)- Cembra-trans-2-trans-7-12(20)-triene-4(S)- 8(S)-11(S)-triol, (1S): Fl 14.5NT575 6(R)-diol, 10(R)-11(R)-epoxy, (1S): Cembra-trans-2-trans-6-12(20)-triene-4(S)- FlNT344 8(S)-11(S)-triol, (1S): FlNT342 Cembra-trans-2-trans-7-12(20)-triene-4(S)- Cembra-trans-2-trans-6-diene-4-12-diol, 8-11- 6(R)-diol, 10(S)-11(S)-epoxy, (1S): FlNT344 epoxy, (1S-4S-8S-11R12S): Lf 0.01NT552 Cembra-trans-2-trans-7-12(20)-triene-4-6-diol, Cembra-trans-2-trans-6-trans-10-triene-4(R)- 11-hydroperoxy, (1S-4R-6R-11S): FlNT569 8(S)-12(R)-triol, (1S): FlNT342 Cembra-trans-2-trans-7-12(20)-triene-4-6-diol, Cembra-trans-2-trans-6-trans-10-triene-4(R)- 11-hydroperoxy, (1S-4S-6R-11S): FlNT569 8(S)-12(S)-triol, (1S): FlNT342 Cembra-trans-2-trans-7-cis-11-triene-4(R)- Cembra-trans-2-trans-6-trans-10-triene-4(S)- 6(R)-10(S)-triol, (1S): FlNT347 8(S)-12(R)-triol, (1S): FlNT342 Cembra-trans-2-trans-7-cis-11-triene-4(S)- Cembra-trans-2-trans-6-trans-10-triene-4(S)- 6(R)-20-triol, (1S): FlNT346 8(S)-12(S)-triol, (1S): FlNT342 Cembra-trans-2-trans-7-dien-6-one, 11(S)- Cembra-trans-2-trans-6-trans-11-triene-4-6- 12(S)-epoxy-4(S)-hydroxy, 1(S): FlNT328 diol, 4-O-methyl, (1S-4R): LfNT570 Cembra-trans-2-trans-7-diene-4(R)-6(R)-diol, Cembra-trans-2-trans-6-trans-12-trien-4-ol, 11(R)-12(R)-epoxy, 2(S): FlNT344 8-11-epoxy, (1-2-4-R-8R-11S): Lf 0.03NT546 Cembra-trans-2-trans-7-diene-4(S)-6(R)- Cembra-trans-2-trans-6-trans-12-trien-4-ol, 11(S)-12(R)-tetraol, (1S): FlNT341 8-11-epoxy, (1S-4S-8R-11S): Lf 0.2NT546 Cembra-trans-2-trans-7-diene-4(S)-6(R)-diol, Cembra-trans-2-trans-6-trans-12-triene-4-6- 11(R)-12(R)-epoxy, 1(S): FlNT344 diol, 12-hydroperoxy, (1S-4R-6R-12S): Cembra-trans-2-trans-7-diene-4(S)-6(R)-diol, LfNT570 11(S)-12(S)-epoxy: LfNT553 Cembra-trans-2-trans-7-trans-10-triene-4-6- Cembra-trans-2-trans-7-diene-4-6-diol, 11-12- diol, 12-hydroperoxy, (1S-4S-6R-12R): epoxy, (1S-4R-11S-12S): Lf 0.09NT546 FlNT569 Cembra-trans-2-trans-7-trans-10-trans-6-one, Cembra-trans-2-trans-7-trans-10-triene-4-6- 4(S)-12(S)-dihydroxy, 1(S): FlNT328 diol, 12-hydroperoxy, (1S-4S-6R-12S): Cembra-trans-2-trans-7-trans-10-triene-4(R)- FlNT569 6(R)-12(R)-triol, (1S): Fl 13.3NT575 Cembra-trans-2-trans-7-trans-11-triene, 4(S)- Cembra-trans-2-trans-7-trans-10-triene-4(R)- 10(S)-dihydroxy, (1S): FlNT347 6(R)-12(S)-triol, (1S): Fl 21.7NT575 Cembra-trans-2-trans-7-trans-11-triene-10-one, Cembra-trans-2-trans-7-trans-10-triene-4(S)- (1S): FlNT347 6(R)-12(R)-triol, (1S): Fl 20.5NT575 Cembra-trans-2-trans-7-trans-11-triene-10-one, Cembra-trans-2-trans-7-trans-10-triene-4(S)- 4(R)-6(R)-dihydroxy, (1S): FlNT347 6(R)-12(S)-triol: LfNT553 Cembra-trans-2-trans-7-trans-11-triene-4(R)- Cembra-trans-2-trans-7-trans-11-triene-4(R)- 6(R)-10(R)-triol, (1S): FlNT347 6(R)-diol: LfNT553 Cembra-trans-2-trans-7-trans-11-triene-4(R)- Cembra-trans-2-trans-7-trans-11-triene-4(S)- 6(R)-10(S)-triol, (1S): FlNT347 6(R)-diol: LfNT553 Cembra-trans-2-trans-7-trans-11-triene-4(R)- Cembra-trans-2-trans-7-trans-11-triene-4-6- 6(R)-13(R)-triol, (1S): FlNT346 diol, 4-O-methyl, (1S-4R-6R): LfNT570 Cembra-trans-2-trans-7-trans-11-triene-4(S)- Cembra-trans-2-trans-7-trans-11-triene-4-8- 6(R)-10(R)-triol, (1S): FlNT347 diol, 4-8-di-O-methyl: LfNT570 Cembra-trans-2-trans-7-trans-11-triene-4(S)- Cembratriendiol, α: LfNT509 6(R)-10(S)-triol, (1S): FlNT347 Cembratriendiol, β: LfNT509 Cembra-trans-2-trans-7-12(20)-triene-4(R)- Cembrene: Lf 0.031NT541 6(R)-11(S)-triol, (1S): Fl 36.1NT575 Cembrenodienol, α: LfNT507 Cembra-trans-2-trans-7-12(20)-triene-4(S)- Cembrenodienol, β: LfNT507 6(R)-11(R)-triol, (1S): Fl 9NT575 Cerotic acid: SdNT515 Cembra-trans-2-trans-7-12(20)-triene-4(S)- Cerotic acid: SdNT515 6(R)-11(S)-triol: LfNT553 Chlorogenic acid: LfNT365 NICOTIANA TABACUM 277

Chlorophyll A: Call TissNT411 Cyclopent-1-ene, 2-methyl-5-iso-propyl, 1- Chlorophyll B: Call TissNT411 carboxylic acid: LfNT533 Cholest-7-enol, 4-α-methyl: Sd oilNT491 Cyclopent-2-en-1-one, 2-3-dimethyl: Lf, Rt, Cholest-7-enol: Sd oilNT491 St, Bk, TwNT428 Cholesta-7-24-dien-3-β-ol, 4-α-24-dimethyl: Cyclopropane-1-carboxylic acid-1-amino: Call SdNT490 TissNT564 Cholesta-7-24-dien-3-β-ol, 4-α-methyl-24- Cyperone, α, 2-keto: LfNT565 ethyl: SdNT490 Cysteine: SdNT515 Cholesta-8-24-dien-3-β-ol, 4-α-14-α-24- Damascene, β, 3-hydroxy: Lf EONT559 trimethyl: SdNT490 Damascene, β, 3-hydroxy: Lf, Rt, St, Bk, Cholestanol: SdNT515 TwNT428 Cholesterol acyl glycoside: LfNT368 Damascene, β, 4-hydroxy: Lf EONT559 Cholesterol ester: LfNT368 Damascene, β, 8-9-dihydro, 3-hydroxy: Cholesterol glycoside: LfNT368 Lf EONT559 Cholesterol, 24-methylene: Sd oilNT491 Damascene, β: Lf, Rt, St, Bk, TwNT428 Cholesterol: Sd oilNT491, LfNT540 Damascenone, β: Lf, Rt, St, Bk, TwNT428 Choline, phosphatidyl: PlNT577 Damascenone: Lf, Rt, St, Bk, TwNT428 Choline: PlNT562 Daucosterol: LfNT320 Chrysene: Lf smoke 5.1 μg/100 CigNT434 Debneyol, 1-β-hydroxy, 12-O-β-D-glucoside: Cineol, 1–8: Lf, Rt, St, Bk, TwNT428 Lf 7.4NT343 Cinnamonitrile, dihydro: Cured LfNT472 Debneyol, 1-hydroxy: Pl 3NT602 Cinnamyl alcohol: Lf, Rt, St, Bk, TwNT428 Debneyol, 7-epi: Pl 1.1NT602 Citric acid: LfNT388, cured LfNT544 Debneyol, 8-hydroxy: Pl 3NT602 Citronellol: Lf, Rt, St, Bk, TwNT428 Debneyol: PlNT510 Citrostadienol: Sd oilNT491 Deca-cis-2-trans-4-dienoic acid, 6-iso-propyl-3- Clerosterol: SdNT515 methyl-9-oxo: cured LfNT431 Coenzyme Q-10: PlNT417 Decane: SmokeNT183 Collidine,γ: LfNT472 Deca-trans-2-trans-4-dienoate, 9-oxo-6-iso- Coniferyl alcohol: Lf smokeNT171 propyl-3-methyl, methyl: LfNT530 Cotinine: Lf 95.9NT565 Deca-trans-2-trans-4-dienoic acid, 6-iso-pro- Cotinine: LfNT506 pyl-3-methyl-9-oxo, (–): LfJNT622 Coumarin: Lf, Rt, St, Bk, TwNT428 Deca-trans-2-trans-7-dienoic acid, 6-iso-pro- Cresol, m-: LfNT327 pyl-3-methyl-9-oxo: cured LfNT431 Cresol, ortho: LfNT327 Deca-trans-4-9-dienoic acid, 3-hydroxy-6-iso- Cresol, para: LfNT327 propyl-3-methyl-9-(5-oxo-tetrahydrofuran- Crotonaldehyde: LfNT599 2-yl): LfNT348 Cupalene: Lf, Rt, St, Bk, TwNT428 Dec-trans-4-en-9-one, 1-3-dihydroxy-6-iso- Cupalene: Lf, Rt, St, Bk, TwNT428 propyl-3-methyl, (3-ε-6-ε): 0.009NT549 Curcumene, α: Lf, Rt, St, Bk, TwNT428 Dec-trans-4-enoic acid, 3-ε-hydroxy-9-oxo- Cycloartanol, 24-methylene: LfNT540, SdNT480 3-ε-methyl-6-(S)-iso-propyl: Cured Cycloartanol, 31-nor: SdNT490 LfNT420 Cycloartanol: Sd oilNT491, SdNT480 Dec-trans-4-enoic acid, 3-hydroxy-6-iso-pro- Cycloartenol, 24-methylene: Sd oilNT491 pyl-3-methyl-9-oxo, (6S): Lf 0.037NT514 Cycloartenol, 31-nor: Sd oilNT491 Dec-trans-4-enoic acid, 3-hydroxy-6-iso-pro- Cycloartenol: LfNT540, SdNT480 pyl-3-methyl-9-oxo: Lf 0.008NT514 Cycloeucalenol: Sd oilNT491 Dehydratase, Δ-amino-levulinic acid: Cyclohex-2-en-1-4-dione, 2-6-6-trimethyl-4- Call TissNT386 methylene: Lf, Rt, St, Bk, TwNT428 Dehydrogenase, NADP-linked-glyceraldehyde: Cyclohexanone, 4-hydroxy-2-2-6-trimethyl: PlNT371 Lf, Rt, St, Bk, TwNT428 Docosan-1-ol: LfNT540 Cyclohexanone, 4-hydroxy-3-3-5-trimethyl: Dodeca-trans-6-trans-9-dienoic acid, 3-psi- Lf, Rt, St, Bk, TwNT428 hydrohy-4-psi-9-dimethyl: Cured LfNT473 278 MEDICINAL PLANTS OF THE WORLD

Dotriacontanoic acid: SdNT515 Glycine: SdNT515 Drim-8-en-11-ol: LfNT535 Glycine-betaine: Lf 2.8 mMNT461 Drim-8-en-7-one: LfNT367 Glycoprotein: Call TissNT396 Driman-8-9-(R)-diol, 11-nor: 0.006NT623 Gramisterol: Sd oilNT491 Driman-8-ol, 11-nor, (DL): 0.007NT623 Guaiacol, 4-ethyl: LfNT327 Duva-3-9-(17)-13-trien-1-ol, 5-8-oxido: Lf, Rt, Guaiacol, 4-methyl: LfNT327 St, Bk, TwNT428 Guaiacol, 4-propyl: LfNT327 Duva-4-8-13-triene-1-3-diol: LfNT361 Guaiacol, 4-vinyl: LfNT327 Duvatienediol, α: TrichomeNT444, PlNT445 Guaiacol, methyl: Cured LfNT413 Duvatienediol, β: TrichomeNT444, PlNT445 Guaiacol: LfNT327 Duvatriene-1-3-diol, β-4-8-13: LfNT405 Harman indole: LfNT323 Elem: Lf, Rt, St, Bk, TwNT428 Harman, nor: LfNT323 Esculin: SmokeNT183 Hentriacontane-10-12-dione: StigmaNT522 Estragole: LfNT579 Hept-2-enoate, 6-oxo-3-iso-propyl, methyl: Ethanol, (4-hydroxy-3-methoxy-phenyl)-2: LfNT530 Lf 19NT498 Hept-5-en-2-one, 6-methyl: Lf, Rt, St, Bk, Ethanol, 2-phenoxy: Lf, Rt, St, Bk, TwNT428 TwNT428 Ethanolamine, phosphatidyl: PlNT577 Hept-6-en-2-ol, (E)-5-iso-propyl-7-(2-methy- Eugenol: LfNT327 tetrahydro-fur-2-yl): LfNT372 Eugenol: SmokeNT183 Hept-6-en-2-one, (E)-5-iso-propyl-7-(2-methyl- Fanesyl-acetone: Lf, Rt, St, Bk, TwNT428 tetrahydro-fur-2-yl): LfNT372 Fatty acid: Lf smokeNT171 Hepta-4-(E)-6-dienoic acid, 3-iso-propyl-6- Fluoranthene: SmokeNT183 methyl, methyl ester: Cured Lf 0.075NT398 Formaldehyde: LfNT599 Hepta-4-6-dien-1-ol, 3-iso-propyl-6-methyl, Formic acid: LfNT440 (E): LfNT406 Fructose: SdNT515 Heptacosane-10-12-dione: StigmaNT522 Fucosterol, 28-iso: Sd oilNT491 Heptacosanoic acid: SdNT515 Fumaric acid: cured LfNT544 Heptadeca-8-cis-11-cis dienal: Lf EONT505 Furfural, 5-methoxy-methyl: Cured LfNT544 Heptadeca-8-cis-11-cis-14 cis trienal: Lf EONT505 Furfuryl alcohol: Cured LfNT413 Heptadecanoic acid: Cured LfNT544 Geraniol: Lf, Rt, St, Bk, TwNT428 Heptadecenoic acid: Cured LfNT544 Geranyl-geraniadiene: Lf 720NT557 Heptanoic acid: Cured LfNT413 Geranyl-linalool, 20-hydroxy, 3-O-[α-L- Hept-trans-2-ene-1-6-diol, 3-iso-propyl, (6-ε): rhamnopyranosyl(1-4)]-β-D-glucopyrano- Lf 0.01NT549 side-20-[β-D-glucopyranosyl(1-2)]-[α-L- Hept-trans-2-enoate, 6-oxo-3-iso-propyl, me- rhamnopyranosyl(1-6)]-β-D-glucopyrano- thyl: LfNT530 side (trans-6-trans-10-cis-14): LfNT353 Hepttrans-3-en-2-one, 5-hydroxy-5-iso-propyl, Geranyl-linalool, 20-hydroxy, 3-O-[α-L- (–): LfNT442 rhamnopyranosyl(1-4)]-β-D- Hept-trans-3-en-2-one, 5-hydroxy-5-iso-pro- glucopyranoside-20-O-[α-L-rhamno- pyl: Lf 0.021NT514 pyranosyl(1-4)]-[α-L-rhamnopyranosyl Hex-5-en-2-one: Lx (St)NT376 (1-6)]-β-D-glucopyranoside (trans-6-trans- Hexadecane: SmokeNT183 10-cis-14): LfNT353 Hexan-4-olide, 5-methyl: Lf 0.006NT349 Gibberellin A-1: Call TissNT432 Hexane-1-5-dio, 2-iso-propyl, (2-S-5-ε): Lf Globulin: Cured LfNT359 0.02NT549 Glucose: SdNT515 Hexanoate, 5-oxo-2-(S)-iso-propyl: LfNT530 Glutamic acid: SdNT515 Hexatriacontanon-2-6-10-14-18-22-26-30-33- Glutamyl, γ-L, L-glutamic acid: PlNT385 aen-1-35-diol, 3-7-11-15-19-23-27-31-35- Glutathione: Pl 0.15–0.20 mMNT419 nonamethyl: Cured Lf 4.5NT435 Glutelin: Cured LfNT359 Hexatriaconta-octa-2-6-10-14-18-22-26-30- Glutinosone: LfNT608 en-1-34-diol, 3-7-11-15-19-23-27-31- Glycerol, phosphatidyl: PlNT577 octamethyl-35-methylene: Cured Lf 39NT435 NICOTIANA TABACUM 279

Histidine: SdNT515 Labdane, 15-16-di-nor, 8-13-epoxy: LfNT535 Histones: Call TissNT395 Labdane, 15-16-di-nor, 8-α-13, 9-α-13- Humulene, α: Lf, Rt, St, Bk, TwNT428 diepoxy: LfNT535 Hydrazine sulfate: Lf smokeNT160 Lanos-8-en-3-β-ol, 24-methylene: Sd oilNT491 Hydrocyanic acid inorganic: Cured LfNT423 Lanost-8-en-3-β-ol, 31-nor: Sd oilNT491 Hydroquinone, 2-iso-propyl: LfNT448 Lanost-9(11)-en-3-β-ol, 31-nor, 24-methyl: Hydroquinone: Lf smokeNT171 SdNT490 Hydroquinone: LfNT022 Lanost-9(11)-en-3-β-ol, 31-nor: SdNT490 Hydroxyacetophenone: Lf smokeNT171 Lanosterol, 24-dihydro: Sd oilNT491 Hydroxyphenyl alcohol: Lf smokeNT171 Lanosterol, 31-nor: Sd oilNT491 Indole: Cured LfNT472 Lanosterol: Sd oilNT491 Indole-3-acetic acid: Call TissNT421, PlNT433 Laurc acid: Cured LfNT413 Inositol, phosphatidyl: PlNT577 Leucine, D: Call TissNT392 Ionol, α, 3-oxo: Lf 0.47NT572 Leucine, iso: SdNT515 Ionol, β, 3-hydroxy: Lf, Rt, St, Bk, TwNT428 Leucine, L: Call TissNT392 Ionol, β, 3-hydroxy-5-6-epoxy: Lf 0.046NT534 Leucine: SdNT515 Ionol, β, 7-8-dihydro-3-hydroxy: LfNT374, Rt, Leucinopine lactam: Crown Gall Tumor St, Bk, TwNT428 TissNT583 Ionone, β, 3-hydroxy, (R)-(-): LfNT393 Leucinopine: Crown Gall Tumor TissNT583 Ionone, β, 3-hydroxy: Lf, Rt, St, Bk, TwNT428 Levulinic acid: Cured LfNT544 Ionone, β, 4-oxo: Lf, Rt, St, Bk, TwNT428 Ligase, leucine-tRNA: PlNT571 Ionone, β: Lf, Rt, St, Bk, TwNT428 Limonene: SmokeNT183 Ionyl, β, 3-hydroxy-5-6-epoxy, β-D- Linalool: Lf, Rt, St, Bk, TwNT428 glucopyranoside: Cured LfNT548 Linoleic acid: Sd oilNT400, Cured LfNT544 Iso-amyl acetate: Lf, Rt, St, Bk, TwNT428 Linolenic acid: Sd oilNT400, Cured LfNT544 Isoperoxidase (A-A): PlNT389 Loliolide, dehydro: Lf 0.027NT547 Isoperoxidase (A-B): PlNT389 Loliolide-β-D-glucopyranoside: Lf 8.3NT558 Isoperoxidase (A-D): PlNT389 Lophenol, 24-(R)-ethyl: SdNT490 Isoperoxidase (A-E): PlNT389 Lophenol, 24-methyl: SdNT490 Isoperoxidase (C-N): PlNT389 Lophenol: Sd oilNT491 Isophorone: Lf, Rt, St, Bk, TwNT428 Lubimin: LfNT446 Isoprene: LfNT022 Lupein: LfNT363 Kaempferol-3-rhamnoglucoside: Lf 0.02%NT484 Lupeol: Sd oilNT491 Kaepferol: Lf 50NT484 Lutidine, 2-3: LfNT322 Kynurenic acid, 6-hydroxy: PlNT562 Lutidine, 2-4: LfNT322 Labd-13-en-15-ol, 8-12-epoxy, 12(R)-13-trans: Lutidine, 2-5: LfNT322 FlNT338 Lutidine, 2-6: LfNT322, Cured LfNT543 Labd-13-en-15-ol, 8-12-epoxy, 12(S)-13-trans: Lutidine, 3: Cured LfNT543 FlNT338 Lutidine, 3-5: Cured LfNT472 Labd-13-ene- 8-12-15-triol, 12(S)-13-trans: Lyase, L-phenylalanine ammonia: PlNT624 FlNT338 Lysine: SdNT515 Labd-14-ene, 13-η-hydroxy-8-α-12-η-epoxy: Magestigma-4-trans-7-diene-3(S)-9(R)-diol, LfNT373 6(R): LfNT503 Labd-8(17)-en-12-al, 13-14-15-16-tetra-nor: Maleimide, methyl-ethyl: Lf, Rt, St, Bk, LfNT535 TwNT428 Labd-8(17)-en-13-one, 15-16-dinor: LfNT535 Malic acid: Cured LfNT544 Labd-8-en-12 al, 13-14-15-16-tetra-nor: Malonic acid: Cured LfNT544 LfNT535 Megastigma-4-trans-7-diene-3(S)-9(S)-diol, Labd-8-en-13-one, 15-16-di-nor: LfNT535 6(R): LfNT503 Labd-8-ene-7-13-dione, 14-15-di-nor: FlNT338 Megastigma-5(13)-(E)-dien-6-9-diol: Cured Labdan-13-one, 11-12-epoxy-8-hydroxy-14- LfNT479 15-di-nor, 11(S)-12(R): FlNT338 Megastigma-5-trans-8-dien-4-one: LfNT529 280 MEDICINAL PLANTS OF THE WORLD

Megastigmastrienone, 8-9-dihydro, 8-9- Nicotine, nor, 1'-acetyl: LfNT550 dihydroxy: LfNT500 Nicotine, nor, 1'-hexanoyl: LfNT550 Megastigmastrienone, iso, 8-9-dihydro, 8-9- Nicotine, nor, 1'-octanoyl: LfNT550 dihydroxy: LfNT500 Nicotine, nor, 1'-propionyl: LfNT550 Megastigmastrienone: Lf, Rt, St, Bk, TwNT428 Nicotine, nor, N-(4-dimethyl-amino- Megastigum-7-ene-5-6-9-triol, (5R-6S-7-trans- butanoyl): Lf 0.83NT531 9S): LfNT597 Nicotine, nor, N'-acetyl: LfNT506 Melissic acid: SdNT515 Nicotine, nor, N'-butanoyl: LfNT506 Methionine: SdNT515 Nicotine, nor, N'-carboethoxy: Lf 4NT531 Mikimopine: Rt 480NT339 Nicotine, nor, N'-formyl: LfNT506 Morpholine, N-nitroso: LfNT599 Nicotine, nor, N'-hexanoyl: LfNT506 Myosmine: LfNT322, Cured LfNT543 Nicotine, nor, N'-iso-propyl: PlNT562 Myristic acid: Cured LfNT544 Nicotine, nor, N'-nitroso: LfNT378, Cured Lf N1-nitrosonornicotine: LfNT072 1.1–1.8NT407, PlNT562 Naphthalene, 1-2-dihydro, 3-iso-propenyl-5- Nicotine, nor, N'-octanoyl: LfNT506 methyl: LfNT487 Nicotine, nor: AnNT391, Call TissNT499, Naphthalene, 2-methoxy: Lf, Rt, St, Bk, LfNT526, PlNT437, Rt, CxNT508 TwNT428 Nicotine: LfNT360, Cured LfNT408, AerNT436, Naphthalene, methyl: Lf, Rt, St, Bk, TwNT428 PlNT562, Call Tiss 11.46 mg/5.05 gNT576 Naphthalene: Lf, Rt, Stem, Bk, TwNT428 Cured Lf smokeNT543, Rt, Stigma/Style, Naphthalene-1-ol, 1-2-3-4-tetrahydro, cis-2- Stamen, Ovary, Petal, Cx, Sd (immature), iso-propenyl-8-methyl: LfNT487 Sd, Ovule, FlNT508 Naphthoquinone, 1-4, 2-3-6-trimethyl: LfNT326 Nicotine-N'-oxide: Cured Lf smokeNT543 Nectarin I: FlNT357 Nicotinic acid, 6-hydroxy: PlNT562 Neophytadiene: LfNT540 Nicotinic acid, methyl ester: Lf, Rt, St, Bk, Neoxanthin: LfNT363 TwNT428 NT425 NT562 NH3 inorganic: Lf Ju Nicotinic acid, N-glucoside: Pl Nicotanoside A: Sd 0.13%NT351 Nicotinic acid: PlNT562 Nicotanoside B: Sd 0.29%NT351 Nicotinoyl-1-O-β-D-glucopyranose: PlNT354 Nicotanoside C: Sd 0.71%NT352 Nicotyrine: AnN06589, LfNT440, Cured Lf Nicotanoside E: Sd 0.16%NT351 smokeNT543 Nicotanoside F: Sd 1.155%NT352 N'-nitrosoanabasine: LfNT087 Nicotelline: PlNT562 N'-nitrosoanatabine: LfNT166 Nicotiana tabacum diterpene I: FlNT336 N'-nitrosonornicotine: LfNT087 Nicotiana tabacum glycoprotein: Lf, Lf smoke N-nitrosoproline: PlNT107 Condensate, Lf TarNT603 N-nitrosopyrrolidine: LfNT087 Nicotiana tabacum heptaacyl glyceride 3: N-nitrososarcosine: PlNT107 StigmaNT563 N-N-octanoylnornicotine: LfNT294 Nicotiana tabacum heptaacyl glyceride: Non-3-en-8-one, 2-5-diepoxy-2(R)-hydroxy- StigmaNT563 5(R)-iso-propyl: LfNT348 Nicotiana tabacum pentaacyl glyceride 2: Non-3-en-8-one,1-5-epi-dioxy-2(S)-hydroxy- StigmaNT563 5-iso-propyl: LfNT348 Nicotiana tabacum tetraacyl glyceride: Non-3-ene-2-8-diol, 5-iso-propyl, (E): LfNT406 StigmaNT563 Non-6-en-2-one, 5-iso-propyl-8-hydroxy, (E): Nicotiana tabacum virus inhibitor: Lf, StNT527 LfNT406 Nicotianamine: Lf 0.05% μMNT439 Non-6-en-2-one, 5-iso-propyl-8-hydroxy-8- Nicotianine: LfNT324 methyl, (E): LfNT406 Nicotine, nor, 1'-(6-hydroxy-octanoyl): Lf Non-8-en-4-olide, 3(R)-7(R)-epoxy-4(R)-8- 1.6NT565 dimethyl: Lf 0.002NT349 Nicotine, nor, 1'-(7-hydroxy-octanoyl): LfNT550 Nonacosane-8-10-dione: StigmaNT522 Nicotine, nor, 1'-(hydroxy-octanoyl): Lf Nonan-2-ol, 3-3-5-trimethyl-8-iso-propyl-4-9- 1.1NT565 dioxa-bicyclo-(3.3.1): LfNT406 NICOTIANA TABACUM 281

Nonan-2-one, 5-iso-propyl-6-7-epoxy-8- Pent-2-en-4-olide, 3-iso-propyl: Lf 0.008NT349 hydroxy-8-methyl, (E): LfNT406 Pent-2-en-4-olide, 4-methyl-3-(3-oxo-1- Nonane-2-8-diol, 3-4-epoxy-5-iso-propyl, (2-ε- butyl): Lf 0.005NT349 3-5-4-S-5-S-8-ε): Lf 0.001NT549 Pent-2-en-5-olide, 5-propyl: Lf, Rt, St, Bk, Nonane-2-8-diol, 3-4-epoxy-5-iso-propyl-2- TwNT428 metyl, (3-R-4-S-5-S-8-ε): Lf 0.006NT549 Pentacosane-8-10-dione: StigmaNT522 Nona-trans-2-en-8-ol, 3-methyl-4-oxo: LfNT476 Pentadeca-4-9-dien-14-on-1-al, 6-8- Nona-trans-2-trans-6-dienal, 5-iso-propyl-2- dihydroxy-11-iso-propyl-4-8-dimethyl: methyl-8-oxo: Lf 0.004NT514 LfNT494 Non-cis-6-en-4-olide: Lf 0.36NT349 Pentadecan-15-olide: LfNT535 Non-trans-2-en-4-one, 3-methyl: LfNT535 Pentadecan-2-one, 6-10-14-trimethyl: Lf, Rt, Non-trans-3-en-8-one, 1-2-dihydrohy5-iso- St, Bk, TwNT428 propyl-2-methyl, (5-S): Lf 0.03NT549 Pentadecanal, 6-10-14-trimethyl, trans-2- Non-trans-3-en-8-one, 1-2-dihydrohy5-iso- ethylidene: LfNT535 propyl-2-methyl, 2-epi, (S-5): Lf 0.4NT549 Pentadecanal: Lf EONT500 Non-trans-5-en-4-olide, 2(R)-7-iso-propyl- Pentadecanoic acid: Cured LfNT413 4(S)-methyl: LfNT348 Pentadeca-trans-3-trans-8-cis-12-14-tetraen-2- Nonvolatile acids: LfNT493 one, 5-iso-propyl-8-12-dimethyl: Lf Nuclease: PlNT422 smokeNT554 Nucleotidase, 3': PlNT576 Pentadeca-trans-3-trans-8-12-14-tetraen-2-one, Obtusifoliol: Sd oilNT491 5-iso-propyl-8-12-dimethyl: Lf smokeNT554 Occidenol: LfNT608 Pentadeca-trans-4-trans-9-dienoic acid, 6(R)- Occidentalol: LfNT608 8(R)-dihydroxy-4-8-dimethyl-11(S)-iso- Occidol: LfNT565 propyl-14-oxo: LfNT332 Oct-2-en-4-olide, 3-methyl-7-oxo: Lf 0.003NT349 Pentadeca-trans-4-trans-9-dienoic acid, 6(R)- Octa-5-trans-7-dienoic acid, 4-iso-propyl-7- 8(S)-dihydroxy-4-8-dimethyl-11(S)-iso- methyl, methyl ester: cured Lf 0.75NT398 propyl-14-oxo: Fl, LfNT332 Octacosanoic acid: SdNT515 Pentan-2-one: Lx (St)NT376 Octadec-trans-9-en-18-olide: LfNT535 Pentan-4-olide, 3(R)-methyl, 4(R): Octan-2-one, 7-hydroxy-3-3-dimethyl: Cured Lf 0.002NT349 LfNT478 Pentan-4-olide, 3(R)-methyl, 4(S): Octanoic acid: LfNT440 Lf 0.002NT349 Octa-trans-2-7-diene-1-6-(S)-iol, 2-6-dim- Pentan-4-olide, 4(5-methyl-2-furyl): ethyl: Lf 0.03NT532 Lf 0.022NT349 Oct-trans-2-enoic acid, Y-iso-propyl-7-oxo: Pentan-5-olide, 3-iso-propyl: Lf, Rt, St, Bk, Cured LfNT431 TwNT428 Oct-trans-5-en-4-olide, 4-iso-propyl-7-oxo: Pentan-5-olide, 5-pentyl: Lf, Rt, St, Bk, Lf 0.016NT514 TwNT428 Oleic acid: Sd oilNT400, Cured LfNT544 Pentan-5-olide, 5-propyl: Lf, Rt, St, Bk, Oleic acid: SmokeNT183 TwNT428 Oxalic acid: Cured LfNT544 Peroxidase, iso, A-1: PlNT370 Oxidase, β-indolyl-acetic acid: Call TissNT390 Peroxidase, iso, A-2: PlNT370 Oxidase, indole-acetic acid: Stem pithNT384 Peroxidase: Call TissNT383, CyNT387, LfNT409 Palmitic acid, methyl ester: Lf, Rt, St, Bk, Phenol, 2-6-dimethoxy: LfNT327 TwNT428 Phenol, m-ethyl: LfNT327 Palmitic acid: Sd oilNT400, LfNT540, Cured Phenol, m-methoxy: LfNT327 LfNT544 Phenol, ortho-tert-butyl: Cured LfNT413 Palmitin, mono: PlNT416 Phenol, para-ethyl: LfNT327 Pantolactone: Lf, Rt, St, Bk, TwNT428 Phenol, para-methoxy: LfNT327 Pent-2-4-dienen-5-olide, 3-iso-propyl: Phenol: LfNT327 Lf 0.005NT349 Phenol: SmokeNT183 Pent-2-en-4-olide, 3-ethyl-4-methyl: Lf 0.005NT349 Phenolic cyano compound: Lf smokeNT171 282 MEDICINAL PLANTS OF THE WORLD

Phenyl acetate, methyl: Lf, Rt, St, Bk, TwNT428 Pyrazine, propyl: Cured Lf smokeNT543 Phenylacetic acid: Lf 46NT498 Pyrazine, triethyl: Cured LfNT472 Phenylethanol, 2: Lf, Rt, St, Bk, TwNT428 Pyrene: Lf smoke 6.8 mg/100 CigNT434 Phenylethyl, 2-iso-valerate: LfNT535 Pyrene: SmokeNT183 Phorbol myristate acetate: SmokeNT183 Pyrid-2-(1-H)-one, 5-6-dihydro: cured LfNT472 Phosphatase, acid: LfNT409 Pyridine, 2(14), 5-6-dihydro: Lf 37NT498 Phosphatidic acid: PlNT577 Pyridine, 2-acetyl: Cured Lf smokeNT543 Phthadiene, neo: LfNT399 Pyridine, 2-ethyl: Cured LfNT472 Phthalate, dibutyl: Lf, Rt, St, Bk, TwNT428 Pyridine, 3-(dimethyl-pyrryl): Cured LfNT472 Phthalate, diethyl: Lf, Rt, St, Bk, TwNT428 Pyridine, 3-acetyl: Cured Lf smokeNT543 Phytofuran: LfNT399, Rt, St, Bk, TwNT428 Pyridine, 3-aldehyde: Cured LfNT472 Phytol: LfNT540 Pyridine, 3-cyano: Cured Lf smokeNT543 Phytuberin: LfNT446 Pyridine, 3-cyano: Cured LfNT472 Phytuberol, dihydro, 2-α-methoxy: PlNT539 Pyridine, 3-ethyl: LfNT322 Phytuberol, dihydro, 2-β-methoxy: PlNT539 Pyridine, 3-hydroxy: Cured LfNT472 Phytuberol: PlNT539 Pyridine, 3-vinyl: LfNT322, Cured Lf Picoline, 2: Cured Lf smokeNT412 smokeNT543 Picoline, 3: Cured Lf smokeNT412 Pyridine, butenyl: Cured Lf smokeNT543 Picoline, α: LfNT322 Pyridine, phenyl-3: Cured LfNT472 Picoline, β: LfNT322 Pyridine, propenyl: Cured Lf smokeNT543 Picoline, γ: LfNT322 Pyridine: LfNT322, Cured LfNT412, Cured Lf Piperidin-2-one, N-methyl: Cured Lf smokeNT543 smokeNT543 Piperidin-2-one: Cured Lf smokeNT543 Pyridyl, 2-3'-bi: Cured Lf smokeNT543 Piperonal: Lf, Rt, St, Bk, TwNT428 Pyridyl, 2-3'-di: LfNT322 Plastohydroquinone 9: Call TissNT411, Rt, Pyridyl, 2-4'-di: LfNT502 LfNT379 Pyridyl, 3-3'-di: LfNT502 Plastoquinone 9: Call TissNT411, Rt, LfNT379 Pyridyl, 4-4'-di: LfNT502 Polysaccharide(pectic): Pl 0.078%NT504 Pyrindin-7-one, 3-6-6-trimethyl-5-6-dihydro- Proline: Call TissNT392 7-(H)-2: LfNT369 Propan-2-ol, 2-(1-methyl-4-iso-propyl-7-8-dioxa- Pyrogallol: SmokeNT183 bicyclo-(3.2.1)-oct-6-yl), endo: LfNT406 Pyrrole, 1-acetic acid, 2-formyl-5-ethoxy- Propionaldehyde: LfNT022 methyl): Lf 36NT498 Propionamide: Cured Lf smokeNT543 Pyrrole, 1-methyl: Lx (St)NT376 Propionic acid: LfNT440, AnNT391 Pyrrole, 2-acetyl: Cured LfNT472 Propionitrile: Lx (St)NT376 Pyrrole, N-methyl-2-acetyl: Lf, Rt, St, Bk, Protein (fraction I): LfNT545 TwNT428 Protein (Nicotiana tabacum): PlNT474 Pyrrole: Cured LfNT472 Protein PR-R: LfNT523 Pyrrolid-2-one, N-methyl: Cured Lf Protein: Stem pithNT384, Call TissNT394 smokeNT543 Putrescine, caffeoyl: PlNT562 Pyrrolid-2-one: Cured Lf smokeNT543 Putrescine, feruloyl: PlNT562 Pyrrolidine, N-nitroso: LfNT599 Putrescine, N-methyl: PlNT562 Pyrrolidinyl-β-D-fructopyranose, 1-deoxy-1- Putrescine, para-coumaroyl: PlNT562 (S)-2-(3-pyridyl)-1: LfNT555 Putrescine: PlNT562 Quercetin: LfNT591 Pyrazine, 2-3-dimethyl: Cured LfNT472 Quercetin: SmokeNT183 Pyrazine, 2-5-dimethyl: Cured LfNT472 Quercitrin, iso: Cured LfNT410, Lf 50NT484 Pyrazine, 2-ethyl-6-methyl: Cured LfNT472 Quinolin-9-one, iso, 1-3-6-6-tetramethyl-5-6- Pyrazine, 2-methyl: Cured Lf smokeNT412 7-8-tetrahydro: LfNT369 Pyrazine, butyl: Cured Lf smokeNT543 Quinoline, iso: Cured LfNT472 Pyrazine, ethyl: Cured Lf smokeNT543 Quinoline: Cured LfNT472 Pyrazine, methyl: Cured LfNT472 Raffinose: SdNT515 Pyrazine, pentyl: Cured Lf smokeNT543 Resorcinol: SmokeNT183 NICOTIANA TABACUM 283

Ribonuclease, deoxy: PlNT576 Squalene-2-3-oxide: Seedling, LfNT325 Ribonuclease: PlNT576 Stachyose: SdNT515 Rishitin: LfNT565 Starch: Call TissNT394 Rishitin-3-O-(α-L-rhamnopyranosyl(1-4)-β-D- Stearic acid: Sd oilNT400, LfNT540, Cured glucopyranosyl(1-4)-β-D-glucopyranoside): LfNT544 Lf 2.2NT625 Stigmast-7-en-3-β-ol: SdNT515 Rishitin-β-sophoroside: LfNT573 Stigmastal-2-3-dien-ol: SdNT515 Rutin: Lf 25-9700NT484, NT615 Stigmastenol, δ-7: SdNT515 Saccharopine, L: Lf 0.67NT489 Stigmasterol acyl glycoside: LfNT368 Salicylate, iso-amyl: Lf, Rt, St, Bk, TwNT428 Stigmasterol ester: LfNT368 Scopoletin: LfNT401 Stigmasterol glycoside: LfNT368 Scopolin: LfNT401, PlNT562 Stigmasterol: LfNT368, PlNT424, Call TissNT382, Serine, O-acetyl: PlNT471 Sd oilNT491, LfNT540 Serine: SdNT515 Styrene: Lx (St)NT376 Sitosterol acyl glycoside: LfNT368 Succinamopine antibiotic: Crown Gall Tumor Sitosterol ester: LfNT368 TissNT492 Sitosterol glycoside: LfNT368 Succinic acid: Cured LfNT544 Sitosterol, β: LfNT368, PlNT424, Sd oilNT491 Succinimide, trans-2-ethylidene-3-methyl: Lf Skatole: Cured LfNT472 5NT498 Solanadione, nor: Lf, Rt, St, Bk, TwNT428 Sucrose, 6-O-acetyl-2-3-4-tri-O-(3S-methyl- Solanascone, 10-β-hydroxy, β-D-glucoside: pentanoyl): FlNT501 Lf 6.8NT340 Sucrose: SdNT515 Solanascone, 13-hydroxy, β-D- Sulfurylase, ATP: PlNT418 glucopyranoside: Lf 0.6NT331 Syringone, aceto, α-hydroxy: RtNT519 Solanascone, 15-hydroxy, β-D- Syringone, aceto: RtNT519 glucopyranoside: Lf 0.4NT331 Terpineol, α: Lf, Rt, St, Bk, TwNT428 Solanascone, 15-hydroxy, β-D-glucoside: Tetradecane: SmokeNT183 Lf 12.3NT462 Theaspirone, 8-9-dehydro: Lf EONT556 Solanascone, 2-3-dehydro: LfNT565 Threonine: SdNT515 Solanascone, 3-hydroxy, β-sophoroside: Thunberga-trans-2-trans-6-diene-4-11-diol, Lf 5.7NT496 8-12-epoxy, (1S-4S-8R-11S-12R): Cured Solanascone, 3-hydroxy-β-sophoside: LfNT568 LfNT429 Solanascone, 9-β-D-glucoside: Lf 1.2NT340 Thunberga-trans-2-trans-6-diene-4-12-diol, Solanascone: LfNT528 8-11-epoxy, (1S-4R-8R-11S-12R): Lf Solanascone: LfNT565 0.016NT536 Solanascone-3-O-β-sophoroside: Lf 10NT625 Thunberga-trans-2-trans-6-diene-4-12-diol, Solanesol: Cured LfNT475, Lf 0.74%NT560 8-11-epoxy, (1S-4S-6R-11S-12R): LfNT536 Solanofuran: Lf, Rt, St, Bk, TwNT428 Thymol: Lf, Rt, St, Bk, TwNT428 Solanol: Lf, Rt, St, Bk, TwNT428 Tobacco F-1 protein: LfNT542 Solanone: Lf, Rt, St, Bk, TwNT428 Tobacco glycoprotein: Cured LfNT163 Solanoquinone: LfNT626 Tobacco saponin A: SdNT610 Solavetinon-3-O-β-D-glucoside: Lf 9.3NT625 Tobacco saponin B: SdNT610 Solavetinone, (–): Cured Lf NT477 Tocopherol, α: LfNT540, Call TissNT411, RtNT379 Solavetinone, 13-hydroxy: Cured Lf NT477 Tocoquinone, α: Call TissNT411, Lf, RtNT379 Solavetinone, 3-hydroxy: LfNT568 Toluene: Lx (St)NT376 Solavetinone, 9-β-hydroxy: Cured Lf NT477 Transferase, amino, alanine: Call TissNT366 Solavetinone: Cured LfNT488, LfN1657 Trichodiene, 15-hydroxy: Pl 0.2NT355 Solavetinone: Lf 0.03NT488 Trideca-5-10-12-trien-2-one, (E)-6-12-dim- Solavetivone: Cured LfNT488 ethyl-9-iso-propyl: LfNT372 Spiloxabovolide: Lf, Rt, St, Bk, TwNT428 Tridecan-2-one: LfNT535 Squalene: LfNT540 Trideca-trans-3-trans-7-diene-2-12-dione, 6- Squalene: SmokeNT183 hydroxy-9-iso-propyl-6-methyl: Fl 0.04NT514 284 MEDICINAL PLANTS OF THE WORLD

Tyramine: LfNT520 produced a significant elevation of 8-oxode- Tyrosine: SdNT515 oxyguanosine in lung DNA 2 hours after the NT627 Ubelliferone: Pl last administration. A single-dose treatment NT427 Ubiquinone 10: Call Tiss 0.0075 , Pl (4 mg/mouse) produced an insignificant 360NT426 Undec-5-en-4-olide, (E)-4-methyl-7-iso-pro- increase of lesion in the lung DNA. In the pyl-10-oxo: LfNT372 liver, the increase was only significant by Undeca-2-one, 6-10-dimethyl: Lf, Rt, St, Bk, multiple doses of the higher dose. At 4 and TwNT428 24 hours after treatment, the 8-oxode- Undeca-3-trans-6-dien-2-ol, 2-6-dimethyl-10- oxyguanosine levels declined to the basal oxo: LfNT476 levels in both liver and lung. Administra- Undeca-5-9-dien-2-one, 6-19-dimethyl: Lf, Rt, tion of a single dose (20 mg/animal) to F344 NT428 St, Bk, Tw rats, produced a significant increase of 8- Undecane: SmokeNT183 oxodeoxyguanosine in rat lung DNA and an Undecen-4-olide, 5-(E), 7(S)-10-oxo-4: LfNT375 insignificant increase in liver DNA. The 8- Undec-trans-5-en-10-one, 1-4-epoxy-2(R)- oxodeoxyguanosine level in rat kidney, a hydroxy-7-iso-propyl-4(R)-methyl: LfNT348 nontarget tissue, was inert to nitrosamine Undec-trans-5-en-10-one, 1-4-epoxy-2(R)- treatmentNT090. hydroxy-7-iso-propyl-4(S)-methyl: LfNT348 Abortifacient effect. The smoke of the Undec-trans-5-en-4-olide, 2(R)-hydroxy-7(S)- dried leaf by pregnant women was act- NT348 iso-propyl-4(S)-methyl-10-oxo: Lf iveNT486. Undec-trans-5-ene, 2-10-dihydroxy-1-4-epoxy- Acetylhydrolase activity. Smoke extract, 7-iso-propyl-4-methyl: LfNT537 Undec-trans-5-ene, 2-10-dione, 4-hydroxy-7- administered to rats at a dose of 0.5 ciga- iso-propyl-4-methyl: Lf 0.005NT514 rettes/kg for 5 days, did not alter plasma Undec-trans-5-ene, epi, 2-10-dihydroxy-1-4- platelet-activating factor acetylhydrolase epoxy-7-iso-propyl-4-methyl: LfNT537 activity during the treatment. Combination Valeric acid, β-methyl: LfNT440 of smoke extract and 17-α-ethynylestradiol Valeric acid, iso: LfNT440 decreased plasma platelet-activating factor NT440 NT391 Valeric acid: Lf , An acetylhydrolase activity by 90%. The effect NT515 Valine: Sd of medroxyprogesterone on plasma platelet- Vanillin: Lf 1.51NT450 Vetivone, β, 11-12-dihydroxy: Cured LfNT477 activating factor acetylhydrolase activity NT267 Violaxanthin: LfNT363 was not influenced by smoke extract . Virg-3-ene, 18-oxo: FlNT334 Administration of an increasing concen- Vitamin K-1: Call TissNT411, Rt, LfNT379 trations of extract to confluent cultures of Xylenol, 2-3: LfNT327 collagen-producing mouse fibroblasts or Xylenol, 2-4: LfNT327 primary osteoblasts from chick embryo NT327 Xylenol, 2-5: Lf calvarias, produced no effect on glycolysis NT327 Xylenol, 2-6: Lf and DNA synthesis. There was no influence Xylenol, 3-5: LfNT327 Zeaxanthin: LfNT363 on cell proliferation in fibroblasts, but it was inhibited at the highest extract con- PHARMACOLOGICAL ACTIVITIES centration in osteoblasts. Adenosine tri- AND CLINICAL TRIALS phosphatase (ATPase) activity was not 8-Oxodeoxyguanosine level increase. detectable in fibroblast medium but was Nitrosamine 4-(methylnitrosamino)-1-(3- decreased in osteoblast medium. At the high- pyridyl)-1-butanone, administered intra- est concentration, [3H]hydroxyproline and gastrically to A/J mice at doses 0.25 or 0.5 [3H]proline contents in the cell layers were mg/mouse, three times a week for 3 weeks, decreased to the following respective values: NICOTIANA TABACUM 285 fibroblasts 56% and 45% and osteoblasts corticosterone production but inhibited al- 50% and 29%, respectively. When incuba- dosterone production in a dose-dependent tion with smokeless tobacco (STE) was dis- manner. The relative inhibitory potency continued for 1 day, recovery did not was: cotinine > anabasine > nicotine. occurNT094. Cotinine, anabasine, and nicotine, at a con- Age-related alterations. Smoke, adminis- centration of 100 mM, inhibited adrenocor- tered to old CBA/CA mice, produced spon- ticotropic hormone (ACTH)-stimulated taneous death more frequently than in the aldosterone synthesis by 75, 44, and 21%, control animals. Prevalence of hepatocellu- respectively. Angiotensin (ANG)-II-stimu- lar carcinoma was higher and body weight lated aldosterone synthesis was inhibited by was lower in the smoke-treated mice than 92, 78, and 62%, respectively. The plasma in controls. There were differences in organ cotinine concentration range attained in indices. The reactivity against sheep eryth- tobacco smokers was between 1 and 10 mM. rocytes antigen was lower in mice kept in When tested with [3H]corticosterone and smoke than in controls. The ratio of normal [3H]progesterone as exogenous substrates, reactivity (against sheep erythrocytes) and 1–10 mM cotinine produced a significant autoreactivity (against mouse erythrocytes) dose-dependent inhibition of ACTH- and showed a decrease in the smoke-treated ANG-II-stimulated aldosterone synthe- miceNT108. sisNT276. Airspace permeability increase. Cigarette Allergenic activity. Cigarette smoke con- smoke condensate in rat lungs produced a densate, in cell culture at concentrations of 59.7% increase in epithelial permeability 6.6–20 μg/mL, produced an inhibition of over control values, peaking 6 hours after cell surface antigen-presenting major histo- instillation and returning to control values compatibility complex class I expression by 24 hours. Instillation of human recombi- and immunoglobulin (Ig) synthesis. Intrap- nant tumor necrosis factor (TNF)-α pro- eritoneal administration to C57BL/6 mice duced an increase in epithelial permeability before challenge with ovalbumin antigen in the rat lung. Only a vestigial amount of produced a decrease of antiovalbumin-spe- TNF-α was detected in bronchoalveolar cific antibody response. This inhibition af- lavage fluid in vivo or in culture medium fected Ig protein synthesis then membrane from bronchoalveolar lavage leucocytes bound major histocompatibility complex from smoke-treated animals. Anti-TNF class I expression. Supplementation with antibody did not abolish the increased epi- selenium significantly reduced the inhibi- thelial permeability produced by cigarette tory effectsNT004. IgE antibodies against crude smoke condensate. One hour after instilla- tobacco leaf were present in smokers, non- tion of cigarette smoke condensate there smokers, and ex-smokers, and the atopic in- was a marked decrease in the reduced glu- dividuals were far more likely to show such tathione content in the lung in association responses than nonatopic individuals. It has with increased oxidized glutathione levels. also been established that IgE antibodies Reduced glutathione levels in bronchoal- can be detected against at least three spe- veolar lavage fluid decreased following ciga- cific tobacco leaf allergens, namely crossed rette smoke condensateNT264. immunoelectrophoresis (CIE) antigens 19, Aldosterone synthesis inhibition. Nico- 23, and 30, but these IgE antibodies did not tine, anabasine, and cotinine, in freshly correlate with any type of clinical smoke isolated rat adrenal cells at concentrations sensitivity. There is no concrete evidence up to 100 mM, did not inhibit stimulated for the presence of IgE antibodies in man 286 MEDICINAL PLANTS OF THE WORLD against smoke extract. There is preliminary component that causes an autonomic evidence that smoke challenge under con- imbalance, hence rendering the mice more trolled conditions in an environmental susceptible to histamineNT185. Tobacco leaf chamber does not induce significant de- extract, administered to CFW female mice creases in forced expiratory volume in 1 sec- with developed type 1 skin and mast cell ond (FEV1) or peak flow in smoke-sensitive sensitivities, produced IgG1- and IgE- subjects, even though they complain of tobacco-mast-cell-sensitizing antibodies symptoms. Tobacco leaf was immunogenic detected by 2 and 48 hours after immuniz- in rabbits, but it is not known if any tobacco ationNT186. incineration products per se are immuno- Alveolar macrophages fluorescence. genic in manNT143. Tobacco glycoprotein Cigarette smoke, administered to rats at a from the cured leaf, administered intra- dose of two cigarettes for 1 or 5 days, pro- dermally by three injections to mice, pro- duced an increased fluorescence after 1 day duced a long-lasting IgE antibody response. of exposure and enhanced after 5 consecu- No hemagglutinating antibodies were pro- tive days. Larger and more granular/complex ducedNT163. Smoke from Kentucky Reference alveolar macrophages were more fluores- IRI cigarettes, administered in a Prototype cent than smaller and less granular/complex Mark II Walton Horizontal Smoke Expo- cells. Smoke-exposed rats (5 days of expo- sure Machine to Balb/c mice within 24 sure) lavaged immediately after the exposure hours after birth for up to 10 weeks, pro- had less cells in their bronchoalveolar lav- duced no difference in the magnitude of the age fluid than control animals. Rats lavaged splenic plaque-forming cells response in 3 smoke-free days after the exposure, pro- smoke-exposed and untreated control ani- duced an increase in cell recovery, probably mals immunized with sheep red blood resulting from to less airway obstructionNT283. cells on sequential days up to day 9 postpar- Analgesic activity. Nicotine or tobacco tum. On day 10, the plaque-forming cells’ smoke, administered to male Sprague– response of smoke-exposed mice was Dawley rats, produced analgesia measured reduced by 33%, on day 14, there was a by tail-flick latencies. A second treatment, 60% reduction, whereas animals exposed 24 hours after the first, failed to produce to smoke from 4 to 10 weeks showed a 90% analgesia, thereby demonstrating the rapid reduction of the splenic plaque-forming development of tolerance. The restraint, cells responseNT175. Tobacco smoke, admin- which was a necessary part of the tobacco istered to normal CFW mice, produced a smoke exposure, also produced analgesia, significantly increased susceptibility to the although of a more transient nature and lethal effects of histamine. The lethal dose lesser magnitude than that resulting from

(LD)50 for mice subjected to smoke was 45 tobacco smoke exposure. Tolerance also de- mg/kg of histamine, whereas in normal veloped to restraint stress-induced analge-

CFW mice the LD50 was 1.1 g/kg. The hista- sia. The long-term (43 weeks) daily mine susceptibility of smoked mice was exposure of rats to tobacco smoke or re- markedly diminished by injecting the straint stress resulted in the development of animals with isoproterenol. Normal CFW cross-tolerance. Long-term tobacco smoke mice and sham control mice exhibited an exposure resulted in increased tail-flick la- epinephrine-induced hyperglycemia, whereas tency when the animals had been with- the blood glucose values for smoked mice drawn from tobacco smoke for 24 hoursNT298. given epinephrine were similar to those for Anesthetic activity. Nicotine, adminis- sham mice given only saline. Results indi- tered to mice, increased the latent time of cated that tobacco smoke can contain a biting the clip in the tail press test (p < NICOTIANA TABACUM 287

0.001) and retarded tail withdrawal latency phytes var. granulareNT516. Undiluted metha- in the tail immersion test (p < 0.01), com- nol extract of the fresh leaf, on agar plate, pared to controlsNT081. was active on Aspergillus fumigatusNT604. Sa- Angiogenesis inhibition. Cigarette smoke ponin solution of the fresh seed, adminis- or smoke extract, administered to ulcerated tered to infected plants, was active on rats once daily for 3 days, produced con- Puccinia reconditaNT610. comitant and dose-dependent reduction of Antiglaucomic activity. Water extract of angiogenesis and constitutive nitric oxide the callus tissue, administered intrave- synthase activityNT232. nously to rabbits at a dose of 250 μg/animal, Antibacterial activity. Tincture of the produced a 55% drop in intraocular pres- dried leaf (10 g plant material in 100 mL sureNT443. ethanol), on agar plate at a concentration Antioxidant activity. Smoke, administered of 30.0 μL/disc, was inactive on Escherichia by inhalation to mice for 10 weeks, pro- coli, Pseudomonas aeruginosa, and Staphylo- duced an increase of catalase, glutathione coccus aureusNT607. Methanol extract of the peroxidase and glutathione reductase activ- dried leaf, on agar plate at a concentration ity. The activity of superoxide dismutase of 25 mg/mL, was active on Bacillus subtilis, was unalteredNT019. Administration to DBA/ Corynebacterium pyogenes, Pseudomonas 2, C57BL/6J, and ICR mice at a dose of 3 aeruginosa, Serratia marcescens, Shigella cigarettes/day 5 days/week for 7 months, dysenteriae, and Staphylococcus aureus and produced a decrease in the antioxidant inactive on Escherichia coli, Klebsiella defense of bronchoalveolar lavage fluids in pneumoniae, and Proteus vulgarisNT482. Smoke the DBA/2 and C57BL/6J strains and an condensate, in murine alveolar macrophage increase in ICR mice. Lung elastin content cell line (MH-S) cells, significantly en- was significantly decreased in DBA/2 and hanced the replication of Legionella C57BL/6J mice but not in ICR mice. Em- pneumophila in macrophages and selectively physema was present in DBA/2 and C57BL/ downregulated the production of inter- 6J but not in ICR mice. When administered leukin (IL)-6 and TNF-α induced by bacte- to pallid mice with a severe serum α(1)-pro- rial infectionNT027. teinase inhibitor (α[1]-PI) deficiency for 4 Anti-convulsant activity. Methanol (50%) months, there was an acceleration of the extract of the dried leaf, administered to development of the spontaneous emphy- mice, was active vs leptazol-induced sema assessed with morphometrical and convulsionsNT591. Ethanol (70%) extract of biochemical (lung elastin content) meth- the fresh leaf, administered intraperito- odsNT034. Rutin and chlorogenic acid from neally to mice of both sexes at variable STE leaf extract, in murine mast cell cul- doses, was active vs metrazole- and strych- ture, reduced reactive oxygen species levels nine-induced convulsionsNT580. and inhibited histamine release in antigen- Anti-estrogenic effect. Aqueous extract of IgE-activated cells. They augmented the the dried leaf smoke, administered to female inducible cytokine messages, i.e., IL-10, IL- adults at a concentration of 25.0 μL/plate, 13, interferon (IFN)-γ, IL-6, and TNF-α in was active on granulosa cells. Results signifi- IgE-sensitized mast cells after antigen cant at p < 0.001 levelNT595. challenge. Results indicated that tobacco Antifungal activity. Hot water extract of polyphenolic antioxidants differentially af- the dried leaf, in broth culture, was inactive fected two effector functions of antigen-IgE- on Epidermophyton floccosum, Microsporum activated mast cellsNT042. Cigarette smoke, canis, Trichophyton mentagrophytes var. administered to Sprague–Dawley rats for 2 algondonosa, and Trichophyton mentagro- hours/day for 4 weeks, enhanced N-methyl- 288 MEDICINAL PLANTS OF THE WORLD

D-aspartate receptor (NMDAR) subunits control levels. The distribution of manga- 2A and 2B concentrations in the hippoc- nese superoxide dismutase expression was ampus. Lipid peroxidation and antioxidant similar in control and smoke-exposed ani- enzyme activities did not show any change. mals. Catalase, copper–zinc superoxide The results indicated that cigarette smoke dismutase, glutathione peroxidase, and induces NMDAR 2A and 2B expression in metallothionein showed widespread expres- the hippocampus not because of an in- sion in the lung by in situ hybridization. creased lipid peroxidation but because Copper–zinc superoxide dismutase, glu- cigarette smoke has no effect on lipid tathione peroxidase, and metallothionein peroxidation and antioxidant enzyme were highly expressed in bronchial epithe- activities in the hippocampusNT199. Tobacco lium. Catalase expression levels were simi- smoke, administered to rats for 2 days or 8 lar in all cell types. Results indicated that weeks (6 hours/day, 3 days/week), signifi- most of these antioxidant enzymes and cantly increased the number of cells recov- scavengers showed prominent bronchial ex- ered by bronchoalveolar lavage (BAL). pression but that manganese superoxide Manganese(III)meso-tetrakis(N,N'-diethyl- dismutase showed a unique pattern, with 1,3-imidazolium-2-yl) porphyrin 10150 sig- intense hot spots in the epithelium of the nificantly decreased BAL cell number in small airwaysNT249. Water-soluble substances tobacco smoke-treated rats. Squamous cell in cigarette smoke in nerve terminals pre- metaplasia, following 8 weeks of tobacco pared from the rat cerebral cortex, signifi- smoke exposure, was 12% of the total air- cantly reduced the spontaneous increase in way epithelial area in animals exposed to thiobarbituric acid-reactive substances in tobacco smoke without AEOL 10150, com- synaptosomes in a dilution factor-depen- pared with 2% in animals exposed to to- dent manner. The aqueous extract also in- bacco smoke, but treated with AEOL 10150 hibited the elevation of lipid peroxidation (p < 0.05)NT201. Cigarette smoke, adminis- induced by 2,2'-azobis (2-amidinopropane) tered to albino rats for 30 minutes/day for dihydrochloride, a peroxyl radical genera- 30 days, increased the lipid peroxide levels tor. Smoke substances scavenged superox- in liver, lung, and kidney of smoke-treated ide radicals generated from stimulated rats. No changes were found in the brain human leukocytes and from the xanthine/ and heart. The activity of the antioxidant xanthine oxidase system. These effects were enzymes was also elevated in the livers, not mimicked by nicotine. The antioxidant lungs, and kidneys of the test animals. Brain effects of smoke substances were preserved and heart did not show any change in the for several days at 5°C or –80°CNT252. Ciga- activities of all of these antioxidant en- rette smoke, administered to rats for 3 zymes, except an increase of glutathione-S- months, decreased activities of glutath- transferase in brain. The level of reduced ione reductase, catalase, and brush-border glutathione was lowered in the livers, lungs, enzyme L-glutamyl transpeptidase and the and kidneys of the test animals when com- levels of glutathione in the kidney. The pared to controls. There were no significant activities of glutathione peroxidase and changes in brain and heartNT220. Whole ciga- lipid peroxide levels were increased. Urinary rette smoke, administered to rats daily for 1, excretion of L-glutamyl transpeptidase, glu- 2, 7, or 14 days, increased expression of tathione, and lipid peroxide were also manganese superoxide dismutase, glu- higherNT263. tathione peroxidase, and metallothionein. Antistress effect. Smoke of the dried leaf, Copper–zinc superoxide dismutase and administered to rats at variable doses, pro- catalase expression did not change from duced equivocal activity. Smoke, adminis- NICOTIANA TABACUM 289 tered to C57B1/6 and Balb/c mice, and induced apoptosis. A mixture of sidestream MNRA and MR rats in a chamber for 19 and mainstream smoke, administered to days, produced no emotional-stress reaction. Sprague–Dawley rats for 28 days, produced A difference in the free preference of space a more than 10-fold increase in the fre- containing tobacco smoke was observed quency of pulmonary alveolar macrophages among inbred animals with active and undergoing apoptosis. Exposure to smoke passive emotional-stress reaction pheno- produced an acute increase of cells positive typesNT043. for proliferating cell nuclear antigenNT213. Antiviral activity. Leaf, on agar plate at a Cigarette smoke, administered to rats at concentration of 2%, was active on herpes concentrations of 2 and 4% for 1 hour daily simplex 1 virus and reduced plague forma- for 1, 3, 6, and 9 days, produced a time- and tion in monkey kidney cells. Undiluted concentration-dependent increase in apop- leaves produced strong activity on Cox- tosis in the rat gastric mucosa. The effect sackie B5 virus, herpes simplex 1 virus, and was accompanied by an increase in xanthine measles virus. Viral reproduction was inhib- oxidase activity. The increased apoptosis itedNT574 and xanthine oxidase activity could be Anti-yeast activity. Tincture of the dried detected after even a single exposure. In leaf (10 g plant material in 100 mL etha- contrast, the p53 level was elevated only in nol), on agar plate at a concentration of 30 the later stage of cigarette smoke exposure. μL/disc, was inactive on Candida albi- The apoptotic effect could be blocked by cansNT607. pretreatment with xanthine oxidase inhibi- Apoptosis. Smoke extract, in rat lung al- tor (allopurinol, 20 mg/kg intraperitoneally) veolar L2 cells, induced apoptotic cell or a hydroxyl free radical scavenger (dim- death. A concentration of 0.25% resulted in ethyl sulfoxide [DMSO], 0.2%, 1 mL/kg in- a 50% increase of caspase-3 and matrix travenously). Neither of these treatments metalloproteinase activitiesNT191. Chloro- had any effect on the p53 level of the form extract of the cigarette smoke, in a mucosaNT221. human gastric epithelial cell line (AGS) for Aromatase inhibition. Aqueous extract of 5 hours, induced apoptosis in a dose- and cigarette smoke, administered to female time-dependent manner in AGS cells and a adults at a concentration of 25 μL/plate, was decrease of bcl-2 and an increase of caspase- active on granulosa cellsNT595. Synthesis and 3 activity. Pretreatment with Z-DEVD- testing of a series of acylated nornicotines FMK (specific inhibitor of caspase-3) and anabasines for their ability to inhibit dose-dependently blocked the DNA frag- aromatase showed an interesting correlation mentation induced by the chloroform of activity with the length of the acyl car- extract. Chloroform extract time- and dose- bon chain, with maximum activity at C-11. dependently increased the level of cyto- The acylated derivatives showed activity, chrome C in the cytoplasm, which might which was significantly greater than that of activate caspase-3. The ethanol extract was nicotine and anabasine. In vivo studies in not activeNT197. Mainstream cigarette smoke, rats indicated that administration of this administered to Sprague–Dawley rats for 18 inhibitor delayed the onset of nitroso- or 100 days, produced a significant and methyurea (NMU)-induced breast carci- time-dependent increase in the proportion noma and altered the estrous cycle by of apoptotic cells in the bronchial and bron- suppression of the aromatase enzyme system. chiolar epithelium. Oral N-acetylcysteine Toxicity studies indicated relatively low did not affect the background frequency of toxicity with LD50 for N-N-octanoylnorni- apoptosis but significantly decreased smoke- cotine at 367 mg/kg body weightNT294. 290 MEDICINAL PLANTS OF THE WORLD

Arrhythmogenic effect. Water extract of cantly increased the colony numbers of all the dried leaf, administered intravenously to isolated bacteria species in smoke-treated cats at doses of 10–20 mg/kg, produced weak rats than in the control group and in the activityNT588. smoke- and vitamin E-supplemented rats Arterial endothelial injury. Environmen- (p < 0.05). Only Staphylococcus aureus and tal smoke, administered to ovariectomized Staphylococcus epidermidis were isolated from rats treated with subcutaneous placebo or vitamin E-supplemented ratsNT234. 17-β-estradiol pellets for 6 weeks, produced Behavioral changes. Nicotine, adminis- a more than fourfold increase of carotid ar- tered to rats for 7 days, significantly in- tery low-density lipoprotein (LDL) accumu- creased rat locomotion activity. This lation compared with filtered air exposure. sensitization to nicotine was blocked by The effect was largely mediated by increased mecamylamine (1 mg/kg) and by the admin- permeability. No protective effect of estra- istration of 6 mg/kg of the following diol was observed. Acute smoke exposure of cembranoids: eunicin, eupalmerin acetate a buffer solution containing LDL produced (EUAC), and (4R)-2,7,11-cembratriene-4- a more than sixfold increase in the highly 6-diol (4R). None of these compounds reactive carbonyl glyoxal. Perfusion of this modified locomotor activity of nonsensi- solution through carotid arteries produced tized ratsNT210. Nicotine, administered by 105% increase in permeability. Perfusion of continuous infusion to adolescent rats on glyoxal alone produced a 50% increase in postnatal days 30 to 47.5, using a dosage carotid artery permeabilityNT202. regimen that maintains plasma levels simi- Aryl hydrocarbon hydroxylase induc- lar to those found in smokers or in users of tion. Smoke of cured leaf, administered by the transdermal nicotine patch, produced a inhalation to mice and rats at an undiluted decrease of grooming in female rats on 44 concentration, produced an induction in day of administration, an effect not seen in lungs and kidneys. There was no induction males. This effect is opposite to the effects in bowels and liverNT403. of nicotine in adult rats. Two weeks after Atherogenic effect. Smoke, administered cessation of nicotine administration, fe- by inhalation to mice for 10 weeks, pro- males showed deficits in locomotor activity duced an increase of lipid peroxidation and and rearing. The males again were unaf- a decrease of reduced glutathione level in fected. The behavioral deficits appeared at the heart. Levels of total cholesterol, LDL the same age at which gender-selective cholesterol, and triglycerides were in- brain cell damage emerges. Nicotine expo- creased. The high-density lipoprotein sure enhanced passive avoidance, with the (HDL) cholesterol levels decreased in effect intensifying and persisting throughout serumNT019. the posttreatment periodNT216. Smokeless to- Bacterial colonization of lower respira- bacco extract (STD), administered by gav- tory tract. Cigarette smoke, administered age to pregnant Sprague–Dawley rats on for 3 days before and after intratracheal in- gestational days 6–20 at doses equivalent to stillation of bacterial suspension containing 1.33 (STD-1), 4 (STD-2), and 6 mg nico- six bacterial species (Staphylococcus aureus, tine/kg (STD-3) three times daily, reduced Staphylococcus epidermidis, Streptococcus maternal weight gain at the 2 higher doses. pneumonia, Proteus mirabilis, Haemophilus in- During the preweaning period, significant fluenza, Peptostreptococcus spp.) to male pup weight reductions were noted in the Wistar albino rats with or without vitamin STD-2 pups until postnatal day 6 and in the E supplements (100 mg/kg/day), signifi- STD-3 group until postnatal day 15. In the NICOTIANA TABACUM 291

STD-1 group, no statistically significant divided into two groups. One was fed a vita- weight reduction was noted. The incidence min A diet, and the other was fed a vitamin of deaths was increased in a dose-related A-deficient diet. In the vitamin-deficient manner. No significant differences were group, treatment with the extract increased noted for pinna detachment and incisor benzphetamine demethylase level vs con- eruption. Smoke treatment significantly trolNT519. affected earlier eye opening and vaginal Biochemical effect. Tobacco smoke was ad- patency. No significant effects were seen on ministered by inhalation in Hamburg II ma- negative geotaxis, but for surface righting, a chine to senescence accelerated SAM-P/8 decreased success rate was noted. Open field and SAM-R/1 mice 10 minutes/day, 5 days/ activity increased from the preweaning to week for 5 weeks. The treatment increased postweaning periods. During the prewean- lung weight and the ratio of albumin to total ing period, the STD-3 offsprings were more protein in the bronchoalveolar lavage fluid, active, and during postweaning, the STD-1 a decrease elastase inhibitory capacity/ offsprings were more active. No difference trypsin inhibitory capacity in broncho- was noted in vertical activity or in the num- alveolar lavage fluid, and a decrease in the ber of stereotypical movements. No treat- glutathione (GSH) content and the GSH/- ment-related difference was noted in the sulfhydryl (SH) ratio of the lung, compared active avoidance shuttle boxNT277. with those not exposed. There was focal in- Benzo(a)pyrene hydroxylase induction. filtration of macrophages into alveoli with Masheri, a pyrolyzed tobacco product, ad- hyaline membrane and thickened alveolar ministered orally to Swiss mice, Sprague– wall in SAM-P/8 with tobacco exposureNT110. Dawley rats, and Syrian golden hamsters at Birth-weight effect. Cigarette smoke, ad- a dose of 10% diet for 20 months, produced ministered to pregnant rats daily for a 2- a significant induction of cytochrome P450 hour period throughout gestation, and benzo(a)pyrene hydroxylase in proxi- significantly decreased the average birth- mal and distal parts of the three species NT100. weight of pups compared with both pair-fed Benzopyrene hydroxylase induction. and ad libitum control groups. The body Methyl chloride extract of the leaf, admin- weights of the pups exposed to smoke were istered intragastrically to rats at a dose of 3 no longer significantly different from those mg/animal daily for 21 months in DMSO in the pair-fed and ad libitum control groups solvent, was active. The rats were divided at weeks 1 and 2 after birth, respectively. into two groups. One was fed a vitamin A The study indicated that fetal growth retar- diet, and the other was fed a vitamin A-de- dation caused by exposure to cigarette ficient diet. Treatment with the extract in- smoke during pregnancy does not persist creased pulmonary and hepatic benzopyrene after birthNT273. hydroxylase level over controls in both Blood pressure effect (biphasic). Water groups. The vitamin A-deficient group had extract of the dried leaf, administered intra- significantly higher hepatic and lower pul- venously to cats and rats at doses of 0.1 and monary levels when compared to the vita- 5–20 mg/kg, produced an initial hypoten- min-fed groupNT519. sive effect followed by hypertensionNT588. Benzphetamine demethylase stimula- Breathing inhibition. Cigarette smoke tion. Methyl chloride extract of the leaf, ad- from low-nicotine research cigarettes and ministered intragastrically to rats at a dose gas phase smoke obtained by passing the of 3 mg/animal daily for 21 months in smoke through a glass-fiber Cambridge filter DMSO solvent, was active. The rats were was administered to anesthetized Sprague– 292 MEDICINAL PLANTS OF THE WORLD

Dawley rats at a dose of 6, 50%. Inhalation of values significantly higher than those in gas phase smoke alone evoked a transient in- marijuana smoke-treated mice. Mice ex- hibitory effect on breathing, prolonging ex- posed to six or eight puffs of tobacco smoke piratory time (Te) to a peak of 159 ± 6% of had mean carboxyhemoglobin values of the base line. The response was similar to 24.6 and 28.5% saturation, respectively. No that triggered by inhaling the unfiltered acute lethal effects were observed in mice smoke (Te = 177 ± 12%). The bradypnea receiving multiple daily episodes of eight started within 1–4 breaths after the onset of puffs per episode of marijuana smoke, smoke inhalation, lasted for three to five whereas mice exposed to a single eight-puff breaths and was completely abolished by episode of tobacco smoke suffered approx vagotomy. This inhibitory effect of gas phase 50% acute lethal effectsNT135. smoke on breathing was also largely prevented Carcinogenic activity. Methyl chloride after a pretreatment with either intravenous extract of the leaf, administered intragas- infusion or aerosol inhalation of a hydroxyl trically to rats at a dose of 3 mg/animal daily radical scavenger, dimethylthioureaNT292. for 21 months in DMSO solvent, was active. Bronchoconstrictor activity. Inhalation The rats were divided into two groups. One of cured leaf, administered to adults as an was fed a vitamin A diet, and the other was undiluted concentration, was active on fed a vitamin A-deficient diet. Cumulative asthmaNT381. tumor incidence in vitamin-deficient rats Bupivacaine kinetics. Smoke, adminis- was significantly greater than that in vita- tered by Hamburg II smoking machine to min-fed rats. Vitamin-deficient rats had a mice for 4 or 8 days, produced no effect after preponderance of pituitary adenomas, 4 days and a significant increase of metabo- whereas vitamin-fed rats showed lung and lism and elimination of bupivacaine in the forestomach tumorsNT519. Smoke and snuff of treated group. The smoke acted at different the dried leaf, administered to adults at vari- levels, i.e., metabolism, elimination and able doses, were activeNT329. Forty-one users binding of bupivacaine, increased the per- of STE and 38 cigarette smokers, produced meability of the cell membranes, and facili- a decrease of total [4-(methylnitrosamino)- tates the penetration of bupivacaine and 1-3-pirydyl)-1-butanone and its glucu- desbutylbupivacaine in erythrocytesNT067. ronide] in users of STE and smokers. The Cadmium-induced alterations. Main- 1-hydroxypyrene level was unchanged in stream smoke generated from University of tobacco smokers and reduced in smokers Kentucky 2R1 reference cigarettes, admin- who used medicinal nicotine (nicotine istered to cadmium-treated young female patch). The overall mean total [4-(methyl- Long–Evans rats at a dose of 10 puffs daily nitrosamino)-1-3-pirydyl)-1-butanone and for 12 weeks, produced no significant its glucuronide] levels among smokers who changes in lung function or morpho- used the nicotine patch was significantly metryNT285. lower than among smokers who used the Carboxyhemoglobin effect. Cigarette OMNI cigaretteNT001. A mixture of side- smoke was administered by inhalation with stream and mainstream smoke, adminis- a modified Walton horizontal smoke expo- tered to male A/J mice at concentrations of sure machine to mice at intermittent doses. 99, 120, and 176 mg/m3 of total suspended During the first 30 seconds of each 1-minute particulate material for 5 months, produced cycle, the subjects were exposed to smoke significantly more lung tumors by the high- diluted either 1:10 or 1:5 with air. This est smoke concentrations, although re- treatment produced carboxyhemoglobin sponse to the high dose was slightly less than NICOTIANA TABACUM 293 response from the medium dose. Lung tumor for 90 days, produced an accumulation of incidences were in all three groups signifi- indistinct filamentous material in the cantly higher than in controls. Lung dis- perisinusoidal spaces, disintegration of lip- placement volume and plasma cotinine ids, and a significant increase in heat stress/ level were increased in a dose-dependent shock protein 90 expressionNT058. Environ- mannerNT006. Tobacco specific nitrosamines mental tobacco smoke, administered by were administered to a line of human whole body exposure to male strain A/J mice papillomavirus-immortalized bronchial epi- at concentrations of 87 mg/m3 of total sus- thelial cells at concentrations of 100 or 400 pended particulate matter, 16 mg/m3 nico- μg/mL for 7 days. The transformed cells tine, and 246 ppm CO for 6 hours/day, 5 produced progressively growing subcutane- days/week 5 months, produced lung tu- ous tumors on inoculation into nude mice. mors. More than 80% of all tumors were Immunofluorescence staining for keratin adenomas, and the rest were adenocarci- expression confirmed the epithelial nature nomasNT064. Mainstream smoke, adminis- of the tumor cells. There was an increased tered to male Balb/c mice for 4 months expression of p16, β-catenin and proliferat- starting 10 or 30 days before the administra- ing cell nuclear antigen (PCNA) in the tion of ethyl carbamate, produced 7.6% de- established cell lineNT014. Smoke, adminis- crease of lung adenoma multiplicity. The tered to male strain A/J mice at a concen- number of ethyl carbamate-induced lung tration of 140 mg/m3, 6 hours a day, 5 days/ tumors was not significantly affected by week for 4–5 months, increased plasma β- exposure to cigarette smoke when ethyl car- carotene level and lung tumor multiplicities bamate was injected intraperitoneally in and incidences but had no significant effect single doses of 0.5 or 1 g/kgNT073. Smoke con- on lung β-carotene levels. β-carotene sup- densate, administered dermally to Balb/c plementation failed to modulate tumor mice, increased the density and changed the development under all exposure condit- morphology of Langerhans’ cells. The num- ionsNT026. Smoke was administered to male ber of Langerhans’ cells in epidermal sheets strain A/J mice on a diet of Bowman–Birk of treated mice was significantly higher than protease inhibitor concentrate (BBIC) at a in the controls and remained elevated for concentration of 1% in AIN-93G diet ei- 35 weeks. Langerhans’ cells became less ther during smoke exposure, after exposure dendritic, or even rounded in shape, and or for 9 months. The mice were exposed to smaller in size. The function of the morpho- 89% cigarette sidestream and 11% main- logically altered Langerhans’ cells was im- stream smoke 6 hours a day, 5 days/week for paired. There was skin tumor development 5 months and then allowed to recover for in all treated mice. After stopping the treat- another 4 months in air. As a positive con- ment, Langerhans’ cells number in skin trol, the mice were injected with 3-methyl- tumors and around lesions remained in- cholanthrene and fed a diet containing 1% creased. Tumor regression occurred in 23% BBIC. These animals were sacrificed 5 of tumors. The remaining tumors showed a months later. In the animals treated with 3- 50% reduction in sizeNT077. Smoke, in pulmo- methylcholanthrene, BBIC decreased lung nary and liver microsomes of male NMRI tumor multiplicities, whereas in the smoke- mice, induced the enzymatic activities exposed mice, BBIC did not modulate lung cata-lyzed by CYP1A1, CYP2B, CYP2C, tumor developmentNT028. Aqueous extract of CYP2D, CYP2E1, and CYP3A in liver the STE, administered orally to female microsomes. Immunoquantification of Sprague–Dawley rats at a dose of 25 mg/kg lung and liver CYP1A1, 2E1, and 3A dem- 294 MEDICINAL PLANTS OF THE WORLD onstrated the following: CYP1A1 was in- smoke-treated mice. Comparing the treated duced in lung and liver; CYP3A subfamily groups with the negative controls, the over- was induced in liver and not detected in all carcinogenic effect observed was statisti- lung; and CYP2E1 was slightly induced in cally significant. Comparing both treated liver, whereas its pulmonary expression groups with each other, the overall carcino- was more largely increased (6.8 fold) than genic effect of sidestream smoke was much CYP1A1 (twofold). This indicates that higher than that of mainstream smokeNT113. CYP2E1, which is known to be expressed N-nitrosamines: 3-(methylnitrosamino)- in human lung, could actively participate in propionic acid (NMPA), NNK, and iso- pulmonary carcinogenesis induced by NNAC, evaluated in A/J mice, produced cigarette smokeNT080. Six tobacco-specific the following results in the lung (total N-nitrosamines and two major volatile N- dose in micromol mouse/lung tumors per nitrosamines of cigarette smoke, adminis- mouse): NMPA (200/7.1 ± 2.9), NNK (2/ tered to female A/J mice, were active. 15.7 ± 4.1), iso-NNAC (200/0.24 ± 0.43), N-nitrosodimethylamine was the most po- and saline control (0.2 ± 0.4)NT115. Brown tent inducer of lung adenoma in the A/J and black varieties of a pyrolyzed tobacco mouse model, followed in order of de- (masheri), was administered to Sprague– creasing potencies by 4-(methylnitro- Dawley rats, Swiss mouse, and Syrian golden samino)-1-(3-pyridyl)-1-butanone (NNK), hamsters at a dose of 10% of diet. In 4-(methylnitrosamino)-1-(3-pyridyl)-1-bu- Sprague–Dawley rats, only brown masheri tanol (iso-NNAL), N-nitrosopyrrolidine was used, whereas in Swiss mice and Syrian (NPYR), N'-nitrosonornicotine (NNN), golden hamsters, both varieties were used. and N'-nitrosoanabasine (NAB). NNK and Forestomach papillomas were induced in 4-(methylnitrosamino)-4-(3- 37% of the rats, 42–47% of the mice, and pyridyl)butyric acid (iso-NNAC) were 25–43% of the hamsters. No malignant inactiveNT087. Iso-NNAC, administered to changes were observed in any of the groups strain A mice, was inactive as a tumorigenic except two of the 23 male hamsters that agent, and it did not induce DNA repair in showed forestomach carcinoma in the black primary rat hepatocytesNT107. Acetone/meth- masheri diet groupNT122. NNN, NNK, NPYR, anol extracts of sidestream and mainstream 5'-carboxy-N '-nitrosonornicotine smoke condensates of a filtered commercial (CNNN), N-nitrosoproline (NPRO), and brand of blond cigarettes, administered on 1-(3-pyridyl)-2-buten-1-one (PBO), admin- the shaved skin of female NMR1 mice twice istered to A/J mouse, produced the follow- a week for 3 months, produced no signifi- ing results (dose in micromol per mouse/ cant difference between the life span of lung tumors per mouse): NNN (100/1.8 ± mainstream smoke-treated and untreated 1.4), NPYR (100/3.9 ± 1.5), CNNN (200/ mice. The life spans of sidestream smoke- 0.3 ± 0.5), CNNN (100/0.5 ± 0.6), NPRO treated mice were significantly shorter than (100/0.6 ± 0.7), NNK (20/7.2 ± 3.4), PBO those of mainstream smoke-treated mice. (20/0.7 ± 1), and saline control (0.5 ± 0.7). The numbers of tumors or lesions in main- NNK and NPYR were more tumorigenic stream smoke-treated mice were not in- than NNN. CNNN was nontumorigenicNT123. creased dose-dependently. The initiation of Smoke condensate, administered intragastri- lesions in sidestream smoke-treated mice was cally to Swiss mice, did not produce any tu- dose-dependent. The sidestream smoke- mor. Bidi concentrate, at the same dose, treated mice developed two to six times induced liver hemangiomas, forestomach more skin tumors than the mainstream papilloma, and carcinomas of the esophagus NICOTIANA TABACUM 295 and forestomach. Bidi concentrate had a tions, produced in mice, significantly el- higher benzo[a]pyrene level than cigarette evated levels of blood COHb and pulmo- smoke condensateNT126. NNK, iso-NNAL, nary aryl hydrocarbon hydroxylase activity, and NNN, administrated dermally to female and a fivefold to sevenfold increase in the SENCAR mice at an initiator dose of 28 number of bronchoalveolar lavage cells. μmol/mouse in 10 subdoses administered The proportion of neutrophils increased to every second day. Promotion commenced 18 ± 3% in smoke-exposed mice as com- 10 days after the last initiator dose and con- pared to less than 1% in controls. Cessation sisted of twice weekly application of 2. μg of of smoke treatments returned the propor- tetradecanoylphorbol acetate for 20 weeks. tion of neutrophils to those of controls NNK induced a 79% incidence of skin within 5 weeks. Smoke exposure of rats for tumors with an average of 1.6 tumors/mouse up to 32 weeks induced appreciable changes and a 59% incidence of lung adenomas. Iso- in the number and proportion of macro- NNAL and NNN were not active. At a total phages and neutrophils. Large brown mac- initiator dose of 28 and 5.6 μmol/mouse, rophages were observed in smoke-exposed NNK induced a 59 and 24% incidence of groups of both species. Bronchoalveolar la- skin tumors, respectively. In this dose re- vage cells from smoke-treated mice but not sponse bioassay, NNK at a total initiator rats released greater amounts of superox- dose of 28 μmol induced a 63% incidence of ides than controls under resting and lung adenomas. The numbers of lung ad- phagocytically stimulated conditions. The enomas induced at the lower doses em- activity of N-acetylglucosaminidase was ployed were not significant. NNK, at a total increased in both species. The activity of 5'- initiation dose of 1.4 μmol, did not exhibit nucleotidase was significantly reduced in significant tumorigenic activityNT129. Fresh, macrophages from mice but not rats. The whole cigarette smoke of Kentucky refer- activity of leucine aminopeptidase remained ence 2R1 cigarettes was administered intra- unaltered in both speciesNT141. Tobacco al- nasally to 2053 (C57BL/Cum × C3H/ coholic extract, administered intragastri- AnfCum)F1 female mice daily 5 days/week, cally or in the diet of male Swiss mice, for 110 weeks, produced a weak carcino- increased the incidence of lung and liver genic activity in mouse lung tissue, and an tumors. An additive effect of tobacco ex- increased incidence of pigmented alveolar tract and hexachlorocyclohexane on liver macrophage accumulation, otitis media, tumor induction was foundNT154. The weakly head and neck fibrosarcoma, and deposition acidic fraction of cigarette smoke conden- of smoke particulates approx 125–200 mg sate subfractions II, administered dermally total particulate matter/lung/day. The only with 0.003% benzo[a]pyrene to noninbred lung cancers observed in 19 of 978 smoke- Ha:ICR Swiss albino mice, produced signifi- exposed mice were diagnosed as alveolar cant cocarcinogenic activity (subfractions adenocarcinomas. A significant increase in A-C and F-J); subfractions A, F, and H were the incidence of lung cancer was observed the most active. Catechol was a major com- in one subset, but this difference was not ponent of subfraction A and was also de- found in the population as a whole or as a tected in subfractions B–D and F. Major result of any other analysesNT140. Fresh main- components of the other subfractions in- stream smoke from one University of cluded hydroquinone (B), coniferyl alcohol Kentucky reference cigarette (2R1), admin- (C and H), hydroxyphenyl alcohols (D), istered intranasally to male C57BL mice and alkyl-2-hydroxy-2-cyclopenten-1-ones (C, F-344 rats daily under standardized condi- D, and F), hydroxyacetophenones (F), phe- 296 MEDICINAL PLANTS OF THE WORLD nolic cyano compounds (F), and fatty acids inhibited benzo[a]pyrene carcinogenicity (F). The results indicated the importance completely: esculin, quercetin, squalene, of catechol as a cocarcinogen in the weakly and oleic acid. Phenol, eugenol, resorcinol, acidic fraction of cigarette smoke conden- hydroquinone, hexadecane, and limonene sateNT171. Methanol (80%) insoluble fraction partially inhibited benzo[a]pyrene carcino- of aqueous extract of tobacco combined genicity. No direct correlation existed be- with the methanol soluble fraction was tween tumor-promoting activity and administered to mice treated with 7,12- cocarcinogenic activity. The cocarcinogens dimethylbenz[a]anthracene. The subfraction pyrogallol and catechol did not show tumor- (D) with a presumptive molecular weight promoting activity. Decane, tetradecane, greater than 13,000 produced a significantly anthralin, and phorbol myristate acetate higher tumor incidence and tumor yield, showed both types of activitiesNT183. Acetone together with a significantly shorter latent and alcohol extracts of the flue-cured to- period than the other subfractions. Sub- bacco, administered dermally to mice, pro- fraction D contained approx 12% of the duced weak activity. Chloroform/water total 80% methanol insoluble material. extract produced tumor in 38% of the ani- All of the other subfractions exhibited mals and was about fivefold more active significant but less pronounced tumor than smoke condensate derived from an copromoting activityNT173. Undifferentiated equal weight of tobaccoNT184. NNN induced carcinomas of the salivary glands were found adenomas of the lung in mice. Bioassays of in two of 44 strain A mice injected intrap- NNN in rats indicated carcinogenic activi- eritoneally with an N-nitrosonornicotine. ties on the esophagus and the nasal The presence of intranuclear rodlets in the cavityNT187. Weakly acidic fraction of ciga- salivary carcinomas provided the first dem- rette smoke particulate matter were tested onstration of such structures in a non- on initiated mouse skin by long-term appli- neuronal tumor in mice. Two types of cation. Two of these subfractions (40% of rodlets were exhibited: one was composed weakly acidic fraction) were inactive, and of fibrillar filaments arranged in bundles, the 18 and 35% of weakly acidic fractions and the other was much thicker and branch- showed tumor-promoting activity. Cat- ing in form. Results indicated that these echol, hydroquinone, 3-hydroxypyridine, 6- intranuclear rodlets were closely associ- methyl-3-hydroxypyridine, linolenic acid, ated with nuclear chromatin or nucleoliNT179. and linoleic acid were inactive as tumor pro- NNK, NNN, and 4-(N-methyl-N-nitro- moters in the experimental animalNT188. [5- samino)-4-(3-pyridyl)butanal (NNA), ad- (3)H]-(S)-NNN, in rat esophagus culture ministered to strain A mice, were active. at a concentration of 1 μM, was predomi- NNK induced more lung adenomas per nantly metabolized to products of 2'- mouse than NNN, and NNA was less active hydroxylation, 4-oxo-4-(3-pyridyl)butanoic than NNN. Two cases of undifferentiated acid (ketoacid), and 4-hydroxy-1-(3-pyridyl)- carcinoma of the salivary glands occurred in 1-butanone. The major metabolite of (R)- the NNN experimental groupsNT181. Smoke NNN under these conditions was 4-hy- components, administered dermally to droxy-4-(3-pyridyl)butanoic acid, a product female ICR/Ha Swiss mice three times a of NNN 5'hydroxylation. The 2'-hydroxyla- week with 5 μg benzo[a]pyrene per applica- tion:5'-hydroxylation metabolite ratio tion, enhanced the carcinogenicity of benzo- ranged from 6.22 to 8.06 at various time in- [a]pyrene by catechol, pyrogallol, decane, tervals in the incubations with (S)-NNN. undecane, pyrene, benzo[e]pyrene, and The corresponding ratios were 1.12-1.33 in fluoranthene. The following compounds the experiments with (R)-NNN. These dif- NICOTIANA TABACUM 297 ferences were statistically significant (p < wood smokes condensates were evaluated 0.001). Because 2'-hydroxylation is thought on isolated capsulated rat lenses incubated to be the major metabolic activation for varying periods, with and without anti- pathway of NNN in the rat esophagus, the oxidants, in the presence and absence of results demonstrated that (S)-NNN is meta- light. The smoke condensates permeated bolically activated more extensively than the lens capsule and impart color and (R)-NNN and, therefore, may be more opacify to the lens in a light- and dose-de- carcinogenic. [5-(3)H]-(R)-NNN, [5-(3)H]- pendent manner. Antioxidants offer partial (S)-NNN, or racemic [5-(3)H]NNN, admin- inhibition against the damages. Smoke-in- istered intragastrically to rats at dose of 0.3 duced damage possibly occurs through sys- mg/kg, was metabolized to hydroxylacid and temic absorption and transport of toxic ketoacid. Products of 2'-hydroxylation pre- components to several tissues, specially into dominated in the urine of the rats treated the lens. The turnover is slow, leading to with (S)-NNN, whereas products of 5'-hy- chronic accumulation causing oxidative droxylation were more prevalent in the rats damage to the constituent molecules and NT274 treated with (R)-NNN. 2'-Hydroxyla- consequently to lenticular opacity . tion:5'-hydroxylation metabolite ratios Cell differentiation induction. Water ex- ranged from 1.66 to 2.04 in the urine at vari- tract of the dried leaf, administered to CBA/ N strain mice at a concentration of 0.5%, ous times after treatment with (S)-NNN, was active on lymphocytes BNT449. A to- while the ratios were 0.398–0.450 for the bacco-specific carcinogen NNK, in cell rats treated with (R)-NNN (p < 0.001). The culture, produced activation of the phos- results indicated that the carcinogenicity of phatidylinositol 3'-kinase/Akt pathway (S)-NNN, the predominant enantiomer in (P13K/Akt). The pathway was evaluated in tobacco products, may be greater than that NT223 isogenic immortalized or tumorigenic hu- of (R)-NNN or racemic NNN . man bronchial epithelial cells in vitro and Cardiovascular effect. Water extract of in progressive murine lung lesions. Com- the dried leaf, administered intravenously to pared with immortalized cells, tumorigenic cats and rats at doses of 10–20 mg/kg, in- cells had greater activation of the P13K/Akt duced variable electrocardiogram patterns, pathway, enhanced survival, and increased including increases in the height of the apoptosis in response to inhibition of the QRS complexes, S-T segment elevation, pathway. In vivo, increased activation of occasional extrasystoles, and arrhyth- Akt and mammalian target of rapamycin miasNT588. were observed with increased phenotypic Cataractogenic effect. Cigarette smoke progressionNT005. was administered to male Wistar rats for 90 Cell metabolism induction. Methanol ex- days, with or without vitamin E supplement. tract of STE, in collagen-producing cells, The treatment significantly increased iron stimulated glycolysis by 80% in cartilage but levels in the lenses of smoke-treated group. was not affected in the other tissues. Me- Smoke-treated rats and smoke-treated and dium alkaline phosphatase activity was un- vitamin-supplemented rats had significantly affected. In the frontal bone and cartilage, higher cadmium levels. Vitamin E treat- [3H]hydroxyproline and [3H]proline con- ment prevented iron accumulation in tents were decreased. Neither was affected smoke-treated and vitamin-supplemented in the aorta. rats. Distinct histopathological changes Cell proliferation. Snuff extract in combi- observed in smoke-treated rats were not nation with DMBA, in primary embryonal present in smoke-treated and vitamin- mouse tongue culture, inhibited the prolif- supplemented ratsNT236. Cigarette and fire- eration of cells and decreased ornithine 298 MEDICINAL PLANTS OF THE WORLD decarboxylase and hydrocarbon hydroxy- a normal complement of β-receptor bind- lase activities, compared to controlNT109. ing sites. In the heart, smoke evoked a de- NNN, in embryonic mouse tongue epithe- crease in M2-receptor expression. In both lial cells, increased [3H]dT uptake, and or- tissues, the effects of postnatal smoke, nithine decarboxylase and aryl hydrocarbon mimicking passive smoking, were equiva- hydroxylase activities. NNK produced fur- lent to adenylyl cyclase level or greater than ther increases of [3H]dT uptake, cell count, (M2-muscarinic cholinergic receptors) and ornithine decarboxylase. The extract those seen with prenatal smoke mimicking had an inhibitory effect on cell count, active smoking. The effects of combined [3H]dT uptake, ornithine decarboxylase, prenatal and postnatal exposure were and aryl hydrocarbon hydroxylase activi- equivalent to those seen with postnatal ex- ties when administered alone or in combi- posure alone. The smoke exposure evoked nation with NNN or NNKNT120. Tobacco changes in cell signaling that recapitulate and tobacco smoke constituents, in ascites those caused by developmental nicotine sarcoma BP8 cell culture, indicated that treatmentNT208. the most active constituents were unsat- Cervical carcinoma. Smoke condensate, urated aldehydes and ketones, phenols, in human papillomavirus 18-immortalized and indolesNT189. Smoke, administered to ectocervical cells (HEC-18-1C), produced Sprague–Dawley rats at a dose of 10 ciga- an invasive squamous cell carcinoma, from rettes (smoke only), or the smoke of 10 ciga- which was established a clonal line of cells rettes after iv infusion of endothelin A (HEC-18-1CT). The moderate passage ma- antagonist BQ-610 (smoke and BQ-610), lignantly transformed HEC-18-1CT dis- produced significant cell proliferation in played severe dysplasia/carcinoma in situ in the airway epithelium and wall, in the raft cultureNT620. peribronchiolar arterial endothelial com- C-fos expression. Mainstream smoke partment, and in the endothelial and wall trapped in PBS solution, in quiescent Swiss compartments of the perialveolar ductular 3T3 cells, produced dose-dependent expres- arteries. Pretreatment with BQ-610 reduced sion of c-fos mRNA and protein. C-fos tran- the peribronchiolar arterial endothelial and scripts in cells exposed to 0.03 puffs (approx the perialveolar ductular arterial wall pro- 1 cm3) of smoke per medium, accumulated liferation to control levels and reduced, but slowly but were still seen after 8 hours. The did not totally abrogate, the smoke-induced maximum expression rates were between proliferation of the airway epithelial, airway 2 and 6 hours of exposure. An increase of wall, and perialveolar ductular arterial c-fos message stability was observed in addi- endothelial compartments. Results indi- tion to slight transcriptional activation of cated that cigarette smoke-induced cell pro- the c-fos promoterNT075. liferation of the airways and pulmonary Chemiluminescence. Cigarette smoke in arterial vessels is at least partially mediated determined quantity was streamed through through stimulation of the endothelin-A physiologic saline solution, blood plasma, or receptorsNT255. ex vivo excised rat lung. The solutions and Cell signaling. Environmental tobacco the supernatants from lung tissue homoge- smoke, administered to rats during gesta- nate produced a significant increase in tion, the early neonatal period, or both, elic- chemiluminescence after t-butyl hydroper- ited induction of total adenylyl cyclase. In oxide inductionNT280. the brain, the specific coupling of β-adren- Chromosome aberrations induction. Wa- ergic receptors to adenylyl cyclase was in- ter extract of the dried leaf, in cell culture hibited in the smoke-treated groups, despite at a concentration of 15 mL, was active on NICOTIANA TABACUM 299

Chinese hamster ovary cells. The number of pulmonary diseaseNT025. A polyphenol re- aberrant metaphases increased in cultures agent isolated from cigarette smoke conden- with 15 mL tobacco extract per milliliter of sate primed purified human neutrophils. A growth mediaNT445. Water extract of the mouse monoclonal antiidiotypic antibody dried leaf, administered to mice at a dose of directed against the polyphenols-reactive 9.40 g/kg, 6 days a week for 10 months, was determinants on a rabbit polyclonal antito- active on bone marrow. A combination of bacco glycoprotein antibody was generated Piper betle, Areca catechu, and Nicotiana and also primed neutrophils. After priming tabacum was usedNT524. Seed, administered by the isolated polyphenol reagent or to- orally to adults with oral cancer and oral bacco antiidiotypic antibody, there was a submucosal fibrosis and to healthy chewers, 2.5-fold to threefold increase in CD11b/18 was active. An average of 6 quids of tobacco expression and doubling of the number of leaf, Areca nuts, and lime were chewed formyl-methionyl-leucyl-phenylalanine re- dailyNT521. ceptors on the cells. The primed cells pro- Chronic bronchitis. Cigarette smoke, ad- duced a twofold increase in production of ministered to rats for 2 weeks, produced a superoxide and release of neutrophil elastase significantly higher mean basal secretion of after stimulation with formyl-methionyl- fucose in “bronchitic” rats than in the con- leucyl-phenylalanine. The inflammatory trols. In control and bronchitic animals, process contributing to progression of acute administrations of cigarette smoke, chronic obstructive pulmonary disease in blown directly through the laryngeo-tra- ex-smokers may be in part driven by tobacco cheal segment after equilibration, produced antiidiotypic antibodiesNT041. significant transient increases in the secre- Chylomicron metabolism. Smoke, admin- tion of fucose, hexose, and protein but not istered to rats injected intravenously with albuminNT299. Cigarette smoke, administered 14C- and 3H-labeled chylomicrons, produced to the specific pathogen-free rats at a dose no difference in the initial plasma clearance of 25 cigarettes daily for 14 days and con- time of labeled chylomicrons between currently given N-acetylcysteine (NAC) as smoke-treated and control animals. Hepatic 1% of their drinking water, increased the uptake of chylomicron cholesterol was thickness of the epithelium by 37–72% at slower in smoke-treated animals than in three of the airway levels studied. The num- controls. More labeled chylomicrons re- ber of secretory cells was increased at all air- mained in the heart of smoke-treated rats way levels distal to the upper trachea than controlsNT284. 102–421%. Secretory cells containing neutral Cimetidine kinetics. Low- or high-nicotine glycoproteins were reduced in number, but tar, administered orally and parenterally to this was more than offset by a large increase rats for 10 minutes immediately after admin- in the number of secretory cells containing istration of cimetidine, produced lower acidic glycoproteins at all airway levelsNT300. plasma level after orally administered Chronic obstructive pulmonary disease. cimetidine in the absorption phase in the Smoke-conditioned media, administered smoke inhaling groups than in the non- intranasally to Balb/c mice for 40 days, sig- smoking control group. It was particularly nificantly increased bronchoalveolar lavage marked in the high-nicotine tar cigarette neutrophils, lymphocytes, chemokine, smoke-inhaling group. No significant differ- TNF-α, and mucin. There were changes in ence was found in cimetidine plasma level pulmonary reactivity to methacholine, in- between the cigarette smoke inhaling group flammation, and cellular lung changes char- and the nonsmoking control group when acteristic for human chronic obstructive administered intraperitoneally or intrave- 300 MEDICINAL PLANTS OF THE WORLD nously. The cigarette smoke inhalation pro- in the peripheral blood of mice treated twice duced suppression or a delay in cimetidine daily for 30 minutes, starting after 48 hours absorption from the gastrointestinal tract, of exposureNT124. and the degree of influence was dependent Central nervous system depressant activ- on the content of nicotine tar in the ciga- ity. Ethanol (70%) extract of the fresh leaf, rette smokeNT290. administered intraperitoneally to mice of Clastogenic activity. Water extract of the both sexes at variable doses, produced dried leaf, administered to mice at a dose of strong activity. Initial excitation was fol- 9.4 g/kg, 6 days/week for 10 months, was lowed by marked sedative effectNT580. active on bone marrow. A combination of Collagenase activity. Smoke was adminis- aqueous extracts of Piper betle, Areca cat- tered to Guinea pigs at a dose of 20 ciga- echu, and Nicotiana tabacum was usedNT524. rettes per day for 8 weeks. At 6 and 8 weeks Seed, administered orally to adults, pro- of exposure, lungs exhibited interstitial and duced an increase in micronuclei in healthy peribronchiolar inflammation and moderate chewers and chewers with oral submucosal emphysematous changes. There was patchy fibrosis. An average of 6 quids of tobacco expression of collagenase mRNA mainly in leaf, Areca nuts, and lime were chewed macrophages but also in alveolar epithelial dailyNT521. Mainstream smoke, administered and interstitial cells. Immunoreactive pro- by whole-body exposure to male albino tein was detected in alveolar macrophages, Swiss mice, produced a significant increase in alveolar walls, and in interstitium. Col- in the number of micronucleated bone lagenolytic activity increased beginning in marrow polychromatic erythrocytes. A high the fourth week of exposure. Collagen con- correlation was observed among the num- centration decreased from 50.7 ± 8.5 mg/g ber of micronucleated polychromatic dry weight in control lungs to 40.2 ± 5 and erythrocytes and the content of tar and 42.9 ± 6 at 6 and 8 weeks of exposure, nicotineNT082. Smoke, administered to preg- respectivelyNT260. nant BDF1 (C57B1 × DBA2) mice at a dose Comutagenic activity. Cigarette smoke of 600 cm3 of smoke, four times of 15 min- condensate, in Salmonella typhimurium utes each with 1 minute intervals on day strains TA98 and TA98/1.8DNP6, spe- 16/17 of gestation, produced a two- to three- cifically enhanced the mutagenicity of fold increase in the number of micro- polyaromatic amines, such as 2-aminofluor- nucleated polychromatic erythrocytes in ene, 2-acetylaminofluorene, 4-acetylamino- fetal liver and liver of newborn mice (1–5 fluorene, and 2-aminoanthracene. Both hours after birth). Administration of smoke black and blond tobacco proved to interact for 60 minutes/day repeatedly from day 11 synergistically with 2-aminoanthracene of gestation produced slightly greater micro- mutagenicity. Administration of 2-amino- nucleus response in fetuses. Smoke, admin- anthracene/smoke condensate mixtures, istered transplacentally to newborn mice previously shown to be comutagenic in during the last trimester of pregnancy, vitro, failed to demonstrate a synergistic produced greater clastogenic activity than effect in sister chromatid exchange induc- in their 6-month-old mothersNT118. Smoke, tion in bone marrow cells of miceNT103. administered to BDF1 mice at a dose of 600 Connective tissue breakdown. Whole cm3, two to six exposures of 30 minutes cigarette smoke, administered to C57-BL/6 each, produced 3.5-fold increase of the mice, produced a dose-response increase in number of micronucleated polychromatic lavage neutrophils, desmosine, and hydrox- erythrocytes in born marrow after 24 hours yproline, but not lavage macrophages of exposure, and a two- to fivefold increase (MACs). The effect was evident after 6 NICOTIANA TABACUM 301 hours of exposure to two cigarettes. Pre- drial Adenosine triphosphatase (ATPase) treatment with an antibody against poly- and cytochrome C oxidase activities in a morphonuclear leukocytes (PMNs) reduced dose-dependent manner. The effect of ex- lavage PMNs to undetectable levels after tract on mitochondria swelling response to smoke exposure. It did not affect MAC calcium stimulation was dependent on cal- numbers and prevented increases in lavage cium concentrations. The extract treatment desmosine and hydroxyproline. Intraperi- induced mitochondrial inner membrane toneal injection of a commercial human damage and vacuolization of the matrix, α1-antitrypsin (α1AT) 24 hours before whereas the outer mitochondrial membrane smoke exposure increased serum α1AT lev- was preserved. Nicotine produced no signifi- els threefold and completely abolished cant damageNT007. smoke-induced connective tissue break- Cytochrome P450 induction. STE, in down and the increase in lavage PMNs, murine system at doses of 50 or 100 mg/kg without affecting MAC numbersNT045. body weight/day, elevated microsomal CuZn-superoxide dismutase activity. cytochrome b5, cytochrome P450 (CYP), Cigarette smoke was administered to the and malondialdehyde levels. These results osteogenic disorder Shionogi (ODS) rats at indicated the inhibitory potential of STE on doses of 4 mg/day, S4 or 40 mg/day, and S40 garlic-induced hepatic glutathion-S-trans- of ascorbic acid and exposed to smoke daily ferase (GST)/GSH system besides signifi- for 25 days. The treatment produced a sig- cant augmentation on garlic-, mace- or nificant decrease of CuZn-superoxide black mustard-induced microsomal cyto- dismutase (SOD)NT196. chromesNT059. Methyl chloride extract of the Cyclin D1/2 expression. Smoke, admin- leaf, administered intragastrically to rats at istered to male strain A/J mice fed a diet a dose of 3 mg/animal daily for 21 months in with chemopreventive agents, produced a DMSO solvent, was active. The rats were decrease in cyclin D1/2 expression. Expres- divided into two groups, one was fed a vita- sion of cyclin may be a useful marker in the min A diet, and the other a vitamin A-defi- identification of chemopreventive agents cient diet. Treatment with the extract from tobacco smokeNT030. increased pulmonary CYP over controls in Cyclo-oxygenase activity. Aqueous ciga- vitamin-deficient animals and among rette tar extracts, in rat pulmonary alveolar treated animals more so in the vitamin- macrophages, increased cyclo-oxygenase deficient groupNT519. Crude cigarette smoke activity threefold above the initial activity condensate, in human liver microsomes, within 2 hours of incubation and gradually inhibited P450 1A2 cytochrome. The decreased below the initial activity after 8 tobacco-specific nitrosamines were acti- hours of incubation. Accumulated levels of vated by a number of P450 enzymes. P450 prostaglandin-2 increased dramatically after 1A2, 2A6, and 2E1 activated nitrosamines 12 hours of incubationNT233. to genotoxic productsNT079. Aged and diluted Cytochrome b5 induction. STE, in mu- sidestream cigarette smoke, administered to rine system at doses of 50 or 100 mg/kg body timed pregnant rats and their pups four weight/day, elevated microsomal cyto- times a days from gestational day five to chrome b5, cytochrome P450, and malondi- postnatal day 21, produced no alterations in aldehyde levelsNT059. mRNA in the fetal lung beginning at gesta- Cytochrome C oxidase inhibition. Smoke tional day 17. Continued exposure signifi- extract, in the mouse brain mitochondria cantly induced CYP1A1 but not other P450 culture in the presence or absence of vita- genes as early as one day after birth. Results min C for 60 minutes, inhibited mitochon- indicated that smoke-induced pulmonary 302 MEDICINAL PLANTS OF THE WORLD

CYP1A1 in the first day of life fetal cyto- ucts than lung cells. When smoke conden- chrome P450 genes were not induced by sate and tobacco extract were mixed with maternal exposure to smoke. In the fetal Lewis lung adenocarcinoma cells and then lung, CYP1A1 and 1B1 can be induced by inoculated into mice, they did not modify β-naphthoflavoneNT224. Mainstream ciga- the size of the local Lewis lung adenocarci- rette smoke, administered to F344 rats at a noma-induced tumors or the number or dose of 100 mg total particulate matter/m3 appearance time of lung metastasis, for 2 or 8 weeks, induced CYP1A1 in respi- although there was an increase in spleen ratory and olfactory mucosae, liver, kidney, weightNT116. Mainstream and sidestream and lung. CYP1A2 levels increased slightly smoke from the same cigarette, in mono- in the liver and olfactory mucosa. CYP2B1/ layer cell culture of mouse fibroblast-like 2, which increased in the liver, decreased in L-929 cells, produced a decrease of cytotox- the upper and lower respiratory tissues. icity with increasing smoke age (up to 8.7 Intense immunoreactivity was found in seconds), smoke dilution, and the quantity epithelia throughout the nasal cavity of of activated charcoal in filters. Acetate fil- smoke-exposed rats. Ethoxyresorufin O- ters had little effect on cell mortality, and demethylase activity (associated with the age-of-smoke effect was not evident for CYP1A1/2) decreased approximately two- mainstream smoke generated with a low puff fold in olfactory mucosa but increased in volume and rapid dilution. The cytotoxic- nonnasal tissues. Methoxy- and pentoxy- ity of sidestream smoke also decreased rap- resorufin O-dealkylase activities (associated idly with increasing smoke age and with CYP1A2 and CYP2B1/2, respectively) dilutionNT146. Smoke condensate from the decreased in olfactory and respiratory mu- mainstream smoke of TOB-HT, lR4F, and cosae and lung (CYP2B1/2) but increased 1R5F cigarettes, in human bronchial/tra- in liverNT246. Masheri, a pyrolyzed tobacco cheal epithelial cells, coronary artery product, administered orally to Swiss mice, endothelial cells, coronary artery smooth Sprague–Dawley rats, and Syrian golden muscle cells, foreskin keratinocytes, and hamsters at a dose of 10% diet for 20 WB-344 rat liver epithelial cell line exposed months, produced a significant induction of for 1 hour, produced no inhibition of gap cytochrome P450 in proximal and distal junction intercellular communication by parts of the three speciesNT100. TOB-HT in any of the human cell types Cytotoxic effect. Gas phase of mainstream tested at concentrations where 1R4F and cigarette smoke, in monolayer culture of lR5F did inhibit (p < 0.05). TOB-HT did mouse lung epithelial cells, produced an not elevate lactate dehydrogenase release, increase in cytotoxicity in a dose-dependent when tested at concentrations where lR4F manner. Cell viability of cultures exposed and lR5F did. Smoke condensate from to gas phase with only the nonorganic TOB-HT cigarettes is less damaging to the components was equivalent to controls. structure or function of the cellular plasma Removal of volatile organic constituents membranes of a variety of human cell lines resulted in almost elimination of cytotoxic- than from 1R4F and 1R5F tobacco burning ity of the smokeNT021. Smoke condensate and reference cigarettesNT226. tobacco extract, at high concentrations in Dermal tumor. Smoke condensates were Lewis lung adenocarcinoma cells and mice administered externally to female SENCAR spleen lymphocytes, were cytotoxic. Smaller mice at doses of 10, 20, or 40 mg Eclipse or doses increased thymidine incorporation in 1R4F cigarette smoke condensates three both cell types. Lymphocytes were more sus- times a week for 29 weeks. The treatment ceptible to the toxic effect of tobacco prod- was initiated with a single topical applica- NICOTIANA TABACUM 303 tion of 7,12-dimethylbenzanthracene. The a dose of 1 g/kg, produced strong activ- treatment did not alter body weight, ityNT605. survival, or other indicators of subchronic DNA adduct formation. Mainstream toxicity. In 7,12-dimethylbenzanthracene- Eclipse or 1R4F cigarettes smoke conden- initiated mice, there were significant in- sate was administered dermally to SENCAR creases in both the number of tumor-bearing mice at doses of 30, 60, or 120 mg/animal animals and dermal tumors at all 1R4F doses three times a week for 30 weeks. The treat- and the high-dose EclipseNT003. ment produced distinct time and dose-de- Desensitization of nicotinic receptor. S- pendent diagonal radioactive zones in the (-)-Nicotine (10 and 100 nM) diminished DNA from lung, heart and skin tissues of [3H]overflow from 3H-dopamine-preloaded 1R4F-treated mice. The relative adduct la- rat striatal slices after subsequent super- beling values of lung, heart, and skin DNA fusion with 10 μM S-(-)-nicotine (46 and from reference smoke condensate-treated 74%, respectively) or 10 μM S-(-)-nor- animals were significantly greater than nicotine (59 and 81%, respectively). S-(-)- those of the solvent controls were. No di- nornicotine (1 and 10 μM) diminished the agonal radioactive zones were observed at response to subsequent superfusion with 10 any dose from the DNA of animals treated NT055 μM S-(-)-nornicotine (85 and 97%, respec- with smoke condensate from Eclipse . Smoke condensate from cigarette and a ref- tively) or 10 μM S-(-)-nicotine (82 and erence tobacco-burning cigarette (1R4F) 88%, respectively). Thus, similar to S-(-)- were administered dermally to CD-1 mice nicotine, S-(-)-nornicotine-desensitized three times a week for 4 weeks at mass up to nicotinic receptors, but with approx 12-fold 180.0 mg “tar” per week per animal. Distinct lower potency. Cross-desensitization sug- diagonal radioactive zones in the DNA from gested involvement of common nicotinic NT204 both skin and lung tissues of animals dosed receptor subtypes . with reference cigarette smoke was pro- Diltiazem kinetics. Cigarette smoke, ad- duced. No corresponding diagonal radioac- ministered to rats for 10 minutes using a tive zones were observed from the DNA of Hamburg II smoking machine, immediately animals dosed with the test cigarette smoke after oral administration of diltiazem (10 or acetone (solvent control). The relative mg/kg), produced plasma diltiazem levels in adduct labeling values of skin and lung the rats exposed to cigarette smoke reached DNA from reference-treated mice were sig- the maximum (4.3 μg/kg) after 4 hours. In nificantly greater than those of the test ciga- the nonsmoking nonrestrained rats, plasma rette-treated mice. The relative adduct diltiazem levels increased rapidly and labeling values of the test cigarette-treated reached the maximum (7.1 μg/kg) 2 hours animals were no greater than those of sol- after administration and decreased gradually vent controlsNT096. Smoke condensate, ad- thereafter. In the nonsmoking restrained ministered topically to female ICR mice at rats, plasma diltiazem levels increased four doses equivalent to three cigarettes rapidly but showed almost constant levels daily, elicited aromatic adducts in most tis- between 1 hour and 8 hour after administra- sues, but not in white blood cellsNT111. Ciga- tion. The maximum level (5.4 μg/kg) was rette smoke administered by inhalation, shown after 2 hours. Results indicated that cigarette smoke condensate administered absorption of orally administered diltiazem intraperitoneally, or neutral fraction in ge- is inhibited and delayed by cigarette netically responsive C57BL/6 (B6) and smokeNT254. nonresponsive DBA/2 (D2) mice for 3–16 Diuretic activity. Decoction of the dried days, produced no detectable levels of leaf, administered nasogastrically to rats at benzo[a]pyrene-7,8-diol-9,10-epoxide 304 MEDICINAL PLANTS OF THE WORLD

(BPDE)-DNA in lungs or liver. Aryl hy- els of 8-oxo-2'-deoxyguanosine in maternal drocarbon hydroxylase (AHH) activity was lungs by 23 and 32%, respectively. In ma- induced in the lungs of B6 mice. Benzo- ternal liver, a 38% increase was observed [a]pyrene, administered intraperitoneally to after multiple dose treatment. In the fetuses, mice at doses of 20–80 mg/kg, produced a 45% increase in 8-oxo-2'-deoxyguanosine dose-dependent amount of BPDE-DNA- levels was observed in liver after multiple adducts in lung and liver. Administration of dosesNT061. Aqueous extract of smoke con- 4 mg/kg benzo[a]pyrene produced no effect. densate, in rat lung culture in the absence In B6 mice aryl hydrocarbon hydroxylase of microsomes, produced radioactively la- was induced in lungs and livers, but not in beled bulky reaction products accumulating D2 mice, although the levels of BPDE- in a time- and dose-dependent manner. Pre- DNA-adducts were higher than in B6 treatment of extract with radical scaven- miceNT119. Sidestream cigarette smoke, ad- gers/reducing agents (ascorbic acid, GSH), ministered by a whole-body exposure to fe- diminished adduct formation in a concen- male Sprague–Dawley rats for 6 hours/day tration-dependent manner. Adduct frac- for 4 weeks, produced one major and several tions derived from in vitro and in vivo minor smoke-related adducts in lung, tra- experiments showed similar chromato- chea, heart, and bladderNT218. Mainstream graphic behaviorNT091. Smoke condensate, cigarette smoke, administered by whole- administered dermally to female ICR mice body exposure to female BD6 rats, 1 hour/ at a dose being equivalent of 4.5 cigarettes day, 5 days/week for 8 months, produced no for 6 days, produced DNA damages in lung, significant increase of DNA-protein cross- heart, skin, and kidneys higher than in the links in liver, lung, or heart. Cigarette liver. Spleen DNA was virtually adduct free. smoke induced formation of DNA adducts Preference for heart and lung was observed in the lung and heart but not in the esopha- for mice treated for 1 and 3 daysNT128. Ciga- gus or liver. The combined ingestion of rette tar, administered dermally to ICR mice ethanol resulted in a significant formation at doses being equivalent to 1.5, 3, 6, and 9 of smoke-related DNA adducts in the cigarettes for 4, 3, 5, and 7 days, respec- esophagus and dramatic increase in the tively, produced 12 distinct 32P-labeled heartNT245. DNA adduct spots, and diagonal radioactive DNA damages. Environmental smoke was zone. One derivative in particular (adduct 1) administered by whole-body exposure to increased rapidly during the early treatment adult female Balb/c mice in a regimen con- phase and persisted to 8 days after treat- sisting of sequences of a 30 minutes expo- ment. The prominent adduct 1 was observed sure followed by a 90 minutes nonexposure. in the same location on the fingerprints This regimen was performed once for the of DNA samples from human smokers. Co- single exposure and repeated three times for chromatography experiments suggested the triple exposure. The exposure increased identity of human and mouse DNA adduct 8-hydroxy-2'-deoxyguanoside levels in the 1. Several other human and mouse adducts heart, lung, and liver. In some instances, the (adducts 3, 5, 6, and 9) appeared identical, increased level returned to normal by the and the diagonal radioactive zone was also end of the nonexposure period, whereas present on DNA adduct maps from other tissues showed a further increase fol- smokersNT138. Mainstream whole-smoke lowing nonexposureNT056. NNK, adminis- DMSO and phosphate buffer solutions tered to pregnant Swiss mice in a single or induced DNA single-strand breakage in multiple doses, significantly increased lev- mice testicular cells. DMSO solution of NICOTIANA TABACUM 305 cigarette smoke produced stronger cytotox- returned to normal levels within 1 week, icity and genotoxicity than the phosphate but the UDS response to DNA damage buffer solutionNT211. Cigarette smoke, admin- remained depressed up to 5 months after istered in combination with asbestos to rats ending smoke exposureNT168. for 1, 2, and 14 days, increased in 2'- DNA synthesis inhibition. Leaves, on agar dioxyuridine-5'-triphosphate (dUTP)-bi- plate at a concentration of 50%, produced otin nick end labeling-positive, necrotic weak activity on monkey kidney cellsNT574. epithelial cellsNT219. Smoke of the dried leaf, administered to rats DNA deletion. Filtered and unfiltered at variable doses, produced weak activ- smoke and smoke condensate were admin- ityNT590. istered by whole-body exposure for 4 hours Dominant-lethal mutations. Whole tobac- to pregnant pink eye-unstable C57BL/6J co smoke was administered to male Balb/c, mutant mice or 15 mg/kg of smoke conden- DF1 and H mice at two doses: low 1-hour sate during 10th day of gestation. A signifi- treatment/day and high 2-hour treatment/ cant increase in the number of DNA day, 5 days/week for 8 weeks. Dominant-le- deletions in the embryo, as evidenced by the thal mutations in both experimental groups spotted offspring in both smoke-exposed of Balb/c, BDF1, and H mice were signifi- groups, was observedNT053. cantly induced (p < 0.001), but some strain DNA synthesis stimulation. Smoke of the differences existed. In Balb/c and BDF1 dried leaf, administered to rats at variable mice, the smoke-induced dominant-lethal doses, was active. The effect of a combina- mutations were found mainly in spermato- tion of cigarette and hashish smoke on stress cytes, spermatogonia, and gonial stem cells. response was measured in rats held in a wire In H mice, only spermatids and spermato- cage inside of a larger cage with a cat. Brains cytes were affected. Exposure produced a were measured for protein and catechola- twofold to threefold increase in the number mine levelsNT590. Whole Kentucky reference of micronucleated polychromatic erythro- 2A1 cigarette smoke, administered to hy- cytes in the bone marrow of Balb/c and brid strain BC3F1/Cum (C57BL/Cum X BDF1 mice in both dose groups. In H mice, C3H/AnfCum) mice, increased DNA re- this effect was observed only on days 19 and plicative activity more than twofold within 38 of sampling. No cumulative or dose-de- 1 week of beginning smoke exposure and pendent effects were detectedNT086. remained elevated as long as smoke ex- Dopamine protection. Cigarette smoke, in posure was continued. Treatment of lung 1-methyl-4-phenyl-1,2,3,6-tetrahydro- tissues in vitro with either the lung carcino- pyridine (MPTP) mouse model, partially gen 4-nitroquinoline-1-oxide or methyl- protected against corpus striatal dopamine methane sulfonate stimulated unscheduled depletion by MPTP. This protection was DNA synthesis. Until the 10th to 12th associated with monoamine oxidase week of smoke exposure, at which time (MAO) inhibition in brain and liver and the accumulated deposition of total parti- CYP induction. β-naphthoflavone pre- culate material in the lung was approx 40 treatment also partially protected against mg, the level of unscheduled DNA synthe- MPTP-induced depletion of striatal do- sis (UDS) stimulated by the alkylating pamine. The results indicated that both chemicals declined to approx 50% of that MAO inhibition and CYP induction may seen in lung tissue from sham-exposed con- play a role in any biochemical protection af- trol mice. If the mice were removed from forded by cigarette smoke exposure against smoke exposure, DNA replicative activity the development of Parkinson’s diseaseNT621. 306 MEDICINAL PLANTS OF THE WORLD

Nicotine, 4-phenylpyridine, and hydra- and reduced nicotinamide adenine dinucle- zine, administered to mice, prevented the otide oxidation. Intact mitochondria were decrease in dopamine metabolite levels less sensitive to extracts of tar than submi- induced by MPTP, but there was no signifi- tochondrial particles. The nicotinamide ad- cant effect on dopamine levels. The com- enine dinucleotide (NADH)-ubiquinone pounds did not inhibit monoamine oxidase (Q) reductase complex was more sensitive (MAO) activity in cerebral tissue in vivo. to inhibition by tar extract than the succi- In vitro, an extract produced significant nate-Q reductase and cytochrome com- inhibition of MAO A and B activities in the plexes. Nicotine or catechol did not inhibit brainNT102. respiration of intact mitochondria. Treat- Dopaminergic activity. Smoke was admin- ment of submitochondrial particles with istered intranasally to mice for 20 minutes cigarette tar resulted in the formation of twice daily for 3 days before methamphet- hydroxyl radicalsNT287. amine treatment. The treatment signifi- Embryotoxic effect. Water extract of the cantly attenuated the neurotoxicity as dried leaf, administered by gastric intuba- judged by a lesser depletion of dopamine, tion to pregnant rats, was active. Preimplan- dihydrophenylacetic acid, and homovanillic tation and implantation periods were most acid. The lesser effect of methamphetamine sensitiveNT578. on the content of serotonin level was unal- Emphysematous influence. Smoke was ad- tered by prior inhalation of smokeNT039. To- ministered to mice at a dose of one cigarette bacco glycoside, administered to mice, daily for up to 6 months. Some animals re- increased behavior via dopamine 2 neuronal ceived 20 mg of human A1AT (Prolastin) activity but not dopamine 1 activity in a every 48 hours. The treatments produced dose-dependent manner. The results indi- 63% protection against increased airspace cated that smoking can affect the human size and abolished smoke-mediated increase brain function via not only the nicotinic in plasma TNF-αNT018. Smoke, administered cholinergic neuron but also the dopamine 2 by whole-body exposure to B6C3F1 mice neuronNT017. and Fischer-344 rats at a concentration of Duodenal ulcer. Tobacco cigarette smoke, 250 mg total particulate matter/m3 for 6 administered to mepirizole-treated rats, in- hours/day, 5 days/week for 7 or 13 months, hibited hyperemia at the ulcer margin after produced an enlargement of parenchymal exposureNT270. air spaces in both mice and rats. The alveo- E-cadherin expression. Smoke extract, on lar air space was increased significantly only pig airway epithelial cells and mouse tra- in mice. Tissue loss was decreased at both chea, produced a decrease of E-cadherin ex- time points in mice, but not in rats. Mor- pression on membrane and an increase of phometric differences in the mice at 13 cytoplasmic expression at 12 and 24 hours months were greater than at 7 months. In- after exposure. The expression at 24 hours flammatory lesions within the lungs of mice was higher than at 12 hoursNT032. contained significantly more neutrophils Electron transport inhibition. Acetoni- than those lesions in ratsNT046. Smoke, ad- trile extracts of cigarette tar inhibited stage ministered to macrophage elastase-deficient three and four respiration of intact mito- (MME-/-) mice, produced no increase in the chondria. Exposure of respiring submito- numbers of macrophages in their lungs and chondrial particles to the acetonitrile did not develop emphysemaNT060. Cigarette extracts of cigarette tar results in a dose-de- smoke, administered to male weanling rats pendent inhibition of oxygen consumption at a dose of 20 nonfiltered commercial ciga- NICOTIANA TABACUM 307 rettes/day, 5 days/week for 6 weeks, signifi- tion, elastase-like activity, elastase inhibi- cantly decreased vitamin A levels in serum, tory capacity in bronchoalveolar lavage lung, and liver. Histological examination fluid, and destructive index were compa- revealed the presence of interstitial pneu- rable to that of tobacco-exposed animals on monitis along with severe emphysema. a normal diet. Mean linear intercept was There was a significant inverse relationship markedly decreased with thickened epithe- between vitamin A concentration in the lium and shrunk alveolar spaceNT268. lung and the severity of emphysema (p < Endogenous formation of tobacco- 0.03). Detachment or hyperplasia (and specific nitrosamines. (S)-Nicotine and metaplasia) of the tracheal epithelium and NaNO2 were administered intragastrically liver vacuole formation also were evident in to rats at doses of 60 μmol/kg and 180 μmol/ the smoke-treated ratsNT194. Cigarette smoke kg, respectively, and (S)-nicotine adminis- was administered to rats immunized with tered at a dose of 12 nmol/kg twice daily for rabbit antineutrophil antibody or anti- 4 days. The treatments produced no me- monocyte/macrophage antibody and ex- tabolites of NNK;, and its glucuronide in posed to cigarette smoke 7 days/week for 2 the urine of treated rats. This indicated that months. Specific suppression of neutro- endogenous conversion of nicotine to NNK phil accumulation and neutrophil-related did not occur. The urine contained NNN, elastinolytic burden in the lungs of the N'-nitrosoanabasine (NAB), and N'-nitro- antineutrophil antibody-treated smoke- soanatabine (NAT). (S)-Nicotine used in exposed rats was observed, in contrast to this experiment demonstrated that it con- specific suppression of macrophage accumu- tained trace amounts of nornicotine, ana- lation and macrophage-related elastinolytic basine, and anatabine. (S)-Nicotine and burden in the lungs of the antimonocyte/ synthetic (R,S)-nicotine with NaNO2 macrophage antibody-treated smoke-ex- supplement, administered to rats, produced posed rats. Cigarette smoke exposure- NNN-, NAB-, and NAT-detectable levels induced lung elastin breakdown and in the urine of the rats treated with the (S)- emphysema in the lungs were not prevented nicotine and NaNO2. NNN, but not NAB in the lungs of antineutrophil antibody- or NAT, was present in the urine of the rats treated smoke-exposed rats but was clearly treated with synthetic (R,S)-nicotine and prevented in lungs of the antimonocyte/ NaNO2. NNN probably formed via nitro- macrophage antibody-treated smoke- sation of metabolically formed nornicotine. exposed rats. Results indicate that macro- These results demonstrated that endo- phages rather than neutrophils were the genous formation of tobacco-specific nitro- critical pathogenic factor in cigarette samines occurred in rats treated with NT238 NT256 smoke-induced emphysema . Tobacco tobacco alkaloids and NaNO2 . smoke was administered to weanling Wistar Endothelial dysfunction. Cigarette smoke- rats on vitamin E-depleted or normal diet treated Krebs buffer was evaluated on rat for 4 weeks. The smoke induced emphyse- aortic rings. Agonist-stimulated endothe- matous changes with significant increases in lium-dependent vasorelaxation was mea- the mean linear intercept and the destruc- sured. Relaxations to receptor-dependent tive index. This was supported by an in- agonists, acetylcholine, and adenosine 5'- crease in elastase-like activity and a diphosphate (ADP), as well as to a recep- decrease in elastase inhibitory capacity in tor-independent agonist, A23187 (Ca2+ bronchoalveolar lavage fluid in the normal ionophore) were significantly impaired by diet group. In addition to vitamin E deple- cigarette smoke. Cigarette smoke did not 308 MEDICINAL PLANTS OF THE WORLD impair relaxations to sodium nitroprus- in a 50% and 40% reduction, respectively, side, indicating preserved guanylate cyclase of the maximum ornithine decarboxylase activity. Cigarette smoke did not affect activity induced as a result of treatment endothelial nitric oxide synthase (NOS) with TPA. In initiation-promotion experi- catalytic activity in homogenates from ments, α-CBT markedly inhibited the endothelial cells or aortas previously ex- promoting effect of TPA on skin tumor posed to cigarette smoke-treated Krebs formation in mice that were initiated with buffer. Treatment with superoxide dismu- 7,12-dimethylbenz[a]anthracene. The β- tase or ifetroban and in a lesser degree by CBT was less effective. Application of 3.3 indomethacin prevented cigarette smoke- μM of α-CBT 40 minutes before treat- induced endothelial dysfunctionNT205. ment with TPA (1 μg) resulted in a 53% Enzymatic activity. STE, administered to reduction in the number of papillomas per lactating mice and suckling neonates at mouseNT147. doses of 50 or 100 mg/kg body weight/ Estrogenic effect. Tobacco smoke, admin- day, inhibited phytic acid-induced GST/ istered to rats, induced no changes in the GSH system efficiency and significantly rat uterus weight or in oestrus cycle. It de- augmented phytic acid- or butylated hy- creased estradiol (E2) concentration in the dro-xyanisole-induced microsomal phase I uterus tissue and increased and later de- enzymesNT057. STE, in murine system at creased the proliferation index and percent- doses of 50 or 100 mg/kg body weight/day, age of the cells in the S-phase. The results elevated microsomal cytochrome b5, CYP, indicated a phasic character of changes in and malondialdehyde levels. These results the reproductive system under the effect of indicated the inhibitory potential of STE on tobacco smoke and corroborated the con- garlic-induced hepatic GST/GSH system cept of the role of smoking in the shifting besides significant augmentation on garlic-, the type of hormonal carcinogenesis from mace- or black mustard-induced microsomal promotional to genotoxicNT227. Mainstream cytochromesNT059. cigarette smoke, administered to female rats Epstein–Barr virus early antigen induc- aged 2.5–3 and 6 months, 2 hours/day for 3 tion. Methanol extract of the dried leaf, in weeks or 3 months, did not induce any cell culture at a concentration of 1 μg/mL, changes in uterine weight or estrous cycle. was inactive. The assay was designed for It decreased estradiol (E2) concentration in tumor-promoting activityNT414. Two diastere- uterine tissue (especially in adult rats or in oisomers of 2,7,11-cembratriene-4,6-diol young rats after 3 months of experiment). (α- and β-CBT) from the neutral fractions No signs of aneuploidy were found in the of cigarette smoke condensate, in Raji cells, uterus through proliferation index. The per- produced potent inhibitory effects on the centage of cells in S-phase were increased induction of Epstein–Barr virus (EBV)-EA by 3 weeks and decreased by 3 months of by 12-O-tetradecanoylphorbol-13-acetate experimentNT240. (TPA). The doses of α- and β-CBT required Fish poison. Water extract of the fresh leaf NT601 for 50% inhibition of EBV-EA induction by was active, LD50 0.23% . TPA were 7.7 and 6.7 mg/mL, respectively. Follicular fluid mutagenicity. In 24 pa- Application of α- and β-CBT to mouse skin tients, 12 smoking and 12 nonsmoking, who before treatment with TPA, inhibited TPA- were treated in an in vitro fertilization pro- induced ornithine decarboxylase activity in gram, the mutagenicity of follicular fluid a dose-dependent manner. Application of was not influenced by the number of ciga- 16.5 μM/mouse of α- and β-CBT resulted rettes smoked. However, urine samples of NICOTIANA TABACUM 309 smoking patients showed a dose-dependent cantly reduced mucous synthesis and orni- elevation of mutagenicityNT319. thine decarboxylase activity but not its Foot-and-mouth disease. Tobacco trans- mRNA expression in MKN-28 cellsNT217. genized with foot-and mouth disease virus Cigarette smoke and its extract, in human (FMDV) serotype O using a recombinant MKN-28 cells, markedly decreased mucus tobacco mosaic viruses (TMV)F11 and synthesis in vivo and in vitro and suppressed TMVF14 was administrated by parental in- ornithine decarboxylase activityNT225. jection to guinea pigs. The treatment pro- Gastric secretory stimulation. Smoke of duced a protection against FMDV challenge the dried leaf was administered to smoking in case of using TMVF11, TMVF14, or the adults with duodenal ulcers at variable mixture TMVF11/TMVF14, but not wtTMV. doses. The treatment reduced the anti- The TMVF11/TMVF14 mixture protected secretory effect of cimetidine from 86 to all animals when challenged in 150 guinea 38% and inhibited pepsin secretion by 14% pig 50% infection dosage. Oral administra- during smoking compared with 80% by non- tion of the mixture (3 mg total) protected smokers taking cimetidine. In a study with 3/8 guinea pigs against the same FMDV healthy adults, smoking had no effect on challenge. Most of the suckling mice paren- cimetidine-induced inhibition of pentagas- tally injected with antiserum from guinea trin-stimulated gastric acid secretion. The pigs immunized with the TMVF11/TMVF14 results were significant at p < 0.05NT589. mixture, but not with wtTMV, were also pro- Gastric ulcerations. Cigarette smoke was tected against FMDV challenge with 10 administered to rats at doses of 2 or 4% of NT009 suckling mouse LD50 . for three 1-hour periods during a 24-hour Gastric mucosal exfoliant activity. Leaf, starvation before ulcer induction. The treat- administered orally to adults at a dose of 200 ment potentiated ulcer formation, which mg/person, was active. Results were signifi- was accompanied by a reduction of gastric cant at p < 0.05NT458. blood flow at the ulcer base and ulcer mar- Gastric mucosal hyperemia inhibition. gin. Smoke exposure alone did not produce Tobacco cigarette smoke, administered to any macroscopic injury in the stomach but rats at doses of 3 and 18 mL/minutes, sig- significantly decreased the basal gastric nificantly attenuated hyperemia and aggra- blood flow in a concentration-dependent vated hypertonic saline-induced lesion in a manner, which was coupled with an in- dose-dependent manner. Administration of crease in mucosal xanthine oxidase activity. 18 mL/min of tobacco cigarette smoke and The increment of constitutive NOS activ- the dose of iv nicotine blocked injury- ity but not prostaglandin-E2 level was mark- induced hyperemia. The treatment also edly attenuated by cigarette smoke aggravated saline-induced gastric damage exposureNT247. Tobacco cigarette smoke and and gastric mucosal damage induced by subcutaneous nicotine, administered to rats, acidified aspirin or acidified ethanolNT269. significantly attenuated the ulcer margin Gastric mucus synthesis inhibition. Ciga- hyperemia in a dose-related manner. Re- rette smoke, at concentrations of 2 or 4%, peated exposure to tobacco cigarette smoke was administered to intact animals and increased ulcer size in the acute and the animals with ulcers. The treatment signi- healing stages. Subcutaneous nicotine also ficantly reduced the thickness of the mu- increased the size of ulcers in the acute cous-secreting layer and gastric mucosal stageNT272. ornithine decarboxylase activity in animals Gene expression. Aqueous extract of the with or without ulcers. The extract signifi- smoke (smoke-bubbled phosphate-buffered 310 MEDICINAL PLANTS OF THE WORLD saline), in Swiss 3T3 cell culture for 24 utes. Kidney, brain, and bone marrow DNA hours, produced differential gene expres- were not damaged. Twelve- or 24-fold sion, mainly antioxidant response genes, smoke dilution did not produce DNA dam- genes coding for transcription factor, cell age. Single oral pretreatment (100 mg/kg) cycle-related genes, and genes-mediators of either ascorbic acid or α-tocopherol ac- of an inflammatory/immune-regulatory etate 1 hour before inhalation, prevented responseNT029. Cigarette smoke was adminis- single-strand breaks in the stomach and tered to the ODS rats at doses of 4 mg/day, liver, while α-tocopherol acetate but not S4 or 40 mg/day, S40 of ascorbic acid, and ascorbic acid significantly reduced single- exposed to smoke daily for 25 days. The strand breaks in the lung. Five consecutive treatment produced a significant decrease of days of either ascorbic acid or α-tocopherol SOD, MnSOD, catalase and protein disul- acetate (100 mg/kg/day) pretreatment com- fide isomerase (PDI) by high-dose ascorbic pletely prevented single-strand breaks in the acid administration, and a nonsignificant lung, stomach, and liverNT044. Smoke con- decrease of plasma glutathione peroxidase. densate, in two hepatoma cell lines, induced Cigarette smoke exposure slightly increased a higher frequency of micronuclei in gene expression of PDI and catalase, but not Hepa1c1c7 cells relative to TAOc1BP(r)c1 significantly. The differently expressed 27 cells, which express 10-fold less aromatic genes in the liver were found by differential hydrocarbon receptor (AhR). Smoke con- display methods. From 27 genes, altered densate, administered intraperitoneally to expression of plasma proteinase inhibitor, Ahr+/+ and Ahr–/– mice at doses of 0.5–10 α-1-inhibitor III and CYP1A2 were con- μg/kg/day for 3 days, produced an increase firmed by competitive RT-PCRNT196. Side- in the incidence of micronucleated reticu- stream smoke was administered to male locytes in Ahr+/+ mice, and no increase in Wistar rats with a single intratracheal instil- the null allele animals. The frequency of lation of 2 mg of chrysotile or refractory micronucleated erythrocytes was slightly ceramic fiber. The rats were exposed to but significantly higher in Ahr+/+ relative smoke 5 days/week for 4 weeks. Administra- to Ahr–/– miceNT051. Mainstream smoke tion of smoke alone increased IL-1(α) from TOB-HT or 1R4F cigarettes, adminis- mRNA levels in alveolar macrophages. The tered intranasally to male B6C3/F1 mice at smoke stimulated gene expression of induc- concentrations of 0.16, 0.32, and 0.64 mg ible NOS in alveolar macrophages and IL-6 total particulate matter/L of air 1 hour/day and basic fibroblast growth factor in lungs 5 days/week for 4 weeks, produced an expo- treated with chrysotile; IL-1(α) in alveolar sure-dependent increase of DNA adducts in macrophages and basic fibroblast growth lung and heart of animals exposed to 1R4F factor in lungs did the same in lungs with smoke at all concentrations. The concen- refractory ceramic fiberNT239. tration of DNA adducts in lung and heart of Genotoxicity. Cigarette smoke, adminis- TOB-HT cigarette-treated mice was not sig- tered to male ICR mice, produced DNA nificantly increasedNT066. Aqueous suspen- single-strand breaks measured 15, 30, 60, sion of the acetone extract of the paste-like 120, and 240 minutes after the exposure. tobacco preparation, administered orally to Fifteen minutes after the animals were mice at single or multiple doses, induced exposed for 1 minute to a sixfold dilution of significantly high frequencies of chromo- smoke, the effect appeared in the lungs, some aberrations, micronuclei, and sister stomach, and liver. The damage in the lungs chromatid exchange. Single treatment with and liver returned to almost control levels different doses revealed a distinct dose- by 60 minutes and the stomach by 120 min- dependent increase of the effect. There was NICOTIANA TABACUM 311 a significant positive correlation between alkylating species, which bind covalently to time-course of chronic treatment and cellular macromolecules. Within 4 hours of frequencies of micronucleated cells. Inci- the injection, a considerable proportion of dences of chromosome aberrations, micro- NNK metabolites present in the fetal tissues nuclei, and sister chromatid exchange in were excreted in the amniotic fluid via the bone marrow cells after repeated treatment fetal urinary tract. Incubation of tissue slices for different periods did not differ signifi- with NNK indicated that the nose, the lung, cantly from each other and from the respec- and the liver of 13-day-old fetuses could tive single treatment data for the same reduce NNK to 4-(methylnitrosamino)-1- doseNT092. Aqueous extract of Swedish moist (3-pyridyl)butan-1-ol (NNA1), but could oral snuff, in human V79 lymphocytes, not activate NNK by α-carbon hydroxyla- induced sister chromatid exchange and tion. Activating enzymes were competent in chromosome aberrations, with and without 18-day-old fetuses, and the activities in- NT158 metabolic activation. No induction of point creased during the first 6 days of life . mutations was detected. The methylene NNK and NNN, in Salmonella TA100, chloride extract produced genotoxicity, but TA7004, 7005, and 7006 at concentrations no induction of gene mutations in V79 cells of 250–2000 mg/plate, produced missense was observed. The extract did not induce backmutations. NNN was active on TA100 of micronuclei in mice or of sex-linked and TA7004 but inactive in the presence of rat or hamster S9. NNK was mutagenic only recessive lethal mutations in Drosophila in TA7004 strain with rat or hamster S9, melanogasterNT097. Smoke, in Salmonella but not in TA100. NNK and NNN, in dark typhimurium TA97a, TA100, and TA102, mutant M-169 of Vibrio fischeri at con- produced a threefold to ninefold increase in centrations up to 1 mg/mL, were active the frequency of his+ revertants. Activation (Mutatox test). Nicotine, cotinine, trans-3- by a postmitochondrial fraction from liver hydroxycotinine, cotinine-N-oxide, and of rats pretreated with Aroclor-1254 or nicotine-N-oxide were not mutagenic to methylcholanthrene was required. Fractions Salmonella TA100 and TA7004 in the pres- from phenobarbital-pretreated or untreated ence or absence of rat or hamster S9. The rats had no effect. Vitamins A and E, but Mutatox test produced direct mutagenicity not C, inhibited the smoke-induced mu- for COT, 3HC, and NNO, but not CNO. tagenesis. Treatment of mice with smoke for The latter was mutagenic in the Mutatox 60 minutes/day increased the frequency of test with rat or hamster S9, but only rat S9 micronuclei in polychromatic erythrocytes was effective for COT, NNO, and 3HC. In- in bone marrow and in fetal liver, and the hibitory potentiations of NNN by NIC and number of micronucleated normochromatic COT were observed on strain TA7004 and erythrocytes in peripheral blood by four- to by NIC on strain TA100. There were no fivefold. Simultaneous treatment of mice interactions on NNK in the presence of S9 with smoke and Na2SeO3 reduced the for strain TA7004 or TA100. In contrast, a clastogenic effect of tobacco smoke. Ascor- complex inhibition and enhancement bic acid had no effect on clastogenicity but behavior occurred in the Mutatox test for reduced toxicity as measured by body weight each interaction, but no effects were lossNT105. NNK, administered intravenously observed for CNO on NNK without S9, and to pregnant C57Bl mice, diffused through few for NIC on NNK with hamster S9NT206. the placenta and reached the fetal tissues. Glutathione formation induction. Methyl During the last days of gestation, nasal, pul- chloride extract of the leaf, administered monary, and hepatic tissues developed the intragastrically to rats at a dose of 3 mg/ani- enzymatic capacity to activate NNK to mal daily for 21 months in DMSO solvent, 312 MEDICINAL PLANTS OF THE WORLD was active. The rats were divided into two levels in cigarette smokers were signifi- groups: one was fed a vitamin A diet, and cantly higher than those in nonsmokersNT248. the other a vitamin A-deficient diet. Treat- Hematopoiesis inhibition. Smoke, in ment with extract increased glutathione bone-marrow culture in a long-term treat- levels in both liver and lung in the vitamin- ment, produced an inhibition of hemato- fed rats. In the vitamin-deficient group, he- poiesis. Nicotine significantly delayed the patic and pulmonary glutathione levels were onset of hematopoietic loci and reduced decreased by treatment with extractNT519. their size, the number of long-term culture- GSH peroxidase activity. Cigarette smoke initiating cells, nonadherent mature cells, was administered to the ODS rats at doses and their progenitors but failed to influence of 4 mg/day, S4 or 40 mg/day, S40 of ascor- the proliferation of committed hematopoi- bic acid, and exposed to smoke daily for 25 etic progenitors when added into methylcel- days. The treatment produced a significant lulose cultures. Exposure to nicotine decrease of CuZn-SOD, MnSOD, catalase, decreased CD44 surface expression on pri- and PDI by high-dose ascorbic acid admin- mary bone marrow-derived fibroblast-like istration, and nonsignificant decrease of stromal cells and MS-5 stromal cell line but plasma GSH peroxidaseNT196. not on hematopoietic cells. Mainstream GST activity. Cigarette smoke, adminis- smoke altered the trafficking of hematopoi- tered intranasally to young male C57BL etic stem/progenitor cells (HSPC) in vivo. mice fed 0, 5, and 100 ppm of vitamin E, 20 Smoke exposure produced an inhibition of minutes/day for 8 weeks, produced no effect HSPC homing into bone marrow. Nicotine GSTNT153. and cotinine treatment resulted in reduc- GST inhibition. Methyl chloride extract of tion of CD44 surface expression on lung the leaf, administered intragastrically to rats micro-vascular endothelial cell line (LEI- at a dose of 3 mg/animal daily for 21 months SVO) and bone marrow-derived (STR-12) in DMSO solvent, was active. The rats were endothelial cell line. Nicotine increased divided into two groups: one was fed a vita- E-selectin expression on LEISVO cells but min A diet, and the other a vitamin A-defi- not on STR-12 cellsNT035. cient diet. In the vitamin-deficient group, Heme oxygenase expression. Mainstream the treatment decreased GST levels in smoke trapped in phosphate-buffered saline liver and lung vs control and vitamin-fed solutions, in Swiss albino 3T3 fibroblasts, groupsNT519. produced dose-dependent and transiently Glycation products formation. Reactive elevated expression of heme oxygenase. glycation products from an aqueous extract Heme oxygenase protein and its mRNA of tobacco and tobacco smoke reacted with were detectable between 1 and 24 hours proteins to form advanced glycation end after exposure to 0.03 puffs (approx 1 cm3/ products. The end products circulated in mL of medium). A nearly 50-fold increase high concentrations in the plasma of pa- in the amount of heme oxygenase mRNA tients with diabetes or renal insufficiency was determined after 8 hours of exposure, and have been linked to the accelerated compared to control levels. A decrease of vasculopathy seen in patients with these more than 60% in glutathione levels was diseases. Glycotoxins (glycation products) observed after the exposure. No elevated exhibited a specific fluorescence when amounts of heme oxygenase mRNA cross-linked to proteins and were muta- appeared in smoke treated-cells when cys- genic. Glycotoxins were transferred to the teine was exogenously addedNT083. serum proteins of human smokers. Ad- Hepatic enzymes activity. Tobacco vanced glycation end products (AGE)- smoke, administered by Hamburg II ma- apolipoprotein (apo) B and serum AGE chine to mice at a dose of eight cigarettes NICOTIANA TABACUM 313 per day for 2, 4, 8, or 31 days, significantly E, 20 minutes/day for 8 weeks, increased increased HbCO after 4 or 8 days of expo- hepatic lipid peroxidationNT153. sure and decreased after 31 days. The Histological changes. Mainstream smoke enzymate activities were significantly higher from a 1R4F and 2R4F research cigarette during the period of exposureNT069. was administered intranasally to rats at Hepatic lipid peroxidation. Aqueous doses of 0.06, 0.20, or 0.80 mg wet total par- extract of STE activated macrophages with ticulate matter per liter of air for 1 hour/day, the resultant production of reactive oxygen 5 days/week for 13 weeks. The treatment species, including nitric oxide. Administra- produced no significant differences between tion to rats at doses of 125–500 mg/kg both tobacco types. After 13 weeks of the induced dose-dependent increase in mito- recovery period, there were no statistically chondrial and microsomal lipid peroxi- significant differences in histopathological dation, enhanced DNA single-strand findings observed between the 1R4F and the breaks, and significantly increased the uri- 2R4F cigarettes. The complete toxicologi- nary excretion of the lipid metabolites cal assessment in this comparative inhala- malondialdehyde, formaldehyde, acetalde- tion study of 1R4F and 2R4F cigarettes hyde, and acetone. Extract, administered suggests no overall biologically significant orally to female Sprague–Dawley rats at a differences between the rats exposed to the NT192 dose of 25 mg/kg daily for 105 days, in- two cigarettes . Flue-cured tobacco was creased lipid peroxidation 1.4- to 3.3-fold in administered to rats at doses of 0.06, 0.20, hepatic mitochondria and microsome. or 0.80 mg wet total particulate matter per liter of air for 1 hour/day, 5 days/week, for Maximum increase in lipid peroxidation 13 weeks. The only significant difference and DNA single-strand breaks occurred was increased epithelial hyperplasia of the between 75 and 90 days of treatment. Maxi- anterior nasal cavity in males in the high- mum increase of urinary excretion of the exposure group for the heat-exchanger ciga- four lipid metabolites malondialdehyde, rette. At the end of the exposure period, formaldehyde, acetaldehyde, and acetone subsets of rats from each group were main- was observed between 60 and 75 days of tained without smoke exposures for an ad- NT242 treatment . Aqueous STD, administered ditional 13 week (recovery period). At the to rats at doses of 125, 250, and 500 mg/kg, end of the recovery period, there were no produced dose-dependent increase of 1.8, statistically significant differences in histo- 2.3, and 4.4-fold in mitochondrial and 1.5, pathological findings between heat-ex- 2.1, and 3.6-fold in microsomal lipid changer-cured tobacco cigarette when peroxidation at doses tested, respectively, compared to direct-fired cured tobacco relative to control values. At the same three cigaretteNT195. doses of the extract, 1.3, 1.4, and 2.7-fold Hypercholesterolemic activity. Leaf, ad- increases in hepatic DNA single-strand ministered by inhalation to adults of both breaks occurred relative to control values. sexes at variable concentrations, was active. Administration also resulted in significant Serum cholesterol was higher in persons increases in excretion of urinary metabo- smoking cigarettes in all age groups. The lites. Urinary excretion of the four lipid number of cigarettes smoked per day had a metabolites, malondialdehyde, formalde- direct correlation with the serum total cho- hyde, acetaldehyde, and acetone, were lesterol, which increased as the number of increased at every dose and time point with cigarettes smoked per day increasedNT582. maximum increase between 12 and 24 hours Hyperplasia induction. Smoke condensate after treatmentNT275. Cigarette smoke, ad- with nonpolar arotinoid, Ro 15-0778, in ro- ministered intranasally to young male dent respiratory epithelia organ culture C57BL mice fed 5 and 100 ppm of vitamin antagonized the carcinogen-induced hy- 314 MEDICINAL PLANTS OF THE WORLD perplasia and metaplasia. In neonatal rat (1 mg/mL), an inhibitor of leukotrienes bio- tracheas and fetal mouse lungs grown in synthesis, decreased hypoxic pulmonary vitro, 3,4-benzpyrene and cigarette smoke vasoconstriction before and after smoking. condensate induced an increased prolifera- After perfusion with both indomethacin tion of epithelial cells associated with a loss and DEC, hypoxic pulmonary vasoconstric- of secretory activity and ciliary function. In tion also decreased. Results indicated that explants pretreated with cigarette smoke leukotrienes act as mediators, whereas pros- condensate, Ro 15-0778 reversed the high taglandins as modulators in hypoxic pulmo- proliferation rate and restored secretory dif- nary vasoconstriction and prostaglandins ferentiation and ciliary functionNT132. Ciga- and leukotrienes may play an important role rette smoke condensate, in fetal mouse lung in the increase of hypoxic pulmonary and neonatal rat tracheas organ cultures, vasoconstriction by cigarette smokingNT286. induced a striking increase of epithelial Cigarette smoke extract, administered in- mitosis within 12–14 days of treatment. travenously to Wistar rats during hypoxic The increase was associated with a loss of ventilation, produced significant decrease secretory activity and of ciliary function. in microvascular internal diameter of pul- Administration of etretinate with smoke monary arterioles and venules. After pre- condensate inhibited the increase in cell treatment of animal with smoke extract, division and prevented the loss of secretory much more remarkable pulmonary vasocon- activity or ciliary function. In explants pre- striction was induced by hypoxia than treated with cigarette smoke condensate, before injection of the extract. During hy- etretinate reduced the smoke condensate- poxia, mean pulmonary arterial pressure induced increase in mitotic activity to increased by 13.53% before administration normal levels and restored secretory differ- of smoke extract and by 30.57% after entiation and ciliary functionNT165. administration, respectively. Results indi- Hypersecretion of mucous. Cigarette cated that smoke extract can strengthen smoke, in rat larynx and trachea prepara- pulmonary vasoconstriction and hyperten- tion exposed for 2 weeks, significantly sion induced by acute alveolar hypoxiaNT288. increased the secretion of fucose-contain- Immunogenicity. Tobacco was transferred ing glycoconjugates above normal levelNT295. by cholera toxin B (CTB) subunit of Vibrion Hypertensive activity. Water extract of cholerae encoding gene. An aliquot of total the dried leaf, administered intravenously to protein from the transgenic leaf tissue, cats and rats at doses of 1–4 mg/kg, produced administered intradermally to Balb/c (H2K- an initial hypertension followed by [d]) mice at a concentration of 5 μg/mL hypotensionNT588. recombinant CTB, produced CTB-specific Hypoxic pulmonary effect. Cigarette serum IgG in animals. Macrophages isolated smoke, in isolated rat lungs perfused with from mice immunized with native or plant- blood, produced no change in pulmonary expressed CTB showed enhanced secretion vascular resistance. The hypoxic pulmonary of IL-10. The secretion of lipopolysaccha- vasoconstriction was significantly enhanced ride-induced IL-12 and TNF-α was inhib- by smoking. Indomethacin, an inhibitor of ited. Results indicated that plant-expressed prostaglandins biosynthesis, administered in protein behaved like native CTB regarding the perfusing blood (20 μg/mL) increased effects on T-cell proliferation and cytokine hypoxic pulmonary vasoconstriction in the levelsNT008. Tobacco transgenized with re- nonsmoking lungs but not in lungs after combinant FaeG protein (major subunit smoking. Diethylcarbamazine citrate (DEC) and adhesion of K88ad fimbriae), adminis- NICOTIANA TABACUM 315 tered to mice, produced immunogenicity and mice. The immunogen is apparently not comparable to that generated with tradi- a product of incineration because air passed tional approachesNT012. Tobacco, trans- through unlit cigarettes clearly extracted genized with an anti-hepatitis B virus the antigenic componentNT174. surface antigen mouse IgG-1 monoclonal Immunostimulatory activity. Water ex- antibody, was activeNT015. Extract of the leaf tract of the dried leaf, administered to mice expressing Norwalk virus-like particles, at a dose of 0.5%, was active on splenocytes administered intragastrically to CD1 mice, and produced polyclonal AB responseNT449. produced serum and secretory specific Mouse-tobacco hybrid calli and complete IgANT070. Transgenic tobacco expressing plants generated by somatic cell fusion of genes encoding Escherichia coli heat-labile mouse spleen cells and tobacco mesophyll enterotoxin or Escherichia coli heat-labile protoplasts produced mouse Ig-γ-3-heavy enterotoxin fusion protein, administered and λ-light chainsNT078. Aqueous extract of intragastrically to mice, resulted in pro- the STD, in mouse lymphoid cells, produced duction of serum and gut mucosal anti- a significant increase in the proliferation of Escherichia coli heat-labile enterotoxin spleen cells. The polyclonal IgM antibody immunoglobulins that neutralized the responses were elevated in smoke-stimu- enterotoxin in cell protection assayNT074. lated spleen cell cultures. Similar immuno- Transgenic tobacco leaf expressing recom- stimulatory results were found in the binant hepatitis B surface antigen produced mesenteric lymph node cells. The extract response qualitatively similar to those stimulated the spleen cells of the immune obtained by immunizing mice with com- defective CBA/N mice. The extract was mercial vaccine. T-cells were obtained from mitogenic to B- and T-cells in the li- mice primed with the tobacco-derived popolysaccharide-resistant C3H/HeJ mice recombinant hepatitis B surface antigenic spleen cells. The proliferation of T cells was peptide that represents part of the a deter- not accompanied by secretion of IL-2 or minant of hepatitis B surface antigenNT076. expression of IL-2 receptors on T-cells. Tobacco smoke administered to mice for There was an increase of IL-1 activity in 3 days, 18 or 28 weeks before sheep red spleen cells. Activation of B- or T-lympho- blood cell (SRBC) inoculation, produced cytes did not result in the elevation of intra- “shorter-lived” splenomegaly. Mice exposed to cellular calcium levelsNT088. smoke for 3 days or 18 weeks produced a Immunosuppressive activity. Water- reduction in both the magnitude and the soluble condensate of tobacco smoke, ad- duration of the primary immune response as ministered to C57Bl/6 mice at sublethal evidenced by the pattern of expansion of doses, inhibited the ability to respond to splenic white pulp and “RNA-rich” white immunization with sheep erythrocytes by pulp volumes. Mice exposed to smoke for 28 the formation of plaque-forming cells. weeks produced white pulp and “RNA-rich” Spleen cells from water-soluble condensate- white pulp volumes similar to those of con- treated mice were unable to mount a pri- trol miceNT170. Extract of tobacco leaf and mary response to SRBC in vitro. There was tobacco smoke components, administered a decrease in T-lymphocytes in the spleens to mice and rabbits, produced reaginic anti- of treated mice. T-cells from water-soluble body in mice and precipitating antibody in condensate-treated mice were unable to rabbits. The results indicated that tobacco cooperate with normal B-cells and macro- smoke extracts stimulated immune re- phages in the response to SRBC. A less sponses to tobacco leaf antigens in rabbits marked suppression of B-cell function was 316 MEDICINAL PLANTS OF THE WORLD noted in condensate-treated mice. Al- rat, was able to inhibit intercellular commu- though B-cells from such animals were able nication in human and rat cells in a dose- to co-operate with normal T-cells and mac- dependent manner up to 60%NT291. rophages to give a detectable primary Interferon-ααα/βββ production. Mainstream response to SRBC, the response was de- and sidestream smoke from Kentucky 2R1 pressed. Macrophages from water-soluble reference cigarette, in murine L-929 cells condensate-treated animals enhanced the were administered at the highest doses pos- response of normal T- and B-cells to sible to generate a minimum toxic effect. SRBCNT172. The dose was then serially diluted to lower Inflammation induction. Water extract of doses. The treatment produced viability of the leaf, administered intragastrically to exposed cells equivalent to control cell cul- mice at a dose of 4.9 g/kg 6 days per week for tures. Addition of polyriboinosinic–poly- 5 months, was active. The extract consisted ribocytidylic acid to the cells reduced the of 15 g Areca catechu nut, 10 g tobacco leaf, IFN production in viable smoke-exposed and either 3 or 10 g lime to which was added cells. Aging of smoke by delaying time of water extract of Piper betle leaf. Addition of exposure of the cells to the smoke or filtra- the latter enhanced the effect, whereas the tion of smoke through activated charcoal larger dose of lime antagonized the has substantially decreased the alteration of effectNT612. Ether extract of the dried leaf, IFN production by smoke exposureNT142. 4- administered externally to mice at a dose of aminobiphenyl, aniline-HCl, hydrazine sul- 10 mL, was inactiveNT414. fate, and 2-methylquinoline, administered Insecticidal activity. Alkaloid fraction and intraperitoneally to mice, induced IFN pro- methanol extract of the leaf were active on duction at 2, 24, or 48 hours after treatment. Culex pipens larvae. Fifty or more percent Mice treated with 4-aminobiphenyl showed lethality after 24–48 hours was obtainedNT613. some depression of IFN production 2 hours Acetone extract of the dried leaf, at vari- after treatment. Maximum inhibition of able doses, produced 80.6% mortality vs IFN induction was observed 24 hours after snout moths larva of riceNT441. Water extract treatment and a return to control levels 48 of the dried leaf was active on Phyllocnistis hours after treatment. Mice treated with citrellaNT616. Methanol extract of the dried hydrazine sulfate showed maximum inhibi- leaf, at a dose of 50 mg/mL, was inactive on tion of IFN induction 24 hours after treat- Rhinocephalus appendiculatus. Inhibition of ment, but no effects at any other treatment oviposition was used as a measure of time. Treatment of mice with aniline-HCl ascaricidal activityNT593. Ethanol (95%) ex- resulted in marginal depression of IFN tract of the dried leaf, at a concentration induction 24 hours after treatment. 2- of 50 μg/mL, was inactive on Rhodnius ne- methylquinoline had no effectNT160. 4- glectusNT456. Methanol extract of the dried aminobiphenyl and aniline-HCl from root, at a concentration of 50 μg/mL, was sidestream cigarette smoke, in mouse em- active on Rhipicephalus appendiculatus. The bryo fibroblast cell cultures, produced se- extract of dried stem was inactive. Inhibi- verely reduced levels of α/β IFN after tion of oviposition was used as a measure of challenge with polyriboinosinic–polyribo- ascaricidal activityNT593. cytidylic acid when compared to control Intercellular communication inhibition. cultures. Treatment of additional cell cul- Cigarette smoke condensate, administered tures with 2-methylquinoline and interme- by the microinjection-dye transfer tech- diate-level component of sidestream nique to smooth muscle cells of human and tobacco smoke or hydrazine-sulfate also NICOTIANA TABACUM 317 resulted in inhibition of IFN induction with intraepithelial mucosubstances in the ven- polyriboinosinic acid–polyribocytidylic tral septum similar to controls. Smoke-ex- acidNT164. posed rats humanely killed 14 days after IL-12 activity stimulation. STD stimulated exposure still had increased amounts of p40 and p35 promoter activity of the IL-12 intraepithelial mucosubstances in the dor- (p70), and enhanced IFN-γ-induced p40 sal septal region. There was no effect in and p35 promoter activity. It had no effect regions of squamous metaplasia or amounts on lipopolysaccharide-induced p35 and p40 of intraepithelial mucosubstances in the promoter activity and diminished IFN-γ /li- midseptal and ventral septal regions that popolysaccharide-induced p35 promoter ac- were different from air-exposed controls. tivity. The results indicated that tobacco Smoke exposure resulted in a significant extract stimulation of bioactive IL-12 pro- increase in the unit length-labeling index at duction is correlated with its effect on both 1 day but not 14 days after exposure in the p35 and p40 subunits. Stimulation of IL-12 ventral and midseptal regions onlyNT271. production can increase the chances of oral Intraocular pressure reduction. Water inflammatory diseaseNT016. STD, in cell cul- extract of the dried leaf, administered intra- ture, decreased production of IL-12 p40 and venously to rabbits at a dose of 250 μg/ani- p70 from lipopolysaccharide-stimulated mal, was activeNT512. peritoneal macrophages, lipopolysaccha- Irradiation-induced pneumonitis sup- ride/IFN γ-stimulated peritoneal and splenic pression. Diluted mainstream tobacco macrophages, and increased production of smoke was administered intranasally to rats IL-12 p40 and p70 from IFN γ/CD40-stimu- at a concentration of approx 0.4 mg/L for 1 lated splenic macrophages or IFN-γ-stimu- hour/day, 1–5 days/week for 10 weeks, 3 lated peritoneal macrophages. None of the weeks before irradiation. The treatment effects resulted from nicotine, rutin, or chlo- produced less inflammation in the alveolar rogenic acid. Nicotine, at a concentration tissue in the irradiated smoke-exposed group of 100 μg/mL, significantly elevated produc- than in the irradiated not exposed to smoke tion of IL-12 p40 and p70 from splenic group. Mast cells were increased 100-fold in macrophages stimulate by IFN-γ/lipopo- the lung interstitium and 30-fold in the lisaccharideNT031. peribronchial area in the irradiated not IL-I formation stimulation. Water extract exposed to smoke group, whereas no of the dried leaf, administered to mice at a increase was found in the irradiated smoke- concentration of 0.05%, was active on exposed group or in the controls. The alveo- splenocytesNT449. lar septa of the irradiated not-exposed group IL-II receptor gene stimulation. Water ex- were thickened, with occurrence of inflam- tract of the dried leaf, administered to mice matory cells and mast cells, whereas the at a concentration of 1%, was inactive on irradiated smoke-exposed group displayed T-lymphocytesNT449. no difference as compared to controlsNT282. Intraepithelial mucosubstance effect. L-Ascorbic acid influence. Sidestream Diluted mainstream cigarette smoke was cigarette smoke, administered to male administered to F344 rats for 9 days for a Wistar rats for 2 hours daily for 25 days, pro- 2-week period. After the last exposure, duced an increase of the excreted amount of the treatment produced 270% more intra- L-ascorbic acid in the urine. At the end of epithelial mucosubstances in the dorsal the experimental period, the L-ascorbic acid septum, 58% less intraepithelial mucosub- content of the plasma and tissues, liver cy- stances in the midseptum, and amounts of tochrome P450 content, and the activities 318 MEDICINAL PLANTS OF THE WORLD of drug-metabolizing enzymes in the test vironmental tobacco smoke, administered group were higher than the controlNT243. to rats, produced an increase in the rate of Leukocyte dynamics. The effect of chronic LDL accumulation. LDL accumulation was smoking on the microcirculation immedi- primarily dependent on LDL interaction ately after exposure to smoke for 2, 4, and 6 with environmental tobacco smoke–plasma weeks and after withholding smoke for 2 rather than the interaction of environmen- weeks from those previously exposed for 4 tal tobacco smoke–plasma with the artery weeks was investigated. The mean rolling wallNT261. leucocytes at 2, 4, and 6 weeks were 11.10 ± Lung aryl hydrocarbon hydroxylase 1.8, 23.7 ± 2.3, 40.2 ± 3.9 (p < 0.001). The activity. Cigarette smoke, administered rolling leukocytes, after smoking for 4 weeks intranasally to young male C57BL mice fed and then having smoke withheld for 2 5 and 100 ppm of vitamin E, 20 minutes/day weeks, was 9.6 ± 1.4. The mean adherent for 8 weeks, produced no effect on hepatic leucocytes were 5 ± 0.7, 7.5 ± 1.1, 12.6 ± aryl hydrocarbon hydroxylase. All of the 1.8 (p < 0.001). The adherent leucocytes, mice on the vitamin E-free diet showed after smoking for 4 weeks and then having reduced lung aryl hydrocarbon hydroxylase smoke withheld for 2 weeks, was 3.5 ± 0.5. activity. Lung aryl hydrocarbon hydroxylase The results confirmed those of many previ- activity was increased in all of the smoke- ous studies of the adverse effects of cigarette exposed miceNT153. smoking and that those deleterious effects Lymphocyte viability and proliferation. are time-dependent. The reversibility of the Acetaldehyde, benzene, butyraldehyde, iso- deleterious effect of cigarette smoking after prene, styrene, and toluene in mouse lym- cessation of cigarette smoking before face- phocytes cell culture for 3 hours produced lift or flap reconstruction is at least 2 weeks. no effect on either viability or proliferation. This information is also important for clini- Formaldehyde, catechol, acrylonitrile, cal management of patients who smoke and propionaldehyde, and hydroquinone sig- are scheduled for face-lift and flap recon- nificantly inhibited T-lymphocyte and struction. Two weeks without cigarettes is a B-lymphocyte proliferation, inhibitory × –5 × necessary period for successful elective plas- concentration (IC)50 1.19 10 M to 8.20 tic surgeryNT200. 10–4 M. Acrolein and crotonaldehyde inhib- Lipemic activity. Cigarette smoke extract, ited T-cell and B-cell proliferation and × 5 in macrophages with LDL culture at a dose acted on viability with IC50 2.06 10 M to of 100 μg/mL, stimulated cholesteryl oleate 4.26 × 10–5 M. Mixtures of acrolein, formal- synthesis approximately equal to 12.5-fold. dehyde, and propionaldehyde or croto- Enhancement in cholesteryl ester synthesis naldehyde interactive effects at 0.5 and 1 × NT022 was dependent on the concentration of IC50 were observed . smoke-modified LDL and exhibited satura- Malignant cell transformation. Smoke of tion kinetics. There was extensive fragmen- cured leaf, administered to leaf-cutter ants tation of apo B. This LDL modification at an undiluted concentration, was active depended on the incubation time and con- on primary spermatocytesNT404. centration of the smoke extract. Superox- MAO inhibition. 2-Naphthylamine from ide dismutase inhibited LDL modification smoke, in cell culture, inhibited mouse by 52%, suggesting that superoxide anion is brain MAO A and B by mixed competitive- involved. The results indicated that smoke and noncompetitive-type inhibitionNT038. extract alters LDL into a form recognized Mastocytoma induction. Cigarette smoke and incorporated by macrophagesNT125. En- condensate suspensions (“tars”) from differ- NICOTIANA TABACUM 319 ent cigarettes, administered to female CD-1 activity or ciliary function. In explants mice, produced cutaneous mastocytomas pretreated with cigarette smoke conden- accompanied by diffuse dermal mast cell sate, etretinate reduced the smoke conden- infiltrationNT145. Cigarette smoke condensate sate-induced increase in mitotic activity to suspensions (“tar”), administered to CAF1/ normal levels and restored secretory differ- J and ARS-HA (ICR) female mice on long- entiation and ciliary functionNT165. term application, produced a significant Metaplasia induction. Water extract of the incidence of cutaneous mastocytomas. The leaf, administered intragastrically to mice at skin mastocytomas were constantly accom- a dose of 4.9 g/kg, was active. The extract panied by diffuse dermal mast cell infiltra- consisted of 15.0 g Areca catechu nut, 10 g tion, which was also seen in the tumor-free tobacco leaf, and either 3 or 10 g lime to skin of the “tar”-treated miceNT169. which was added water extract of Piper betle Metabolizing enzymes induction. Mash- leafNT612. Cigarette smoke, administered to eri, a pyrolyzed tobacco product, adminis- rats at a dose of 250 mg total particulate tered orally to Swiss mice, Sprague–Dawley matter/m3 6 hours/day for 5 days, increased rats, and Syrian golden hamsters at a dose of the number of small mucous cells in the res- 10% diet for 20 months, produced a signifi- piratory epithelium of the nasal septum in cant induction of CYP and benzo(a) pyrene the early stages of squamous differentiation, hydroxylase in proximal and distal parts of but they were gradually replaced by squa- the three species. GSH and GST were de- mous metaplastic cells. At 5 days after the pleted on masheri treatment in all three spe- withdrawal of cigarette smoke exposure, the cies only in proximal and distal parts of the morphology of the midseptal epithelium intestineNT100. returned to that of a pseudostratified Metaplasia induction. Smoke condensate mucociliary epithelium and the epithelia with nonpolar arotinoid, Ro 15-0778, in lining the maxilloturbinates to that of a rodent respiratory epithelia organ culture, transitional epitheliumNT265. antagonized the carcinogen-induced hyper- Mitochondrial ATPase inhibition. Smoke plasia and metaplasia. In neonatal rat tra- extract, in the mouse brain mitochondria cheas and fetal mouse lungs grown in vitro, culture in the presence or absence of vita- 3,4-benzpyrene and cigarette smoke con- min C for 60 minutes, inhibited mitochon- densate induced an increased proliferation drial ATPase and cytochrome C oxidase of epithelial cells associated with a loss of activities in a dose-dependent manner. The secretory activity and ciliary function. In effect of extract on mitochondria swelling explants pretreated with cigarette smoke response to calcium stimulation was depen- condensate, Ro 15-0778 reversed the high dent on calcium concentrations. The ex- proliferation rate and restored secretory tract treatment induced mitochondrial differentiation and ciliary functionNT132. inner membrane damage and vacuolization Cigarette smoke condensate, in fetal mouse of the matrix, whereas the outer mitochon- lung and neonatal rat tracheas organ cul- drial membrane was preserved. Nicotine tures, induced a striking increase of epithe- produced no significant damageNT007. lial mitosis within 12–14 days of treatment. Mitogenic activity. Water extract of the The increase was associated with a loss of dried leaf, administered to mice at a concen- secretory activity and of ciliary function. tration of 0.05%, was active on lymphocytes Administration of etretinate with smoke from mesenteric lymph node and lympho- condensate inhibited the increase in cell cytes B and T. Intracellular Ca2+ level was division and prevented the loss of secretory unchanged. The extract was active on 320 MEDICINAL PLANTS OF THE WORLD splenocytes. There was an effect in cells infiltration) in a significant number of ani- from strains irresponsible to lipopolysa- mals. Tobacco or HSV-1 when adminis- ccharideNT449. tered alone did not induce dysplasia in the Mitotic effect. STE, administered to the epithelium of labial mucosa. The result buccal mucosa of 15 female HMT rats, 6 indicated that HSV-1 and tobacco could months of age, weekly for 1 year, produced possibly act synergistically in the develop- hyperorthokeratosis, acanthosis, numerous ment of precancerous oral lesions and oral binucleate spinous cells, and subepithelial cancerNT152. Fresh smoke, administered to connective tissue hyalinization. Verrucous Balb/c mice at a daily equivalent of 30 high- carcinoma and squamous cell carcinoma tar filtered cigarettes for up to 95 weeks, were not seen. Karyotyping revealed that produced an induction or production of sig- lymphocytes of tobacco-treated, as well as nificant numbers of malignant tumors of control rats, had normal chromosome num- several types. Significant histopathological ber and morphology. However, approx 25% changes that consisted mainly of interstitial of buccal epithelial cells of the tobacco- pneumonia and focal low-grade emphysema treated rats were tetraploid and 5% octa- were observedNT167. Alveolar and bronchi- ploid, compared with only 11% tetraploid olar spaces in the lungs of cigarette smokers and no octaploid in the controls. Results contained numerous macrophages with pig- indicated that the mitotic process could be mented cytoplasmic granules resulting from disturbed by tobacco treatmentNT297. increased numbers of lysosomes and phago- Molluscicidal activity. Water extract of lysosomes and “smokers’ inclusions” in the the dried leaf, at a concentration of 168 interstitial and alveolar macrophages of ppm, produced equivocal effect on Lymnaea cigarette users. The inclusions have been luteolaNT551. referred to as “needle-shaped” and “fiber- Morphologic and pathological changes. like.” Thin sectioning techniques impart Cigarette smoke inhalation and hydrocorti- varying lengths to the inclusions, suggest- sone acetate (HCA), administered to ing that they have a disc, or platelet, con- C57BL/6 male mice, induced in the lungs a figuration. Surgically resected lung tissue marked reduction of pulmonary macrophage contained varying numbers of hexagonal population that is normally elevated by plate-like particles that had features consis- smoke inhalation, an accumulation of tent with those of the aluminum silicate surfactant and flocculent material in alveoli, kaolinite, and energy-dispersive X-ray a decrease in alveolar space surrounded by spectrometry confirmed the presence of normal septal tissue, and an increase in these two elements. The origin of aluminum hypertrophied alveolar parenchyma. Con- silicate inclusions in pulmonary macro- comitant with altered lung morphology, phages has yet to be determined, although lung volume and gas diffusing capacity were preliminary evidence strongly suggests that significantly compromised. Smoke inhala- they were derived from inhaled tobacco tion or HCA administration alone had no smokeNT190. A mixture of mainstream and ill effectsNT150. Tobacco application (snuff sidestream cigarette smoke, administered by water extract or smoking tar condensate) whole-body exposure to Sprague–Dawley and herpes simplex virus (HSV)-1 inocula- rats for 28 days, produced dramatic alter- tion, administered to mice for 2 months, ations of DNA adducts in bronchoalveolar produced epithelial dysplasia and other lavaged cells, tracheal epithelium, lung, and histomorphologic changes (hyperkeratosis, heart. Oxidative damage to pulmonary increased granular cell layer thickness, DNA, hemoglobin adducts of 4-amino- acanthosis, and increased inflammatory cell biphenyl and benzo(a)pyrene-7,8-diol-9,10- NICOTIANA TABACUM 321 epoxide, micronucleated and polynucleated cells at 1:102 to 1:103 dilutions or 1–100 μg/ alveolar macrophages, and micronucleated mL nicotine for 48 and 72 hours of stimula- polychromatic erythrocytes in bone marrow tion with anti-CD3, produced an increase were also observedNT209. Mainstream smoke of percentage and intensity of CTLA-4 ex- from an Eclipse and 1R4F reference ciga- pression and a decrease of CD28 expression rettes, administered to Sprague–Dawley rats during an exposure to a 1:102 dilution. Ex- of each gender at concentrations of 0, 0.16, posure to nicotine decreased the percentage 0.32, or 0.64 mg wet total particulate mat- of CD4+ T-cells expressing both CD28 and ter/liter air for 1 hour/day, 5 days/week for CTLA-4 and decreased the intensity of 13 weeks, produced a decrease of respiratory CD28 expression. Responding T-cells ex- rate at all concentrations of 1R4F smoke posed to nicotine produced significantly less and at the high concentration of Eclipse Th1 cytokines, IL-2 and IFN-γ, but signifi- smoke. Tidal volume was depressed and cantly more Th2 cytokines, IL-4, and IL-10. minute volume was lower for all smoke- Cytokine specific mRNA expression was exposed rats. Carboxyhemoglobin and only slightly affected by the exposure to serum nicotine were directly related to the nicotineNT068. exposure concentrations of carbon monox- Murine embryopathy. NNK, administered ide and nicotine in an exposure-dependent intraperitoneally to pregnant CD-1 mice manner. Body weights were slightly lower in during organogenesis at a dose of 100 mg/ smoke-exposed rats. The only treatment- kg, produced open eye and one case of a cleft related effect found in organ weights was an palate in 3 of 374 fetuses, which were not increase in heart weight in females in the observed in 160 controls. With phenobar- Eclipse high-concentration exposure group. bital plus NNK, two fetuses had a cleft pal- Nasal epithelial hyperplasia and ventral ate, two had exencephaly and one had a laryngeal squamous metaplasia were noted kinky tail, although phenobarbital controls after exposure to either the 1R4F or Eclipse showed no anomalies. NNK-initiated fetal smoke. The degree of change was less in postpartum lethality was enhanced by phe- Eclipse smoke-exposed rats. Lung macro- nobarbital pretreatment. There were no fe- phages were increased to a similar extent in tal skeletal anomalies or alterations in the Eclipse and 1R4F smoke-exposed resorptions or fetal body weight in any groups. Brown/gold pigmented macrophages group. In embryo culture, gestational day were detected in the lungs of rats exposed to 9.5 embryos exposed to and 10 μM of NNK 1R4F smoke, but not those exposed to had decreased yolk sac diameter, crown- Eclipse smokeNT214. rump length and somite development, and mRNA expression. Cigarette smoke was 100 μM of NNK decreased anterior neu- administered to intact animals and animals ropore closure and crown-rump length (p < with ulcers at concentrations of 2 or 4%. 0.05). Embryos exposed to 100 μM of NNK The treatment significantly reduced the were assessed for K-ras codon 12 mutations thickness of the mucous secreting layer and and none was detectedNT050. gastric mucosal ornithine decarboxylase ac- Mutagenic activity. Smoke of cured leaf, tivity in animals with or without ulcers. The in broth culture was active on Salmonella extract significantly reduced mucus synthe- typhimuriumNT402. Environmental cigarette sis and ornithine decarboxylase activity but smoke, administered by whole-body to p53 × not its mRNA expression in MKN-28 mutant (UL53-3 A/J)F1 mice of both gen- cellsNT217. ders for up to 9.5 months, produced similar Murine CD4 T-cell costimulatory count- oxidative DNA damage in lung and heart of erreceptors. STD, in splenic mononuclear both mutants and wild-type littermate con- 322 MEDICINAL PLANTS OF THE WORLD trols, proliferation of the bronchial epithe- exposure and activated by S9 mix, induced lium, and levels of p53 oncoprotein as a threefold to ninefold increase of sponta- assessed after exposure for 28 days. Smoke- neous His+ reversion mutation rate in Sal- exposed mutant mice underwent a lower monella typhimurium TA98, but not TA97a, induction of apoptosis in bronchial epithe- TA100 and TA102. Smoke, administrated lium, a greater formation of DNA adducts to BDF1 mice at a dose of 600 cm3, two ex- in lung and heart, and a more intense posures of 30 minutes each, produced a two- cytogenic damage. At the end of experi- fold dose-dependent elevation of the ment, DNA adducts were not repaired in number of micronucleated polychromated either wild-type or mutant mice after dis- erythrocytes in bone marrow. No cumula- continuing exposure to smoke for 1 week. A tive effect was detected when mice were weak but significant increase of lung tumor treated with tobacco smoke for 2 to 28 con- incidence and multiplicity was induced in secutive days. The effect observed 24 hours p53 mutant mice after exposure to smoke for after tobacco-smoke exposure was abolished either 5 months. No tumorigenic effect was 48 hours later. Tobacco smoke (180 or 360 observed in their wild-type controls, carry- cm3), passed through the culture medium ing a 99.9% A/J background and 5% FVB (with or without S9 mix) of human periph- genomeNT020. Leaf, administered intragastri- eral lymphocytes, did not increase the spon- cally to rats at a dose of 150 mg/animal twice taneous rate of UDSNT133. Masheri extract daily 5 days-week for 15 weeks, was active was highly mutagenic in the presence of an on natural-killer (NK) cells. Activity of exogenous metabolic system in the Ames peripheral NK cells was assayed by lysis of test and in the micronucleus test, in a dose- YAC-1 lymphoma cellsNT525. Smoke conden- dependent manner. It also induced 8-aza- sate, in combination with a 2 Gy dose of guanine-resistant mutants in Chinese γ-rays, in C3H 10T1/2 cell system, induced hamster V79 cells. Dermal administration a toxicity and transforming response that produced weak carcinogenic effect in Swiss was largely additive in nature. Similar addi- nude mice. The saliva of masheri users pro- tive modes of interaction were observed duced high levels of NNN (14–43 ppb) and when smoke condensate was combined with NPYR (2.2–8.3 ppb). The condensates He4 ions at a dose that was equivalent in collected after pipe smoking of a natural cell death to that used for γ-raysNT089. Smoke, tobacco and a cavendish type tobacco at a concentration of 240 cm3 for 1 or 5 min- produced an increase of the number of re- utes, was active on Salmonella typhimurium vertants induced with cavendish type to- TA98 in an S9 mix-type-dependent man- bacco on Salmonella typhimurium TA100 nerNT124. Black and brown masheri, a pyro- and TA98 in the presence of S9 activation lyzed tobacco product, were active on in both strains compared to the natural Salmonella typhimurium TA98 with meta- tobacco. The increase in the number of bolic activation and on V79 Chinese ham- revertants (approximately three times) was ster cells producing 8-azaguanine resistant found when the tobacco was smoked after mutations. Both tobacco varieties induced paper wrapping “savers”NT148. Alcoholic ex- statistically significant increase in micronu- tract of the chewing tobacco, in Salmonella clei formations compared to the solvent typhimurium TA98 culture, was active after controls and structural chromosomal aber- activation with S9 mix. Extract induced 8- rations in bone marrow cells of miceNT130. azaguanine-resistant mutation in V 79 Chi- Smoke, at concentrations of 120–480 cm3 nese hamster cellsNT154. Urine concentrates in a 16-1 glass chamber, for 1–10 minutes of from smokers, chewers, and nonsmokers, in NICOTIANA TABACUM 323

Salmonella typhimurium TA1538 with meta- with an apparent dose-effect relationship bolic activation by S9, produced an effect (p < 0.01)NT212. by cigarette and bidi smokers’ urine, Neuronal acetylcholine receptor block- whereas nonsmokers’ urine was devoid of ade. Cembranoids ([4R]-2,7,11-cembra- mutagenic effects. Urine of tobacco chew- triene-4-6-diol and its diastereoisomer 4S), ers produced variation in its mutagenic po- in SH-EP1-hα4β2 cell line heterologously tential. Bidi smokers’ urine showed expressing human α4β2-nicotine acetyl- maximum activityNT155. Bidi (Indian ciga- choline receptors (nAChRs), the SH-SY5Y rette) smoke condensate, produced frame- neuroblastoma line naturally expressing shift mutations in Salmonella typhimurium human ganglionic α3β4-nAChRs, and the TA98 and TA1538, and induced 8- TE671/RD cell line naturally expressing azaguanine-resistant mutations in V79 Chi- embryonic muscle α1β1γδ-nAChRs, blocked nese hamster cells in the presence of S9 carbamylcholine-induced (86)Rb(+) flux mixture. Administration to Swiss mice in- with IC50 in the low micromolar range. duced elevated frequencies of micro- Tobacco ([4R]-2,7,11-cembratriene-4-6-diol nucleated erythrocytes in the bone and its diastereoisomer 4S) cembranoids marrowNT156. A crude alcoholic extract of blocked binding of the noncompetitive tobacco containing N-nitrosonornicotine inhibitor [3H]tenocyclidine to nAChRs and NNK, in histidine-deficient Salmonella from Torpedo californica electric organ. IC50 typhimurium TA98 in the presence of 9000 values were in the submicromolar to low- × g supernatant fraction, was activeNT159. micromolar range, with (4R)-2,7,11- NK-cell activity. Cigarette smoke, admin- cembratriene-4-6-diol displaying an order of istered to mice preimmunized with a suble- magnitude higher potency than its diastere- thal infection of influenza virus daily for 36 oisomer, 4SNT210. Presynaptic nAChRs me- weeks, mounted a secondary immune re- diated a calcium influx that enhanced the sponse of normal height on subsequent chal- release of both glutamate and γ-amino- lenge with the homologous virus strain. The butyric acid (GABA). Fura-2 detection of response was less specific than that elicited calcium in single mossy fiber presynaptic in control mice, with high titers of cross-re- terminals indicated that nAChRs directly acting antibody by hemagglutination inhi- mediated a calcium influx. In hippocampal bition to the following strain in the same neurons in primary culture, both spontane- antigenic series. Return of antibody to the ous vesicular release and evoked release of previous level in the antigenic series was not glutamate and GABA were enhanced by observedNT178. Snuff, administered orally to nicotine. The nicotinic current displayed male adult rats for 15 weeks, significantly rapid desensitization kinetics, and the decreased NK-cell activity in peripheral response to nicotine was inhibited by α-bung- blood against murine NK-cell-sensitive tar- arotoxin and methylcaconitine, suggesting get cells (YAC-1 lymphoma)NT289. that nAChRs containing the α-7 subunit Nervous system development. Water- mediated the effect. Modulation of synaptic soluble substances of cigarette smoke and activity by presynaptic calcium influx may combined effect of smoke and high tempera- represent a physiological role of acetylcho- ture was investigated in pregnant rats at the line in the brain, as well as a mechanism of 8th–11th day of gestation. The treatment action of nicotineNT237. produced changes of all indices correlated Neuroprotective effect. 2,3,6-trimethyl- with embryonic nervous system develop- 1,4-naphthoquinone, administered to C57 ment and morphological differentiation, BL/6 mice, protected against MPTP Park- 324 MEDICINAL PLANTS OF THE WORLD inson’s disease-mediated depletion of neo- cyanobutyl)-TIQ (CBTIQ) acted as com- striatal dopamine levels and lowered the petitive inhibitors for both MAO-A and NT037 brain MAO activity . Smoke, adminis- MAO-B. Ki values ranged from 16.4 to 37.6 tered to N-methyl-4-phenyl-1,2,3,6-tetra- μM. N-(Cyanomethyl)-TIQ (CMTIQ) was μ NT257 hydropyridine-treated C57 black mice, not to be an inhibitor (Ki > 100.0 M) . produced no protective effectNT134. Main- 1,2,3,4-TIQ, a presumed proneutrotoxin stream of cigarette smoke from 15 Kentucky linked with Parkinson’s disease, interacted 2R1F research cigarettes (28.6 mg tar, 1.74 with some components of cigarette smoke. mg nicotine/cigarette), administered to The in vitro formation of these compounds kainic acid-treated rats for 10 minutes daily, under physiological conditions occurred 6 days/week, for 4 weeks, indicated pre- rapidly and with a high yield. Significant exposure to smoke significantly reduced the differences in the recovery of the different seizures, mortality, and severe loss of cells in compounds were obtained for Burley regions CA1 and CA3 of the hippocampus tobacco compared to Bright tobacco. After after kainic acid administration and attenu- chronic administration of TIQ and a ated the kainic acid-induced increased Fos- solution of cigarette smoke to rats, the related antigen immunoreactivity in the presence of some of these compounds was hippocampus. In contrast, pretreatment also detected in the brainNT262. with central nicotinic antagonist, mecamy- Nicorandil kinetics. Cigarette smoke, ad- lamine (2 or 10 mg/kg, intraperitoneally) ministered to rats at a dose of 10 mg/kg for blocked the neuroprotective effects medi- 8 minutes, produced the maximum ated by smoke in a dose-dependent manner. nicorandil plasma levels in the rats inhal- Results indicated that smoke exposure ing standard cigarette and nicotine-less provided neuroprotection against the kainic cigarette smoke 4.7 and 4.9 μg/mL, respec- acid insulted via nicotinic receptor activ- tively, after 1–2 hours, compared to the ationNT229. 1,2,3,4-tetrahydro-β-carboline controls. Nicorandil plasma level reached (TH β C), an endogenous or environmen- the maximum (7.6 μg/mL) after an hour tal neurotoxic factor putatively involved and then decreased graduallyNT293. in the development of Parkinson’s disease, NOS activity. Cigarette smoke or smoke reacted in vitro with some components of extract, administered to ulcerated rats once cigarette smoke. Significant differences in daily for 3 days, produced concomitant and the recovery of some of TH β C-derivatives dose-dependent reduction of angiogenesis were obtained for Burley and Bright to- and constitutive NOS activity. The same bacco. Several of the reported compounds treatments also delayed ulcer healingNT232. showed reversible and competitive MAO- Sidestream smoke was administered to A inhibitory properties. The detection of male Wistar rats with a single intratra- some of these compounds in rat brain after cheal instillation of 2 mg of chrysotile or chronic administration of TH β C and a refractory ceramic fiber. The rats were ex- solution of cigarette smoke proved that the posed to smoke 5 days/week for 4 weeks. reported interactions also occur in vivoNT241. Administration of smoke alone increased 1,2,3,4-tetrahydroisoquinoline (TIQ) and IL-1[α] mRNA levels in alveolar macro- some components of tobacco smoke were phages. The smoke stimulated the gene investigated for their ability to inhibit expression of inducible NOS in alveolar rat brain MAO. 1-Cyano-TIQ (1CTIQ), macrophages and IL-6 and basic fibroblast N-(1'-cyanoethyl)-TIQ (CETIQ), N-(1'- growth factor in lungs treated with chryso- cyanopropyl)-TIQ (CPTIQ), and N-(1'- tileNT239. NICOTIANA TABACUM 325

Non-Hodgkin’s lymphoma. The 1450 month study, did not increase the tumor in- cases of non-Hodgkin’s lymphoma (NHL) cidence. Administration to rats at a concen- and 1779 healthy controls from 11 Italian tration of 5% for 18 months produced no areas with different demographic and pro- result. Administration to hamsters at a dose ductive characteristics were included in a of 20% for 2 years, produced forestomach study, corresponding to approx 7 million tumors. Snuff, administered orally to ham- residents. Odds ratios (ORs) adjusted for ster, produced a high incidence of squamous age, gender, residence area, educational cell carcinomas. No carcinogenic activity level, and type of interview were estimated was observed when snuff was inserted into by unconditional logistic regression model. the cheek pouch of the hamster or spread A statistically significant association (OR = over the oral mucosa. This negative result 1.4, 95% confidence interval [CI] 1.1–1.7) was obtained in numerous experiments was found for blond tobacco exposure and whether snuff was applied once only and NHL risk. A dose-response relationship was left in place for several months or inserted limited to men younger than 52 years. Sub- repeatedly for up to 2 years. In the rat, a few jects starting smoking at an early age tumors were observed when snuff was showed a higher risk in men younger than inserted into the artificial lip canalNT052. 65 years, whereas no clear trend was evident Tobacco smoke tar condensate or water- for the other age and gender subgroups. The extract of snuff was administered dermally analysis by Working Formulation categories to mice in upper lips inoculated with latent showed the highest risks for follicular lym- HSV, for 2–3 months. Tar condensate phoma in blond (OR = 2.1, 95% CI 1.4– induced reactivation of latent HSV in the 3.2) and mixed (OR = 1.8, 95% CI 1.1–3) ganglia of 10–20% of the animals, but snuff tobacco smokers and for large cell within extract did not. The infectious virus was also the other Working Formulation group (OR detected in the lips after chronic application = 1.6, 95% CI 1.1–2.4) only for blond of tar condensate in 10% of the animals. tobaccoNT301. Three months’ exposure to tobacco pro- NF-κκκB inhibition. Aqueous extract of duced epithelial dysplasia and other changes mainstream smoke (smoke-bubbled phos- in a significant number of latent HSV- phate-buffered saline), in Swiss 3T3 cells, infected mice. Tobacco alone did not decreased DNA binding of NF-κB during induce dysplasia in the labial epithelium of the first 2 hours of exposure and increased uninfected miceNT137. Nicotine, administered more than twofold over controls after 4–6 by surgically created canals in the mandibu- hours of exposure. There was lack of phos- lar lips of male Sprague–Dawley rats twice phorylation and degradation of IκB-α and daily for 6 weeks, decreased the thrombox- a significant increase in thioredoxin reduc- ane B2 levels in nicotine treated tissues. tase mRNA after 2–6 hours of exposure. Within the nicotine group, thromboxane Results indicated that the activity of NF-κB B2 concentrations were lower at the nico- in smoke-treated cells was subject mainly to tine site compared to the posterior site (18.3 a redox-controlled mechanism dependent ± 5.4 pg/mg). There was also a trend toward on the availability of reduced thioredoxin reduced 6-keto-PGF1α in the nicotine- rather than being controlled by its normal treated tissues compared to saline-exposed regulator, IκB-αNT040. sites. These alterations in cyclo-oxygenase Oral tumorigenic effect. Snuff, adminis- metabolites were not accompanied by tered to mice in the diet at concentrations changes in epithelial proliferation or histo- of 25% gradually decreasing to 5% in a 14- logic parameters. 12(S)-hydroxyeicosate- 326 MEDICINAL PLANTS OF THE WORLD traenoic acid and leukotriene B4 were not exposed to aqueous smoke fractions was affected by nicotineNT259. inhibited by either the superoxide-scaveng- Ornithine decarboxylase activity. Ciga- ing enzyme superoxide dismutase, in combi- rette smoke was administered to intact nation with catalase, or the NO-scavenger animals and animals with ulcers at concen- oxyhemoglobin (HbO2). Activation of trations of 2 or 4%. The treatment signifi- guanylate cyclase in rat lung cells was cantly reduced the thickness of the mucous observed only when bubbling was performed secreting layer and gastric mucosal orni- with filtered smoke and with whole smoke thine decarboxylase activity in animals with in the presence of SOD/catalaseNT065. STD, or without ulcers. The extract significantly in macrophage J774A.1 cell culture, pro- reduced mucus synthesis and ornithine duced an increase of lactate dehydrogenase decarboxylase activity but not its mRNA in concentration- and time-dependent expression in MKN-28 cellsNT217. Cigarette manner. The addition of 250 μg/mL dose smoke and its extract, in human MKN-28 produced 2.9-fold increase in the release of cells, markedly decreased mucus synthesis in lactate dehydrogenaseNT072. Tobacco smoke vivo and in vitro and suppressed ornithine condensate, in rat pulmonary microvascu- decarboxylase activityNT225. lar endothelial cell culture at a concentra- Ovarian toxicity. Cigarette smoke, admin- tion of 20 μg/mL, significantly upregulated istered to pregnant C57BL/6 and DBA/2 xanthine dehydrogenase/oxidase activity inbred strain mice during days 1–18 of preg- after 24 hours of exposure. Longer exposure nancy, did not affect the number of primor- (1 week) to a lower concentration of dial follicles in the ovaries of the mothers. smoke (2 μg/mL) also produced an increase Counts were significantly decreased (31%) in xanthine dehydrogenase/oxidase activity. in the ovaries of DBA/2 offspring, and not Unlike hypoxia, smoke treatment did not significantly (20%) decreased in the ovaries alter the phosphorylation of xanthine of C57BL/6 offspringNT151. dehydrogenase/oxidase, but increased XO Oxidative stress. Smoke, administered to mRNA expression and the xanthine dehy- mice for 10 weeks, produced an increase in drogenase/oxidase gene promoter activity. the levels of lipid peroxidation in the heart, Actinomycin D blocked the activation of catalase activity, and a decrease in glu- xanthine dehydrogenase/oxidase by smoke tathione level. Superoxide dismutase and concentrateNT198. Gas-phase cigarette smoke, heat-stable lactate dehydrogenase in serum in rat lung tissue, produced infiltration of activities were not affectedNT010. Smoke, ad- the terminal bronchioles by lymphocytes in ministered to mice, produced a significant the peribronchiolar region and a mild to decrease in total antioxidant capacity in moderate degree of emphysema in the bronchoalveolar lavage fluid and significant alveolar spaces. The terminal bronchioles changes in oxidized glutathione, ascorbic also produced marked lipid peroxidation, acid, protein thiols, and 8 epi-PGF(2α). dilatation, and peribronchiolar fibrosis. The Treatment with smoke induced a 50% expression of inducible NOS, NF-κB, decrease in the inhibitory activity of hu- mitogen-activated protein kinases (MEK1, man recombinant SLPINT036. Peroxynitride ERK2), phosphotyrosine protein, and c-fos formed by smoke in aqueous solutions, in was increased in the terminal bronchioles Swiss 3T3 cells, sustained c-fos expression but protein kinase C (PKC), MEKK-1, c- was obtained for smoke-bubbled PBS, jun, p38 and c-myc was not changedNT207. peroxynitrite itself, and a compound known Smoke, administered to rats once only or to stoichiometrically release superoxide and daily for 1, 2, 7, or 28 days, did not change nitric oxide (NO) (3-morpholino-sydnoni- NOS-1 gene expression and protein levels. mine [SIN-1]). c-fos expression in cells Levels of NOS-2 expression was twofold NICOTIANA TABACUM 327 higher in smokers at day 1 and decreased to male C57BL mice fed 0, 5, and 100 ppm of control values during 1 month with daily vitamin E, 20 minutes/day for 8 weeks, pro- smoke exposure, whereas protein levels did duced no effect parathion esterase or par- not change. NOS-2 was diffusely expressed athion desulfurase activitiesNT153. in the lung parenchyma, airways, and ves- Periodontal disease. A total of 1085 sels. NOS-3 expression was increased people who smoke were examined for peri- approx 35% after 2 days of smoke exposure odontal status. There was a significant dose- and remained increased to 28 days, whereas effect relationship between the exposure to protein levels were increased by approx 60% tobacco smoke and the extent of periodon- at day 7 and remained elevated. NOS-3 was tal disease assessed as attachment loss and strongly expressed in vascular endothelium. tooth loss. There was a gene–environmen- Protein distribution was identical to mRNA tal interaction. Subjects bearing at least one tissue distribution, and these distributions copy of the variant allele 2 at positions IL- were not changed by smokeNT235. 1A-889 and IL-1B+3954 had an enhanced p53 Mutations. Four head and neck squa- smoking-associated periodontitis as com- mous cell carcinomas from three patients pared with their IL-1 genotype-negative using snuff and one patient not using snuff counterpartsNT302. Snuff, at a dose of 500 mg showed p53 mutations in tumors resected (1% nicotine), induced a rapid increase gin- from two of three patients using snuff. No gival blood flow that was higher than the p53 mutations were observed in the tumor increase in blood pressure, indicating an from the patient not using snuff. No K-ras active vasodilatation, partly blocked by (codons 12 and 13) or H-ras (codon 12) muta- infraorbital nerve block anesthesia and tions were found in any of the tumorsNT071. more so by the superficial mucosal anesthe- Smoke condensate, in sarcoma derived sia. Piroxicam and dexchlorpheniramine from Rat-1 cells transformed by smoke con- had no effectNT303. In 240 patients, smoking densate-treated human fetal lung DNA, had a 2.7 times greater probability to have produced overexpression of p53 and contri- established periodontal disease in smokers buted to the initiation of human lung and 2.3 times in former smokers compared carcinogenesisNT085. to nonsmokers, independent of age, sex, and Pancreatic effect. Cigarette smoke, admin- plaque index. Among cases, probing depth, istered to anesthetized rats alone or in com- gingival recession, and clinical attachment bination with iv ethanol infusion, reduced level were greater in smokers than in former pancreatic blood flow temporarily and smokers or nonsmokers. The plaque index increased leukocyte–endothelium interac- did not show differences. Bleeding on prob- tion (roller p < 0.001, sticker p < 0.01 vs ing was less evident in smokers than in non- baseline). Cigarette smoke potentiated the smokers. There was a dose-dependent impairment of pancreatic capillary perfusion relationship between cigarette consumption caused by ethanol, and both the number of and the probability of having advanced rolling leukocytes and myeloperoxidase periodontal diseaseNT304. activity levels were increased compared Plasma lipid profile. Tobacco was admin- with ethanol or nicotine administration istered to 184 patients with head and neck aloneNT215. Tobacco-specific nitrosamines, cancer, 153 patients with oral precancerous administered to rats, induced pancreatic aci- conditions, and 52 controls. The treatment nar cell and ductal cell neoplasms. One of produced a significant decrease in plasma the tumors had a mixed ductal-squamous- total cholesterol and HDL cholesterol in islet cell componentsNT296. patients with cancer and oral precancerous Parathion esterase activity. Cigarette conditions, compared to controls. The smoke, administered intranasally to young plasma very low-density lipoproteins (VLDL) 328 MEDICINAL PLANTS OF THE WORLD and triglycerides levels were significantly 2/30 (6.7%) of nonsmokers. There was not lower in patients with cancer compared to convincing evidence of NNAL-Gluc in the patients with oral precancerous condi- the amniotic acidNT307. A total of 40 very- tions and controls. The results indicated low-birth-weight infants (750–1500 g) of that the tobacco habituates showed lower smoking during pregnancy (50%) and alco- plasma lipid levels than the nonhabitu- hol-consuming (42%) mothers were hospi- atesNT002. talized and ventilated for respiratory distress Polymorphonuclear cells. High-tar (16 syndrome. At birth, infants of mothers who mg tar/cigarette) filtered cigarettes, admin- smoked and consumed alcohol during istered to Balb/c and C57 Black mice for up pregnancy had significantly higher blood to 32 weeks, produced in Balb/c mice less docosahexaenoic acid (DHA) than in- phagocytic and degradative capacities of fants of nonsmoking and nondrinking polymorphonuclear cells than those of C57 mothersNT308. Mothers of 91 cases and 321 Black mice. Heat inactivation of comple- population controls matched for age, sex, ment within the serum reduced the differ- and residence and smoking during preg- ences between smoke-exposed animals and nancy produced higher an odds ratio of 1.7 age-matched controls in both strains of (95% CI 0.8, 3.8) of brain tumor in their mice. The treatment effects were seen at all children, although this was not statistically times tested from 3 days to 32 weeks of to- significant. Among nonsmoking mothers, bacco smoke exposure. The results indicated the risk for light and heavy exposure to pas- that fc-receptor site activity of PMN cells sive smoking was 1.7 (0.8, 3.6) and 2.2 (1.1, was not significantly affected by smoke ex- 4.5), respectively, and a statistically sig- posure but that complement interactions nificant dose–response relationship was within the phagocytic process are signifi- foundNT309. Maternal use of masheri to- cantly suppressedNT161. bacco in pregnancy was associated with low Prenatal influence. In 589 10-year-old birth-weight of the offspring, lower birth- children who have been observed from their weights in girls than in boys, and decreased gestation to tobacco smoke, half were fe- male:female ratio in live newbornsNT310. males and 52% were African-American. Mainstream and sidestream smoke, ad- During pregnancy, 52.6% of the mothers ministered by inhalation to hamsters, were smokers, 59.7% were smokers when retarded transport of preimplantation em- their children were 10 years old. Six percent bryos through the hamster oviduct. Oviduc- of the children (37/589) reported ever tal muscle contraction rate decreased smoking cigarettes. Maternal smoking was significantly during a single exposure of ani- significantly associated with an increased mals to either mainstream or sidestream risk of the child’s tobacco experimentation. smoke, and contraction rate failed to return Offspring exposed to more than half a pack to initial control values during a 25-minute per day during gestation had a 5.5-fold in- recovery period. Both preimplantation em- creased risk for early experimentation. Pre- bryo transport and muscle contraction were natal tobacco exposure had a direct and more sensitive to sidestream than main- significant effect on the child’s smoking and stream smokeNT311. predicted child anxiety/depression and ex- Progesterone production inhibition. ternalizing behaviors. Maternal current Nicotine, cotinine, and anabasine, together, smoking had no significant effectNT305. Cell- or an aqueous extract of cigarette smoke, in free amniotic acid from groups of smokers MA-10 Leydig cells, produced a dose- and nonsmokers showed a presence of dependent inhibition of progesterone and NNAL in 11/21 (52.4%) of smokers and in 20-α-dihydroprogesterone synthesis. The NICOTIANA TABACUM 329 number of cells in the treated dishes was less tion of hashish and cigarette smoke on brain than the controls. Growth of MA-10 cells proteins and catecholamines was measured. was inhibitedNT306. Cotinine, anabasine, a This was compared with the effects of ani- combination of nicotine, cotinine and ana- mals under stressNT590. basine, or an aqueous extract of cigarette Pulmonary arterial effects. Cigarette smoke in human granulose cells produced smoke, administered to 2- and 3-month-old an inhibition of progesterone synthesis. The rats at a dose of one cigarette 10 times a day, alkaloids and some extract decreased the increased significantly the volume fractions DNA content of the culture dish. Both of the fibroblasts, the collagenous bundles, cotinine and anabasine slightly stimulated and the elastic laminae of the pulmonary the synthesis of normalized estradiol. Nico- arteries. The volume fractions of smooth tine, combination of the three alkaloids, muscle cells and the remainder were and cigarette smoke extract had no signifi- decreased significantly in both groups com- cant influence on estradiol productionNT318. pared to controls. An increase in the stiff- Prostaglandins formation. Aqueous ciga- ness of the pulmonary arteries was found in rette tar extracts, in rat pulmonary alveolar both the 2- and 3-month smoke-exposed macrophages, increased cyclo-oxygenase ratsNT281. activity threefold above the initial activity Pulmonary effect. Smoke, administered to within 2 hours of incubation and gradually mice at a dose of two cigarettes daily, 5 days/ decreased below the initial activity after 8 week for 2–4 months, decreased the number hours of incubation. Accumulated levels of of dendritic cells in the lung tissue and re- prostaglandin-2 increased dramatically after duced the percentage of B7.1-expressing 12 hours of incubation. Release of arachi- dendritic cells. Inoculation with 2 × 108 pfu donic acid from the cells was dramatically of a replication-deficient adenovirus three increased in cells incubated with smoke times 2 weeks apart during the last month extracts in parallel to prostaglandins accu- of tobacco exposure, prevented the expan- mulationNT233. sion and maximal activation of CD4 Prostate tumorigenic effect. Tobacco T-cells and reduced the number of both smoke was administered to rats with im- activated CD4 and CD8 T-cells. Smoke planted bilaterally with Dunning R3327 exposure shifted the activated CD4:CD8 tumor fragments at 10 weeks of age and T-cells ratio from 3 to 1.5, and decreased smoke exposed for an hour each day, 5 days serum adenovirus-specific pan IgG, IgG1, a week, for 9 or 20 weeks. The treatment and IgG2a levelsNT013. NNK, in pulmonary produced only minor changes in the growth cells, produced promutagenic adduct O-6- rates of both the control and the irradiated methylguanine. Administration of doses tumors. At the cellular level, smoking from 0.1 to 50 mg/kg increased the number produced a small, but significant, increase of adducts (3- to 30-fold) in Clara cells in the fraction of tumor cells relative to those detected in type II cells and whole controls. The main difference observed lung. Very low rates of repair of this adduct was in the mast cell numbers. Smoking were detected in Clara cells, whereas effi- produced a fourfold increase in mast-cell cient adduct removal occurred in type II density. The combination of smoking and cells. There was a strong correlation irradiation resulted in a 10-fold intermedi- between the concentration of O-6- ate increaseNT228. methylguanine in Clara cells and tumor Protein synthesis stimulation. Smoke of incidence in the Fischer rat with NNK the leaf, administered to rats at variable doses from 0.03 to 50 mg/kg. No differences doses, was active. The effect of a combina- in adduct concentration between type II 330 MEDICINAL PLANTS OF THE WORLD and Clara cells from A/J mice were observed enhanced the carcinogenicity of benzo(a)- under conditions resulting in pulmonary pyrene in murine pulmonary tissue. A tumor formation. Activation of the K-ras potentially important observation was that gene was detected in lung tumors from A/J whereas hepatic tissue is capable of acti- mice. An early proliferative lesions observed vating whole cigarette smoke condensate in both mice and rats involved the alveolar to mutagenic forms in vitro, murine pul- areas. Ultrastructural examination of these monary tissue does not seem capable of lesions and adenomas revealed morphologic such activation. Although these pulmo- features characteristic of the type II cellNT098. nary-derived tissue homogenates had sig- Masheri (pyrolyzed tobacco), administered nificant aryl hydrocarbon hydroxylase orally to Swiss mice, Sprague–Dawley rats, activity and can metabolize Aflatoxin B1, and Syrian golden hamsters at a dose of 10% 2-aminofluorene, and 7, 8-dihydro-7,8- of the diet for 20 months, produced signifi- dihydroxybenzo(a)pyrene to mutagenic cant increase in activities of phase I activat- forms, these homogenates failed to activate ing enzymes and a remarkable decrease in both cigarette smoke condensate and the the phase II detoxification system in most promutagen 6-aminochryseneNT180. Smoke, extrahepatic tissues of the treated animals administered to Sprague–Dawley rats at a of the three speciesNT099. Cigarette smoke dose of seven cigarettes/day for 5 days/week and hydrocortisone acetate (HCA), admin- during a total period of 12 months, produced istered to C57BL/6J male mice, induced early abnormalities in pulmonary function, marked abnormalities in lungs, high conges- with the forced expiratory volume in one tion with surfactant and flocculent material second/forced vital capacity (FEV1/FVC) in alveoli, prominent alveolar collapse, and ratio, showing an acceleration of ageing septal hypertrophy. Results indicated that effect, particularly between 4 and 8 months the genesis of abnormal conditions that re- of exposureNT253. semble pulmonary alveolar proteinosis is Pulmonary macrophage mobilization. potentiated by cumulative effects of differ- Smoke, administered to smoke-exposed and ent treatments (i.e., smoke, HCA, and subsequently halothane anesthetized nor- stress), most significant being the interac- mal and to C57BL/6 mice, produced airway tion between cigarette smoke and the cilia shorter in stature and fewer in number. steroidNT162. Whole cigarette smoke from There was also disorientation of ciliary basal reference cigarettes administration pro- bodies. Airway macrophages were larger in duced the prompt (maximal activity was 6 size and contained more lysosomes and in- hours), but fairly weak (similar to twofold), clusions than phagocytes in airways of all induction of murine pulmonary microsomal other animals. Smoke inhalation alone pro- monooxygenase activity not unequivo- duced a significant increase in the number cally linked to the Ah locus. This activity of lung parenchymal macrophages when can be detected by using as substrates either compared to the number of cells in sham- benzo(a)pyrene or ethoxyresorufin and can treated and control animals. The total be inhibited by treatment with cyclohexim- macrophage population was significantly ide or actinomycin D. Whole-smoke con- greater in lungs of smoke-exposed mice densate and fractions induced pulmonary 48 hours after anesthesia than in lungs of monooxygenase activity, inhibited ben- smoke-exposed mice not subjected to zo(a)pyrene metabolism in vitro, were halothane anesthesia and to those of metabolized to forms mutagenic to Salmo- sham-treated and control animals. Airway nella typhimurium TA153 and TA98, trans- macrophage numbers were significantly formed C3H 10T1/2 cells in vitro, and elevated in smoke-exposed mice 48 hours NICOTIANA TABACUM 331 after halothane when compared to those of cantly increased in the nephrectomized all other groups, but the number of paren- animalsNT203. chymal macrophages decreased in lungsNT144. Respiratory system toxicity. Smoke of Pulmonary surfactant activity. Smoke cured leaf, administered by inhalation to from Kentucky cigarette, administered in- adults at an undiluted concentration, was tranasally to female Sprague–Dawley rats active on asthmaNT380. twice daily for 60 weeks, produced no differ- RNA synthesis inhibition. Smoke of the ence in total phospholipids content of the leaf, administered to rats at variable doses, bronchoalveolar lavage fluids and the lung was active. The effect of a combination of tissues among the groups. Desaturated phos- cigarette and hashish smoke on stress re- phatidylcholine levels in the broncho- sponse were measured in rats held in a wire alveolar lavage fluids were significantly cage inside of a larger cage with a cat. Brains decreased. The lung tissue desaturated phos- were dissected and measured for protein and phatidylcholine content in smoke-treated catecholamine levelsNT590. rats was not significantly different compared Serotonin uptake. Cigarette smoke, ad- to controls. Phospholipids profile analysis ministered to mice, increased serotonin did not reveal any significant differences concentration as a function of the frequency among other major constituents of surfac- of exposure. Serotonin uptake by the skin tant from control and smoke-treated was maximally increased after two 8-minute ratsNT266. exposures. MAO activity for serotonin, but Red blood cell labeling inhibition. To- not for tyramine, was decreased by cigarette bacco decreased the labeling of blood ele- smoke exposure of more than 8 minutesNT182. ments with technetium-99m and plasma Sister chromatid exchange inhibition. proteins. This effect possibly resulted from Water extract of the dried leaf, in cell cul- either a direct or an indirect effect (reactive ture at a concentration of 20 μL/mL, was oxygen species [ROS]) of tobacco by oxida- active on Chinese hamster ovary cells. tion of the stannous ion, possible damages There was an elevation in frequency in cul- caused in plasma membrane and/or possible tures treated with 20 μL/mL of growth chelating action on the stannous and/or mediaNT445. Seed, administered orally to pertechnetate ionsNT244. adults, was active in chewers with oral can- Renal damages. Cigarette smoke conden- cer or oral submucosal fibrosis and healthy sate was administered to the oral mucosa of chewers, compared to control. An average subtotally nephrectomized Sprague–Dawley of 6 quids of tobacco leaf, Areca nut and rats, and to sham-operated Sprague–Dawley lime were used dailyNT521. Whole Kentucky rats daily for 12 weeks. The treatment in- reference 3A1 and American Blend ciga- creased the indices of structural renal dam- rettes smoke were administered intranasally age in the nephrectomized group. The to B6C3F1 mice at a dose of 10% v/v 1, 4, 9, cigarette smoke condensate increased the and 18 exposures/day (one exposure equal indices of glomerulosclerosis and tubuloin- to one cigarette smoke) 5 days/week for 2 terstitial damage in nephrectomized, but weeks. The treatment increased bone mar- not sham-operated rats. This increase was row sister chromatid exchange for both ciga- completely prevented by renal denerva- rette types in a dose-dependent manner. tion. Urinary albumin excretion went in There was no effect on bone marrow cell parallel with the indices of glomeruloscle- replication kineticsNT149. Whole cigarette rosis and tubulointerstitial damage and smoke, administered intranasally to B6C3F1/ urinary endothelin-1 excretion was signifi- Cum mice daily for 1 to 46 weeks, produced 332 MEDICINAL PLANTS OF THE WORLD a twofold increase in sister chromatid ex- eri) extracts were administered dermally to change over sham-exposed control mice. In Swiss mice and Swiss bare mice. In Swiss animals exposed either chronically or for 1 mice, there was no tumorigenic effect but a week to either type of smoke, the increase marginal synergistic effect of 7,12-dimethyl- in sister chromatid exchange persisted for benz[a]anthracene (DMBA). The effect of at least 1 week after cessation of smoke black masheri extract was observed when exposureNT157. Smoke, administered to young DMBA was used as an initiator. In Swiss adult male mice, elevated pulmonary ma- bare mice, black masheri extract induced crophage population. Pulmonary macro- tumors in 20–35% of the animals the two phages (free, attached, and septal or doses tested. In an initiation/promotion interstitial) divided only rarely. During the protocol with DMBA as an initiator, induc- marked progressive increase in the labeled tion of tumors in 50–52% of the Swiss bare macrophage population in the lungs, the mice and a slight synergistic effect of black number of silver grains over the nuclei of masheri extract were observed with a low labeled macrophages did not become signifi- dose of DMBA, suggesting a synergistic cantly diluted. Results indicated that the effectNT121. markedly elevated macrophage population Small airway remodeling. Airway remod- resulted from the immigration of cells from eling is usually attributed to the effects of bone marrow rather than in situ division of cigarette smoke-induced inflammation in resident macrophagesNT176. Cigarette smoke, the airway wall, but little is known about its administered to adult male mice for 42 to pathogenesis. Cigarette smoke, in rat tra- 82 days, induced increased DNA activity in cheal explants at 24 hours after smoke pulmonary tissue. No such induction was exposure, produced a dose-dependent noted in the liver or spleen. An increase in increase in gene expression of procollagen DNA activity reflected a marked increase in and a significant increase in tissue hydrox- the number of labeled pulmonary macro- yproline, a measure of collagen content. phages. At times, more than 50% of the Greater increases in procollagen gene total pool of labeled cells were identifiable expression were found with repeated smoke as macrophagesNT177. exposures. Results indicated that cigarette Skin tumorigenic effect. Aqueous extract smoke can directly induce airway remodel- of bidi tobacco, administered dermally ac- ing, specifically airway wall fibrosis, probably cording skin tumorigenesis protocol to hair- through active oxygen species-dependent less S/RV Cri-ba mice, did not exhibit transactivation of the epidermal growth carcinogenesis and effectively promoted factor receptor and subsequent NF-κB acti- skin papilloma formation in 7,12-dimethyl- vation. Smoke-evoked inflammatory cells benz[a]-anthracene-initiated mice. An in- were not required for this processNT193. Ciga- crease in papilloma yield above the control rette smoke, in rat bronchioles previously was noted only after 30 weeks of promotion. exposed to smoke in vivo, induced a small At week 40 weeks of promotion with 5 mg but consistent degree of contraction of the and 50 mg extract, it was significantly airways in vitro, which could be reduced by higher than that in the control mice. Mild an endothelin receptor antagonist in the epidermal hyperplasia, increase in mitotic animals which had no previous smoke ex- activity and dermal thickness induced by a posure in vivo, and reduced by the oxidant single application of extract persisted on scavengers SOD or catalase in the animals multiple treatment and correlated well with with previous smoke exposure. Results indi- its tumor-promoting activityNT084. Brown and cated that cigarette smoke induced acute black varieties of pyrolyzed tobacco (mash- small airways constriction through both NICOTIANA TABACUM 333 endothelin release and direct oxidant logic abnormalities, particularly bicephali, effectsNT230. Mainstream cigarette smoke, ad- did not differ significantlyNT314. Cigarette ministered to rats at a dose of 250 mg total smoke, at doses of 10 cigarettes per day (57 particulate matter/m3 air for 6 hours/day, 5 cases), 11–20 (115 cases) or more than 20 days/week, for 2 weeks, increased the type II (25 cases), produced significantly poorer epithelial BrdU labeling index (LI). The sperm density, lower viability, motility and axial airway and terminal bronchiolar LIs morphology in smokers. These parameters were enhanced only in the pump-labeled were worse in the heavy smoking groupsNT315. group. In the pump-labeled rats, the type II The ejaculate content of seminal vesicles, LI elevation was greater than the LI eleva- prostate gland, and epididymis of 29 smok- tion in conducting airways, suggesting that ers and 25 chewers produced a significant the parenchyma may have been injured decrease in vesicular and prostatic param- more than the conducting airways. The eters in smokers compared to nonusers of exposure did not increase the total number tobacco, whereas these parameters were of mucosubstances-containing cells or the unchanged in chewers. The activity of α- total number of axial airway epithelial cells, 1,4-glucosidase was significantly lowered in but there was a phenotype change in the both types of tobacco usersNT316. Serum lev- mucosubstance cells. Neutral mucosub- els of estradiol, prolactin, and total test- stance cells (periodic acid-Schiff-positive) osterone in 50 heavy smokers (median 23.5 were significantly decreased, while acid cigarettes/day), produced higher levels of mucosubstance cells (Alcian blue-positive) estradiol and prolactin, but not testos- were slightly increased by smoke exposure. teroneNT317. Either cell replication and differentiation or Sudden infant death syndrome. Water- differentiation alone may have changed the soluble smoke extract, in cell culture super- phenotype in the smoke cell populationNT231. natants of mouse fibroblasts (L-929 cell Spermatozoal effect. Filtered and non- line), produced an increase in TNF-α from filtered cigarette smoke, streamed at a rate respiratory syncytial virus-infected cells. It of 100 mL/second into chamber with decreased TNF-α from cells incubated with washed human spermatozoa, produced a toxic shock syndrome toxin. Incubation dramatic drop in sperm motility, which with cigarette smoke extract decreased the caused sperm immobilization in about 15 NO production from respiratory syncytial minutes. This effect showed dose-response virus-infected cells and increased the NO relationship with the amounts streamed or production from cells incubated with toxic with the time of exposition and was almost shock syndrome toxin. Monocytes from a the same for filtered or unfiltered smokeNT312. minority of individuals demonstrated ex- Semen of 119 tobacco chewers and 218 treme TNF-α responses and/or very high or smokers selected from an idiopathically very low NO. The proportion of samples in hypofertile population, produced some de- which extreme responses with a very high crease in the ejaculating volume, density TNF-α and very low NO were detected was and total count compared to non-smokers, increased in the presence of the three agents but statistically insignificant. No difference to 20% compared with 0% observed with was found in motility and morphologyNT313. toxic shock syndrome toxin. One to 4% was Sperm of 103 smokers produced a significant observed with cigarette smoke extract or decrease of density and motility compared respiratory syncytial virusNT047. with nonsmokers. Seventy-five percent of Symphatomimetic activity. Water extract smokers vs 26% of nonsmokers had a sperm of the dried leaf, administered intravenously density under 40 × 106 sperm/mL. Morpho- to cats at doses of 0.05 and 10–20 mg/kg, 334 MEDICINAL PLANTS OF THE WORLD enhanced the contractile response of the cat ment inhibited mitogen-induced IL-2 pro- nictitating membrane evoked by pregangli- duction by 76 ± 7% without affecting lym- onic cervical sympathetic nerve stimulation. phocyte/macrophage agglutination or blast At higher doses it produced contractions transformation. The effect of p-benzo- and nictitating membrane contraction quinone appeared to be specific for IL-2 pro- without nerve stimulationNT588. duction, since de novo induction of the IL-2 Systemic inflammatory cytokine produc- receptor α-chain (CD25) and intercellular tion. Sidestream smoke was administered to adhesion molecule-1 (CD54) and upregula- mice at 60 and 120 minutes per day, 5 days/ tion of LFA-1 α/β (CD11a and CD18) were week for a 16 weeks. The treatment pro- unaffectedNT063. Smoke, administered by duced a significant increase in the pro- inhalation to mice, inhibited the antigen- inflammatory cytokines, IL-6, TNF- α, and specific T-cell proliferative response of IL-1 β in 120-minutes smoke exposed mice. lung-associated lymph nodes. Cell-mixing A decrease of the stroke volume, cardiac experiments demonstrated that the defect and hepatic antioxidant vitamin E levels, in smoke exposed mice resulted from an and heart pathology and increased periph- abnormality in T-lymphocyte function. The eral arterial resistance were observed in 120- activity of antigen-presenting cells was minute smoke-exposed mice. Hepatic lipid similar in smoke-exposed and sham-smoke- peroxides were increased on 60-minute exposed control animalsNT112. Diluted, main- smoke exposureNT024. stream cigarette smoke was administered to Tachycardiac activity. Water extract of rats for up to 30 months or nicotine at a the dried leaf, administered intravenously to concentration of 1 mg/kg body weight/24 cats and rats at doses of 10–20 mg/kg, was hours via mini-osmotic pumps for 4 weeks. active. Results were significant at p < 0.05 The treatment decreased antigen-mediated levelNT588. T-cells proliferation and constitutive ac- T-cells influence. SSTE and nicotine were tivation of protein tyrosine kinase and incubated in splenic mononuclear cells at phospholipase C-γ1 activities. Spleen cells concentrations of 1:102 or 1:103 dilutions of from smoke-exposed and nicotine-treated STD, or 10 or 100 μg/mL nicotine, during 4 animals have depleted inositol-1, 4,5- days of stimulation with anti-CD3. The trisphosphate-sensitive Ca2+ stores and a de- treatment sustained expression of IL-2, creased ability to raise intracellular Ca2+ IFN-γ, IL-10, and IL-4 cytokine mRNA at levels in response to T-cell antigen receptor 100 μg/mL nicotine. STD did not exhibit ligation. The results indicated that chronic residual expression of cytokine mRNA. smoking affects T-cell anergy by impairing Restimulated STD exhibited maximum IL- the antigen receptor-mediated signal trans- 2, IL-4, IFN- γ, and IL-10 mRNA at 48 duction pathways and depleting the inosi- hoursNT049. STE, in splenic mononuclear cell tol-1,4, 5-trisphosphate-sensitive Ca(2+) culture at 1:102 to 1:104 dilutions, increased stores. Moreover, nicotine may account for IL-2 production and decreased IL-10 at or contribute to the immunosuppressive 1:102 dilution. IFN-γ production was properties of cigarette smokeNT222. decreased at all concentrations. STE did not Teratogenic effect. Stem, administered alter IL-4 productionNT062. orally to pigs, produced 80% congenital de- P-benzoquinone, a thiol-reactive benzene formities if eaten between days 10 and 30 of derivative from cigarette tar, was incubated pregnancyNT439. STE was administered to 65 in human peripheral blood mononuclear pregnant CD-1 mice at the following doses: cells at a concentration of 10 μM. The treat- equivalent to 8 mg/kg nicotine (group ST), NICOTIANA TABACUM 335 ethanol 1.8 g/kg (EtOH), a combination of decrease in ossificationNT101. Aqueous extract ST and EtOH in the same dosages, or D-glu- of the STE, administered intragastrically to cose (controls and ST alone) three times CD-1 mice at doses of: 1× extract equiva- daily on 6–15 days of gestation. The mean lent to 4 mg/mL nicotine/kg body weight; 3 maternal plasma drug levels were: nicotine, × 12 mg nicotine, and 5 × 20 mg nicotine, 321 ng/mL and ethanol, 0.105 g%. No sig- three times daily for gestation days 1–17, nificant differences were observed in ma- produced no significant effect on the weight ternal weight gain, litter size, or in the gain in comparison to treated control. Dif- incidence of resorptions, deaths, and/or ference was significant in comparison to malformations. Fetal weights were reduced untreated controls. Placental weighs were in the three treatment groups, with the unaffected by the extract. The lowest ex- greatest reduction (13% decrease) recorded tract dosage produced a negligible effect on in the ST group, and a 7% decrease in the the CD-1 mouse and the fetus. The highest ST/EtOH group. Placentas of the ST group dose demonstrated embryotoxicity, growth weighed significantly less than controls. retardation, few malformations, and mater- Ossification of the fetal skeleton, observed nal toxicity. The intermediate dose showed in 10 sites, was affected to the greatest a range of effects between the highest and extent in the ST group, followed by the lowest doses to both the fetus and the EtOH and ST/EtOH groups. Craniofacial motherNT114. NNK was administered intrap- measurements were significantly affected in eritoneally to A/J, C3B6F1, and Swiss out- all three treatment groups, compared to bred Cr:NIH(S) mice at a dose of 100 mg/ controlsNT093. Aqueous extract of STE was kg on days 14, 16, and 18 of gestation to A/ administered intragastrically to CD-1 mice J and C3H/He mice and on days 15, 17, and at doses: ST/D-1 and ST/D-2, equivalent of 19 of gestation to the Swiss mice. There was 12 and 20 mg/nicotine kg body wt, respec- significant incidences of tumors in the lungs tively, three times daily for 5 weeks: 2 weeks of A/J progeny and in the livers of male before conception, during conception, and C3B6F1 and Swiss progeny. A lung tumor during gestational days 0–17. The weight incidence in male offspring of treated A/J gain was not significantly affected. The mice vs control was not statistical signifi- mean maternal plasma nicotine level for the cant but was significantly greater in prog- low-dosage group was 363 ng/mL and 481 eny A/J mice of both sexes compared to ng/mL for the high-dosage group. Maternal controls. The incidence of liver tumors in lethality for the low and high doses were at the male C3B6F1 mice exposed transpla- 9.6% and 28.2%, respectively. No signifi- centally to NNK was 40%, compared with cant differences were found between control 17% in controls. No effect of postnatal so- and ST/D-1 maternal and/or fetal values. In dium barbital or PCB was observed on trans- ST/D-2 group, fetal weights were reduced by placental NNK tumorigenicity in C3B6F1 5.4%; decreased ossification in femur mea- mice. The combined incidence of liver car- surements and in 9 of 10 characteristics cinoma in male mice in all NNK-treated measured; the frequency of resorptions was groups was significantly greater than in con- twofold higher than in controls; and the fre- trols. In male Swiss mice exposed transpla- quency of deaths and malformations was not centally to NNK, the incidence of liver affected. The low dose produced a negligible tumors was 5%, compared to 0% in controls, effect on the CD-1 mouse fetus. The high and postnatal treatment with PCB on day dose demonstrated growth retardation, 56 produced a significant increase in the increased embryotoxicity, and a significant incidence of NNK-induced liver tumors. 336 MEDICINAL PLANTS OF THE WORLD

The combined incidence of liver tumors in Testosterone effect. Cigarette smoke di- the male offspring of the Swiss mice treated luted with 90% air, administered to 12 male with NNK, with or without PCB, was 10%, adult rats for 2 hours/day for 60 days, pro- compared to 0% in controlsNT117. Aqueous duced significant decrease of the mean extract of STE was administered intra- plasma testosterone level. The mean plasma gastrically to pregnant Sprague–Dawley rats luteinizing hormone and follicle-stimulat- three times daily on gestational days 6–18 ing hormone levels of the two groups did not at doses equivalent to 1.33 mg nicotine/kg change significantly after exposure. Histo- body weight (STD-1) or 6 mg nicotine/kg logical examination of the testes showed body weight (STD-2). The treatments fewer Leydig cells and degeneration of the reduced the weight gain of mothers, but remaining cells. The results indicated that fetal weights were reduced in the STD-2 the decrease in plasma testosterone levels group only. Placental weights, litter size, induced by exposure to smoke was not asso- resorptions, deaths, and malformations were ciated with changes in plasma gonadotro- not significantly affected. Skeletal examina- phin levels. The decrease in testosterone tions revealed several dose-related differ- levels may be related to the toxic effects of ences between the smoke extract-treated smoke on Leydig cellsNT258. and control groups. In the STD-1 group, Tourette’s syndrome. Administration of reductions in ossification were seen in the nicotine (either 2 mg nicotine gum or 7 mg nasal and femur width measurements only. transdermal nicotine patch) potentiated the In the STD-2 group, reductions in ossifica- therapeutic properties of neuroleptics in tion were seen in femur length and width, treating patients with Tourette’s syndrome, in the number of ossification centers in the and a single patch may be effective for a forelimb, and in the maxillary, mandibular, variable number of days. These findings and nasal bone measurementsNT278. STE was suggest that transdermal nicotine could administered continuously via Alzet os- serve as an effective adjunct to neuroleptic motic mini-pumps to CD-1 mice at doses of therapyNT251. 3.2 mg/mL (dosage I) and 6.4 mg/mL (dos- Toxicity. Fresh tobacco smoke, adminis- age II) for gestational days 7–14 and 6–13. tered to high leukemic AKR strain of mice The treatment produced plasma nicotine at low levels for 1 day, produced signifi- levels in the range of 29.4 ± 4.8 ng/mL to cantly different mortality profiles associated 44.3 ± 16 ng/mL for dosage I and in the with the sex of the animals and the age at range of 34.6 ± 10.9 ng/mL to 75.5 ± 19.9 which smoke exposure commenced. Fe- ng/mL for the dosage II. Dosage I produced males were more susceptible and died sooner a tendency toward weight reduction, an than males, where a significant propor- increase in the incidence of hemorrhages tion of animals survived longer than age- and supernumerary ribs, and significant matched controls. This prolongation of life delay in ossification of the supraoccipital appeared to result from a failure of the leu- bone, the sacrococcygeal vertebrae, and the kemic state to be mobilized in the smoke- bones of the forefoot and hindfoot. Dosage exposed males. Exposure of both females II produced a significant (8.6%) weight and males to the smoke did not induce sig- reduction from normal and an increase in nificant detectable immunological reactiv- fetal deaths. There were no significant ity against the leukemic cells for the differences between placental weights. parameters tested. This possibly resulted Weights of mothers were significantly re- from a significant enhancement of suppres- duced only at the higher dosesNT127. sor activity in the serum of the chronically NICOTIANA TABACUM 337 exposed animals that also occurs in age- transcriptional and translational changes matched control animalsNT139. Smoke of and changed the mRNA and protein levels cured leaf, administered by inhalation to of the cell cycle and cell differentiation adults, was activeNT362. Leaves, on agar plate markers Ki-67, PCNA, p21, cyclin D1, p53, at a concentration of 50%, produced filaggrin, loricrin, and cytokeratins 1 and changes in cell morphology of the monkey 10. Environmental cigarette smoke or kidney cellsNT574. Leaf, administered orally to drinking water containing equivalent adults, was active. Ultrastructure abnor- concentrations of nicotine that are patho- malities included discontinuous and frag- physiologically relevant, administered to mented basement membrane, reduction in rats and mice for 3 weeks, produced changes hemidesmosomes, and widened intercellu- of the nicotinic acetylcholine receptors and lar spaces of the esophageal mucosaNT453. the cell cycle and cell differentiation genes Leaf, administered by inhalation to male similar to those found in vitroNT033. adults at a dose of 15 g/day, was active vs Transglutaminase activity. Water-soluble various male sex gland functions in tobacco extract of gas-phase cigarette smoke was smokers. An 8-month-old infant ate two incubated with mouse bone marrow-derived cigarette butts. On presentation 2.5 hours macrophage culture containing both tissue- later, she was very lethargic and had type transglutaminase and factor XIII-asso- depressed respiration, subsequently became ciated transglutaminase for 15 minutes at somnolent with difficulty breathing. Urine 37°C. A dose-dependent decrease in tissue- toxicity screen was positive only for nico- type (thrombin-independent) transglutami- tine. She recovered with supportive treat- nase activity was produced, as compared to mentNT511. Fresh leaf, administered externally control cells. Factor XIII (zymogen) was not to adults, was active vs green tobacco sick- inactivated after incubation of macrophages ness in tobacco workersNT483. The exposure with smoke extracts. Smoke exposure had of 47 patients to wet leaves resulted in nico- no effect on cell viability or adherence. The tine toxicity, specifically nausea, vomiting, results indicated that bone marrow-derived weakness, and dizziness. Mean time from macrophages contain factor XIII and tissue- exposure to onset of symptoms was 10 type transglutaminase. Gas-phase cigarette hoursNT452. Smoke extract, in the mouse smoke can inactivate tissue transglutami- brain mitochondria culture in the presence nase within viable murine bone marrow- or absence of vitamin C for 60 minutes, derived macrophages but cannot inactive inhibited mitochondrial ATPase and cyto- zymogenic factor XIIINT131. chrome C oxidase activities in a dose- TNF-F production. Water-soluble ciga- dependent manner. The effect of extract on rette smoke extract and/or respiratory mitochondria swelling response to calcium syncytial virus (RSV), in cell culture, stimu- stimulation was dependent on calcium con- lated TNF-F release from monocytes by centrations. The extract treatment induced both RSV infection and smoke extract and mitochondrial inner membrane damage and an additive effect was observed. There was a vacuolization of the matrix, whereas the decrease in NO release, significant only outer mitochondrial membrane was pre- with smoke extract or a combination of served. Nicotine produced no significant smoke extract and RSV infection. Nicotine damageNT007. Nicotine, preincubated with decreased both TNF-F and NO responses. normal human oral keratinocytes, altered The proportion of extreme responses with the ligand-binding kinetics of their nico- very high TNF-F and very low NO in the tinic acetylcholine receptors. It produced presence of both RSV and smoke extract 338 MEDICINAL PLANTS OF THE WORLD increased to 20% compared with 5% ob- smoke and its extract repressed the processes served with smoke extract or RSV aloneNT048. of new blood vessel formation and NOS Aqueous extract of the STE, in macrophage activity during tissue repair in the gastric J774-A1 cell line and mouse splenocyte mucosaNT232. cultures at low concentrations, enhanced Urinary metabolites. Different biomarkers the production of both TNF-α and IL-1β of NNK exposure and metabolism, includ- and mitogen-induced murine splenocyte ing the urinary metabolite NNAL and the proliferationNT054. Tobacco smoke, in alveo- presumed detoxification product [4-(meth- lar macrophages of C57BL/6 mice in vivo, ylnitrosamino)-1-(3-pyridyl)but-1-yl]-β-O- produced a significant decrease in the pro- D-glucosiduronic acid (NNAL-Gluc) were duction of TNF-α by alveolar macrophages examined along with questionnaire data on with the stimulation of lipopolysaccharide. lifestyle habits and diet in a metabolic epi- In vitro exposure of alveolar macrophages demiological study of 34 black and 27 white to tobacco smoke water-soluble extracts healthy smokers. The results demonstrated decreased the production of TNF-α up to that urinary NNAL-Gluc–NNAL ratios, a 93% of control with stimulation of lipo- likely indicator of NNAL glucuronidation polysaccharide without any decrease in cel- and detoxification, were significantly greater lular viabilityNT095. Smoke was administered in whites than in blacks (p < 0.02). In addi- to rats at a concentration of 10 mg/m3 of tion, two phenotypes were apparent by cigarette smoke for 8 hours daily and the re- probit analysis representing poor (ratio < 6) covered alveolar macrophages were incu- and extensive (ratio ≥ 6) glucuronidation bated with chrysotile or ceramic fibers for groups. The proportion of blacks falling 24 hours. TNF of alveolar macrophages that into the former, potentially high-risk group were not stimulated produced no difference was significantly greater than that of whites between treated and control rats. In alveo- (p < 0.05). The absolute levels of urinary lar macrophages stimulated by chrysotile or NNAL, NNAL-Gluc, and cotinine were ceramic fibers, production of TNF in smoke- also greater in blacks than in whites when exposed rats was higher than that of adjusted for the number of cigarettes controlsNT279. smoked. None of the observed racial differ- Tyrosinase inhibition. Methanol (80%) ences could be explained by dissimilarities extract of the dried aerial parts, at a con- in exposure or other sociodemographic or centration of 100 μg/mL, produced weak dietary factors. Also, it is unlikely that the activityNT415. dissimilarities are due to racial differences UDP–glucuronyltransferase activity. in preference for mentholated cigarettes, Cigarette smoke, administered intranasally because chronic administration of menthol to young male C57BL mice fed 5 and 100 to NNK-treated rats did not result in ei- ppm of vitamin E, 20 min/day for 8 weeks, ther increases in urinary total NNAL or produced no effect on UDP–glucuronyl- decreases in NNAL-Gluc–NNAL ratios. transferaseNT153. Altogether, these results suggest that racial Ulcer healing inhibition. Cigarette smoke differences in NNAL glucuronidation, a or smoke extract, administered to ulcerated putative detoxification pathway for NNK, rats once daily for 3 days, produced con- may explain in part the observed differences comitant and dose-dependent reduction of in cancer riskNT250. angiogenesis and constitutive NOS activity. Vasoconstriction activity. Cigarette The same treatments also delayed ulcer smoke, in isolated rat lungs perfused with healing. Results indicated that cigarette blood, produced no change in pulmonary NICOTIANA TABACUM 339 vascular resistance. The hypoxic pulmonary of 3 mg/animal daily for 21 months in vasoconstriction was significantly enhanced DMSO solvent, was active. Rats were di- by smoking. Indomethacin, an inhibitor of vided or two groups: one was fed a vitamin prostaglandins biosynthesis, administered in A diet, and one a vitamin A-deficient diet. the perfusing blood, increased hypoxic pul- Vitamin C levels in both liver and plasma monary vasoconstriction in the nonsmoking elevated significantly in extract-treated ani- lungs but not in lungs after smoking. Dieth- mals, while vitamin A level decreasedNT519. ylcarbamazine citrate (1 mg/mL), an inhibi- NNN and NNK, administered to Swiss and tor of leukotrienes biosynthesis, decreased Balb/c male mice, produced a significant hypoxic pulmonary vasoconstriction before decrease in liver vitamin A levels by both and after smoking. After perfusion with nitrosamines. NNK treatment also pro- both indomethacin and diethylcarbamazine duced a decrease in the levels of vitamin A citrate, hypoxic pulmonary vasoconstriction in plasmaNT104. also decreased. Results indicated that Weight loss. Smoke of the leaf, adminis- leukotrienes act as mediators whereas pros- tered by inhalation to mice at variable doses taglandins as modulators in hypoxic pulmo- twice daily for 5 days followed by 2 nary vasoconstriction, and prostaglandins nontreatment days, dosed for two to six and leukotrienes may play an important role cycles, was activeNT587. Tobacco smoke, ad- in the increase of hypoxic pulmonary ministered to 3-week-old Wistar rats on a vasoconstriction by cigarette smokingNT286. vitamin E-depleted or normal diet, for 4 Cigarette smoke extract, administered in- weeks, significantly suppressed body weight travenously to Wistar rats during hypoxic increases, particularly in the vitamin E-de- ventilation, produced significant decrease pleted groupNT268. in microvascular internal diameter of pul- REFERENCES monary arterioles and venules. After pre- NT001 Hatsukami, D. K., C. Lemmonds, Y. treatment of animal with smoke extract, Zhang, et al. 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NT130 Kulkarni, J. R., S. Sarkar, and S. V. sis of cigarette smoke-induced DNA Bhide. Mutagenicity of extracts of damage in human tissues and mouse brown and black masheri, pyrolysed skin. Cancer Res 1986; 46(11): 5869– products of tobacco using short-term 5877. tests. Mutagenesis 1987; 2(4): 263–266. NT139 Nguyen D. T., and D. Keast. Effects of NT131 Roth, W. J., H. B. Fleit, S. I. Chung, chronic daily exposure to tobacco and A. Janoff. Characterization of two smoke on the high leukemic AKR distinct transglutaminases of murine strain of mice. Cancer Res 1986; bone marrow-derived macrophages: 46(7): 3334–3340. effects of exposure of viable cells to NT140 Henry, C. J., and R. E. Kouri. Chronic cigarette smoke on enzyme activity. J inhalation studies in mice. II. Effects Leukoc Biol 1987; 42(1): 9–20. of long-term exposure to 2R1 ciga- NT132 Lasnitzki, I., and W. Bollag. Prevention rette smoke on (C57BL/Cum x C3H/ and reversal by a non-polar arotinoid AnfCum)F1 mice. J Natl Cancer Inst (Ro 15-0778) of 3,4-benzpyrene- and 1986; 77(1): 203–212. cigarette smoke condensate-induced NT141 Gairola, C. G. Free lung cell response hyperplasia and metaplasia of rodent of mice and rats to mainstream ciga- respiratory epithelia grown in vitro. Eur rette smoke exposure. Toxicol Appl J Cancer Clin Oncol 1987; 23(6): Pharmacol 1986; 84(3): 567–575. 861–865. NT142 Sonnenfeld, G., and R. W. Hudgens. NT133 Balansky, R. M., P. M. Blagoeva, and Effect of sidestream and mainstream Z. I. Mircheva. Investigation of the smoke exposure on in vitro interferon- mutagenic activity of tobacco smoke. alpha/beta production by L-929 cells. Mutat Res 1987; 188(1): 13–19. Cancer Res 1986; 46(6): 2779–2783. NT134 Perry, T. L., S. Hansen, and K. Jones. NT143 Lehrer, S. B., R. P. Stankus, and J. E. Salvaggio. Tobacco smoke sensitivity: Exposure to cigarette smoke does not a result of allergy? Ann Allergy 1986; decrease the neurotoxicity of N-me- 56(5): 369–381. thyl-4-phenyl-1,2,3,6-tetrahydro- NT144 Hegab, E. S., and D. H. Matulionis. pyridine in mice. Neurosci Lett 1987; Pulmonary macrophage mobilization 74(2): 217–220. in cigarette smoke-exposed mice after NT135 Watson, E. S., A. B. Jones, M. K. halothane anesthesia. Anesth Analg Ashfaq, and J. T. Barrett. Spectropho- 1986; 65(1): 37–45. tometric evaluation of carboxyhemo- NT145 Tanaka, T. and A. Rivenson. Masto- globin in blood of mice after exposure cytoma induced by cigarette smoke to marijuana or tobacco smoke in a particulates: “cigarette tar”. Arch modified Walton horizontal smoke Dermatol Res 1986; 279(2): 130–135. exposure machine. J Anal Toxicol NT146 Sonnenfeld, G., R. B. Griffith, and R. 1987;11(1): 19–23. W. Hudgens. The effect of smoke gen- NT136 Bhide, S. V., J. Kulkarni, U. J. Nair, B. eration and manipulation variables on Spiegelhalder, and R. Preussmann. the cytotoxicity of mainstream and Mutagenicity and carcinogenicity of sidestream cigarette smoke to mono- masheri, a pyrolysed tobacco product, layer cultures of L-929 cells. Arch and its content of tobacco-specific nit- Toxicol 1985; 58(2): 120–122. rosamines. IARC Sci Publ 1987; (84): NT147 Saito, Y., H. Takizawa, S. Konishi, D. 460–462. Yoshida, and S. Mizusaki. Identifica- NT137 Park, N. H., E. G. Herbosa, and J. P. tion of cembratriene-4,6-diol as anti- Sapp. Effect of tar condensate from tumor-promoting agent from cigarette smoking tobacco and water-extract of smoke condensate. Carcinogenesis snuff on the oral mucosa of mice with 1985; 6(8): 1189–1194. latent herpes simplex virus. Arch Oral NT148 Cerna, M. and K. J. Angelis. Mutage- Biol 1987; 32(1): 47–53. nicity in the Salmonella/microsome NT138 Randerath, E., T. A. Avitts, M. V. assay of tobacco condensates formed Reddy, R. H. Miller, R. B. Everson, and during pipe smoking. Mutat Res 1985; K. Randerath. Comparative 32P-analy- 143(3): 161–164. 348 MEDICINAL PLANTS OF THE WORLD

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plants. J Chem Soc Perkin Trans I NT394 Thorpe, T. A., and D. D. Meier. Starch 1973; 2656. metabolism in shoot-forming tobacco NT383 Mader, M. Change of the peroxidase- callus. J Exp Bot 1974; 25: 288. isoenzyme-pattern in callus cultures NT395 Konstantinova, T. N., L. V. Golfstein, independent of the differentiation. O. I. Molodyuk, T. V. Bavrina, and N. Planta Med Suppl 1975; 153. P. Aksenova. Study of histones of cal- NT384 Al-Khateeb, F. A. L. Effect of light luses with vegetative and generative quality on protein synthesis and per- morphogenesis in trapezoid tobacco. oxidase-indoleacetic oxidase activity Dokl Akad Nauk SSR 1974; 216: 226. in cultured tobacco pith tissues. Diss NT396 Ackermann, L. Evidence of a glycopro- Abstr Int B 1974; 35: 2035. tein, until now unknown, in tissue cul- NT385 Kanamaru, K., K. Kato, and M. ture of Nicotiana tabacum. C R Seances Noguchi. Isolation and identification Soc Biol Ses Fil 1974; 168: 344. of gamma-L-glutamyl-L-glutamic acid NT397 Feng, K. A., and J. W. Unger. Presence from tobacco cells in suspension cul- of adenosine triphosphate in tobacco ture. Agr Biol Chem 1974; 38: 2285. (Nicotiana tabacum) tissue grown in NT386 Kaul, K., and P. S. Sabbarwal. Kine- nutrient medium containing various tin induced changes in delta-amino- concentrations of kinetin. Experientia levulinic acid dehydratase of tobacco 1975; 31: 31. callus. Plant Physiol 174; 54: 644. NT398 Chuman, T., H. Kaneko, T. Fuku- NT387 Maeder, P., and M. Bopp. Regulation zumi, and M. Noguchi. Isolation of and significance of peroxidase pattern two terpenoid acids, 4-isopropyl-7- variations during shoot differentiation methyl-5E, 7-octadienoic acid and 3- in callus cultures of Nicotiana tabacum. isopropyl-6-methyl - 4E, 6 - methyl - Planta 1975; 123: 257. 4E, 6 -heptadieonoic acid from Turk- NT388 Laurent’eva, L. M., and M. P. Pyat- ish tobacco. Agr Biol Chem 1974; niskii. Quantitative determination of 38: 2295. citric acid in tobacco. Patent-USSR- NT399 Fujimori, T., R. Kasuga, H. Kaneko, and 454,458 1974. M. Noguchi. Isolation of 3-(4,8,12- NT389 Leu, S. L. K., S. H. Wender, and E. C. trimethyltridecyl)-furan (phytofuran) Smith. Effect of darkness on isoperoxi- from burley tobacco. Agr Biol Chem dases in tobacco tissue cultures. Phy- 1974; 38: 2293. tochemistry 1975; 14: 2551–2554. NT400 Wojnarowicz, C. Tobacco seed oil. NT390 Chirek, Z. Physiological and bio- Tluszcze Jadalne 1974; 18: 7. chemical effects of morphactin IT3233 NT401 Legrand, M., B. Fritig, and L. Hirth. on callus and tumor tissues of Nicoti- Metabolism of phenylpropanoids in ana tabacum cultured in vitro. IV. Beta- the leaf veins of healthy hypersensitive indolylacetic acid oxidase activity. tobacco or tobacco infected by tobacco Oat Coleoptile. Acta Soc Bot Pol 1974; mosaic virus. C R Acad Sci Ser D 43: 177. 1974; 279: 1043. NT391 Izman, G. V., N. A. Sherstyannykh, NT402 Kier, L. D., E. Yamasaki, and and B. N. and L. G. Astaghova. Analysis of the Ames. Detection of mutagenic activ- tobacco haploids, produced by cultur- ity in cigarette smoke condensates. ing anthers in vitro, in regards to their Proc Natl Acad Sci USA 1974; 71: content of alkaloids and volatile acids. 4159. Genetika (Moscow) 1975; 11(3): 50. NT403 Van Cantfort, J., and J. Gielen. Organ NT392 Kemp, J. D. Protein metabolism in cul- specificity of aryl hydrocarbon hy- tured plant tissues. V. Identification of droxylase induction by cigarette smoke the nonprecursor pool as L-leucine. in rats and mice. Biochem Pharmacol Physiol Plant 1975; 35: 53. 1975; 24: 1253. NT393 Fujimori, T., R. K. Asuga, and M. NT404 Benedict, W. F., N. Rucker, J. Faust, Nouchi. Isolation of R-(-)-3-hydroxy- and R. E. Kouri. Malignant transforma- beta-ionone from burley tobacco. Agr tion of mouse cells by cigarette smoke Biol Chem 1974; 38: 891. condensate. Cancer Res 1975; 35: 857. NICOTIANA TABACUM 361

NT405 Perkins, D. L., and L. S. Ciereszko. NT416 Park, K. H., J. D. Park, K. H. Hyun, M. Effect of macrocyclic diterpene from Nakayama, and T. Yokota. Brassino- tobacco on Tetrahymena pyriformis. steroids and monoglycerides with Proc Okla Acad Sci 1974; 54: 34–35. brassinosteroid–like activity in imma- NT406 Demole, E., and C. Demole. A chemi- ture seeds of Oryza sativa and Perilla cal study of burley tobacco flavour frutescens and in cultured cells of (Nicotiana tabacum). VII. Identifica- Nicotiana tabacum. Biosci Biotech tion and synthesis of twelve irregular Biochem 1994; 58(12): 2241–2243. terpenoids related to solanone, includ- NT417 Aragozzini, F., R. Gualandris, E. ing 7,8-dioxabicyclo[3,2,1]-octane and Maconi, and R. Craveri. Coenzyme 4,9-dioxabicyclo[3.3.1]nonane deriva- Q-10 in plant cell cultures. Ann tives. Helv Chim Acta 1975; 58: 1867. Microbiol Enzimol 1984; 34(1): 75–81. NT407 Bharadwaj, B. V., S. Takayama, T. NT418 Reuveny, Z. Regulation of ATP sul- Yamada, and A. Tanimura. N'-nitro- furylase in cultured tobacco cells. Diss sonornicotine in Japanese tobacco Abstr Int B 1976; 36: 4450. products. Gann 1975; 66: 585. NT419 Rennenberg, H. Glutathione in condi- NT408 Randolph, H. R. Gas chromatographic tioned media of tobacco suspension determination of nicotine in an isopro- cultures. Phytochemistry 1976; 15: pyl alcohol extract of smoke particu- 1433–1434. late matter. Tobacco 1974; 176: 44. NT420 Chuman, T., and M. Noguchi. The NT409 Yung, K. H., and D. H. Northcote. structure of a new terpenoid acid 6(S)- Enzymes in the walls of mesophyll cells isopropyl-3 epsilon methyl-3-epsilon-hy- of tobacco leaves. Biochem J 1975; droxy-9-oxo-4E-decenid acid, isolated 151: 141. from Turkish tobacco. Agr Biol Chem NT410 Semenova, N. I., V. V. Chenikov. E. N. 1976; 40: 1793–1796. Shopovalov, and A. D. Zelenskaya. NT421 Nishio, M., C. S. Zushi, and T. Ischii. Effect of isoquercitrin on the taste Mass fragmentation determination of indexes of tobacco. Ezv Vyssh Uchebn indole-3-acetic acid in callus tissues of Zaved Pishch Tekhnol 1974; 1974(5): Panax ginseng and Nicotiana tabacum. 167–168. Chem Pharm Bull 1976; 24: 2038. NT411 Lichtenthaler, H. K., V. Straub, and K. NT422 Janski, A. M. Purification and charac- H. Grumbach. Unequal formation of terization of a sugar unspecific nuclease prenyl-lipids in a plant tissue culture from tobacco suspension cultures. Diss and in leaves of Nicotiana tabacum. Abstr Int B 1976; 36: 6128. Plant Sci Lett 1975; 4: 61. NT423 Kamenshchikova, S. V., and I. G. NT412 Moree-Testa, P., M. Donzel, M. H. Moknachev. Hydrogen cyanide in to- Bergerol, and M. M. Luzinier. Deter- bacco smoke. Tabak (Moscow) 1975; mination of pyridinic and pyrazinic 1975(2): 49. compounds in tobacco and cigarette NT424 Colledge, A., and W. W. Reid. The smoke. Ann Tab Sect 1974; 1(12): 27. phytochemistry of the genus Nicoti- NT413 Richter, M. Composition of essential ana. Part V. The biosynthesis of is– oils in tobacco. III. Analysis of phe- abienol and phytosterols in Nicotiana nolic fraction. Ber Inst Tabakforsch tabacum PB. Ann Tab Sect 2 1974; (Dresden) 1974; 21: 52. 1974(11): 177. NT414 Ilham, M., M. Yaday, and A. W. NT425 Harrell, T. G., K. L. Rush, and A. J. Norhanom. Tumour-promoting activ- Sensabaugh Jr. Colorimetric method ity of plants used in Malaysian tradi- for the determination of ammonia in tional medicine. Nat Prod Sci 1995; tobacco smoke. Tob Sci 1975; 19: 154. 1(1): 31–42. NT426 Ieda, T., T. Matsumoto, and M. NT415 Shin, N. H., K. S. Lee, S. H. Kang, K. Noguchi. Culture conditions of higher R. Ming, S. H. Lee, and Y. S. Kim. In- plant cells in suspension culture. Part hibitory effect of herbal extracts on 7. Formation of ubiquinone by tobacco DOPA oxidase activity of tyrosinase. plant cells in suspension culture. Phy- Nat Prod Sci 1997; 3(2): 111–121. tochemistry 1976; 15: 568–569. 362 MEDICINAL PLANTS OF THE WORLD

NT427 Noguchi, M., T. Matsumoto, K. NT438 Viesca-Trevino, C. Estudios sobre Okunishi, and T. Ikeda. Production of etnobotanica y antropologia medica. ubiquinone 10 from callus. Patent-Ja- Inst Mexicano Para Est Pl Medic, pan Kokai-76 32,788 1976. Mexico 1976: 104. NT428 Fujimori, T., R. Kasuga, H. Matsuhita, NT439 Noma, M., and M. Noguchi. Occur- H. Kaneko, and M. Noguchi. Neutral rence of nicotianamine in higher aroma constituents in burley tobacco. plants. Phytochemistry 1976; 15: Agr Biol Chem 1976; 40: 303. 1701–1702. NT429 Aasen, A. J., A. Pilotti, C. R. Enzell, J. NT440 Nagaraj, G., and M. K. Chakraborty. E. Berg, and A. M. Pilotti. Tobacco Alkaloids and volatile acids of natu chemistry 31. (1S,4S,8R,11S,12R)- tobacco (Nicotiana tabacum) Indian J 8,12-epoxy-2E,6E-thunbergadiene- Chem 1979; 17B (6): 648–649. 4,11-diol, a new constituent of Greek NT441 Zao, S. H., and X. Zhang. On the tobacco. Acta Chem Scand Ser B antifeedant and toxicities of natural 1976; 30: 999. organic insecticides against snout NT430 Demole, E. and P. Enggist. A chemical moth’s larva of rice. Chin J Agr Sci study of Virginia tobacco flavour (Nic- 1982; 1982(2): 55–60. otiana tabacum). I. Isolation and syn- NT442 Shimazaki, M., and A. Ohta. Asym- thesis of two bicyclodamascenones. metric synthesis of (-)-(E)-5-hydroxy- Helv Chim Acta 1976; 59: 1938. 5-isopropyl-3-hepten-2-one, a NT431 Chuman, T., H. Kaneko, and T. cembrane-derived compound from Fukuzumi. Acidic aroma constituents Greek tobacco. Synthesis 1992; of Turkish tobacco: terpenoid acids 1992(10): 957–958. related to tobacco thunberganoids. NT443 Hodges, L. C., G. W. Robinson, and Agr Biol Chem 1976; 40: 587. K. Green. Extract of tobacco callus NT432 Lance, B., R. C. Durley, D. M. Rreid, with antiglaucoma activity. Phytother T. A. Thorpe, and R. P. Pharis. Me- Res 1991; 5(1): 15–18. tabolism of (3H)gibberellin A-20 in NT444 Nielsen, M. T., and R. F. Severson. light and dark-grown tobacco callus Inheritance of diterpene constituent in cultures. Plant Physiol 1976; 58: 387. tobacco trichome exudates. Crop Sci NT433 Nishinari, N., and T. Yamaki. Relation 1992; 32(5): 1148–1150. between cell division and endogenous NT445 Miedzybrodzka, M. B. W., and M. M. auxin in synchronously-cultured to- Yeoman. Effect of culture origin and bacco cells. Bot Mag (Tokyo) 1976; conditions of duvatrienedol accumula- 89: 73. tion in shoot cultures of tobacco. J Exp NT434 Novotny. M., M. L. Lee, and K. D. Bot 1992; 43(256): 1419–1427. Bartle. A possible chemical basis for NT446 Trivgedi, A. H., B. J. Dave, and S. G. the higher mutagenicity of marijuana Adhvaryu. Genotoxic effects of to- smoke as compared to tobacco smoke. bacco extract on Chinese hamster Experientia 1976; 32: 280. ovary cells. Cancer Lett 1993; 70(1/2): NT435 Yasumatsu, N., M. Eda, Y. Tsujino, and 107–112. M. Noguchi. Isolation of oxygenated NT447 Guedes, M. E. M., J. Kuc, R. derivatives of solanesol from burley to- Hammerschmidt, and R. Bostock. bacco. Agr Biol Chem 1976: 40: 1757. Accumulation of six sesquiterpenoid NT436 Hutchinson, C. R., M. T. S. Hsia, and phytoalexins in tobacco leaves infil- R. A. Carver. Biosynthetic studies with trated with Pseudomonas lachrymans. 13 CO2 secondary plant metabolites. Phytochemistry 1982; 21(12): 2987– Nicotiana alkaloids. 1. Initial experi- 2988. ments. J Am Chem Soc 1976; 98: NT448 Hayashi, K., Y. Shimizu, and H. 6006. Takahara. Extraction of nerve growth NT437 Leete, E., and S. A. Slattery. Incorpo- factor biosynthesis promoters from to- ration of (2-14C) nicotinic acid into bacco. Patent-Japan Kokai Tokkyo the tobacco alkaloids. Biosynthesis of Koho-04 210,643 1992; 5 pp. anatabine and alpha, beta-dipyridyl. J NT449 Goud, S. N., L. Zhang, and A. M. Am Chem Soc 1976; 98: 6326. Kaplan. Immunostimulatory potential NICOTIANA TABACUM 363

of smokeless tobacco extract in in vitro NT461 Selvaraj, G., R. K. Jain, D. J. Olson, R. cultures of murine lymphoid tissues. Hirji, S. Jana, and L. R. Hogge. Immunopharmacology 1993; 25(2): Glycinebetaine in oilseed rape and flax 95–105. leaves: detection by liquid chromatog- NT450 Demian, B. A. Trace analysis of vanil- raphy/continuous flow secondary ion- lin in tobacco. J Liq Chromatogr mass spectrometry. Phytochemistry 1993; 16(161): 3563–3574. 1995; 38(5): 1143–1146. NT451 Ollson, E., A. Holth, E. Kumlin, L. NT462 Tazaki, H., H. Kodama, M. Fujimori, Bohlin, and I. Wahlberg. Structure- and A. Onishi. Extraction of 15- related inhibiting activity of some hydroxysolanascone-beta-glucoside, tobacco cembranoids on the prostag- and flavoring agent of tobacco. Patent- landin synthesis in vitro. Planta Med Japan Kokai Tokkyo Koho-61 227,587 1993; 59(4): 293–295. 1986; 4 pp. NT452 Anon. Green tobacco sickness in to- NT463 Bhattarai, N. K. Medical ethnobotany bacco harvesters-Kentucky 1992. Mor- in the Karnali zone, Nepal. Econ Bot bid Mortal Wkly Rep 1993; 42(13): 1992; 46(3): 257–261. 237–240. NT464 Giron, L. M., V. Freire, A. Alonzo, and NT453 Shankaran, K., S. V. Kandarkar, Q. Q. A. Caceres. Ethnobotancal survey of Contractor, R. H. Kalro, and H. G. the medicinal flora used by the Caribs Desai. Ultrastructural changes in of Guatemala. J Ethnopharmacol esophageal mucosa of chronic tobacco 1991; 34(2i3): 173–187. chewers. Indian J Med Res 1993; NT465 Barrett, B. Medicinal plants of Nicara- 98(1): 15–19. gua’s atlantic coast. Econ Bot 1994; NT454 Vogeli, U., R. Vogeli-Lange, and J. 48(1): 8–20. Chappell. Inhibition of phytoalexin NT466 Loewenthal, R., and J. Peer. Tradi- biosynthesis in elicitoritreated tobacco tional methods used in the treatment cell-suspension cultures by calcium/ of ophthalmic diseases among the calmodulin antagonists. Plant Physiol Turkana tribe in north west Kenya. J 1992; 100: 1369–1376. Ethnopharmacol 1991; 33(3): 27–229. NT455 Holdsworth, D., and L. Balun. Medici- NT467 Singh, V. K., Z. A. Ali, and M. K. nal plants of the East and West Sepik Siddioui. Ethnomedicines in the provinces, Papua New Guinea. Int J Bahraich district of Uttar Pradesh, In- Pharmacog 30(3): 218–222. dia. Fitoterapia 1996; 67(1): 65–76. NT456 Schmeda-Hirschmann, G., and A. NT468 Coee, F. G., and G. J. Anderson. Rojas de Arias. A screening method for Ethnobotany of the Garifuna of east- natural products on triatomine drugs. ern Nicaragua. Econ Bot 1996; 50(1): Phytother Res 1992; 6(2): 68–73. 71–107. NT457 Wibberley, M. S., J. R. Lenton, and S. NT469 Flores, J. S., and R. V. Ricalde. The se- J. Neill. Sesquiterpenoid phytoalexins cretions and exudates of plants used in produced by hairy roots of Nicotiana Mayan traditional medicine. J Herbs tabacum. Phytochemistry 1994; 37(2): Spices Med Plants 1996; 4(1): 53–59. 349–351. NT470 Comerford, S. C. Medicinal plants of NT458 Parkih, S. S., K. B. Chopra, R. H. two Mayan healers from San Andres, Kalro, and H. G. Desai. The effect of Peten, Guatemala. Econ Bot 1996; chewing toacco on portal hypertensive 50(3): 327–336. gastric mucosa. J Clin Gastroenterol NT471 Smith, I. K. Evidence for o-acetyl- 1994; 18(4): 348–350. serine in Nicotiana tabacum. Phy- NT459 Tabata, M., E. Sezik, G. Honda, et al. tochemistry 1977; 16: 1293–1294. Traditional medicine in Turkey. III. NT472 Ishiguro, S., and S. Sugawara. Com- Folk medicine in East Anatolia, Van parison of volatile N-containing com- and Biltis provinces. Int J Pharmacog pounds in the smoke of Lamina and 1994; 32(1): 3–12. Midrib of flue-cured tobacco leaves. NT460 Misuzaki, S., D. Yoshida, and Y. Saito. Agr Biol Chem 1977; 41: 377. Antineoplastic agent. Patent-PCT Int NT473 Chuman, T., M. Noguchi, A. Okhubo, Apl-86 02,835 1986; 26 pp. and S. Toda. The structure of a novel 364 MEDICINAL PLANTS OF THE WORLD

acid '3 XI-hydroxy-4 XI, 9-dimethyl- NT482 Akinpelu, D. A. and E. M. Obuotor. 6E, 9E-dodecadienedioic acid’ isolated Antibacterial activity of Nicotiana from Turkish tobacco. Tetrahedron tabacum leaves. Fitoterapia 2000; 1(2): Lett 1977; 1977: 3045–3048. 199–200. NT474 Zelcer, A. and E. Galun. Culture of NT483 Ballard, T., J. Ehlers, E. Freund, M. newly isolated tobacco protoplasts: Auslander, V. Brandt, and W. precursor incorporation into protein, Halperin. Green tobacco sickness: RNA and DNA. Plant Sci Lett 1976; occupational nicotine poisoning in to- 7: 331. bacco workers. Arch Environ Health NT475 Deki, M. Determination of solanesol in 1995; 50(5): 384–389. tobacco extracts by thin layer chro- NT484 Ulbelen, A., G. Iskender, G. Topcu, matography and high pressure liquid and S. Atmaca. Flavonoids of the chromatography. Kanzei Chuo Bun- cured tobacco leaves from black sea sekishoho 1977; 17: 9. area. J Fac Pharm Istancul Univ 1981; NT476 Behr, D., I. Wahlberg, T. Nishida, and 17: 71–76. C. R. Enzell. Tobacco chemistry. 34. NT485 Pakrashi, A., and S. Chatterjee. Effect (3E,6E)-2,6-dimethyl-10-oxo-3, of tobacco consumption on the func- 6-undecadien-2-ol and (2E)-3-me- tion of male accessory sex glands. Int J thyl-4-oxo-2-nonen-8-ol. Two new Androl 1995; 18(5): 232–236. constituents of Greek Nicotiana taba- NT486 Anon. Cigarette smoking and sponta- cum. Acta Chem Scand Ser B 1977; neous abortion. Br Med J 1978; 1: 259. 31: 573. NT487 Demole, E., and P. Enggist. A chemical NT477 Anderson, R. C., D. M. Gunn, J. study of Virginia tobacco flavour Murray-Rust, P. Murry-Rust, and J. S. (Nicotinia tabacum). II. Isolation and Roberts. Vetispirane sesquiterpene synthesis of cis-2-isopropenyl-8-me- glucosides from flue-cured Virginia to- thyl-1,2,3,4-tetrahydro-1-naph- bacco: structure, absolute stereochem- thalemol and 3-isopropenyl-5-methyl- istry, and synthesis. X-ray structure of 1,2-dihydronaphthalene. Helv Chim the P-bromobenzenesulphonate of one Acta 1978; 61: 1335. of the derived aglycones. Chem Com- NT488 Fujimori, T., R. Kasuga, H. Kaneko, mun 1977; 1977: 27. and M. Noguchi. Isolation of solaveti- NT478 Behr, D., I. Wahlberg, and C. R. vone from Nicotiana tabacum. Phy- Enzell. Tobacco chemistry. Structure tochemistry 1977; 16: 392. elucidation and synthesis of 3,3-dim- NT489 Kawashima, N., N. Inoue, and M. ethyl-7-hydroxy-2-octanone, a new Noma. Saccharopine from tobacco seco nor-carotenoid constituent of leaves. Phytochemistry 1978; 17: 991A. Greek tobacco. Acta Chem Scand Ser NT490 Itoh, T., T. Ishii, T. Tamura, and T. B 1977; 31: 793. Matsumoto. Four new and other 4-al- NT479 Behr, D., I. Wahlberg, T. Nishida, and pha-methylserols in the seeds of Solan- C. R. Enzell. Tobacco chemistry. Struc- aceae. Phytochemistry 1978; 17: ture elucidation and synthesis of 971–977. 5(13),7E-megastigmadien-6,9-diol, a NT491 Jeong, T. M., M. S. Yang, and H. H. new constituent of Greek tobacco. Acta Nah. Sterols compositions in three Chem Scand Ser B 1977; 31: 609. Solanaceae seed oils. Hanguk Non- NT480 Itoh, T., T. Tamura, and T. Matsu- ghwa Hakhoe Chi 1978; 21(1): 51–57. moto. Triterpene alcohols in the seeds NT492 Chilton, W. S., J. Temple, M. Marzke, of Solanaceae. Phytochemistry 1977; and M. D. Chilton. Succinamopine: A 16: 1723–1726. new crown gall opine. J Bacteriol NT481 Desmarchelier, C., A. Gurni, G. 1984; 157(2): 357–362. Ciccia, and A. M. Giuletti. Ritual and NT493 Puangnak, W. and S. Vorabhleuk. medicinal plants of the Ese’ejas of the Studies on organic acids in Thai flue– Amazonian rainforest (Madre de Dios, cured tobaccos and their relationship Peru). J Ethnopharmacol 1996; 52(1): to quality. Thai J Agr Sci 1984; 17(2): 45–51. 103–118. NICOTIANA TABACUM 365

NT494 Sinnwell, V., V. Heemann, A. M. NT505 Takagi, Y., T. Fujimori, H. Kaneko, Bylov, W. Hass, C. Kahrec, and F. and K. Kato. C-15 and C-17 aldehydes Seehofer. A new cembranoid from to- from Japanese domestic tobacco, Nic- bacco, IV. Z Naturforsch Ser C 1985; otiana tabacum cv. Suifu. Acta Biol 39(11/12): 1023–1026. Chem 1981; 45(3): 769–770. NT495 Plowman, T. The ethnobotany of coca NT506 Burton, H. R., R. A. Andersen, P. D. (Erythroxylum spp., Erythroxylaceae). Fleming, and L. R. Walton. Changes Advances in Economic botany ethno- in chemical composition of burley to- botany in the Neotropics G. T. Prance, bacco during senescence and curing. 2. and J. A. Kallunki (eds.) New York J Agr Food Chem 1988; 36(3): 579–584. Botanical Garden, Bronx, NY 1984; 1: NT507 Begley, M. J., L. Crombie, D. Mc 62–111. Namara, D. F. Firth, S. Smith, and P. NT496 Anon. 3-Hydroxysolamascone-beta- C. Bevan. Cembrenediols in the cut- sophoroside. Patent-Japan Kokai Tok- ting of tobacco. X-ray crystal structures kyo Koho-59 141,595: 4 pp (1984). of beta-cembrenediol and alpha-cem- NT497 Gupta, M. and T. Chatterjee. Effects breneketol. Phytochemistry 1988; of citrinin on cigarette smoke inhaled 27(6): 1695–1703. and nicotine treated mice. Indian NT508 Saitoh, F., M. Noma, and N. Kawa- Drugs 1981; 18: 309–316. shima. The alkaloid contents of sixty NT498 Anderson, R. C., A. G. Kelly, and J. S. Nicotiana species. Phytochemistry Roberts. Two new acidic constituents 1985; 24(3): 477–480. of flu-cured Virginia tobacco. J Agr NT509 Kolossa, E., B. Deus-Neumann, and M. Food 1983; 31(2): 458–459. H. Zenk. Radioimmunoassays for the NT499 Tiburcio, A. F., R. Ingersoll, and A. W. quantitative determination of cembra- Galston. Modified alkaloid pattern in trienediol. Planta Med 1987; 53(5): developing tobacco callus. Plant Sci 449–456. 1985; 38(3): 207–212. NT510 Whitehead, I. M., D. R. Trelfall, and D. NT500 Takagi, Y., T. Fujimori, H. Kaneko, F. Ewing. 5-Epi-aristolochene is a com- and K. Kato. Isolation of new tobacco mon precursor of the sesquiterpenoid constituents, 8,9– phytoalexins capsidiol and debneyol. dihydroxymegastigmatrienone, from Phytochemistry 1989; 28(3): 775–779. Japanese domestic suifu tobacco. Agr NT511 Borys, D. J., S. C. Setzer, L. J. Ling. Biol Chem 1981; 45(3): 787–788. CNS depression in an infant after the NT501 Wahlberg, I., E. B. Walsh, I. Forsblom, ingestion of tobacco: A case report. et al. Tobacco chemistry 64. A new Vet Hum Toxicol 1988; 30(1): 20–22. sucrose ester from Greek tobacco. Acta NT512 Deutsch, H. M., K. Green, and L. H. Chem Scand Ser B 1986; 40(9): Zalkow. Water soluble high molecular 724–730. weight components from plants with NT502 Nyiredy, S. Z., G. A. Gross, and O. potent intraocular pressure lowering Sticher. Minor alkaloids from Nicoti- activity. Curr Eye Res 1987; 6(7): ana tabacum. J Nat Prod 1986; 49(6): 949–950. 1156–1157. NT513 Goncalo, M., J. Couto, and S. NT503 Behr, D., I. Wahlberg, T. Nishida, and Goncalo. Allergic contact dermatitis C. R. Enzell. Tobacco chemistry. 47. from Nicotiana tabacum. Contact Der- (3S,6R,7E,9R)- and (3S,6R,7E,9S)- matitis 1990; 22(3): 188–189. 4,7-megastigmadiene-3,9-diol. Two NT514 Walhberg, I., A. M. Eklund, and C. R. new nor-carotenoids of Greek tobacco. Enzell. Tobacco chemistry. Six new Acta Chem Scand Ser B 1978; 32(6): cembrane-derived compounds from to- 391–394. bacco. Acta Chem Scand 1990; 44(5): NT504 Eda, S., K. Miyabe, Y. Akiyama, A. 504–512. Ohnishi, and K. Kato. A pectic poly- NT515 Frega, N., F. Bocci, L. S. Conte, and F. saccharide from cell walls of tobacco Testa. Chemical composition of to- (Nicotiana tabacum) mesophyll. Carbo- bacco seeds (Nicotiana tabacum L.). J hydr Res 1986; 158(12): 205–216. Am Oil Chem Soc 1991; 68(1): 29–33. 366 MEDICINAL PLANTS OF THE WORLD

NT516 Caceres, A., B. R. Lopez, M. A. Giron, NT527 Grasso, S. and R. J. Shepherd. Isola- and H. Logemann. Plants used in Gua- tion and partial characterization of vi- temala for the treatment of dermato- rus inhibitors from plant species phytic infections. I. Screening for taxonomically related to Phytolacca. antomycotic activity of 44 plant ex- Phytopathology 1978; 68: 199. tracts. J Ethnopharmacol 1991; 31(3): NT528 Fujimori, T., R. Kasuga, H. Kaneko, Set 263–276. al. Isolation and structure determina- NT517 Nagaraju, N., and K. N. Rao. A survey tion of solanascone, a new tetracyclic of plant crude drugs of Rayalaseema, sesquiterpene ketone from Nicotiana Andhra Pradesh, India. J Ethno- tabacum. Tennen Yuki Kagobutsu pharmacol 1990; 29(2): 137–158. Toronkai Koen Yoshishu 1978; 417. NT518 Sun, J. S., Z. Q. Zhu, S. Q. Li, and Y. NT529 Demole, E., P. Enggist, M. Winter, et Zhu. Studies on 6-benzuladenine local- al. Megastigma-5,8-dien-4-one, an ization in callus cells of tobacco. Zhiwa aroma constituent of the yellow pas- Xuebao 1986; 25(5): 480–482. sion fruit and Virginia tobacco. Helv NT519 Song, Y. N., M. Shibuya, Y. Ebizuka and Chim Acta 1979; 62: 67. U. Sankawa. Indentification of plant NT530 Chuman, T., and M. Noguchi. Isola- factors inducing virulence gene expres- tion of new terpenoid acids (-)-3-me- sion in Agrobacterium tumefaciens. thyl-6-isopropyl-9-oxo-2E,4E-decadienoic Chem Pharm Bull 1991; 39(9): 2347– acid and 3-isopropyl-6-oxo-2Z-hep- 2350. tenoic acid from Turkish tobacco. Agr NT520 Songstad, D. D., W. G. W. Kurz, and Biol Chem 1975; 39: 1169. C. L. Nessler. Tyramine accumulation NT531 Matsushita, H., Y. Tsujino, D. Yoshida, in Nicotiana tabacum transformed with A. Saito, K. Kato, and M. Noguchi. a chimeric tryptophan decarboxylase New minor alkaloids in flue-cured gene. Phytochemistry 1991; 30(10): tobacco leaf (Nicotiana tabacum cv 3245–3246. BY-260-9). Agr Biol Chem 1979; 43: NT521 Adhvaryu, S. G., B. J. Dave, and A. H. 193–194. Trivedi. Cytogenetic surveillance of NT532 Behr, D., I. Wahlberg, T. Nishid, and tobacco-areca nut (mava) chewers, in- C. R. Enzell. Tobacco chemistry. 45. cluding patients with oral cancers and (2E,6S)-2,6-dimethyl-2,7-octadiene- premalignant conditions. Mutat Res 1,6-diol, a new monoterpenoid from 1991; 261(1): 41–49. Greek tobacco. Acta Chem Scand Ser NT522 Matsuzaki, T. and A. Koiwai. Antioxi- B 1978; 32: 228–234. dative beta-diketones in stigma lipids NT533 Chuman, T., and M. Noguchi. Isola- of tobacco. Agr Biol Chem 1988; tion of a new terpenoid acid 2-methyl- 52(9): 2341–2342. 5-isopropyl-1-cyclopentene-1-carboxylic NT523 Cusack, M. and W. S. Pierpoint. Simi- acid from Turkish tobacco. Agr Biol larities between sweet protein thauma- Chem 1975; 39: 567–568. tin and A pathogenesis-related protein NT534 Takagi, Y., T. Fujimori, H. Kaneko, T. from tobacco. Phytochemistry 1988; Fukuzumi, and M. Noguchi. Isolation 27(12): 3817–3821. of a new tobacco constituent, (3S,5R, NT524 Sen, S., G. Talukder, and A. Sharma. 6S,9Zeta)-3-hydroxy-5,6-epoxy-beta- Betel cytotoxicity: further evidence ionol, from Japanese domestic suifu to- from mouse bone marrow cells. Int J bacco. Agr Biol Chem 1978; 42: Pharmacog 1991; 29(2): 130–140. 1785–1787. NT525 Johansson, S. L., J. M. Hirsch, and D. NT535 Demole, E., and P. Enggist. In- R. Johnson. Effect of repeated oral ad- dentification of twenty-one novel con- ministration of tobacco snuff on natu- stituents of oriental tobacco flavour ral killer-cell activity in the rat. Arch (Nicotiana tabacum L.) including (E)- Oral Biol 1991; 36(6): 473–476. 3-methyl-non-2-en-4-one,15-olide, NT526 Bowman, D. T., W. W. Weeks, and C. 8-alpha,13:9-alpha,13 A. Wilkinson. Stability of alkaloid -diepoxy-15,16-dinorlabdane,(z)- production in flue–cured tobacco. octadec-9-en-18-olide, and (E)-2- Comp Sci 1991; 31(5): 1121–1124. ethylidene-6,10,14-trimethyl, NICOTIANA TABACUM 367

trans-2-ethylidene. Helv Chim Acta other families. Biochem Syst Ecol 1978; 61: 2318–2327. 1975; 2: 193–199. NT536 Behr, D., I, Wahlberg, A. J. Aasen, et NT546 Behr, D., I. Wahlberg, T. Nishida, C. al. Tobacco chemistry. 44. (1S,2E,4R, R. Enzell, J. Berg, and A. Pilotti. To- 6E,8R,11S,12R): and (1s,2E,4S,6E, bacco chemistry. New cembranic 8R,11S,12R)-8,11-eposy-2,6- diterpenoids from Greek tobacco. Acta thunbergadiene-4,12-diol. Two new Chem Scand Ser B 1980; 34: 195–202. diterpenoids of Greek tobacco. Acta NT547 Uegaki, R., T. Fujimori, H. Kaneko, K. Chem Scand Ser B 1978; 32: 221–227. Kato, and M. Noguchi. Isolaton of NT537 Takagi, Y., T. Chuman, T. Fujimori, dehydrololiolide and 3-oxo-actinidol H. Kaneko, T. Fukuzumi, and M. from Nicotiana tabacum. Agr Biol Noguchi. Isolation of new nor–isopre- Chem 1979; 43(5): 1149–1150. noids related to tobacco thunbergan- NT548 Kodama, H., T. Fujimori, and K. Kato. oids from Japanese domestic suifu Non-volatile constituents in tobacco. tobacco. Agr Biol Chem 1978; 42: Part 1. Isolation of a new terpene 327–331. clucoside,3-hydroxy-5,6-epoxy-beta- NT538 Coxon, D. T., A. M. C. Davies, G. R. ionyl-beta-D-glucopyranoside from Fenwick, R. Self, J. L. Firmin, D. flue–cured tobacco. Agr Biol Chem Lipkin and N. F. Janes. Agropine, a 1981; 45: 941–944. new amino acid derivative from crown NT549 Wahlberg, I., D. Behr, A. M. Eklund, gall tumors. Tetrahedron Lett 1980; T. Nishida, and C. R. Enzell. Tobacco 21: 495–498. chemistry. Seven new nor-cembra- NT539 Takagi, Y., T. Fujimori, H. Kaneko, noids isolated from Greek tobacco. and K. Kato. Phytuberol from Japanese Acta Chem Scand Ser B 1980; 34(34): domesto tobacco, Nicotiana tabacum 675–683. cv. Suifu. Agr Biol Chem 1979; 43: NT550 Miyano, M., N. Yasumatsu, H. 2395–2396. Matsushita, and K. Nishida. 1-(6- NT540 Chortyk, O. T., R. F. Severson, and R. F. hydroxyoctanoyl)nornicotine and 1- Arrendale. Isolation and quantitation (7-hydroxyoctanoyl)nornicotine, two of terpenoid and lipid constituents of new alkaloids from Japanese deomestic tobacco. Lloydia 1978; 41(6): 647–648. tobacco. Agr Biol Chem 1981; 45: NT541 Takagi, Y., T. Fujimori, H. Kaneko, 1029–1032. and K. Kato. Cembrene, from Japanese NT551 Rao, V. P., D. Chowdary, and R. domestic tobacco Nicotiana tabacum. Narayanan. Effect of aqueous tobacco Agr Biol Chem 1980; 44: 467–468. extract on the bioenergetis parameters NT542 Kung, S. D., J. A. Saunder, T. C. Tso, of the snail host, Lymnaea luteola. Proc D. A. Vaughan, M. Womack, R. C. Tent Int Congress Trop Med & Ma- Staples, and G. R. Beecher. Tobacco laria 1980; 355–. as a potential food source and smoke NT552 Wahlberg, I., D. Behr, A. M. Eklund, material nutritional evaluation of to- T. Nishida, C. R. Enzell, and J. E. Berg. bacco leaf protein. J Food Sci 1980; 45: Tobacco chemistry. 54. (1S,2E,4S,6E, 320–327. 8S,11R,12S)-8–11-epoxy- NT543 De Salles, L. The water soluble fraction cembradiene-1,12-diol, a new con- of cigarette smoke condensate identi- stituent of Greek tobacco. Acta Chem fication of the principal components. Scand Ser B 1982; 36: 37–41. Ann Tab Sect 1976; 1(14): 119–124. NT553 Wahlberg, I., I. Wallin, C. Narbonne, NT544 Court, W. A., and J. G. Hendel. De- N. Toshiaki, C. R. Enzell, and J. E. termination of nonvolatile organic and Berg. Tobacco chemistry. Three new fatty acids in flue–cured tobacco by gas cemebranoids from Greek tobacco. liquid chromatography. J Chromatogr The stereochemistry of (1S,2E,4S, Sci 1978; 16: 314–317. 6R,7E,11E)-2,7,11-cembratriene-4,6- NT545 Kawashima, N., and Y. Tanabe. Com- diol. Acta Chem Scand Ser B 1982; parison of the primary structure of the 36: 147–153. large and small subunits of fraction 1 NT554 Katz, T., T. P. Pitner, R. D. Kinser, R. protein from Solanaceae plants and N. Gerfuson, and W. N. Einolf. Isola- 368 MEDICINAL PLANTS OF THE WORLD

tion and indentification of two new from flue-cured tobacco leaves. Phy- seco-cembranoids from cigarette smoke. tochemistry 1983; 22(8): 1819–1820. Tetrahedron Lett 1981; 22: 4771– NT566 Matsushima S., T. Ohsumi, and S. 4774. Sugawara. Composition of trace alka- NT555 Siddiqui, I. R., N. Rosa, and G. L. loids in tobacco lean lamina. Agr Biol Benzing. An amadori compound from Chem 1983; 47(3): 507–510. tobacco. Carbohydr Res 1981; 98: NT567 Heemann, V., A. M. Bylov, U. 57–63. Brummer, W. Hass, and F. Seehofer. NT556 Jujimori, T., Y. Takagi, and K. Kato. 3,7,11,15-Cembratetraen-6-ol, a new Isolation of 8,9-dehydrotheaspirone cembranoid from tobacco, III. Z from Nicotiana tabacum. Agr Biol Naturforsch Ser C 1983; 38(7/8): Chem1981; 45: 2925–2926. 517–518. NT557 Uegaki, R., T. Fujimori, H. Kaneko, NT568 Kodama, H., T. Fujimori, and K. Kato. and K. Kato. Isolation of geranyl- Structure determination of new ses- geraniadiene from Nicotiana tabacum quiterpene glycosides from flue–cured cv. burley. Agr Biol Chem 1980; 44: tobacco by two dimensional NMR. 2215. Proc 26th Symposium on the Chemis- NT558 Kodama, H., T. Fujimori, and K. Kato. try of Natural Products, Kyoto, Japan Non-volatile constituents on tobacco. 1983; 26: 1–8. Isolation of a new perpene glucoside, NT569 Wahlberg, I., K. Nordfors, C. Vogt, T. loliolide-beta—D-glucopyranoside Nishida, and C. R. Enzell. Tobacco from flue-cured tobacco. Agr Biol chemistry. Five new hydroperoxy- Chem 1982; 46: 1409–1411. cembratrinediols from tobacco. Acta NT559 Bolt, A. J. N., S. W. Purkis, and J. S. Chem Scand Ser B 1983; 37(7): Sadd. A damascene derivative from 653–656. Nicotiana tabacum. Phytochemistry NT570 Bylov, A. M., U. Brummer, W. Hass, 1983; 22(2): 613–614. F. Seehofer, V. Heemann, and V. NT560 Park, O. S. Isolation of solanesol from Sinnwell. New cembranoids from Korean native tobacco. Korean J tobacco, II. Z Naturforsch Ser C Pharmacol 1981; 12: 211–214. 1983; 38(7/8): 515–516. NT561 Wahlberg, I., A. M. Eklund, T. NT571 Gore, N. R., and J. L. Wray. Leucine: Nishida, C. R. Enzell, and J. E. Berg. tRNA ligase from cultured cells of Tobacco chemistry. 58. 7,8-Epoxy-4- Nicotiana tabacum var. xanthi. Evi- basmen-6-one, a tobacco diterpenoid dence for de novo synthesis and for loss having a novel skeleton. Tetrahedron of functional enzyme molecules. Plant Lett 1983; 24(8): 843–846. Physiol 1978; 61(1): 20–24. NT562 Leete, E. Biosynthesis and metabolism NT572 Kodama, H., T. Fujimori, and K. Kato. of the tobacco alkaloids. Alkaloids: Glucosides of ionone-related com- Chemical and Biological Perspec- pounds in several Nicotiana species. tives. John Wiley and Sons, NY, 1983: Phytochemistry 1984; 23(3): 583–585. 85–152. NT573 Kodama, H., T. Fujimori, and K. Kato. NT563 Matsuzaki, T., A. Koiwai, and N. A nor-sesquiterpene glycoside, Kawashima. Isolation of tetra-, penta-, rishitin-beta-sophoroside, from to- and hepta-acyl glycerides from stigmas bacco. Phytochemistry 1984; 23(3): of Nicotiana tabacum. Agr Biol Chem 690–692. 1983; 47(1): 77–82. NT574 Hirsch, J. M., B. Svennerholm, and A. NT564 Grady, K. L., and J. A. Bassham. 1- Vahlne. Inhibition of herpes simplex Aminocyclopropane-1-carboxylic acid virus replication by tobacco extracts. concentrations in shoot-forming and Cancer Res 1984; 44(5): 1991–1997. non-shoot forming tobacco callus NT575 Wahlberg, I., R. Arndt, I. Wallin, C. cultures. Plant Physiol 1982; 70: Vogt, T. Nishida, and C. R. Enzell. 919–921. Tobacco chemistry. Six new cembra- NT565 Nishikawaji, S., T. Fujimori, S. Matsu- trienetriols from tobacco. Acta Chem shima, and K. Kato. Sesquiterpenoids Scand Ser B 1984; 38(1): 21–30. NICOTIANA TABACUM 369

NT576 Misawa, M. Production of natural sub- NT588 Ojewole, J. A. O., A. D. Adekile, and stances by plant cell cultures described O. O. Odebiyi. Pharmacological stud- in Japanese Patents. Plant Tissue Cul- ies on a Nigerian herbal preparation: ture its Bio–Technol Appl Int Congr 1. Cardiovascular actions of cow’s 1st 1976; 17–26. urine concoction (cuc) and it indi- NT577 Yamada, Y., Y. Hara, M. Senda, M. vidual components. Int J Crude Drug Nishihara, and M. Kito. Phospholipids Res 1982; 20: 71–85. of membranes of cultured cells and the NT589 Boyd, E. J. S., J. A. Wilson, and K. G. products of protoplast fusion. Phy- Wormsley. Smoking impairs therapeu- tochemistry 1979; 18: 423–426. tic gastric inhibition. Lancet 1983; NT578 Sheveleva, G. A., and A. P. Kiryush- 8316: 95–97. chenkov. Effect of nicotine on fetal NT590 Khan, N. A. and S. S. Hasan. Effect of development and offspring (of treated Cannabis hemp (hashish) on normal rats). Akush Ginekol 1981; 6: 31–34. and rats subjected to psychological NT579 Thelestam, M., M. Curvall, and C. R. stress. Proc Indian Acad Sci Anim Enzell. Effect of tobacco smoke com- 1984; 93(2): 121–129. pounds on the plasma membrane of NT591 Adesina, S. K. Studies on a Nigerian cultured human lung fibroblasts. Toxi- herbal anticonvulsant recipe. Int J cology 1980; 15: 203–217. Crude Drug Res 1982; 20: 93–100. NT580 Adesina, S. K. Studies on some plants NT592 Hedberg, I., O. Hedberg, P. J. Madati, used as anticonvulsants in Amerindian K. E. Mshigeni, E. N. Mshiu, and G. and African traditional medicine. Samuelsson. Inventory of plants used Fitoterapia 1982; 53: 147–162. in traditional medicine in Tanzania. II. Plants of the families Dilleniaceae– NT581 Mousdale, D. M. A. Reversed-phase Opilliaceae. J Ethnopharmacol 1983; ion-pair high-performance liquid chro- 9(1): 105–127. matography of the plant hormones NT593 Van Puyvelde, L., D. Geysen, F. X. indolyl-3-acetic, and abscisic acid. J Ayobangira, E. Hakizamungu, A. Chromatogr 1981; 209: 489–493. Nshimiyimana, and A. Kalisa. Screen- NT582 Agarwal, J. L., A. K. Sisodia, C. D. ing of medicinal plants of Rwanda for Pande. An effect of cigarette smoking ascaricidal activity. J Ethnopharma- on serum total cholesterol level. Ann col 1985; 13(2): 209–215. Natl Acad Med Sci (India) 1982; NT594 Singh, Y. N. Traditional medicine in 18(1): 15–20. Fiji: Some herbal folk cures by Fiji NT583 Chang, C. C., C. M. Chen, B. R. Indians. J Ethnopharmacol 1986; Adams, and B. M. Trost. Leucinopine. 15(1): 57–88. A characteristic compound of some NT595 Barrieri, R. L., P. M. Mc Shane, and K. crown gall tumors. Proc Nat Acad Sci J. Ryan. Constituents of cigarette USA 1983; 80: 3573–3576. smoke inhibit human granulose cell NT584 Nemity, W. Agents to wean smokers aromatase. Farmatsiya (Sofia) 1986; from nicotine. Patent-Ger Offen- 46(2): 232–236. 1,911,112: 1970; 8 pp. NT596 Matsuzaki, T., and A. Koiwai. Ger- NT585 Luna, L. E. The concept of plants as mination inhibition in stigma ex- teachers among four Mestizo shamans tracts of tobacco and indentification of Iquitos, northeastern Peru. J Ethno- of MeABA, ABA and ABA-Beta-D- pharmacol 1984; 11(2): 135–156. glucopyranoside. Agr Biol Chem NT586 Kargbo, T. K. Traditional practices 1986; 50(9): 2193–2199. affecting the health of women and chil- NT597 Wahlberg, I., A. M. Eklund, C. R. dren in Africa. Unpublished manu- Enzell, and J. E. Berg. Tobacco chem- script, 1984. istry. (5R,6S,7E,9S)-7-megastigmene- NT587 Bredon, M., A. M. Quero, and A. Ger- 5,6-9-triol, a new constituent of Greek man. Tobacco smoke influence on tobacco. Acta Chem Scand Ser B mice resistance to different viral dis- 1987; 41(6): 455–458. eases. Ann Pharm Fr 1982; 40(2): NT598 Weniger, B., M. Rouzier, R. Daguilh, 153–165. D. Henrys, J. H. Henrys, and R. Anton. 370 MEDICINAL PLANTS OF THE WORLD

Popular medicine of the central pla- Shokubutsu Byori Gakkaiho 1983; teau of Haiti. Ethnopharmacological 49(4): 501–507. inventory. J Ethnopharmacol 1986; NT609 Hirschmann, G. S., and A. Rojas De 17(1): 13–30. Arias. A survey of medicinal plants of NT599 Hoffman, D., J. D. Adams, D. Lisk, I. Minas Gerais, Brazil. J Ethnopharma- Fisenne, and K. D. Brunnemann. col 1990; 29(2): 159–172. Toxic and carcinogenic agents in dry NT610 Grunweller, S., E. Schroder, and J. and moist snuff. J Nat Cancer Inst Kesselmeier. Biological activities of 1987; 79(6): 1281–1286. furostanol saponins from Nicotiana NT600 Arenas, P. Medicine and magic among tabacum. Phytochemistry 1990; 29(8): the Maka Indians of the Paraguayan 2485–2490. Chaco. J Ethnopharmacol 1987; NT611 Holdsworth, D., and H. Sakulas. 21(3): 279–295. Medicinal plants of the Morobe prov- NT601 Kulakkattolickal, A. Piscicidal plants ince part II. The Aseki valley. Int J of Nepal: Preliminary toxicity screen- Crude Drug Res 1986; 24(1): 31–40. ing using grass carp (Ctenopharyngodon NT612 Sen, S., G. Talukder, and A. Sharma. idella) fingerlings. J Ethnopharmacol Potentiation of betel-induced alter- 1987; 21(1): 1–9. ations of mouse glandular stomach NT602 Whitehead, I. M., D. F. Ewing, and D. mucosa by tobacco in studies simulat- R. Threlfall. Sesquiterpenoids related ing betel addiction. Int J Crude Drug to the phytoalexin debneyol from elic- Res 1987; 25(4): 209–215. ited cell suspension cultures of Nicoti- NT613 Yamaguchi, K., T. Suzuki, A. ana tabacum. Phytochemistry 1988; Katayama, M. Sasa, and S. Iida. 27(5): 1365–1370. Insectidcidal action of Japanese plants. NT603 Becker, C. G., D. P. Hajjar, and J. M. II. A general method of detecting ef- Hefton. Tobacco constituents are mi- fective fractions and its application to togenic for arterial smooth-muscle 24 species of insecticidal plants. Botyu cells. Am J Pathol 1985; 120(1): 1–5. Kagaku 1950; 15: 62–70. NT604 Leifertova, I., and M. Lisa. The anti- NT614 Roig, Y., and J. T. Mesa. Plantas fungal properties of higher plants af- Medicinales, Aromaticas o Venenosas fecting some species of the genus de Cuba. Ministerio de Agricultura, Aspergillus. Folia Pharm (Prague) Republica de Cuba, Havana. Book 1979; 2: 29–54. 1945; 872 pp. NT605 Caceres, A., L. M. Giron, and A. M. NT615 Humphreys, F. R. The occurrence and Martinez. Diuretic activity of plants industrial productin of rutin in south- used for the treatment of urinary eastern Australia. Econ Bot 1964; 18: ailments in Guatemala. J Ethno- 195–253. pharmacol 1987; 19(3): 233–245. NT616 Bhasin, H. D. Annual report of the NT606 Ramirez, V. R., L. J. Mostacero, A. E. entomologist to Government, Punjab, Garcia, et al. Vegetales empleados en Lyallpur, for the year 1924–25. Report Medicina Tradicional Norperuana. Operations Dept Agr Punjab 1926; Banco Agrario Del Peru & NACL 1(II): 69–121. Univ Trujillo, Peru, June 1988: 54 pp. NT617 Prance, G. T. An ethnobotanical com- NT607 Caceres, A., L. M. Giron, S. R. parison of four tribes of Amazonian Alvarado, and M. F. Torres. Screening Indians. Acta Amazonica 1972; 2(2): of antimicrobial activity of plants 7–27. popularly used in Guatemala for the NT618 Moller, M. S. G. Custom, pregnancy treatment of dermatomucosal dis- and child bearing in Tanganyika. J eases. J Ethnopharmacol 1987; 20(3): Trop Pediatrics Afr Child Health 223–237. 1961; 7(3): 66–78. NT608 Tanaka, H., R. Uegaki, T. Fujimori, NT619 Schultes, R. E., and R. F. Raffauf. The and K. Kato. Antibacterial activity of Healing Forest: medicinal and toxic sesquiterpenoids from tobacco leaves plants of the northwest Amazonia. elicited by Pseudomonas solanacearum Dioscorides Press, Portland, OR. 1995; and tobacco mosaic virus. Nippon 432–436. NICOTIANA TABACUM 371

NT620 Nakao, Y., X. Yang, M. Yokoyama, M. chemistry. Two new nor-drimanes from M. Pater, and A. Pater. Malignant trans- Greek tobacco. Acta Chem Scand Ser formation of human ectocervical cells B 1981; 35: 307–310. immortalized by HPV 18: in vitro model NT624 Nagai, N., Y. Kojima, M. Shimosaka, of carcinogenesis by cigarette smoke. and M. Okazaki. Effects of kinetin on Carcinogenesis 1996; 17(3): 577–83. L-phenylalanine ammonia–lyase ac- NT621 Shahi, G. S., N. P. Das, and S. M. tivity in tobacco cell culture. Agr Biol Moochhala. 1-Methyl-4-phenyl-1,2,3, Chem 1988; 52(10): 2617–2619. 6-tetrahydropyridine-induced neuro- NT625 Kodama, H., T. Fujimori, and K. Kato. toxicity: partial protection against Three new sesquiterpenoid glycosides striato-nigral dopamine depletion in from tobacco. Agr Biol Chem 1985; C57BL/6J mice by cigarette smoke ex- 49(9): 2537–2541. posure and by beta-naphthoflavone- NT626 Ferguson, F. N., F. F. Whidby., E. B. pretreatment. Neurosci Lett 1991; Sanders, et al. Isolation and character- 127(2): 247–250. ization of 2,3-dimethyl-6-(4,8,12- NT622 Aasen, A. J., T. Chuman, and C. R. trimethyltridecyl)-1,4-naphthoquinone Enzell. (6S)-6-isopropyl-3-methyl-9- from tobacco, and smoke. Tetrahe- oxo-2E, 4E-decadenoic acid from dron Lett 1978; 1978: 2645–2648. Turkish Nicotiana tabacum, assignment NT627 Maisch, R., B. Knoop, and R. Beider- of absolute configuration. Agr Biol beck. Absorbent culture of tobacco cell Chem 1975; 39; 2085. suspensions with different absorbents. NT623 Wahlberg, I., A. M. Ecklund, T. Z Naturforsch Ser C 1986; 41(11/12): Nishida, and C. R. Enzell. Tobacco 1040–1044. OLEA EUROPAEA 373

10 Olea europaea L.

Common Names Aceituna Spain Olijf Netherlands Alyvos Lithuania Oliondo Spain Aseituna Netherlands Antilles Olipuus Estonia Azeitona Portugal Oliv Sweden Culoare masline Romania Oliva europska Slovakia Dege e ullirit Albania Oliva Czech Republic Elia Greece Oliva Ethiopia Euroopa olipuu Estonia Oliva Hungary Eylbert Israel Oliva Italy Jaitun India Oliva Portugal Jitabdoogh Armenia Oliva Romania Jiteni Armenia Oliva Russia Julipe India Oliva Spain Maslin Romania Oliva Ukraine Maslina Bulgaria Olivas Latvia Maslina Croatia Olive England Maslina Serbia Olive France Maslina Ukraine Olive Germany Masline Israel Olive Guyana Masliniu Romania Olive The Isle of Man (Manx) Maslinov Croatia Olive United States Maslinov Serbia Oliveira Portugal Mohlware South Africa Oliven Denmark Ngjyre ulliri Albania Oliven Norway Oastre Spain Olivenbaum Germany Olajbogyo Hungary Olivera Spain Olajfa Hungary Olivgront Sweden Olbaum Germany Olivo Spain Oleifi Netherlands Antilles Olivove drevo Czech Republic Olewydden England Olivovnik europsky Slovakia Oliba Spain Olivovnik Czech Republic Olifa Iceland Olivy Czech Republic Oliif Spain Oliwka Poland Oliivi Finland Oljka Slovenia

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 373 374 MEDICINAL PLANTS OF THE WORLD

Oljypuu Finland Ullir Albania Olyf Cornwall Zaitun Indonesia Olyva Ukraine Zayit Israel Oulivie France Zaytun Arabic countries Oulivie France Zebbug Malta Qolli Boliwia Zeituni Mozambique Qolli Peru Zeituni Tanzania Rabell Spain Zeituni Zaire Saidun India Zetis Georgia Saidun Sri Lanka Zetiskhili Georgia Uliva Switzerland Zeyatin Turkmenistan Ullastre Spain Zeytin Turkey Ulli Albania Zeytoon Armenia

BOTANICAL DESCRIPTION ORIGIN AND DISTRIBUTION Olea europaea is a large evergreen shrub of The name Olea europaea applies to both the the OLEACEAE family. In its native state, wild and domestic olive. The wild olive or it is a multistemmed evergreen tree, 6–9 m oleaster has a disjunctive distribution in the high, with equal or slightly less spread. The Mediterranean region and the Near East trunk is massive, especially in older down to South Africa and has been culti- plantings; gray, gnarled, bumpy, and con- vated by man since ancient times. The ol- torted. Most trees have round, spreading ive was spread throughout Mediterranean crowns, but tall, cylindrical trees are grown Europe and North Africa very early, owing in some parts of Italy, and trees may be trel- to its ease of propagation by seed, cuttings, lised in intensive plantings. Leaves are 7.5 or “ovules” (callus growths on trunks that cm long, narrow, opposite, lanceolate or lin- produce rooted shoots). Trees are extremely ear, with entire margins and acute tips, sil- long-lived (up to 1000 years) and tolerant ver-green, underside lighter. Small creamy of drought, salinity, and almost total neglect white flowers are borne in inflorescences of and have been reliable producers of food 15 flowers in axillary clusters of 1-year and oil for thousands of years. Oil was used wood; blooms in spring. Trees produced for cooking as well as burning in lamps; sev- flowers in 2–3 years, but seedlings have a eral references are made to olive oil lamps long juvenile period. Most flowers undergo in the Bible and other ancient writings. Evi- pistil abortion, leaving only one to two fruits dence of olive stones from archaeological per axil at harvest. Olives are self-fruitful sites in the Near East and Cyprus suggests but bear heavier crops when cross-polli- that olives have been consumed since nated. Wind is the pollinator. Fruits are approx 9000 BC, although it is only from drupes: edible olives, 4 cm across; green in 3500 BC that there is clear evidence of do- late summer, maturing to black; drops when mestication. Olives are most commonly ripe. Trees have a tendency toward heavy linked to Greece, and this country has a alternate bearing, unless fruit are thinned in long tradition of olive cultivation and use. the “on” year. Olives require 6–8 months for By 1300 BC, Greek palaces had rooms de- maturation, but table olives are picked ear- voted to storing jars full of olive oil. lier when firm and oil olives are left on trees Although the primary area of olive cultiva- until oil content reaches 20–30%. tion still lies in the Mediterranean region, OLEA EUROPAEA 375 olives are also cultivated in other parts and to treat renal lithiasis. It is used exter- of the world, such as California and South nally to treat sores, burns, and rheumatism; Africa. to promote circulation; and as a hemostat. Water extract of the fruit’s essential oil is TRADITIONAL MEDICINAL USES used externally to treat sunburns. Decoction Arabic countries. In Unani medicine, of the fruit essential oil is taken orally as a dried plant is taken by fumigation as an diuretic and hypotensiveOE140. Fruit-fixed oil OE179 abortifacient . is taken orally by adults for intestinal ob- Argentina. Decoctions of the dried fruit and structions. Tincture of the leaf is taken of the dried leaf are taken orally for diarrhea orally as a febrifugeOE111. Infusion of the dried and to treat respiratory and urinary tract leaf is taken orally as a hypotensiveOE191 and OE131 infections . is used for its anti-hypertensive proper- Brazil. Hot water extract of the fresh leaf is tiesOE193. Infusion of the fresh leaf is taken taken orally to treat hypertension and to orally as an anti-inflammatoryOE053. Infusion OE183 induce diuresis . of the leaf is taken orally as a hypotensive Canary Islands. An infusion prepared and applied externally as a vulnerary, emol- from the fresh or dried leaf is taken orally as lient for ingrown nails, and restorer of a hypoglycemic agent. Leaves are taken eptheliumOE128. orally as a hypotensive and administered Japan. Hot water extract of the dried bark per rectum for hemorrhoidsOE145. Hot water is taken orally as an antipyretic, for rheuma- extract of dried leaves of Olea europaea and tism, as a tonic, and for scrofulaOE158. Foeniculum vulgare is taken orally as a hypo- Jordan. Seed oil is taken orally as a laxative tensive agentOE184. and applied externally as an emollient and East Africa. Infusion of the trunk bark, pectoralOE142. pounded and soaked overnight, is taken Kenya. Stem, fresh, and dried twigs of Olea orally for tapeworm infestationOE121. europaea ssp. africana are used as a chewing Greece. Hot water extract of the leaf is stickOE168,OE127. taken orally for high blood pressureOE102. Madeira. Infusion of leaves of Olea europaea Iran. Decoctions of the dried bark, applied var. maderensis is taken orally as an antihy- externally or decoction of the dried leaf pertensiveOE139. taken orally, are used for hypertension. Mexico. Decoction of dried leaves is taken Fresh fruit fixed oil is used as food and laxa- orally for diabetesOE147. tive. Seed oil is taken orally as a cholagogue; Morocco. Leaves are taken orally for stom- to remove gallstones; in nephritis associated ach and intestinal diseases and used as a with lead intoxication, spasms associated mouth cleanser. Essential oil made from the with systemic intoxication, dry coughing, leaves is taken orally for constipation, liver and intestinal occlusion and obstructions; pain, and tonic and applied externally for and as a vermicide. Taken with lemon juice, hair careOE144. it is used to prevent vomiting associated Oman. Decoction of the bark is taken orally with rancid olive oil remaining in the intes- for constipation. Barks and leaves are ap- tine. The oil is applied externally as an plied externally for skin rash. Fruit resin emollient before taking a sunbath, prophy- mixed with the gall bladder of sheep or goat laxis for irritations caused by sunburn, and is applied ophthalmically for cataract. The for snake and insect bites. To prevent hair fruit is applied externally for fractured limb. loss, oil is applied every night on the scalp Cataplasm prepared from leaves is applied then shampooed the next morningOE110. externally for ulcersOE126. Italy. Extract of the fruit’s essential oil is Peru. Hot water extract of the dried bark is taken orally as a cholagogue and laxative taken orally for urinary retention, herpes 376 MEDICINAL PLANTS OF THE WORLD simplex, and constipation and to expel Acetic acid: Call TissOE038 OE038 biliary calculiOE189. Acetone: Call Tiss OE029 Reunion Island. Hot water extract of the Aconitic acid: Fr Aesculetin: St 209.2OE091 dried Olea europaea ssp. africana plant is Aesculin: St 2.9OE091 taken orally for diabetes, diarrhea, rheuma- Africanal, (+): HeartwoodOE090 tism, fever, and gastroenteritis in infantsOE098. Alkanes, N: Sd OilOE058 South Africa. Hot water extract of the dried Allergen: PollenOE078 bark of Olea europaea ssp. africana is taken Amyrin, D: Fixed oilOE084 orally as antirheumatic and antifebrile Amyrin, E: LfOE030, FrOE065, Fixed oilOE042 OE011,OE225 agentsOE159, OE072 and as a tonicOE072. Apigenin: Lf Apigenin-4'-O-rhamnosyl-glucoside: Spain. Infusion of the leaf is taken orally for Lf 15OE053 hypertension. Extract of the leaf is taken Apigenin-7-di-O-E-D-xyloside: LfOE032 orally for gastrointestinal colic. Leaves are Apigenin-7-O-glucoside: Dried LfOE225 eaten for diabetes. Fruits are eaten for pain Arachidic acid: Sd oil 0.3%OE034 and wasp stingOE138. Avenasterol, 5-dehydro: Fr fixed oilOE201 Trinidad. Hot water extract of the lead is Avenasterol, 7-dehydro: Fr fixed oilOE201 OE034 taken orally to increase milk supply of nurs- Behenic acid: Sd oil 0.3–0.4% OE048 ing mother. On first day, the mother drinks Benzoic acid, 4-hydroxy: Fr Brassicasterol: Fr fixed oilOE041 tea of Stachytarpheta jamaicensis leaves, on Butan-1-al, 3-methyl: Call TissOE038 the second day, she drinks tea made from Butanol, 3-methyl: Call TissOE038 olive leaves and milk, and on the third day Butyl acetate: Call TissOE038 she will be able to nurse the babyOE198. Butyrospermol: FrOE065, Fr fixed oilOE042, Fixed Tunisia. Extract of the dried leaf is taken oilOE084 OE048 OE050 orally for diabetes and as a hypotensiveOE181. Caffeic acid: Fr , Sd oil , Fr fixed oilOE039 Turkey. The fruit is used externally as a skin OE041 OE141 Campest-7-en-ol: Fr fixed oil cleanser . Campesterol: Fr fixed oilOE031, Fixed oilOE084 Ukraine. Hot water extract of dried plant is Carotene, D, hydroxy: Fr fixed oilOE077 taken orally for bronchial asthmaOE174. Carotene, D: Fr fixed oilOE077 United States. Infusion of the fruit-fixed oil Carotene, E: Fr fixed oilOE077 is taken orally to treat hypertension and agi- Carotene, J: Fr fixed oilOE077 tation. Extract of the fruit-fixed oil is taken Carotene: LfOE017 OE044 orally as a mild laxative and vermicide and Chlorogenic acid: Lf Chlorophyll A: Fr fixed oilOE077 taken externally as a counterirritantOE167. Chlorophyll B: LfOE157, Fr fixed oilOE077 Yugoslavia. Hot water extract of the dried Cholesterol, 24-methylene: Fixed oilOE084 leaf is taken orally for diabetesOE175. Cholesterol: Fr fixed oilOE041 Choline: FrOE004, LfOE012 CHEMICAL CONSTITUENTS Chrysanthemin: FrOE066 (ppm unless otherwise indicated) Chrysoeriol: Lf 16.6OE053 (E)-2-Decenal: PlOE222 Chrysoeriol-7-O-E-d-glucoside: LfOE091 (E)-2-Eptenal: PlOE222 Chrysoeriol-7-O-glucoside: LfOE228 (E)-2-Hexenal: PlOE222 Cinchonidine: LfOE006 (E)-2-Nonenal: PlOE222 Cinchonine, dihydro: Lf 25OE005 (E)-2-Octenal: PlOE222 Cinchonine: Lf 20–170OE005 (E,E)-2,4-Decadienal: PlOE222 Cinnamic acid ethyl ester: Fr fixed oilOE086 3,4-Dihydroxyphenylethyl 4-formyl-3- Cinnamic acid: Fr fixed oilOE039 formylmethyl-4-hexenoate: LfOE221 Citric acid, iso: Fr, LfOE029 Acetaldehyde: Call TissOE038 Citric acid: Fr, LfOE029 OLEA EUROPAEA 377

Citrostadienol, 28-iso: Fixed oilOE084 Fucosterol, 28-iso: Fixed oilOE084 Citrostadienol: FrOE064, Fixed oilOE084 Fucosterol, iso: Fr fixed oilOE031 Cornoside: Kernel 250OE043, FrOE034 Fucosterol: Fr fixed oilOE041, Fixed oilOE084 Cosmosiin: LfOE091 Fumaric acid: Fr, LfOE029 Coumaric acid, para: Fr fixed oilOE039 Gallic acid: Fr fixed oilOE039 Cryptoxanthene: Fr fixed oilOE077 Germanicol: Fixed oilOE084 Cyanidin: FrOE008 Glucose: SdOE059 Cyanidin-3-O-E-D-rutinoside: FrOE066 Glutaric acid, 3-[1-(formyl)-trans-1-propenyl]: Cyanidin-3-O-E-D-glucosyl-rutinoside: FrOE066 Fr 4.6OE025 Cycloartanol, 23-trans-dehydro, 31-nor, Glutaric acid, 3-[1-(hydroxy-methyl)-trans-1- 24-methyl: Fixed oilOE084 propenyl]: Fr 6.9OE025 Cycloartanol, 24-methylene: FrOE065, Fr fixed Gramisterol: FrOE064, Fixed oilOE084 oilOE075, Fixed oilOE084 Hemicellulose B: Fr PuOE081 Cycloartenol, 24-methylene: Fr fixed oilOE042 Heptane, 3-4-dimethyl: Call TissOE038 Cycloartenol, 31-nor: FrOE064 Hesperidin: Dried LfOE225 Cycloartenol: FrOE065, Fr fixed oilOE042, Fixed Hex-3-en-al: Call TissOE038 oilOE084 Hexacosan-1-ol: Fr fixed oilOE068 Cyclobranol: Fr fixed oilOE075, FrOE065, Fixed Hexadecanoic acid, 10-16-dihydroxy: oilOE084 Lf 2.08OE007 Cycloeucalenol: FrOE064, Fixed oilOE084 Hexan-1-al: Call TissOE038 Cycloolivil, (+): Bk 8.7–15OE158 Hexan-1-ol: Call TissOE038 Cyclosadol: Fr fixed oilOE075, Fixed oilOE084 Hexanal: FlavorOE222 Cynaroside: LfOE091 Hexane, N: Call TissOE038 Dammaradienol: Fixed oilOE084 Hex-cis-2-en-1-ol: Call TissOE038 Delphinidin-3-rhamnoglucside-7-xyloside: Hex-cis-3-en-1-ol acetate: Call TissOE038 FrOE094 Hex-cis-3-en-1-ol: Call TissOE038 Eicosenoic acid: Sd oil 0.2–0.3%OE034 Hex-trans-2-en-1-al: Call TissOE038 Elenoic acid glucoside: FrOE083 Hex-trans-2-en-1-ol: Call TissOE038 Elenoic acid, deacetoxy: Fr PuOE151 Hex-trans-3-en-1-ol: Call TissOE038 Elenoic acid: FrOE055 Hexyl acetate: Call TissOE038 Elenolide: Fr, Lf, St Bk 22OE016, Fr Ju 58OE067 Hydroxytyrosol: FrOE224 Eleutheroside: Lf+TwigsOE172 Inositol, myo: SdOE059 Ergosta-7-trans-22-dien-3-E-ol: Fixed oilOE084 Kaempferol: St 1.2OE091, LfOE225 Erythrodiol: LfOE073, Fr fixed oil 7.2%OE041, Lanost-9(11)-en-3-E-ol, 31-nor, 24-methyl: FrOE063, FruitpeelOE047 Fixed oilOE084 Essential oil: LfOE017 Lanost-en-3-E-ol, 24-methylene: FrOE093 Estrone: Kernel 34OE088 Ligstral: LfOE151 Ethan-1-ol, 2-phenyl, 3'-4'-dihydroxy: Lf Ligstroside, 10-hydroxy: LfOE151 73.5OE020 Ligstroside: FrOE055, Kernel 0.15%OE043, Ethanol, 2-(3-4-dihydroxy-phenyl): FrOE056 Lf 32.3OE022 Ethanol, E-(3-4-dihydroxy-phenyl): Fr fixed Linoleic acid: Sd oil 7.5-12.2%OE034 oilOE003 Linolenic acid: Sd oil 0.7-0.8OE034 Ethanol, para-hydroxy-phenyl: Sd oilOE024 Loganin, 7-epi: LfOE151 Ethyl acetate: Call TissOE038 Loganin, keto: LfOE151 Ethyl propionate: Call TissOE038 Lophenol, 24(25)-dehydro, 24-ethyl: Fixed Euphol: FrOE093 oilOE084 Ferulic acid: Fr fixed oilOE039 Lophenol, 24(25)-dehydro, 24-methyl: Fixed Flavone, 4'-hydroxy: FrOE008 oilOE084 Fraxiresinol-1-E-D-glucoside, (+): Bk 31OE021 Lophenol, 24-ethyl: Fixed oilOE084 Fraxiresinol-1-O-E-d-glucoside, (+): Bk Lophenol, 24-methyl: Fixed oilOE084 31OE021 Lophenol, trans-23-dehydro, 24-ethyl: Fixed Fructose: SdOE059 oilOE084 378 MEDICINAL PLANTS OF THE WORLD

Lophenol, trans-23-dehydro, 24-methyl: Fixed Oleoside-7-methyl ester: Lf 15OE070 oilOE084 Oleuropein, dimethyl: FrOE083, Bk 15OE070, Lophenol: FrOE064 LfOE151, KernelOE043 Lutein: Fr fixed oilOE077 Oleuropein: LfOE002, PlOE010, BranchOE049, Lutein-5-6-epoxide: Fr fixed oilOE077 FrOE055, ShOE085, Sd oil 0.566%OE057, Kernel Luteolin: LfOE014, FrOE079 1.03%OE043, BudsOE087, Rt, StOE009, Bk Luteolin-4'-E-D-glucoside: Lf 10OE053 0.15%OE070 Luteolin-4'-O-E-D-glucoside: LfOE091 Oleuroside: Lf 293.5OE022 Luteolin-7-O-glucoside: LfOE225 Olivil, (–): Bk 15OE158 Malic acid: Fr, LfOE029 Olivin: LfOE014 Mannitol: BranchOE054, LfOE017, Lf & St Olivin-4'-di-glucoside: LfOE014 1.5%OE089, SdOE059 Palmitic acid: Sd oil 12.3–15.4%OE034 Maslinic acid, 2-D-3-E-diacetoxy: FrOE037 Palmitoleic acid: Sd oil 1–2.2%OE034 Maslinic acid, G: LfOE018 Parkeol, 24-dihydro, 24-methylene: Fr fixed Maslinic acid: FruitpeelOE047, LfOE030 oilOE075, FrOE093, Fixed oilOE084 Neoxanthene: Fr fixed oilOE077 Parkeol: Fixed oilOE084 Nonal-1-al: Call TissOE038 Pentan-2-one: Call TissOE038 Nonanal: PlOE222 Peroxidase: LfOE017 Nonanoic acid methyl ester: Call TissOE038 Phaeophorbide A: Fr fixed oilOE077 Nuezhenide oleoside: SdOE033, EndospermOE151 Phaeophorbide B: Fr fixed oilOE077 Nuezhenide: SdOE033, EndospermOE151 Phaeophytin A: Fr fixed oilOE077 Obtusifoliol: FrOE064, Fixed oilOE084 Phaeophytin B: Fr fixed oilOE077 Octadecanoic acid, 9-10-18-trihydroxy: Phenol, 4-4-vinyl: Fr fixed oilOE086 Lf 1.28%OE007 Phenylacetic acid, para-hydroxy: Fr JuOE074 Octan-1-al: Call TissOE038 Phenylethanol, 3-4-dihydroxy: FrOE051 Octan-2-ol: Call TissOE038 Phenylethanol, 4-hydroxy, glucoside: FrOE034 Octane, N: Call TissOE038 Phenyl-glycol, 3-4-dihydroxy: FrOE051 Ole e-10: PlOE207 Phytoene: Fr fixed oilOE077 Ole e-7: PlOE027 Phytofluene: Fr fixed oilOE077 Olea europaea compound 5: Sd oilOE024 Phytol: FrOE062 Olea europaea compound 5-A: Sd oilOE024 Pinoresinol, 1-acetoxy, (+): BkOE092 Olea europaea compound 6: Sd oilOE024 Pinoresinol, 1-acetoxy, 4'-E-D-glucoside (+): Olea europaea compound 7: Sd oilOE024 Bk 5.3OE061 Olea europaea compound 7-A: Sd oilOE024 Pinoresinol, 1-acetoxy, 4'-E-D-glucoside-4''-O- Olea europaea derivative 2-A: FrOE026 methyl ether, (+): Bk 55OE021 Olea europaea derivative 2-B: FrOE026 Pinoresinol, 1-acetoxy, 4'-O-E-D-glucoside (+): Olea europaea derivative 3: FrOE026 Bk 50.9OE021 Olea europaea phenolic glucoside 7: LfOE028 Pinoresinol, 1-acetoxy, 4''-methyl ether-4'-O- Olea europaea secoiridoid 2: Lf 15OE020 E-D-glucoside (+): Bk 55OE021 Olea europaea secoiridoid 3: Lf 17.25OE020 Pinoresinol, 1-acetoxy-4''-O-methyl ether (+): Olea galactoglucomann: PuOE186 Bk 46.4OE158 Olea secoirioid 5: Fr Ju 1875OE023 Pinoresinol, 1-hydroxy, (+): Bk 138.4OE158 Olea substance A: LfOE046 Pinoresinol, 1-hydroxy, 1-E-D-glucoside (+): Olea xyloglucan: PuOE097 BkOE092 Oleacein: LfOE052 Pinoresinol, 1-hydroxy, 1-O-E-D-glucoside, Oleanolic acid, 3-acetoxy: FrOE037 (+): Bk 50.1OE021 Oleanolic acid: LfOE157, Fr peelOE047 Pinoresinol, 1-hydroxy, 4'-E-D-glucoside (+): Oleic acid: Sd oil 70.2–75.1%OE034 Bk 11.2OE021 Oleocyanin: FrOE015 Pinoresinol, 1-hydroxy, 4'-methyl ether (+): Oleoeurop: Fr 6.6%OE001 BkOE092 Oleoside methyl ester: LfOE151 Pinoresinol, 1-hydroxy-4''-O-methyl ether (+): Oleoside: LfOE151 Bk 23.2OE158 Oleoside-11-methyl ester: Lf 15OE028 Pinoresinol-4'-E-D-glucoside, (+): BkOE096 OLEA EUROPAEA 379

Quercetin: St1.7OE091, Lf, FrOE079,OE225 Acetoaceyl-CoA thiolase stimulation. Quercetin-3-O-rhamnoside: LfOE228 Fruit fixed oil, administered intragastrically OE040 Quercitrin: Lf to rats at a dose of 2 mL/kg, was activeOE192. Raffinose: SdOE059 Wa- Rhoifolin, iso: LfOE069 Acetylglucoseaminidase inhibition. Rutin: Lf OE225,OE044, HuskOE151 ter extract of the fresh twig of Olea europaea Salidroside: SdOE033 ssp. africana, at a concentration of 500 Pg/ Saponins: PlOE098 mL, was active on Porphyromonas gingivalisOE127. Scopoletin, iso: Bk 32.9OE095 Allergenic activity. Fixed oil, administered Scopoletin: Bk 32.9OE095 externally to adults, was inactive. Most OE072 Scopolin: Bk 180.3 cases of atopy were reclassified as cases of Sedoheptulose: SdOE019 irritationOE114. Dried pollen, administered by Sitosterol, E: Fr fixed oilOE042, LfOE030, Fixed oilOE084 a patch test to adults of both sexes, was ac- Squalene: LfOE013, Fr fixed oilOE036 tive. Skin reaction test, conducted on 1573 Stearic acid: Sd oil 1.5%OE034 patients suspected of respiratory allergy, was Sterols: PlOE098 positive in 1144 cases. Positive skin reac- Stigmast-7-enol: Fr fixed oilOE041 tions to olive pollen among atopic patients OE084 Stigmasta-5-24(25)-dien-3-E-ol: Fixed oil of the population where olive trees are Stigmasterol: Fr fixed oilOE031, Fixed oilOE084 OE029 abundant was high (66%), and lower (29%) Succinic acid: Fr, Lf OE205 Sucrose: SdOE059 where trees are scarce (p < 0.003) . Ole Syringic acid: Fruit fixed oilOE039 e-1 in polyactide coglycolide microparticles, Tannin: LfOE017 administered intraperitoneally to Balb/c Taraxasterol, pseudo: FrOE093 mice, induced specific and long-lasting an- Taraxerol: Fixed oilOE084, FrOE093 tibodies that were predominantly of the im- OE068 Tetracosan-1-ol: Fr fixed oil munoglobulin (Ig)G-2 isotype. Splenic cells OE093 Tirucalla-7-24-dien-3-E-ol: Fr , Fixed from the immunized mice secreted in vitro oilOE084 Tirucallol: Fr fixed oilOE075, Fixed oilOE084 interferon-J, but not interleukin -4, indicat- Tocopherol, D: FrOE076 ing that Ole e-1 containing polyactide Tocopherol, E: FrOE076 coglycolide microparticles elicit a specific Tocopherol, G: FrOE076 T-helper 1-type immune responseOE208. De- Tocopherol, J: FrOE076 pigmented and glutaraldehyde-polymerized OE212 Triacylglycerol: Fr oil pollen extracts, administered by injections Tyrosine: Fr fixed oilOE003 OE035 OE050 to 45 adults at doses of 44 or 4.4 Pg/mL, Tyrosol, hydroxy: Fr fixed oil , Sd oil OE209 Tyrosol: FrOE034, Fixed oil 3.3OE082, Sd oilOE050 produced a dose-dependent effect . Pol- Ursolic acid: Fl 0.5%OE045, Fr PeelOE047 len extract, administered preseasonally to Uvaol: FrOE063, Fr fixed oil 2.1%OE041, LfOE073, patients with rhinitis and/or asthma, mono- Fr peelOE047 sensitized to olive, was active. Eighty-three Vanillic acid: FrOE048, Fr fixed oilOE050 percent of the patients reached the proposed Veratric acid: Fr JuOE074 maximal dose of 75 Bethesda units (45.0 Pg OE071 OE151 OE043 Verbascoside: Fr , Lf , Kernel Ole e-1) with a rate of 0.8% of systemic re- Vitamin D: FrOE004, LfOE017 actions. There was an improvement in the Xyloglucan (Olea europaea): Fr peelOE080 treated group both in nasal (p < 0.05) and PHARMACOLOGICAL ACTIVITIES bronchial (p < 0.05) symptoms, and the AND CLINICAL TRIALS consumption of antihistamines and E 2-ago- Acetoaceyl-CoA ligase stimulation. Fruit nists decreased. A decrease in specific IgE fixed oil, administered intragastrically to and an increase in IgG-1 and IgG-4 were rats at a dose of 2 mL/kg, was activeOE192. foundOE210. Crude protein extracts of the pol- 380 MEDICINAL PLANTS OF THE WORLD len were used to carry out skin prick tests on monosensitized to Olea, with rhinitis and/or 30 patients with allergies to evaluate the bronchial asthma, and SPT positive only to clinical importance of differences between pollens was investigated. Six of seven chil- olive cultivars. Ole e-1 was present in all dren showed a perennial pattern of symp- cultivars, although significant quantitative toms in comparison to 7 of 23 and 3 of 12, differences were detectedOE211. The associa- respectively, in subjects with Parietaria and tion between sensitization to allergens of Gramineae pollinosis. All of the patients olive pollen and confirmed plant-derived with perennial nasal symptoms of the Olea food allergy and hypersensitivity of food al- europaea group exhibited a late nasal re- lergy reaction was studied on 134 patients sponse after specific nasal provocation with Olea pollinosis. Adverse reactions were testOE227. The glycerinated allergenic extract, observed in 40 patients, 21 of whom were administered to 23 atopic rhinitis and/or classified as aral allergy syndrome and 19 as asthmatic patients monosensitized to Olea anaphylaxis. All of the patients showed and tested by skin prick test for Olea positive skin prick test (SPT) against one or europaea, Fraxinus excelsior, and Ligustrum more of Olea allergens. Sensitization to Ole vulgare, produced a statistically significant e-7 was more frequent (p < 0.02) in anaphy- correlation between results of SPT and of lactic patients. In this group, significant specific IgE assayed pollensOE230. An extract association with Olea pollen allergens were of the pollen was administered sublingually found between positive SPT to Rosaceae to group of nine patients with rhinitis and/ fruits and Ole e-3 (p < 0.045) and Ole e-7 (p or rhinoconjunctivitis. The subjects treated < 0.03), Cucurbitaceae and Ole e-7 (p < with extract presented a slightly lower inci- 0.03) and Actinidiaceae with Ole e-3 (p < dence of nasal symptoms of sneezing and 0.04)OE217. Olea pollens were tested on 119 obstruction and developed less dyspnea (p < patients with seasonal rhinitis and/or 0.05) than the control group. No differences asthma and a positive SPT, 10 atopic pa- were observed in the immunological deter- tients without pollinosis and a negative minations. Differences in SPT displayed a SPT. All of the patients had positive skin slight significance between the two groups responses to at least one of the allergen at the end of trialOE231. The extract modified tested. A combination of Ole e-1 and Ole e- with glutaraldehyde was administered to 2, together with a minor allergen Ole e-6 patients with pollinosis, suffering from sea- and Oe e-7, disclosed the same diagnostic sonal rhinoconjunctivitis or rhinocon- value that was obtained with the use of junctivitis and seasonal asthma, and treated crude olive pollen extractOE218. Natural and with conjunctival provocation test with two recombinant Ole e-1 allergens of the Olea types of antigen: Lolium perenne and Olea. pollen, administered intraperitoneally to These extract were tolerated quite well and Balb/c mice, induced high level of specific produced no alterations in specific IgG-4 or IgE and IgG-1 vs low IgG-2 antibody IgE levels. There was a significant decrease levelsOE220. The pollen, in peripheral blood in allergen-specific skin reactivity and in- mononuclear cell culture of Ole e-1-sensi- creased response thresholds to the CPT (p < tized patients, was active. The results indi- 0.01). A high correlation between skin and cated that it is possible to find T cells conjunctival provocation tests was observed reactive to Ole e-1 peptides with and with- at some stagesOE233. A commercial extract, out significant levels of Ole e-1 IgE antibod- administered to 30 patients, produced a sig- ies. The percentage of response was higher nificant decrease in the specific skin reac- in patients with IgE antibodies 71.4 vs tivity (skin index geometrical mean from 25%OE226. The effect of pollen on children 2.73 to 0.88, p < 0.001), the specific IgE OLEA EUROPAEA 381 from 7.76 to 4.74 peripheral resistance unit/ inactive on Escherichia coli, Proteus mirabilis, mL, p < 0.001. The specific IgG in basic Pseudomonas aeruginosa, Staphylococcus au- condition was detectable only in 9 of 30 pa- reus, and Staphylococcus epidermidisOE153. Wa- tients. After immunotherapy they were ter extracts of the dried stem bark and dried found in almost all patients with a remark- stem wood of Olea europaea ssp. africana, on able increase (from 5.48 to 266.89 arbitrary agar plate, were active on Streptococcus viri- unit/mL, p < 0.001). No correlation was dansOE195. Aliphatic long-chain aldehydes found among the changes in the consid- from olive flavor did not exhibit signifi- ered parametersOE235. Fixed oil, administered cant antibacterial activity on standard and externally on human adults, produced freshly isolated bacterial strains that may be irritationOE114. causal agents of human intestinal and respi- Analgesic activity. Fruit essential oil, ad- ratory tract infections. The D- and E-unsat- ministered externally to adults, was active. urated aldehydes have a broad antimicrobial Biological activity reported has been pa- spectrum and produced similar activity on tentedOE194. Gram-positive and Gram-negative microor- Anti-arrhythmic activity Ethanol (95%), ganismsOE222. Two olive secoiridoides (oleu- glycerin, and glycerin/ethanol extracts of ropein and hydroxytyrosol) were tested for the leaf, administered intragastrically to rats in vitro susceptibility to five ATCC stan- at a dose of 25 mg/kg, were active vs ac- dard bacteria strains (Haemophilus influenzae onitine-induced arrhythmiaOE085. Ethanol ATCC 9006, Moraxella catarrhalis ATCC (95%) and glycerin extracts of the seed oil, 8176, Salmonella typhi ATCC 6539, Vibrio administered intragastrically to rats at a dose paraemolyticus ATCC 17802, and Staphylo- of 25 mg/kg, were activeOE085. coccus aureus ATCC 25923) and 44 fresh Anti-atherosclerotic activity. Extracts of clinical isolates (Haemophilus influenzae, leaves of three isolates (Greek olive leaves eight strains; Moraxella catarrhalis, six [GO], African wild olive leaves [AO], and strains; Salmonella sp., 15 strains; Vibrio Cape Town olive leaves [CT]), adminis- cholerae, one strain; Vibrio alginolyticus, two tered to Dahl salt-sensitive, insulin-resistant strains; Vibrio parahaemolyticus, one strain; rats at a dose of 60 mg/kg for 6 weeks, were Staphylococcus aureus, five penicillin-suscep- activeOE214. tible strains and six penicillin-resistant Antibacterial activity. Decoction of the strains). The minimum inhibitory concen- dried fruit, on agar plate, was inactive on trations (MICs) was evidence of the broad Pseudomonas aeruginosaOE131. Water extract antimicrobial activity of hydroxytyrosol, of the dried fruit, on agar plate, was active MIC values between 0.24 and 7.85 Pg/mL on Salmonella typhi, inhibitory concentra- for ATCC strains and between 0.97 and OE113 tion (IC)50 10.3 Pg/mL . Water extract of 31.0 Pg/mL for clinical isolates. Oleuropein the dried fruit, on agar plate at a concentra- inhibited the growth of several strains, MIC tion of 62.5 mg/mL, was inactive on Escheri- values between 62.5 and 500 Pg/mL for chia coli and Staphylococcus aureusOE129. Water ATCC strains and between 31.25 and 250.0 extract of the dried fruit, on agar plate at a Pg/mL for clinical isolates; oleuropein was concentration of 1 mg/mL, was inactive on ineffective against Haemophilus influenzae Salmonella typhiOE113. Hot water extract of the and Moraxella catarrhalisOE224. dried fruit, on agar plate at a concentration Anticlastogenic activity. Polyphenolic ex- of 62.5 mg/mL, was inactive on Escherichia tract of the leaf, in bone marrow of mouse coli and Staphylococcus aureusOE129. Ethanol before and after X-ray irradiation, was de- (100%) extract of the fresh leaf, on agar termined by using the micronucleus test. plate, at a concentration of 2.5 mg/disc, was With treatment before X-irradiation, the 382 MEDICINAL PLANTS OF THE WORLD most effective compounds were: rutin > Antihyperglycemic activity. Powder of the dimethylsulfoxide (DMSO) > olive leaves dried leaf, administered intragastrically to (OL) > propylthiouracil (PTU) > diosmin. rats at a dose of 0.75 g/kg, was inactive vs These results indicated a linear correlation streptozotocin-induced hyperglycemiaOE143. (R2 = 0.965) between anticlastogenic activ- Water extract of the dried leaf, administered ity and antioxidant capacity. The magni- intragastrically to male rats at a dose of 0.5 tude of protection with treatment after g/kg, reduced blood glucose levels of normal X-irradiation was lower, and the most effec- or alloxan-induced diabetic ratsOE118. Decoc- tive compounds were, in order: Olea leaves tion of the dried leaf, administered intra- > diosmin > rutin; DMSO and PTU lacked gastrically to male rabbits, at a dose of 4 mg/ radioprotective activity. Olea leaf is the only kg, was inactive. A dose of 32 mg/kg was substance that showed a significant active on rats vs alloxan-induced hyper- anticlastogenic activity both before and af- glycemiaOE147. Infusion of the dried leaf, ad- ter X-irradiationOE215. ministered in drinking water of male rats at Anticonvulsant activity. Water extract of a dose of 5%, was inactive vs streptozocin- the dried leaf and stem, administered intra- induced diabetesOE155. Water extract of the peritoneally to mice at a dose of 0.6 mL/ani- Olea europaea var. oleaster dried leaf, ad- mal, was inactive vs picrotoxins-induced ministered intragastrically to rats of both convulsionsOE186. sexes at a dose of 15 mL/kg, was active on Anticrustacean activity. Ethanol (10%) plasmaOE152. extract of the fresh leaf was active on Antihypertensive activity. Glycerin/etha-

Artemia salina, lethal dose50 164 Pg/mL. The nol extract of the leaf, administered intra- assay system was intended to predict for an- gastrically to rats at a dose of 250 mg/kg, titumor activityOE153. was active vs desoxycorticosterone acetate- Antidysrrhythmic activity. Oleanolic acid induced hypertensionOE085. Ethanol/chloro- and uvaol, isolated from the leaves of Olea form (25%) extract of the dried leaf, europaea ssp. africana, administered at a dose administered orally to adults, produced a of 40 mg/kg, were active on ischemia and slow decline in blood pressure in moderate reperfusion arrhytmiasOE206. hypertension after prolonged treatmentOE107. Antifungal activity. Hot water extract of Water extract of the dried leaf, administered the dried fruit, on agar plate at a concentra- orally to adults, was activeOE017. Infusion of tion of 62.5 mg/mL, was inactive on As- the dried leaf, administered intravenously to pergillus nigerOE129. Ethanol (50%) extract of rats at a dose of 5%, produced no effect on the dried leaf, on agar plate at a concentra- normal blood pressure but decreased the tion of 500 mg/mL, was active on Botrytis hypertension caused by rennin and no- cinerea, and inactive on Aspergillus fumi- repinephrineOE104. Seed oil, administered gatus, Aspergillus niger, Fusarium oxysporum, intragastrically to rats at a dose of 1 mL/day Penicillum digitatum, Rhizopus nigricans, and for 3 months, was active vs angiotensin II- Trichophyton mentagrophytes. The dose was induced hypertension and inactive vs ren- expressed as dry weight of plantOE185. nin-induced hypertensionOE190. Ethanol/ Antihypercholesterolemic activity. Glyc- chloroform (25%) extract of the dried fruit, erin/ethanol extract of the fresh leaf, ad- administered orally to adults, produced a ministered intragastrically to rats at a dose slow decline in blood pressure in moderate of 500 mg/kg for 15 days, was active vs diet- hypertension after prolonged treatmentOE107. and triton-induced hypercholesterole- Glycerin/ethanol extract of the seed oil, ad- miaOE122. ministered intragastrically to rats at a dose OLEA EUROPAEA 383 of 125 mg/kg, was active vs desoxycorticos- leaf, at a concentration of 0.1%, was active terone acetate-induced hypertensionOE085. vs olive oil rancidityOE105. Methanol extract The extracts of leaves of three isolates: GO, of the dried leaf, at variable concentrations, AO, and CT, administered to Dahl salt- was activeOE123. Maslinic acid obtained from sensitive, insulin-resistant rats at a dose of olive pomace, administered to rats, was ac- 60 mg/kg body weight for 6 weeks, were tive on the susceptibility of plasma or hepa- activeOE214. The aqueous extract of the leaf, tocyte membranes to lipid peroxidation administered to patients with essential hy- induced by hydroxyl radical. Endogenous pertension at a dose of 400 ng u 4/24 hours plasma lipoperoxide (LPO) levels and sus- for 3 months, produced a significant de- ceptibility to LPO were decreased in ani- crease in blood pressure (p < 0.001)OE229. A mals treated with maslinic acid after 2+ specially prepared leaf extract (EFLA 943), exposure to hydroxyl radicals by Fe /H2O2. administered orally to L-NAME (NG-nitro- Coincubation with maslinic acid prevented L-arginine methyl ester) rendered hyperten- hepatocyte membrane LPOOE213. The ex- sive rats at variable doses, produced a tracts of leaves of three isolates—GO, AO, dose-dependent effect against the rise in CT—administered to Dahl salt-sensitive, blood pressure induced by L-NAME, best insulin-resistant rats at a dose of 60 mg/kg effect being induced by a dose of 100 mg/kg for 6 weeks, were activeOE214. of the extract. In rats previously rendered Antipyretic activity. Ethanol (50%) ex- hypertensive by L-NAME for 6 weeks and tract of the plant, administered intraperito- then treated with that dose of the extract neally to guinea pigs, was inactiveOE103. for a further 6 weeks without discontinua- Anti-thrombotic effect. Olive oil extract tion of L-NAME, normalization of the blood of the fruit, administered intragastrically to pressure was observedOE216. male rabbits at a dose of 150 g/kg, was Antihyperuricemic activity. Decoction of active. Lipid profile was improved with de- the dried leaf, administered orally to adults creased platelet hyperactivity and subendot- at a dose of 3 mL/person, was active. Infu- helial thrombogenicity and less severe sion of the dried leaf, administered orally to morphological lesion of the endothelium adults at a dose of 5 mL/person, was and vascular wallOE154. activeOE108. Anti-thyroid activity. Pickled green olives, Anti-inflammatory activity. Seed oil, ad- administered orally to adults at a dose of 200 ministered orally to adults at a dose of 20 g/person, were inactive on iodine uptake by mL/day, was active. Ten patients with rheu- the thyroidOE202. matoid arthritis were given the oil for 12 Anti-ulcer activity. Water extract of the weeks while abstaining from nonsteroidal dried leaf, administered intragastrically to antiinflammatory drugs. Prostaglandin E2 mice, was active against aspirin-induced level decreased in three patients and 6-keto- gastric ulcersOE112. prostaglandin F1-D level increased in two Antiviral activity. Water extract of the patientsOE161. Water extract of the dried leaf, dried fruit, in cell culture at a concentra- administered intragastrically to rats, was ac- tion of 10%, was inactive on herpes virus- tive vs carrageenin-induced paw edemaOE112. type 2, influenza, poliovirus, and vaccinaOE182. Antimycobacterial activity. Ethanol Tincture of the dried fruit, administered (95%) extract of the plant, in broth culture orally to adults of both sexes at a dose of 60 at a dilution of 1:80, was active on Myco- mL/person, was active on herpes virus. PCT bacterium tuberculosis H37RVTMC 102OE169. patent number W096/14064 reported treat- Antioxidant activity. Ethanol (defatted ment of six subjects with herpes virus in- with petroleum ether) extract of the dried fections. The activity was highly dose 384 MEDICINAL PLANTS OF THE WORLD dependent. Biological activity has been dose of 7.4 mL/kg, was activeOE148. Seed oil, patentedOE115. administered to C3H mice at a dose of 10% Anti-yeast activity. Ethanol (50%) extract of diet for more than 50 weeks, was inact- of the dried fruit, on agar plate at a concen- iveOE176. tration of 500 mg/mL, was inactive on Can- Cercarial penetration inhibition. Seed oil, dida albicans and Saccharomyces pastorianus. applied externally to mice at an undiluted The dose was expressed as dry weight of concentration, was inactive on Schistoma plantOE185. Ethanol extract of the fresh leaf, mansoniOE199. on agar plate at a concentration of 2.5 mg/ Cholesterol level decrease. Fixed oil, ad- disc, was inactive on Candida albicansOE153. ministered to rats at a dose of 20% of diet, Apoptosis induction. Allergens, in cell was inactiveOE120. culture, induced apoptosis in peripheral Cholesterol level increase. Fixed oil, ad- blood mononuclear cells from atopic pa- ministered to rats at a dose of 9% of diet, tients with positive reactivity to the aller- was active on liverOE135. gens. Peripheral blood mononuclear cells Chronotropic effect negative. Ethanol from atopic patients proliferated more vig- (50%) extract of the fresh leaf, administered orously than cells from normal subjects af- by gastric intubation to rats at a dose of 40 ter culture in vitro. The percentage of mL/kg, produced weak activity. Results were apoptosis increased when atopic subjects significant at p < 0.05 levelOE183. Glycerin/ had been previously treated with immuno- ethanol extract of the fresh leaf, adminis- therapyOE223. tered intragastrically to dogs at a dose of 20 Arachidonate 12-lipoxygenase inhibi- mg/kg, produced an increase in length of tion. Essential oil of the unripe fruit was ac- sinusal cycle (16%), sinoatrial conduction OE056 tive on platelets, IC50 7 Pg/mL . time (27%), and sinus node recovery time Arachidonate 5-lipoxygenase inhibition. (31%)OE165. Essential oil of the unripe fruit was active, Chronotropic effect positive. Glycerin/ OE056 IC50 8.3 Pg/mL . ethanol extract of the leaf and seed oil, ad- Arachidonate metabolism inhibition. ministered intragastrically to desoxycorti- Seed oil, administered to mice at a dose of costerone acetate-induced hypertensive rats 10% of diet, reduced arachidonic acid in at doses of 500 and 125 mg/kg, respectively, mice lung and spleen without affecting was activeOE085. prostaglandinsOE187. Complement alternative pathway inhibi- Arginine arylamidase inhibition. Water tion. Ethyl acetate and methanol extracts extract of the fresh twig of Olea europaea ssp. of the fresh leaf, administered at concentra- africana, at a concentration of 100 Pg/mL, tion of 50 Pg/mL, were inactive on red blod was active on Porphyromonas gingivalisOE127. cellsOE053. Bile secretion increase. Fixed oil, admin- Complement classical pathway inhibi- istered to rats at a dose of 9% of diet, was tion. Ethyl acetate and methanol extracts inactiveOE135. of the fresh leaf were active on red blood

Bradycardiac activity. Water extract of cells, IC50 greater than 7.7 Pg/mL and greater the dried leaf, administered intravenously to than 5.8 Pg/mL, respectivelyOE053. dogs, was activeOE017. Cyclo-oxygenase inhibition. Essential oil Carcinogenesis inhibition. Fixed oil, ap- of the unripe fruit, at a concentration of 100 plied externally to female mice at a dose of Pg/mL, produced weak activity on 150 Pg/animal, was active vs ultraviolet plateletsOE056. (UV)-induced tumorsOE156. Olive oil extract, Cytotoxic activity. Seed oil, in cell culture administered in the ration of male rats at a at a concentration of 300 Pg/mL, was active OLEA EUROPAEA 385 on human colon cancer HT29 cell lineOE203. tered intragastrically to dogs at a dose of 30 Water extract of the dried fruit, in cell cul- Pg/kg, increased intra-atrial (20%), nodal ture at a concentration of 10%, was inac- (41%), his-Purkinje (14%), intraventricu- tive on HeLa cellsOE182. Methanol extract of lar (12%), and conduction timesOE165. the dried leaf, in cell culture at a concentra- Effective refractory period increase. tion of 100 Pg/mL, was inactive on hamster- Glycerin/ethanol extract of the fresh leaf, chinese-V79 cellsOE130. Ethanol extract of administered intragastrically to dogs at a the fresh leaf, in cell culture was inactive on dose of 30 mg/kg, increased duration of CA-A549, human colon cancer cell line ventricular effective refractory period HT29, and CA-mammary MCF-7OE153. Me- (21%)OE165. thanol extract of the dried leaves and twigs, Estrogenic effect. Seed oil, administered in cell culture, produced weak activity on orally to female mice at a dose of 10% of OE204 OE101 CA-9KB, ED50 31 Pg/mL . Methanol ex- diet, was active . Seed oil, administered tract of the dried leaves and twigs, in cell subcutaneously to ovariectomized female culture, was inactive on leuk-P388, effective mice, produced activity equivalent to 0.25 OE204 OE197 dose (ED)50 greater than 100 Pg/mL . De- units of estrone . coction of the dried leaf, administered orally Fibrinogen level decrease. Seed oil, ad- to adults, at a dose of 3 mL/person, produced ministered orally to female adults at a dose weak activity. Infusion of the dried leaf, ad- of 6 mg/person, lowered fibrinogen and ministered orally to adults, at a dose of 5 mL/ raised plasminogen activator inhibitor lev- person, produced weak activityOE108. Water els in women with high baseline fibrinogen extract of the Olea europaea var. oleaster levelsOE134. dried leaf, administered intragastrically to Gallbladder effect. Seed oil, administered rats of both sexes at a dose of 15 mL/kg, was orally to 11 young normocholesterolemic active on plasmaOE152. males at a dose of 100 g/day, was active. The Dermatitis-producing effect. Fruit-fixed subjects received 3 weeks of a low-fat diet oil, applied externally to adults at an undi- followed by 3 weeks of a diet enriched with luted concentration, was activeOE164. 100 g/daily of olive oil. Mean total choles- Diuretic activity. Decoction and infusion terol, total apolipoprotein (apo) B, low-den- of the dried leaf, administered orally to sity lipoprotein (LDL) cholesterol, and adults at a dose of 5 mL/person for 20–25 triglycerides decreased significantly after the days, increased daily urinary output by 100– olive oil diet. High-density lipoprotein 145 mL, and did not affect blood/sodium, (HDL) cholesterol, apo A-1, cholesterol potassium, and chlorideOE108. Ethanol (50%) saturation of bile, and gallbladder volumes extract of the fresh leaf, administered were unchangedOE188. intragastrically to rats at a dose of 40 mL/kg, Hematological effect. Decoction of the was active. Five parts of fresh plant material dried leaf, administered orally to adults at a in 100 parts water/ethanol was usedOE160. The dose of 3 mL/person, did not alter blood sur- extracts of leaves of three isolates—GO, face tension and viscosity. Infusion of the AO, and CT—administered to Dahl salt- dried leaf, administered orally to adults at a sensitive, insulin-resistant rats at a dose of dose of 5 mL/person, produced no change in 60 mg/kg for 6 weeks, were activeOE214. the blood levels of sodium, potassium, and DNA-binding effect. Methanol extract of chlorideOE108. dried leaves and twigs, at a concentration of 3-Hydroxy-3-methylglutaryl coenzyme 1 Pg/mL, was inactiveOE204. A reductase inhibition. Seed oil, adminis- Dromotropic effect (negative). Glycerin/ tered intragastrically to rats at a dose of 2 ethanol extract of the fresh leaf, adminis- mL/kg, was activeOE192. 386 MEDICINAL PLANTS OF THE WORLD

3-Hydroxy-3-methylglutaryl coenzyme plasmaOE152. The extracts of leaves of three A synthase inhibition. Seed oil, adminis- isolates (GO, AO, and CT), administered tered intragastrically to rats at a dose of 2 to Dahl salt-sensitive, insulin-resistant rats mL/kg, was activeOE192. at a dose of 60 mg/kg for 6 weeks, were Hydrogen peroxide release inhibition. activeOE214. Aqueous leaf extract, adminis- Seed oil, administered to rats at a concen- tered repeatedly to male and female rats at tration of 8% of diet, was active on macro- doses of 37.5, 75, 150, 300, 600, and 1200 phages. Capsaicin or curcumin enhanced mg/kg daily for 60 days, induced an increase the effectOE132. of weight, hypotension, hypoglycemia, and Hypercholesterolemic activity. Fruit hypouricemiaOE232. Seed oil, administered fixed oil, administered orally to adults at a orally to 11 young males who were nor- dose of 60 g/day, was active. The result was mocholesterolemic at a dose of 100 g/day, equivalent to the effect of daily intake of was active. The subjects received 3 weeks of OE036 200–400 mg of squalene . a low-fat diet followed by 3 weeks of a diet Hyperthermic effect. Hot water extract of enriched with 100 g/daily of olive oil. the dried leaf, administered intraperito- Mean total cholesterol, total apo B, LDL OE200 neally to the guinea pig, was inactive . cholesterol, and triglycerides decreased Water extract, administered intravenously significantly after the olive oil diet. HDL to the guinea pig, was activeOE017. cholesterol, apo A-1, cholesterol saturation Fixed oil, Hypocholesterolemic activity. of bile, and gallbladder volumes were administered to rats at a dose of 17% of diet, unchangedOE188. decreased HDL cholesterol levelOE196. Seed Hypotensive activity. Hot water and wa- oil, administered orally to 11 young males ter extracts, administered intravenously to who were normocholesterolemic at a dose cats, were activeOE099,OE100. Chloroform, of 100 g/day, was active. The subjects re- ceived 3 weeks of a low-fat diet followed by methanol, and petroleum ether extracts of 3 weeks of a diet enriched with 100 g/daily the dried fruit, administered intravenously of olive oil. Mean total cholesterol, total to cats and rabbits, were inactive. The ac- apo B, LDL cholesterol, and triglycerides etone and ethanol (95%) extracts produced decreased significantly after the olive oil weak activity. Water extract of the dried diet. HDL cholesterol, apo A-1, cholesterol fruit, administered intravenously to rats, saturation of bile, and gallbladder volumes cats, dogs, and rabbits at a dose of 0.8 mL/ OE012,OE178,OE177 were unchangedOE188. kg, were active . Ethanol (50%) Hypoglycemic activity. Ethanol extract, extract of the fresh leaf, administered by defatted with petroleum ether extract, of gastric intubation to rats at a dose of 40 mL/ the dried leaf, administered by gastric intu- kg, was active. Results were significant at p bation to rabbits, produced a 17–23% de- < 0.05 levelOE183. Ethanol (95%), glycerin, crease in blood sugar levels reaching a and ethanol/glycerin extracts of the seed oil, maximum in 6 hours and returning to nor- administered intragastrically to rats at a dose mal in 48 hoursOE106. Decoction of the dried of 100 mg/kg, were active. Maximum effect leaf, administered intragastrically to rats at was seen 60–120 minutes after administra- a dose of 0.5 g /kg, was active. Leaves col- tion of extractOE085. Aqueous extract of the lected in July, August, and September had leaf, administered repeatedly to male and no effectOE124. Water extract of the Olea female rats at doses of 37.5, 75, 150, 300, europaea var. oleaster dried leaf, adminis- 600, and 1200 mg/kg daily for 60 days, pro- tered intragastrically to rats of both sexes duced an increase of weight, hypotension, at a dose of 15 mL/kg, was active on hypoglycemia, and hypouricemiaOE232. OLEA EUROPAEA 387

Hypothermic activity. Ethanol extract of diet for 6 weeks, was inactive on rat liver the plant, administered intraperitoneally to microsomes. Malondialdehyde concentra- guinea pigs, was inactiveOE103. tion was unchanged among animals given Hypouricemic activity. An aqueous leaf different oils. Vitamin E level decreased extract, administered repeatedly to male among those fed soybean oilOE125. Seed oil, and female rats at doses of 37.5, 75, 150, administered to rats at a dose of 10% of diet, 300, 600, and 1200 mg/kg daily for 60 days, was inactive. High-cholesterol diet with ol- produced an increase of weight, hypoten- ive oil did not stimulate lipid peroxi- sion, hypoglycemia, and hypouricemiaOE232. dationOE150. Immunosuppressant activity. Seed oil, ad- Lymphocyte proliferation inhibition. ministered in ration of mice, was activeOE163. Fixed oil, administered to rats at a dose of Inotropic effect positive. Glycerin/etha- 20% of diet, was active on hypogastric nol extract of the leaf, administered to rab- nerve-vas deferensOE120. bits at a dose of 5 mg/mL, was active on Molluscicidal activity. Methanol extract heartOE085. Ethanol (95%), glycerin, and of the leaf, at a concentration of 2000 ppm ethanol/glycerin extracts of the seed oil, ad- for 2 hours of exposure, was active on ministered to rabbits at a dose of 5 mg/mL, Biomphalaria glabrataOE173. were active on heartOE085. Monophasic action potential. Glycerin/ Insulin level increase. Powder of the dried ethanol extract of the fresh leaf, adminis- leaf, administered intragastrically to rats at tered intragastrically to dogs at a dose of 30 a dose of 0.75 g/kg, was inactiveOE143. mg/kg, increased duration of ventricular Insulin-potentiating effect. Water extract monophasic action potential (16%)OE165. of the Olea europaea var. oleaster dried leaf, Mutagenic activity. Ethanol (100%) ex- administered intragastrically to rats of both tract of the fresh leaf, on agar plate, was ac- sexes at a dose of 15 mL/kg, was active on tive on Salmonella typhimurium T1530OE153. plasmaOE152. Natural-killer cell enhancement. Fixed Insulin release stimulation. Fruit-fixed oil, oil of embryos, administered orally to adults, in cell culture, was active on pancreatic was inactiveOE117. Nonsaponifiable fraction isletsOE119. Decoction of the dried leaf, in cell of fruit fixed oil and seed oil, administered culture at a concentration of 0.4 Pg/mL, was to rats at a dose of 0.3% of diet, were active. active on adrenal glandOE124. The polyphenol stripped seed oil was Intercellular adhesion molecule-1 inhibi- inactiveOE170. tion. Fixed oil of embryos, administered Oxygen radical inhibition. Seed oil, ad- orally to human adults, decreased the ministered to rats at a concentration of 8% expression of intercellular adhesion mole- of diet, was active on macrophages. Capsai- cule-1OE117. cin or curcumin enhanced the effectOE132. LDL oxidation inhibition. Seed oil, admin- Phagocytosis stimulation. Ethanol (95%) istered orally to male adults at a dose of extract and unsaponifiable fraction of the 30.5% of diet, produced weak activity vs dried leaf, administered intraperitoneally to copper catalyzed oxidationOE116. male mice at a dose of 0.5 mL/animal, were LDL-receptor degradation inhibition. inactiveOE180. Seed oil, administered orally to adult males, Platelet aggregation inhibition. Methanol produced weak activityOE109. extract of the fruit, at a concentration of Lipid peroxide formation stimulation. 500 Pg/mL, produced weak activity on hu- Seed oil, administered to rats fed a diet with man platelets vs collagen-induced given composition of fat at a dose of 15% of aggregationOE146. Seed oil, administered 388 MEDICINAL PLANTS OF THE WORLD intragastrically to rats at a dose of 5 mL/kg of 8% of diet, was active on macrophages. for 2 months, was active. Aortas from the Capsaicin or curcumin enhanced the treated rats released higher amounts of effectOE132. antiaggregatory substances vs adenosine 5'- Thromboxane B-2 synthesis induction. diphosphate-induced aggregationOE190. Seed oil, administered orally to 10 patients Prostaglandin induction. Seed oil, admin- with rheumatoid arthritis at a dose of 20 mL/ istered to rats at a concentration of 5% of day for 12 weeks, produced mixed clinical diet, was activeOE162. results. The patients abstained from nonste- Protease inhibition. Water extract of the roidal anti-inflammatory drugs during the dried twig of Olea europaea ssp. africana, was trial period. Thromboxane B-2 level in- OE161 inactive on Bacteroides intermedius, IC50 100 creased in four patients .

Pg/mL and Treponema denticola, IC50 greater Thyroid activity. A freeze-dried aqueous than 250 Pg/mL, and active on Bacteroides extract of the leaf, administered to rats, was OE168 gingivalis, IC50 75 Pg/mL . active. The results suggest a stimulatory ac- Serum HDL-lowering effect. Seed fixed tion of the extract on the thyroid, unrelated oil, administered to male hamsters at a con- to the pituitaryOE219. centration of 19% of diet, was inactiveOE149. Toxic effect. Water extract of the dried Serum LDL-lowering effect Seed oil, ad- leaf, administered orally to adults, was ministered orally to male adults at a dose of inactiveOE017. Infusion of the dried leaf, ad- 30.5% of diet, produced weak activityOE116. ministered in drinking water to male rats at Spasmogenic activity. Water extract of the a dose of 5%, was inactiveOE155. dried leaf, administered to rats at a dose of Tumor-promoting effect. Seed oil, ad- 0.1 Pg/mL was active on ileum and a dose of ministered in ration to rats at a dose of 0.3 Pg/mL was active on ileum vs acetylcho- 3.4% of diet, was active. Rats were given line-induced contractionsOE137. 7,12-dimethylbenz[a]anthracene to induce Spasmolytic activity. Ethanol (95%), tumorigenesisOE166. ethanol/glycerin, and glycerin extracts of Tyrosinase inhibition. Ethanol (50%) ex- the leaf, administered to guinea pigs at a tract of the fresh leaf, at a concentration of dose of 50 mg/kg, was active vs vasopressin- 0.5 mg/mL, was inactiveOE133. induced coronary spasms as determined Vasodilator effect. The decoction of leaves from electrocardiogramOE085. Ethanol (30%) caused relaxation of isolated rat aorta prepa- extract of the dried leaf, administered to rations both in the presence (IC50 1.12 r rabbits at a concentration of 1 mg/mL, was 0.33 mg/mL) and in the absence (IC50 1.67 + OE234 active on aorta vs K -induced contract- r 0.16 mg/mL) of endothelium . ionsOE136. Decoction of the dried leaf, admin- Weight increase. Aqueous leaf extract, ad- istered to rats, was active on aorta, IC50 1.12 ministered repeatedly to male and female mg/mL. The effect of the lyophilized extract rats at doses of 37.5, 75, 150, 300, 600, and on phenylephrine-induced contraction and 1200 mg/kg/24 hours for 60 days, produced endothelium was present. Decoction of the an increase of weight, hypotension, hy- dried leaf, administered to rats, was active poglycemia, and hypouricemiaOE232. on the aorta vs phenylephrine-induced con- REFERENCES traction, IC50 1.16 mg/mL. Water extract of the dried leaf, administered to rats at a dose OE001 Ragazzi, E., and G. Veronese. Presence of demethyloleoeuropeine in olives of of 3 mg/mL, was active on trachea vs acetyl- various cultures. Ann Chim (Rome) OE137 choline-induced contractions . 1973; 63: 21. Superoxide production inhibition. Seed OE002 Panizzi, L., M. L. Scarpati, and G. oil, administered to rats at a concentration Oriente. The constitution of oleuro- OLEA EUROPAEA 389

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OE157 Susnik-Rybarski, I., F. Mihelic, and S. OE167 Giordano, J., and P. J. Levine. Botani- Durakovic. Antioxidation properties cal preparations used in Italian folk of substances isolated from olive medicine: possible pharmacological leaves. Hrana Ishrana 1983; 24(1/2): and chemical basis of effect. Social 11–15. Pharmacol 1989; 3(1/2): 83–110. OE158 Tsukamoto, H., S. Hisada, and S. OE168 Homer, K. A., F. Manji, and D. Nishibe. Lignans from bark of the Olea Beighton. Inhibition of protease ac- plants. I. Chem Pharm Bull 1984; tivities of periodontopathic bacteria by 32(7): 2730–2735. extracts of plants used in Kenya as OE159 Tsukamoto, H., S. Hisada, S. Nishibe, chewing sticks (mswaki). Arch Oral and D. Roux. Phenolic glucosides from Biol 1990; 35(6): 421–424. Olea europaea subsp. africana. Phy- OE169 Grange, J. M., and R. W. Davey. De- tochemistry 1984; 23(12): 155–167. tection of antituberculous activity in OE160 De la Ribeiro, R., F. Barros, M. plant extracts. J Appl Bacteriol 1990; Margarida, et al. Acute diuretic effects 68(6): 587–591. in conscious rats produced by some OE170 Huang, Y. S., P. Redden, X. Lin, R. medicinal plants used in the state of Smith, S. MacKinnon, and D. F. Sao Paulo, Brasil. J Ethnopharmacol Horrobin. Effect of dietary olive oil 1988; 24(1): 19–29. non-glyceride fraction of plasma cho- OE161 Jantti, J., E. Seppala, H. Vapaatalo, lesterol level and live phospholipid and H. Isomaki. Evening primrose oil fatty acid composition. Nutr Res and olive oil in treatment of rheuma- 1991; 11(5): 439–448. toid arthritis. Clin Rheumatol 1989; OE171 Tarzuelo, A., J. Duarte, J. Jimenez, M. 8(2): 238–244. Gonzalez, and M. P. Utrilla. Vasodila- tor effect of olive leaf. Planta Med OE162 Blankenship, J. W., R. Jenks, A. M. 1991; 57(5): 417–419. MacMurray, L. B. Sandberg, and R. J. OE172 Plouvier, V. Occurrence and distribu- Boucek. Uniqueness of dietary olive oil tion of syringoside, calycanthoside and in stimulating aortic prostacyclin pro- similar coumarinic glycosides in sev- duction in post-weanling rats. Prostag- eral botanical groups. C R Acad Sci landins Leukotrienes Essent Fatty Ser II 1985; 301(4): 117–120. Acids 1989; 36(1): 31–34. OE173 Kubo, I., and A. Matsumoto. Molusci- OE163 Watson, J., D. Godfrey, W. H. Stimson, cides from olive Olea europaea and J. J. F. Belch, and R. D. Sturrock. The their efficient isolation by countercur- therapeutic affects of dietary fatty acid rent chromatographies. J Agr Food supplementation in the autoimmune Chem 1984; 32(3): 687–688. disease of the MRL-MP-1PR mouse. OE174 Vardanian, S. A. Phytotherapy of bron- Int J Immunopharmacol 1988; 10(4): chial asthma in medieval Armenian 467–471. medicine. Ter Arkh 1978; 50: 133–136. OE164 Padoan, S. M., A. Pettersson, and A. OE175 Tucakov, J. Ethnophytotherapy of dia- Svensson. Olive oil as a cause of con- betes. SRP Arh Celok Lek 1978; 106: tact allergy in patients with venous ec- 159–173. zema, and occupationally. Contact OE176 Tinsley, I. J., G. Wilson, and R. R. Dermatitis 1990; 23(2): 73–76. Lowry. Tissue fatty acid changes and OE165 Occhiuto, F., C. Circosta, A. Gregorio, tumor incidence in C3H mice ingest- and G. Busa. Olea europaea L. and ing cotton seed oil. Lipids 1982; 17: oleuropein: effects on excito-conduc- 115–117. tion and on monophasic action poten- OE177 Lasserre, B., R. Kaiser, P. Huu Chanh, tial in anesthetized dogs. Phytother N. Ifansyah, J. Gleye, and C. Moulis. Res 190; 4(4): 140–143. Effects on rats of aqueous extracts of OE166 Lasekan, J. B., M. K. Clayton, A. plants used in folk medicine as anti- Gendron-Fitzpatrick, and D. M. Ney. hypertensive agents. Naturwissen- Dietary olive and safflower oils in pro- schaften 1983; 70(2): 95–96. motion of DMBA-induced mammary OE178 Funayama, S., and H. Hikino. Hy- tumorigenesis in rats. Nutr Cancer potensive principles from plants. Het- 1990; 13(3): 153–163. erocycles 1981; 15: 1239–1256. OLEA EUROPAEA 397

OE179 Razzack, H. M. A. The concept of cholesterol saturation. Amer J Clin birth control in Unani medical litera- Nutr 1988; 47(6): 960–964. ture. Unpublished manuscript of the OE189 Ramirez, V. R., L. J. Mostacero, A. E. author 1980; 64 pp. Garcia, et al. Vegetales empleades en OE180 Delaveau, P., P. Lallouette, and A. M. medicina tradicional Norperuana. Tessier. Stimulation of the phagocytic Banco Agrario del Peru & NACL Univ activity of reticuloedothelial system Trujillo, Trujillo, Peru 1988; 54 pp. by plant drugs. Planta Med 1980; 40: OE190 Scholkens, B. A., D. Gehring, V. 49–54. Schlotte, and U. Weithmann. Evening OE181 Boukef, K., H. R. Souissi, and G. primose oil, a dietary prostaglandin Balansard. Contribution to the study precursor, diminishes vascular reactiv- on plants used in traditional medicine ity to rennin and angiotensin II in rats. in Tunisia. Plant Med Phytother Prostaglandins Leukotrienes Med 1982; 16(4): 260–279. 1982; 8(3): 273–285. OE182 May, G., and G. Willuhn. Antiviral OE191 Antonone, R., F. De Simone, P. activity of aqueous extracts from me- Morrica, and E. Ramundo. Traditional dicinal plants in tissue cultures. phytotherapy in the Roccamonfina Arzneim-Forsch 1978; 28(1): 1–7. volcanic group, Campania, southern OE183 De la Ribeiro, R., M. M. R. Fiuza de Italy. J Ethnopharmacol 1988; 22(3): Melo, F. de Barros, C. Gomes, and G. 295–306. Trolin. Acute antihypertensive effect OE192 Salam, W. H., L. M. Cagen, and M. in conscious rats produced by some Heimberg. Regulation of hepatic cho- medicinal plants used in the state of lesterol biosynthesis by fatty acids: Sao Paolo. J Ethnopharmacol 1986; effect of feeding olive oil on cytoplas- 15(3): 261–269. mic acetoacetyl-coenzyme A thiolase, OE184 Darias, V., L. Bravo, E. Barquin, D. M. beta-hydroxy-beta-methylglutaryl- Herrera, and C. Fraile. Contribution to coA synthase, and acetoacetyl-coen- the ethnopharmacological study of the zyme A ligase. Biochem Biohys Res Canary Islands. J Ethnopharmacol Commun 1988; 153(1): 422–427. 1986; 15(2): 169–193. OE193 Lokar, L. C., and L. Poldini. Herbal OE185 Guerin, J, C., and H. P. Reveillere. remedies in the traditional medicine of Antifungal activity of plant extracts the Venezi Giulia region (northeast used in therapy. II. Study of 40 plant Italy). J Ethnopharmacol 1988; 22(3): extracts against 9 fungi species. Ann 231–239. Pharm Fr 1985; 43(1): 77–81. OE194 Arora, V. Topical composition for re- OE186 Abdul-Ghani, A. S., S. G. El-Lati, A. lieving aches and pains. Patent-US- I. Sacaan, M. S. Suleiman, and R. M. 5,223,257 1993; 2 pp. Amin. Anticonvulsant effects of some OE195 Gebre-Mariam, T., Y. Bekele, A. Arab medicinal plants. Int J Crude Hymete, and A. S. Nikoiayev. Com- Drug Res 1987; 25(1): 39–43. parative antimicrobial activity and phy- OE186 Tejero-Mateo, M. P., A. Gil-Serrao, tochemical screening of some Ethiopian and J. Fernandez-Bolanos. Polysaccha- chewing sticks. Indian Drugs 1993; rides in olives. VI. Study of a galacto- 30(5): 225–229. glucomannan isolated from olive pulp OE196 De Bruin, T. W. A., C. B. Brouwer, M. of the variety Gordal. Ann Quim Ser L. S. Trip, H. Jansen, and D. W. C 1986; 82(2): 155–157. Erkelens. Different postprandial me- OE187 Lokesh, B., H. L. Hsieh, and J. E. tabolism of olive oil and soyean oil: a Kinsella. Olive oil enriched diets possible mechanism of the high-den- decreases arachidonic acid without sity lipoprotein conserving effect of ol- affecting prostaglandin synthesis in ive oil. Amer J Clin Nutr 1993; 58(4): mouse lung and spleen. Nutr Res 477–483. 1988; 8(5): 499–507. OE197 Vague, J., J. C. Garrigues, J. Berthet, OE188 Baggio, G., A. Pagnan, M. Muraca, et and G. Favier. The oestrogenic effect al. Olive-oil-enriched diet: effect on of several plant oils. Ann Endocrinol serum lipoprotein levels and biliary 1959; 18: 745–751. 398 MEDICINAL PLANTS OF THE WORLD

OE198 Simpson, G. E. Folk medicine in OE208 Batanero, E., P. Barral, M. Villalba, Trinidad. J Amer Folklore 1962; 75: and R. Rodriguez. Encapsulation of 326–340. Ole e-1 in biodegradable micropart- OE199 Hunter III, G. W., H. A. Kemp, H. E. icles induces Th1 response in mice: a Smalley, O. P. Wilkins, and C. F. potential vaccine for allergy. J Control Dixon. Studies on schistosomiasis. Release 2003; 92(3): 395–398. XII. Some ointments protecting mice OE209 Guerra, F., J. C. Daza, and E. Almeda. against the Cercariae of Schistoma Immunotherapy with a depigmented, mansoni. Amer J Trop Med Hyg 1956; polymerized vaccine of Olea europaea 5: 713–736. pollen allergens. Significantly reduces OE200 Delphaut, J., J. Balansard, and P. specific bronchial and skin test reactiv- Roure. Pharmacodynamic investiga- ity in sensitized patients after one year tions of some plant drugs alleged to of treatment. I Investig Allergol Clin have any antipyretic action. C R Soc Immunol 2003; 13(2): 108–117. Biol 1941; 135: 1458–1460. OE210 Gonzalez, P., F. Florido, B. Saenz de OE201 Tiscornia, E., and G. C. Bertini. Com- San Pedro, F. de la Torre, P. Rico, and position of the stearolic fractions of S. Martin. Immunotherapy with an ex- Olea europaea, Carthamus tinctorius, tract of Olea europaea quantified in and Helianthus annuus. Riv Ital Sos- mass unit. Evaluation of the safety and tanze Grasse 1974; 51(2): 50–61. efficacy after one year of treatment. J OE202 Greer, M. A., and E. B. Astwood. Investig Allergol Clin Immunol 2002; The antithyroid effect of certain foods 12(4): 263–271. in man as determined with radioac- OE211 Castro, A. J., J. de Dios Alche, J. tive iodine. Endocrinology 1948: 43: Cuevas, P. J. Romero, V. Alche, and 105–119. M. L. Rodriguez-Garcia. Pollen from OE203 Salerno, J. W., and D. E. Smith. The different olive tree cultivars contain- use of sesame oil and other vegetable ing varying amounts of the major al- oils in the inhibition of human colon lergen Ole e-1. Int Arch Allergy cancer growth in vitro. Anticancer Res Immunol 2003; 131(3): 164–173. 1991; 11(1): 209–215. OE212 Perona, J. S., J. Canizares, E. Montero, OE204 Pezzuto, J. M., C. T. Che, D. D. J. M. Sanchez-Dominguez, and V. McPherson, et al. DNA as an affinity Ruiz-Gutierrez. Plasma lipid modifica- probe useful in the detection and iso- tions in elderly people after adminis- lation of biologically active natural tration of two virgin olive oils of the products. J Nat Prod 1991; 54(6): same variety (Olea europaea var. 152–153. hojiblanca) with different triacylgly- OE205 Geller-Bernstein, C., G. Arad, N. cerol composition. Br J Nutr 2003; Keynan, C. Lahoz, B. Cardaga, and Y. 89(6): 819–826. Waisel. Hypersensitivity to pollen of OE213 Montilla, M. P., A. Agil, M. C. Olea europaea in Israel. Allergy 1996; Navarro, et al. Antioxidant activity of 51(5): 356–359. maslnic acid, a triterpene derivative OE206 Somova, L. I., F. O. Shode, and M. obtained from Olea europaea. Planta Mipando. Cardiotonic and antidys- Med 2003; 69(5): 472–474. rhythmic effects of oleanolic and OE214 Somova, L. I., F. O. Shode, P. Ram- ursolic acids, methyl maslinate and nanan, and A. Nadar. Antihypertensive, uvanol. Phytomedicine 2004; 11(2-3): antiatherosclerotic and antioxidant 121–129. activity of triterpenoids isolated from OE207 Barral, P., E. Batanero, O. Palomares, Olea europaea, subspecies africana leaves. J. Quiralte, M. Villalba, and R. J Ethnopharmacol 2003; 84(2–3): Rodriguez. A major allergen from pol- 299–305. len defines a novel family of plant pro- OE215 Benavente-Garcia, O., J. Castillo, J. teins and shows intra-and interspecies Lorente, and M. Alcaraz. Radioprotec- cross-reactivity. J Immunol 2004; tive effects in vivo of phenolics ex- 172(6): 3644–3651. tracted from Olea europaea L. leaves OLEA EUROPAEA 399

against X-ray-induced chromosomal A. Saija. On the in vitro antimicrobial damage: comparative study versus fla- activity of oleuropein and vonoids and sulfur-containing com- hydroxytyrosol. J Pharm Pharmacol pounds. J Med Food 2002; 5(3): 1999; 51(8): 971–974. 125–135. OE225 de Laurentis, N., L. Stefanizzi, M. A. OE216 Khayyal, M. T., M. A. el-Ghazaly, D. Mililloand, and G. Tantillo. Fla- M. Abdallah, N. N. Nassar, S. N. vonoids from leaves of Olea europaea L. Okpanyi, and M. H. Kreuter. Blood cultivars. Ann Pharm Fr 1998; 56(6): pressure lowering effect of an olive leaf 268–273. extract (Olea europaea) in L-NAME OE226 Cardaba, B., V. Del Pozo, A. Jurado, et induced hypertension in rats. al. Olive pollen allergy: searching for Arzneimittelforschung 2002; 52(11): immunodominant T-cell epitopes on 797–802. the Ole e 1 molecule. Clin Exp Al- OE217 Florido-Lopez, J. F., J Quiralte-En- lergy 1998; 28(4): 413–422. riquez, J. M. Arias de Saavendra, B. OE227 Liccardi, G., M. Russ, A. Piccolo, et al. Saenz de San Pedro, and E. Martin The perennial pattern of clinical symp- Casanez. An allergen from Olea toms in children monosensitized to europaea pollen (Ole e 7) is associated Olea europaea pollen allergens in com- with plant-derived food anaphylaxis. parison with subjects with Parietaria Allergy 2002; 71: 53–59. and Gramineae pollinosis. Allergy OE218 Quiralte, J., F. Florido, J. M. Arias de Asthma Proc 1997; 18(2): 99–105. Saavedra, et al. Olive allergen-specific OE228 Pieroni, A., D. Heimler, L. Pieters, B. IgE responses in patients with Olea van Poel, and A. J. Vlietinck. In vitro europaea pollinosis. Allergy Suppl anti-complementary activity of favo- 2002; 71: 47–52. noids from olive (Olea europaea L.) OE219 Al-Quarawi, A. A., M. A. Al-Damegh, leaves. Pharmazie 1996; 51(1): 765–768. and S. A. El-Mougy. Effect of freeze- OE229 Cherif, S., N. Rahal, M. Haouala, et al. dried extract of Olea europaea on the A clinical trial of a titrated Olea ex- pituitary-thyroid axis in rats. tract in the treatment of essential arte- Phytother Res 2002; 16(3): 286–287. rial hypertension. J Pharm Belg 1996; OE220 Batanero, E., P. Barral, M. Villalba, and 51(2): 69–71. R. Rodriguez. Sensitization of mice with OE230 Lccardi, G., M. Russo, M. Saggese, M. olive pollen allergen Ole e 1 induces a D’Amato, and G. D’Amato. Evalua- Th2 response. Int Arch Allergy Im- tion of serum specific IgE and skin munol 2002; 127(4): 269–275. responsiveness to allergenic extracts of OE221 Paia-Martins, F., and M. H. Gordon. Oleaceae pollens (Olea europaea, Frax- Isolation and characterization of the inus excelsior and Ligustrum vulgare) in antioxidant component 3,4-dihydroxy- patients with respiratory allergy. phenylethyl 4-formyl-3-formylmethyl- Allergol Immunopathol (Madr) 1995; 4-hexenoate from olive (Olea europaea) 23(1): 41–46. leaves. J Agric Food Chem 2001; 49(9): OE231 Casanovas, M., F. Guerra, C. Moreno, 4214–4219. R. Miguel, F. Maranon, and J. C. Daza. OE222 Bisignano, G., M. G. Lagana, D. Double-blind, placebo-controlled Trombetta, et al. In vitro antibacterial clinical trial of preseasonal treatment activity of some aliphatic aldehydes with allergenic extracts of Olea from Olea europaea L. FEMS Microbiol europaea pollen administered subling- Lett 2001; 198(1): 9–13. ually. J Investig Allergol Clin Im- OE223 Guerra, F., J. Carracedo, J. A. munol 1994; 4(6): 305–314. Madueno, P. Sanchez-Guijo, and R. OE232 Fehri, B., J. M. Aiache, A. Memmi, et Ramirez. Allergens induce apoptosis in al. Hypotension, hypoglycemia and lymphocytes from atopic patients. hypouricemia recorded after repeated Hum Immunol 1999; 60(9): 840–847. administration of aqueous leaf extract OE224 Bisignano, G., A. Tomaino, R. of Olea europaea L. J Pharm Belg 1994; LoCascio, G. Crisafi, N. Uccella, and 49(2): 101–108. 400 MEDICINAL PLANTS OF THE WORLD

OE233 Guerra, F., C. Moreno, J. C. Daza, R. OE234 Zarzuelo, A., J. Duarte, J. Jimenez, M. Miguel, M. Garcia, and P. Sanchez- Gonzalez, and M. P. Utrila. Vasodila- Guijo. Linear monitoring of pa- tor effect of the olive leaf. Planta Med tients sensitive to Olea and grass 1991; 57(5): 417–419. pollens treated with immunotherapy OE235 Macchia, L., M. F. Caiaffa, G. based on glutaraldehyde-modified DiFelice, et al. Changes in skin reactiv- (allergoid) extracts. J Investig Al- ity, specific IgE and IgG levels after one lergol Clin Immunol 1993; 3(4): year of immunotherapy in olive polli- 182–190. nosis. Allergy 1991; 46(6): 410–418. ORYZA SATIVA 401

11 Oryza sativa L.

Common Names Aisskssiinainikimm United States Ilayisi Africa Aleysi Suriname Karga India Aloruz Arabic countries Klao Thailand Araisa Samoa Loso Congo Arisi India Luama Vietnam Aros Netherlands Antilles Mchele Mozambique Aroz France Mchele Tanzania Arros Spain Mchele Zaire Arroz colorado Argentina Mpunga Africa Arroz macho Argentina Mupunga Botswana Arroz preto Brazil Mupunga Zambia Arroz rojo Bolivia Mupunga Zimbabwe Arroz rojo Colombia Nasi Indonesia Arroz rojo Costa Rica No China Arroz rojo Cuba Orez Romania Arroz rojo Ecuador Oriz Albania Arroz rojo Honduras Oriz Bulgaria Arroz rojo Mexico Oriz Macedonia Arroz rojo Nicaragua Orizen Bulgaria Arroz rojo Panama Orizov Bulgaria Arroz rojo Paraguay Padi ketek Indonesia Arroz rojo Peru Paparean Indonesia Arroz rojo Puerto Rico Pirinac Yugoslavia Arroz rojo Venezuela Pirinac Croatia Arroz vermelho Brazil Pirinac Serbia Arroz Portugal Pirinac Turkey Arroz Spain Pirinc Turkey Aruz Ecuador Pugas Hawaii Bariis Somalia Pugas Pacific Islands Beras Malaysia Raihi New Zealand Birhni India Reesa India Bugas Philippines Reis England Com cay lua Vietnam Reis Germany Erus Malaysia Reise The Isle of Man (Manx)

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 401 402 MEDICINAL PLANTS OF THE WORLD

Reisi South Africa Riso Italy Rice Guyana Riz France Rice India Riz Rwanda Rice United Kingdom Rizs Hungary Rice United States Ruzi Greece Riisi Finland Rys Netherlands Rijst Netherlands Rys South Africa Ris Denmark Ryz Poland Ris Faeroe Islands Ryze Czech Republic Ris France Salebyeo Korea Ris Norway Sragne Cambodia Ris Russia Tao China Ris Sweden Umupunga Africa Ris Switzerland Vary Madagascar Ris Ukraine Wild rice Australia Risgryn Sweden

BOTANICAL DESCRIPTION ratio defining size and shape of the grain. Oryza sativa is a perennial, cultivated as an Kernel is usually white, sometimes red, annual of the POACEAE (GRAMINEAE) purple, or brown. family. The root system of the plant is fi- ORIGIN AND DISTRIBUTION brous, with roots rising from the lower nodes Rice is one of the oldest food crops. Cur- of the culm. The plant tiller usually bears rently, it does not seem possible to deter- four or five culms, to 0.6–2.4 m high. Each mine the place of domestication, but it culm has 10–20 internodes and is sur- probably occurred in India or China. Its cul- rounded by sheathes of leaves. Leaf blades tivation in India, Indochina, China, Indo- are narrow, flat, 30–50 cm long and 7–25 nesia, and East Africa is prehistoric. It is mm wide, slightly pubescent with spiny now distributed throughout the tropics and hairs on the margin. The inflorescence is a warm parts of temperate regions of the panicle, 7.5–37.5 cm long, varying from world. The temperate zone varieties were close and compact in some, to loose and named japonica, and the tropical zone vari- spreading in others; exerting or partially ex- eties indica. erting. Panicle branches arise in whorls, each branch bears 75–150 spikelets, each TRADITIONAL MEDICINAL USES with single floret. Large numbers of spike- China. Hot water extract of the dried straw lets are usually associated with smaller size is taken orally for hepatitisOS117. and a densely packed arrangement. The India. Hot water extract of the grain is flower consists of two lodicules, six stamens, taken orally for jaundiceOS136. Powdered and two plumose stigmas on two styles, sur- grain is taken orally for typhoid fever. The rounded by the floral bracks and two small grain is kept for a month with “birbahuti” outer glumes. Lemma and palea surround- (cochineal insects) before givenOS064. ing the kernel, variously colored: golden yel- Indonesia. The charred stem is immersed low, red, purple, brown and black, becoming in water, and the liquid is taken orally by straw or light yellow when the grain ripens. pregnant women as an abortifacientOS003. Grain varying in size from 5 to 14 mm long The stem ash is eaten twice daily as an and 2–3.7 mm broad. The length/breadth abortifacientOS125. ORYZA SATIVA 403

Iran. The grain is taken orally for intestinal 15,16-Epoxy-3 E-palmitoyloxy-kauran-2-one: inflammation and administered rectally for LfOS159 OS159 diarrhea. The grain flour is used externally 15,16-Epoxy-kauran-2,3-dione: Lf 3-Dehydro-6-deoxoteasterone: PlOS158 to reduce topical inflammation, to remove 3-Dehydroteasterone: PlOS158 rash and erythema, and to treat genital irri- 6-Deoxoteasterone: PlOS158 tation in children resulting from contact Abscisic acid: SdOS007 with urine, and it is mixed with talc powder Aconitic acid: AerOS043 to prevent dryness of the skinOS024. Aconitic acid, trans: AerOS112 Japan. The fresh grain is taken orally as a Alanine, D: LfOS099 OS099 general nutrientOS054. Alanyl-glycine, D: Lf Aluminum: LfOS027 Malaysia. Infusion of the root is taken D OS062 Arabino-hexono-1-4-lactone, , 3-deoxy: orally to facilitate parturition . PlOS015 Mexico. The grain is taken orally to treat Arabino-1-4-lactone, D: PlOS015 diarrheaOS070. Arabinol, iso: AerOS006,OS005 Nepal. Water obtained from rice wash Arundoin: AerOS006,OS005 “chaulani” is taken orally to relieve Asparagine: RtOS026 OS117 OS063 Asparatic acid: Pl vaginitis . To relieve leukorrhea, approx OS081 10 g of the flowers of fire-flame bush Auxin: Sh Benzoic acid, 4-hydroxy: StOS044 Woodfordia fruticosa (L.) Kurz. is boiled in Brassicasterol, 22-dihydro: Bran 69.6OS080 600–700 mL of rice wash and the decoction Caffeic acid: StOS044 is cooled and taken orally twice daily for at Campesterol: AerOS127,OS006 least 2 weeksOS063. Campesterol ferulate: Bran 69.6OS080, Sd Nicaragua. The grain is taken orally for di- oilOS055 OS088 arrhea and externally for skin rashesOS069. Castasterone: Sh 13.60 ppt , Aer 13.6 OS089 OS033 Peru. Hot water extract of the dried fruit is , Sd Castasterone, 6-deoxy: SdOS033 used externally for acne and orally for gas- Chrysanthemin: Seedling RtOS030 tric irritation, diarrhea, and bloody Coumaric acid, para: StOS044 dysenteryOS139. Cyanidin: SdOS157 Philippines. Decoction of the dried seed Cyanidin 3-O-E-D-glucoside: PlOS045 hull in used in steam baths for postpartum Cyanidin diglycoside: LfOS144 care. Also, added to the bath are Paspalum Cyanidin monoglycoside: SdOS144 OS002 scrobiculatum, monkey bones, deer antler, Cyanidin-5-glycoside: Lf OS042 incense, Commophora myrrha, salt, and Cycloartanol ferulate: Sd oil OS130 Cycloartanol, 24-methylene, ferulate: Sd rice . oilOS042, Bran 278.7OS080 Taiwan. Hot water extract of the dried root Cycloartenol ferulate: Sd oilOS042, Bran is taken orally for liver diseasesOS138. 139.3OS080 Thailand. Hot water extract of the fresh Cycloartenol ferulic acid ester: BranOS047 seedling is taken orally as a tonicOS145. Cycloeucalenol: Sd oilOS076 Cylindrin: AerOS006,OS005 CHEMICAL CONSTITUENTS Daucosterol: Sd HuOS079 (ppm unless otherwise indicated) Diazepam: SdOS035 15,16-Epoxy-3-oxa-kauran-2-one: LfOS159 Diazepam, N-demethyl: SdOS035 15,16-Epoxy-3 D-palmitoyloxy-kauran-2-one: DNA topoisomerase 1: SeedlingOS109 LfOS159 Dolichosterone: Sh 8.40 pptOS088 OS159 15,16-Epoxy-3 E-dyfroxy-kauran-2-one: Lf Erythrono-1-4-lactone, D: PlOS015 15,16-Epoxy-3 E-myristoyloxy-kauran-2-one: Erythrono-1-4-lactone, D, 2-C-hydroxy- LfOS159 methyl: PlOS015 404 MEDICINAL PLANTS OF THE WORLD

Erythrono-1-4-lactone, D, 2-C- methyl: PlOS015 Oryzenin: SdOS071 Ferulic acid: StOS044, BranOS084 Paeonidin-3-O-E-D-glucoside: Seedling Glucan, D: PlOS098 RtOS030 Glutamic acid: StrawOS117 Palmitin, mono: SdOS033 Glutathione: RtOS052 Pantoyllactone primeveroside: SeedlingOS023 Glycine: StrawOS117 Phytic acid: SdOS038, BranOS051 Kaur-15-ene, ent: ShOS058 Phytin: Sd HuOS095, FrOS111, Epicarp Kaur-16-ene, ent: ShOS058 4.42%OS113, SdOS090 Leucine: StrawOS117 Phytocassane A: Call TissOS029 Leucine, iso: StrawOS117 Phytocassane B: Call TissOS029 Linoleic acid, 12-13-epoxy: LfOS037 Phytocassane C: Call TissOS029 Lutexin: LfOS009 Phytocassane D: Call TissOS029 Lutonaretin: LfOS009 Phytocassane E: Call TissOS029 Lysine: StrawOS117 Prolamine: SdOS040 Lyxono-1-1-lactone, D: PlOS015 Protein: SdOS114 Lyxono-1-4-lactone, D-2-deoxy: PlOS015 Protein (Oryza sativa): Straw 47OS011 Malvidin: SdOS157 Protocatechuic acid: StOS044 Melatonin: Sd 1498OS156 Pyridoxine, 5-O-(E-D-glucopyranosyl): FrOS078 Methionine: StrawOS117 Pyrrolidine, 1 (2 acetyl): SdOS110 Momilactone A: LfOS017 Pyrroline, 1 (2 acetyl): Fr 1.52OS103 Momilactone B: PlOS116 Quinic acid: LfOS025 Momilactone C: HuskOS077 Resorcinol, 5-(heptadec-12-enyl): Nicotianamine: SeedlingOS121 SeedlingOS031 Olein, mono: SdOS033 Resorcinol, 5-heptadecyl: SeedlingOS031 Oryza antifungal protein: SdOS021 Resorcinol, 5-pentadecyl: SeedlingOS031 Oryza protein I: Bran 0.07%OS065 Resorcinol, 5-tridecyl: SeedlingOS031 Oryza sativa lectin: FrOS010 Rhamnono-1-4-lactone, L: PlOS015 Oryza sativa phytoglycolipid: Sd CtOS094 Rice antifungal protein 1: SeedlingOS018 Oryza sativa polysaccharides RBS: FrOS012 Sakuranetin: Lf OS034,OS017 Oryza sativa substance RBF-PM: SdOS118 Salicyclic acid: Sh 61OS053, Seedling Oryza sativa substance RBF-X: SdOS118 37.19OS060 Oryzabran A: Sd CtOS137 Satiomem: SdOS020 Oryzabran B: Sd CtOS137 Serine: StrawOS117 Oryzabran C: Sd CtOS137 Shikimic acid: Lf OS025 Oryzabran D: Sd CtOS137 Sitosterol, E: AerOS127,OS006 Oryzacystatin A: SdOS066 Sitosterol, E cellopentaoside: SdOS115 Oryzacystatin I: SdOS056 Sitosterol, E cellotetraoside: SdOS115 Oryzacystatin II: SdOS056 Sitosterol, E ferulate: Sd oilOS042, Bran 96.9OS080 Oryzalexin A: Lf 1.0OS120 Squalene: SdOS146, ShOS058 Oryzalexin B: LfOS123 Stigmasterol: AerOS127 Oryzalexin C: LfOS123 Stigmasterol ferulate: Sd oilOS042 Oryzalexin D: LfOS017 Teasterone: SdOS033 Oryzalexin F: Lf 2.3OS019 Thiamine: SdOS057 Oryzalexin S: LfOS017 Threonine: StrawOS117 Oryzalide A: Lf 1.2OS016 Tocopherol, D: Fixed oilOS042 Oryzanol: Sd oilOS048 Tocopherol,E: Fixed oilOS042 Oryzanol, J: Sd oilOS032,OS042 Tocopherol, G: Fixed oilOS042 Oryzaran A: RtOS096 Tocopherol, J: Fixed oilOS042 Oryzaran B: RtOS096 Tocotrienol, D: Fixed oilOS042 Oryzaran C: RtOS096 Tocotrienol, E: Fixed oilOS042 Oryzaran D: RtOS096 Tocotrienol, G: Fixed oilOS042 Oryzatensin: SdOS022 Tocotrienol, J: Fixed oilOS042 ORYZA SATIVA 405

Tricin: StrawOS117 Antibacterial activity. Ethanol (95%) and Tricin-5-O-E-D-Glucoside: PlOS008 water extracts of the dried grain, on agar OS117 Tyrosine: Straw plate at a concentration of 50 PL/plate, were Valine: StrawOS117 active on Staphylococcus aureusOS067. Vanillic acid: StOS044 Violanthin: Lf, StOS097 Antidiarrheal activity. A mixture con- Vitexin: Lf OS009 sisted of rice powder and various electrolytes Vitexin, Iso: Lf OS009 dissolved in 1 L of water was successful in Wax (Oryza sativa): Fixed oilOS028 treating 82% of 38 adult patients and 80% children with diarrhea due to Vibrio cholerae. PHARMACOLOGICAL ACTIVITIES The mixture was also successful in treating AND CLINICAL TRIALS 89% of patients with diarrhea resulting 5-D Reductase inhibition. Water extract of from Escherichia coliOS131. Rice flour, used as a the grain, applied externally on adults at a rehydration therapy instead of glucose, was concentration of 10%, was active. The bio- activeOS049. Water extract of the grain, ad- OS072 logical activity has been patented . ministered intragastrically to rats, was ac- Anaphylactic activity. Methanol extract of tive. The extract was tested as an oral grains, administered intraperitoneally to rehydration solution for the treatment of rats at a dose of 1 g/kg, dose-dependently bacterial diarrhea. The solution inhibited inhibited systemic anaphylaxis induced by secretions by inhibiting chloride channel compound 48/80. When the extract was secretion in the small intestineOS075. Rice pretreated at concentrations ranging from powder, administered orally to 96 children 0.001 to 1 mg/g body weight, the serum his- with diarrhea in a study to evaluate the effi- tamine levels were reduced in a dose-depen- cacy of cereal-based oral rehydration dent manner. It also inhibited local therapy compared with World Health Or- anaphylaxis activated by anti-dinitrophenyl ganization oral rehydration therapy recov- immunoglobulin E (IgE). The extract dose- ery, produced 3.5 vs 40% in controlsOS068. dependently inhibited the histamine released Rice water, with NaCl, KCl, and CaCl2 from rat peritoneal mast cells activated by added was used for rehydration in mild to compound 48/80 or antidinitrophenyl IgE. acute diarrhea. The efficacy was as great as The level of cyclic adenosine monophos- World Health Organization oral rehydra- phate in the rat peritoneal mast cells, when tion solutionsOS059. the extract was added, significantly in- Antidysenteric activity. Cooked rice, fed creased compared with the basal cellsOS082. to pigs infected with Serpulina hyody- Methanol extract of the dried seed, in cell senteriae, produced drier colonic contents culture at variable concentrations, inhibited and feces and lighter large intestines, and compound of IgE-induced release from rat the contents of their large intestines had peritoneal mast cells. The methanol extract, increased pH values and decreased total administered intragastrically to rats at a dose volatile fatty acid concentrations than on of 1 g/kg, inhibited the rate of passive cuta- other diets. None of the pigs fed the cooked- neous anaphylaxis reaction. Intraperitoneal rice diet developed colonic changes or dis- administration inhibited systemic anaphy- ease, whereas most pigs on the other diets laxis induced by compound 48/80OS083. developed mucohemorrhagic colitis and Anti-acne activity. Water extract of the dysenteryOS148. grain, applied externally on adults at a con- Antifungal activity. Acetone extract of the centration of 10%, was active. The biologi- fresh leaf, on agar plate at a concentration cal activity has been patentedOS072. of 200 ppm, was active on Pyricularia oryzae 406 MEDICINAL PLANTS OF THE WORLD cultivars Fukuyuki and Fukunishiki using Antihyperglycemic activity. Dried grains, the acidic part and inactive on cultivars taken orally by adults of both sexes, was ac- Sasanishiki using the acid and neutral parts tive. The hypoglycemic response of three and on Fukunishiki and Fukuyuki using the traditional sorghum (both whole and neutral partOS037. dehulled) recipes namely missiroti, upma, Antihistamine activity. Methanol extract and dhokla were studied on six patients with of grains, in cell culture at a concentration noninsulin-dependent diabetes. Consump- of 10 mg/mL, was active on mast cells vs in- tion of whole sorghum recipes resulted in hibition of histamine release induced by significantly lower plasma glucose levels, compound 48/80. The extract, administered lower percent peak rise, and lower area-un- intragastrically to rats at a dose of 1 g/kg, der-the-curve in patients with diabetes was active vs inhibition of histamine release when compared with the consumption of induced by compound 48/80OS082. dehulled sorghum and wheat recipes. The Antihypercholesterolemic activity. Fixed least glycemic response was observed with oil in the ration of adults, at a dose of 35 g/ whole sorghum semolina (75.6 mg), fol- day, was active. Twelve patients with high lowed by whole sorghum missiroti (77.8 mg) serum cholesterol or triglycerides used rice and whole sorghum dhokla (84.5 mg). No bran oil instead of their usual cooking oil significant difference (p < 0.05) was seen in (palm oil) and in similar quantities. Serum the mean peak rise of plasma glucose levels cholesterol and triglycerides were reduced of the subjects fed with wheat and dehulled after 15 days of use. No reduction was seen recipesOS073. The cooked grain, taken orally in the control group using the normal cook- by adults, was inactive vs glucose-induced ing oilOS100. Fixed oil, taken orally by adults, hyperglycemiaOS140. The grain, taken orally was active. Fifteen patients with elevated by eight healthy individuals with normal low-density lipoprotein (LDL) cholesterol glucose tolerance at a dose of 25 g/person, were treated with rice bran oil, which com- was activeOS041. Water extract of the dried prised two-thirds of the fat of a diet with 30% grain, administered intragastrically to mice fat. The patients showed lower levels of LDL at a dose of 1 g/kg, was inactive. The dose cholesterol, and plasma cholesterol levels was given 1 hour after streptozotocin and were similar to those obtained from patients twice daily for 3 subsequent days. Blood glu- consuming canola, corn, and olive oilsOS138. cose was 255.3 vs 236.3 mg/dL for controls Rice bran, taken orally by adults at a dose of vs streptozotocin-induced hyperglycemiaOS108. 100 g/day, produced a reduction in LDL, Antihyperlipemic activity. Fixed oil in the high-density lipoprotein , and very low-den- ration of adults, at a dose of 35 g/day, was sity lipoprotein cholesterol. The treatment active. Twelve patients with high serum was administered to 11 patients with mod- cholesterol or triglycerides used rice brain erately to high blood cholesterol levels for oil instead of their usual cooking oil (palm two 3-week periods. Before the treatment oil) and in similar quantities. Serum choles- phase, a control diet without bran was pro- terol and triglycerides were reduced after 15 vided for 2 weeksOS039. Seed oil, in the ration days of use. No reduction was seen in the of rats at a concentration of 10% of the diet, control group using the normal cooking was active. Rats fed bran oil with cholesterol oilOS100. supplementation had lower serum choles- Anti-inflammatory activity. Methanol ex- terol than those fed similar levels of peanut tract of the bran, used externally on the oil. High-density lipoprotein level was mouse ear, was active vs 12-O-tetradeca- higher in the rice bran oil groupOS102. noylphorbol-13-acetate-induced ear inflam- ORYZA SATIVA 407 mationOS080. Rice germ oil, used externally tive vs water immersion stress-induced on rabbits three times a day for 2 days, ulcersOS122. Freshly harvested grains (milled prevented subsequent sodium dodecyl sul- and unmilled) and fresh bran, in the ration fate-induced blistering, erythema, and of rats, was active vs pylorus ligation-in- edema. The biological activity has been duced ulcersOS101. patentedOS107. Antiviral activity. Aqueous low-speed su- Antimutagenic activity. Water extract of pernatant and juice of the fresh seed, at a the dried seed coat did not affect the mu- concentration of 10%, were active on virus- tagenicities of coffee, black tea, whisky, or top necrosis in plantsOS092 several mutagenic compoundsOS129. Anti-yeast activity. Ethanol (80%) extract Antioxidant activity. Bran, at a concentra- of the dried entire plant, on agar plate at a tion of 65 mg/mL, was active. Superoxide concentration of 1 mg/mL, was inactive on OS126 radicals were generated using the hypoxan- Candida albicans . thine-xanthine oxidase systemOS046. Chloro- Apoptosis induction. Lipoprotein fraction form/methanol and methanol (50%) ex- of the bran, in cell culture at a concentra- tracts of the dried seed hulls were activeOS093. tion of 100 Pg/mL, was active vs human en- dometrial adenocarcinoma cellsOS085. Antisecretory effect. Water extract of the dried grain was active on the small intesti- Atopic dermatitis effect. Rice bran broth, administered to 17 patients with atopic der- nal crypt cells vs cyclic adenosine monophos- matitis as bath therapy, was safe and clini- phate-induced secretion stimulationOS061. cally useful. The rice bran broth was Antispasmodic activity. Ethanol (50%) dissolved in the bathtub as a medicinal bath. extract of grain was active on the guinea pig One of the patients discontinued therapy ileum vs acetylcholine- and histamine-in- after developing redness and itching of the duced spasmsOS001. skin just after bathing. The other 16 pa- Anti-thyroid activity. Boiled rice taken tients continued the bath for 2–5 months orally by adults at a dose of 350 g/person was and recorded skin conditions once a month. OS147 inactive on iodine uptake by the thyroid . The efficacy of the therapy in alleviating Anti-tumor activity. Bran, administered skin symptoms was excellent in four pa- intraperitoneally to mice at a dose of 100 tients, good in seven, slightly effective in mg/kg, was active on Sarcoma 180 (solid). four, and effective in one. Recurrence of The biological activity has been pa- initial symptoms was not detected in any tentedOS119. Fermented grains, in the ration patients during the rice bran broth bath- of rats, were active. Miso, a paste made from ingOS149. the seeds of Oryza sativa and G lycine max Bioavailability of starch. Cooked rice was (soybean), was fed ad libitum. The incidence administered to colectomized rats by gastric of cancers in the miso treated rats was 20% intubation and the recovery of starch in the less than controls vs 7,12-dimethylbenz- ileal digesta measured after 10 hours of in- [a]anthracene -induced carcinogenesisOS104. gestion. Significant starch (11–15%) was Water extract of dried seed hull, adminis- recovered from animals fed peas, lima beans, tered intraperitoneally to mice, was active or kidney beans; 0.2–0.4% of starch from on Sarcoma 180 (ASC). A glycoprotein rice. Oligosaccharide extraction, the size of fraction has been tested. The biological ac- the test meal, and the amount of starch did tivity reported has been patentedOS133. not affect starch biovailabilityOS150. Anti-ulcer activity. A cerebroside fraction cAMP accumulation. Methanol extract of of rice bran, administered intraperitoneally the grain, in cell culture at a concentration to mice at a dose of 100 mg/kg, was inac- of 1 mg/mL, was active on mast cellsOS082. 408 MEDICINAL PLANTS OF THE WORLD

Carcinogenesis inhibition. Polysaccharide Feeding deterrent. The fresh sap and chro- fraction of the dried seed hulls, administered matographic fraction of the fresh sap were to rats by gastric intubation, was active vs active on Nilaparvata lugens OS127. tumor induction with N-ethyl-N-nitro-N- Feeding stimulant. Flavonoid fraction of nitrosoguanidineOS132. Rice bran, adminis- the dried entire plant was active on Lao- tered orally to male rats at a concentration delphax striatellus, Sogatella furcifera, and of 4% of the diet, was active. A 1:1 combi- Nilaparvata lugensOS013. Methanol extract of nation of wheat bran and psyllium, at a to- the fresh leaf, at a concentration of 2%, was tal level of 8% dietary fiber, offers the active on Laodelphax striatellus, Nilaparvata highest protection against colon tumor lugens and Sogatella furcifera. The results developmentOS141. were significant at p less than 0.01 levelOS014. Cell proliferation inhibition. Lipoprotein Fungal stimulant. Dried entire plant, at a fraction of bran, in cell culture at a concen- concentration of 100 ppm, was active on tration of 100 Pg/mL, was active vs Sawano Gerlachia oryzaeOS015. cellsOS085. Glutamate–pyruvate–transminase inhi- Cytotoxic activity. Dried seedling hulls, in bition. Ethanol (50%) extract of the dried cell culture, was active on Cells-HSOS-1, root, in cell culture at a concentration of Cells-Jurkat, Cells-X63-AG8, and Leuk- 1 mg/mL, was inactive on hepatocytes vs OS050 P388 . Ethanol (50%) extract of the prostaglandin E-1- and CCl4-induced hepa- grain, in cell culture, was inactive on CA- totoxicityOS138.

9KB, effective dose50 greater than 20 Pg/ Glycemic index. Rice, consumed by pa- mLOS001. Water extract of the dried grain, in tients with noninsulin-dependent diabetes cell culture at a concentration 500 Pg/mL, mellitus, correlated positively with in vitro was inactive on CA-mammary-microalve- starch digestibility of food slurry and nega- olar cellsOS105. Water extract of the freeze- tively with amylase content of the food. dried grains, in cell culture, was active on Glutinous rice had the highest values and Leuk-P815. The toxic activity of the tumor mung bean noodles the lowestOS152. Rice and was evaluated by culturing mastocytoma combinations of rice and legumes, con- P815 with macrophage cells and measuring sumed by 36 patients with noninsulin- the incorporation of 3H-thymidineOS106. dependent diabetes mellitus, produced Dermatitis-producing effect. A case of significantly lower blood glucose response dermatitis in a female adult was reported 2 hours postprandially as compared with after contact with the fresh leaf OS128. blood glucose responses to a 50 g glucose Diabetes inhibition of development. load for the same group. A higher glycemic Methanol/ethanol/ketone extract of bran, index was obtained for rice with peas; all in the ration of male rats at a dose of 0.5 g/ other combinations yielded lower glycemic kg, was active vs streptozotocin-induced indices. No significant difference was ob- diabetesOS086. served for triglyceride responses of the dif- Estrogenic effect. Polished rice, in the ra- ferent foodsOS153. tion of immature female rats, was activeOS143. Hair-growth stimulant. Water extract of Saponifiable fraction of the embryo, admin- the grain, applied externally on adults at a istered subcutaneously to female mice, was concentration of 10%, was active. The bio- activeOS142. Seed oil, administered orally to logical activity has been patentedOS072. female mice at a dose of 10% of the diet, Hypocholesterolemic activity. Unsaponi- was activeOS004. fiable fraction of seed oil, administered orally to rats at a dose of 0.4% of the diet, ORYZA SATIVA 409 was activeOS134. Seed oil, administered orally ing of mashed potatoes was faster than that to adults and by gastric intubation to dogs, of polished rice and of white beans. Blood was activeOS124. glucose and plasma insulin responses to the Hypoglycemic activity. Dried grain, taken meal with mash potatoes were greater than orally by human adults at a dose of 162 g/ that of polished rice, which also produced a person, was active, results were significant greater glucose response than that of white at p less than 0.001 levelOS091. Water extract beans. The glucose and insulin responses to of the dried seed coat of cultivar Fukuyuki, potatoes and rice were strongly related to administered intraperitoneally to mice at a gastric emptying rate, but other factors dose of 100 mg/kg, was activeOS137. dominates the control of these responses to Hypotensive activity. Ethanol (50%) ex- white beansOS154. tract of the grain, administered intrave- Mutagenic activity. Seed oil was inactive nously to dogs at a dose of 50 mg/kg, was on Salmonella typhimurium TA100 and activeOS001. TA98. Metabolic activation had no effect Interleukin induction. Water extract of on the resultsOS135. freeze-dried grain was active. Interleukin -1 Parkinson’s disease. Unpolished rice, in activity was measured by the interleukin-1 combination with Carica papaya, seaweeds, dependent growth of a T-helper cell and effective micro-organisms, produced lineOS106. potential neuroprotective effects. The treat- Lipid metabolism effects. Grains, in the ment was investigated using the 6-hydro- ration of rats at a dose of 68 g/animal daily xydopamine-lesion rat model of Parkinson’s for 3 months, were active vs rats fed tapi- disease. The nigrostriated dopaminergic oca. Total serum cholesterol and triglycer- neurons were unilaterally lesioned with 6- ides were higher than animals fed tapioca. hydroxydopamine in rats that were treated. Glucose-6-phosphate levels were lower, and Seven days after lesion, the integrity (num- triglyceride lipase and lipoprotein lipase ber of tyrosine hydroxylase-positive cells in were increased over levels found in the tapi- the substantia nigra pars compacta) and oca groupOS087. Seed oil, in the ration of rats functionality (dopamine and its metabo- at a concentration of 10% of the diet, was lites 3,4-dihydroxyphenylacetic acid and active. Liver triglycerides were lower in rats homovanillic acid content in the striata) of fed rice brain oil than those fed peanut nigrostriatal dopaminergic neurons were oilOS102. assessedOS155. Lymphocyte stimulation. Bran fiber hemi- Passive cutaneous anaphylaxis inhibi- cellulose, administered to rats at a dose of tion. Methanol extract of the grain, admin- 10% of the diet, produced weak activity on istered intragastrically to rats at a dose of 1 sperm cellsOS036. g/kg, was active vs anti-2,4-dinitrophenyl Metabolism and gastric emptying. Pol- immunoglobulin administration followed by ished rice, consumed by 13 healthy adults, intravenous antigenic challengeOS082. produced no correlation between gastric Protein secretion stimulation. Decoction emptying and blood glucose or plasma insu- of the grain, administered intraperitoneally lin after the meal. Three meals of equal en- to mice at a dose of 100 mg/kg, increased ergy content consisting of mashed potatoes, protein content of saliva in streptozotocin- polished rice, or white beans were investi- induced diabetic mice. The results were sig- gated. Blood glucose and plasma insulin nificant at p < 0.01 levelOS074. were measured after overnight fast and after Radical scavenging effect. Bran was active ingestion of the test meals. Gastric empty- when scavenging of 1,1-diphenyl 1,2- 410 MEDICINAL PLANTS OF THE WORLD picrylhydrazine radicals was assayed, in- REFERENCES hibitory concentration50 was 0.875 mg/mL; OS001 Dhar, M. L., M. M. Dhar, B. N. scavenging of hydroxyl radicals, inhibitory Dhawan, B. N. Mehrotra, and C. Ray. Screening of Indian plants for biologi- concentration50 2.79 mg/mL and for super- oxide, lethal concentration 0.73 mg/ cal activity: Part I. Indian J Exp Biol 50 1968; 6: 232–247. mLOS046. OS002 Hayashi, K. Anthocyanins. XIII. Sev- Radioprotective effect. 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OS075 Goldberg, E. D., and J. R. Saltzman. carcinoma cells (sawano) by an antitu- Rice inhibits intestinal secretions. mor lipoprotein fraction of rice bran. Nutr Rev 1996; 54(1): 36–37. Gynecol Oncol 2000; 76(2): 170–175. OS076 Itoh, T., K. Uchikawa, T. Tamura, OS086 Ohara, I., D. Agr, R. Tabuchi, K. Onai, and T. Matsumoto. Two new 4-alpha and M. H. Econ. Effects of modified methylsterols in the seeds of Brassica rice bran on serum lipids on taste pref- napus. Phytochemistry 1977; 16: 1448 erence in streptozotocin-induced dia- –1449. betic rats. Nutr Res 2000; 20(1): OS077 Tsunakawa, M., A. Ohba, N. Sasaki, 59–68. et al. Momilactone C, a minor con- OS087 Premakumari, K., and P. A. Kurup. stituent of growth inhibitors in rice Lipid metabolism in rats fed rice and husk. Chem Lett 1976; 1976: 1157. tapioca. Indian J Med Res 1982; 76: OS078 Yasumoto, K., H. Tsuji, K. Iwami, and 488–493. H. Mitsuda. Isolation from rice bran of OS088 Abe, H., K. Nakamura, T. Morishita, a bound form of vitamin B-6 and its M. Uchiyama, S. Takatsuto, and N. identification as 5’-O-(beta-D-gluco- Ikekawa. Endogenous brassinosteroids pyranosyl) pyridoxine. Agr Biol Chem of the rice plant: Castasterone and 1977; 41: 1061. dolichosterone. Agr Biol Chem 1984; OS079 Ahn, E. M., M. H. Lee, Y. D. Rho, and 48(4): 1103–1104. N. I. Baek. Isolation of daucosterol OS089 Ikekawa, N., S. Takatsuto, T. Kitsuwa, from the rice hull of Oryza sativa L. H. Saito, T. Morishita, and H. Abe. Han’guk Nonghwa Hakhoe Chi 1998; Analysis of natural brassinosteroids by 41(6): 486–488. gas chromatography and gas chroma- OS080 Yasukawa, K., T. Akihisa, Y. Kimura, tography-mass spectrometry. J T. Tamuara, and M. Takido. Inhibi- Chromatogr 1984; 290(1): 289–302. tory effect of cycloartenol ferulate, a OS090 Tashmenov, R. S., K. A. Sabirov, and component of rice bran, on tumor pro- S. M. Makhkamov. Improved process motion in two-stage carcinogenesis in for extraction of phytin. Khim Farm mouse skin. Biol Pharm Bull 1998; Zh 1984; 18(10): 1229–1231. 21(10): 1072–1076. OS091 Kamath, P. S., J. B. Dilawari, S. OS081 Kim, Y. S., D. H. Kim, and J. Jung. Iso- Raghavan, R. P. Batta, S. Mukewar, lation of a novel auxin receptor from and R. J. Dash. Plasma insulin response soluble fractions of rice (Oryza sativa to legumes and carbohydrate foods. In- L.) shoots. FEBS Lett 1998; 438(3): dian J Med Res 1982; 76: 583–590. 241–244. OS092 Roy, A. N., B. P. Sinha, and K. C. OS082 Kim, H. M., C. S. Kangk, E. H. Lee, Gupta. The inhibitory effect of plant and T. Y. Shin. The evaluation of the juices on the infectivity of top necrosis antianaphylactic effect of Oryza sativa virus of pea. Indian J Microbiol 1979; L. subsp. hsien ting in rats. Pharmacol 19: 198–201. Res 1999; 40(1): 31–36. OS093 Osawa, T., T. Narasimhan, S. OS083 Kim, H. M., D. K. Yi, and H. Y. Shin. Kawakishi, M. Namiki, and T. Tashiro. The evaluation of the antianaphy- Antioxidative defense systems in rice lactic effect of Oryza sativa L. in rats. hull against damage caused by oxygen Amer J Chinese Med 1999; 27(1): radicals. Agr Biol Chem 1985; 49(10): 63–71. 3085–3087. OS084 Taniguchi, H., A. Hosoda, T. Tsuno, OS094 Ito, S., M. Kojima, and Y. Fujino. Oc- Y. Maruta, and E. Nomura. Prepara- currence of phytoglycolipid in rice tion of ferulic acid and its application bran. Agr Biol Chem 1985; 49(6): for the synthesis of cancer 1873–1875. chemopreventive agents. Anticancer OS095 Anon. Isolation of phytin from rice Res 1999; 19(5A): 3757–3761. bran. Patent-Japan Kokai Tokkyo OS085 Fan, H., T. Morioka, and E. Ito. Induc- Koho-60 58,993 1985: 2 pp. tion of apoptosis and growth inhibition OS096 Hikino, H., M. Murakami, Y. Oshima, of cultured human endometrial adeno- and C. Konno. Isolation and hypogly- ORYZA SATIVA 415

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OS118 Kawai, K., K. Sugawara, and T. Morin- planthopper. Agr Biol Chem 1982; gag. Antitumor substance. Patent-Eur 46(11): 2877–2879. Appl-27,514 1981; 45 pp. OS128 Nakamura, T. Contact dermatitis to OS119 Ito, E. Antitumor agents from rice bran. Oryza. Contact Dermatitis 1983; Patent-Japan Kokai Tokkyo Koho-81 9(1): 80. 29,519 1981; 12 pp. OS129 Suwa, Y., T. Kobayashi, N. Kiyotan, OS120 Akatsuka, T., O. Kodama, H. Kato, Y. and H. Yoshizumi. Antimutagenic Kono, and S. Takeuchi. 3-Hydroxy-7- agent and method of inactivating the oxo-sandaaraco-primaradiene mutagenicity of foods and beverages by (Oryzalexin A), a new phytolexin iso- using this agent. Patent-Eur Pat Appl- lated from rice blast leaves. Agr Biol 124,891 1984; 36 pp. Chem 1983; 47(2): 445–447. OS130 Velazco, E. A. Herbal and traditional OS121 Fushiya, S., K. Takahaashi, S. Nakat- practices related to maternal and child suyama, Y, Sato, S. Nozoe, and S. health care. Rural Reconstruction Takagi. Co-occurrence of nicotian- Review 1980; 35–39. amine and avenic acids in Avena sativa OS131 Molla, A. M., M. Hossain, S. A. and Oryza sativa. Phytochemistry Sarker, A. Molla, and W. B. Green- 1982; 21: 1907–1908. ough III. Rice-powder electrolyte solu- OS122 Okuyama, E., and M. Yamazaki. The tion as oral therapy in diarrhoea due to principles of Tetragonia tetragonoides Vibrio cholerae and Escherichia coli. having anti-ulcerogenic activity. Ll. Lancet 1982; 1(8285): 1317–1319. Isolation and structure of cerebro- OS132 Minaguchi, S., E. Sudoh, M. Takeshita, sides. Chem Pharm Bull 1983; 31(7): et al. Effects of various immuno- 2209–2219. potentiators on ENNG-induced car- OS123 Kono, Y., S. Takeuchi, O. Kodama, cinogenesis in rats. Igaku No Ayumi and T. Akatsuka. Absolute configura- 1985; 133(5): 321–322. tion of Oryzalexin A and structures of OS133 Yamazaki, N., T. Otomo, and K. Kawai. its related phytoalexins isolated from Antitumor glycoprotein extraction rice blast leaves infected with from rice bran. Patent-Japan Kokai Pyricularia oryzae. Agr Biol Chem Tokkyo Koho-61 143,323. 1986; 9 pp. 1984; 48(1): 253–255. OS134 Sharma, R. D. and C. Rukmini. OS124 Chindavanig, A. Effect of vegetable Hypocholesterolemic activity of unsa- oils on plasma cholesterol in man and ponifiable matter or rice bran oil. In- dog. Thesis-Master Department of Bio- dian J Med Res. 1987; 3: 278–281. chemistry, Mahidol University, Bang- OS135 Polasa, K., and C. Rukmini. Mutage- kok, Thailand, 1971; 58 pp. nicity tests of cashewnut shell liquid, OS125 Hirschhorn, H. H. Botanical remedies rice-bran oil and other vegetable oils of the former Dutch East Indies (In- using the Salmonella typhimurium/mi- donesia). l. Eumycetes, Pteridophyta, crosome system. Food Chem Toxicol Gymnospermae, Angiospermae (mono- 1987; 25(10): 763–766. cotyledons only). J Ethnopharmacol OS136 Hemadri, K., and S. S. Rao. Jaundice: 1983; 7(2): 123–156. Tribal medicine. Ancient Sci Life OS126 Al-Shamma, A., and L. A. Mitscher. 1984; 3(4): 209–212. Comprehensive survey of indigenous OS137 Hikino, H., M. Takahashi, Y. Oshima, Iraqi plants for potential economic and C. Konno. Isolation and hypogly- value. l. Screening results of 327 cemic activity of Oryza brans A, B, C species for alkaloids and antimicro- and D, glycans of Oryza sativa bran. bial agents. J Nat Prod 1979; 42(6): Planta Med 1988; 54(1): 1–3. 633–642. OS138 Yanfg, L. L., K. Y. Yen, Y. Kiso, and H. OS127 Shigematsu, Y., N. Murofushl, K. Ito, Kikino. Antihepatotoxic actions of C. Kaneda, S. Kawabe, and N. Formosan plant drugs. J Ethnophar- Takahashi. Sterols and asparagines in macol 1987; 19(1): 103–110. the rice plant, endogenous factors OS139 Ramirez, V. R., L. J. Mostacero, A. E. related resistance against the brown Garcia, et al. Vegetales empleados en ORYZA SATIVA 417

medicina tradicional norperuana. tial vitamin K supply from enteric bac- Banco Agrario Del Peru & NACL terial menaquinones in rats. Br j Nutr Univ Trujillo, Peru 1988; 54 pp. 1990; 63(3): 639–652. OS140 Dilavari, J. B., V. K. A. Kumar, S. OS152 Juliano, B. O., C. M. Perez, S. Komindr, Khurana, R. Bhatnagar, and R. J. Dash. and S. Banphotkasem. Properties of Effect of legumes on blood sugar in dia- Thai cooked rice and noodles differing betes mellitus. Indian J Med Res 1987; in glycemic index in non-insulin- 85(2): 184–187. dependent diabetics. Plant Foods Hum OS141 Alabaster, O., Z. C. Tang, A. Frost, Nutr 1989; 39(4): 369–374. and N. Shivapurkar. Potential syner- OS153 Mani, U. V., S. Bhatt, N. C. Mehta, S. gism between wheat bran and psyllium: N. Pradhan, V. Shah, and I. Mani. Enhanced inhibition of colon cancer. Glycemic index of traditional Indian Cancer Lett 1993; 75(1): 53–58. carbohydrate foods. J Am Coll Nutr OS142 Ashikari, H. Estrone-like substance 1990; 9(6): 573–577. present in rice embryo. Arb Med OS154 Torsdottir, I., M. Alpsten, D. Anders- Fakultat Okayama 1940; 6: 448. son, R. J. Brummer, and H. Anderson. OS143 Reiss, M., and S. Pereny. Estruation Effect of different starchy foods in effect of feeding polished rice on rats. composite meals on gastric emptying Endocrinologie 1928; 1: 411–418. rate and glucose metabolism. I. Com- OS144 Krishnamoorthy, V. and T. R. Sesha- parisons between potatoes, rice and dri. Survey of anthocyanins from In- white beans. Hum Nutr Clin Nutr dian sources: Part III. J Sci Ind Res-B 1984; 38(5): 329–338. 1962; 21: 591–593. OS155 Datla, K. P., R. D. Bennett, V. Zbarsky, OS145 Wasuwat, S. A list of Thai medicinal et al. The antioxidant drink ’effective plants. Research Report, ASRCT, No microorganism-X (EM-X)” pre-treat- 1 on Res. Project 17. 1967; 22 pp. ment attenuates the loss of nigros- OS146 Fitelson, J. The occurrence of squalene triatal dopaminergic neurons in in natural fats. J Ass Offic Agr Chem 6-hydroxydopamine-lesion rat model 1943; 26: 506–511. of Parkinson’s disease. J Pharm Phar- OS147 Greer, M. A., and E. B. Astwood. The macol 2004; 56(5): 649–654. antithyroid effect of certain foods in OS156 Badria, F. A. Melatonin, sertonin, and man as determined with radioactive io- tryptamine in some Egyptian food and dine. Endocrinology 1948; 43: 105–119. medicinal plants. J Med Food 2002; OS148 Siba, P. M., D. W. Pethick, and D. J. 5(3): 153–157. Hampson. Pigs experimentally in- OS157 Hyun, J. W., and H. S. Chung. Cyani- fected with Serpulina hyodysenteriae can din and Malvidin from Oryza sativa cv. be protected from developing swine Heugjinjubyeo mediate cytotoxicity dysentery by feeding them a highly di- against human monocytic leukemia gestible diet. Epidemiol Infect 1966; cells by arrest of G(2)/M phase and in- 116(2): 207–216. duction of apoptosis. J Agric Food OS149 Jujiwaki, T., and K. Furusho. The ef- Chem 2004; 52(8): 2213–2217. fects of rice bran broth bathing in pa- OS158 Hong, Z., M. Ueguchi-Tanaka, K. tients with atopic dermatitis. Acta Umemura, Set al. A rice brassino- Paediatr Jpn 1992; 3495): 505–510. steroids-deficient mutant, ebisu-dwarf OS150 Hildebrandt, L. A., and J. A. Marlett. (d2), is caused by a loss of function of a Starch bioavailability in the upper gas- new member of cytochrome P450. trointestinal tract of colectomized rats. Plant Cell 2003; 15(12): 2900–2910. J Nutr 1991; 121(7): 1141. OS159 Kono, Y., A. Kojima, R. Nagai, et al. OS151 Mathers, J. C., F. Fernandez, M. J. Hill, Antibacterial diterpenes and their fatty P. T. McCarthy, M. J. Shearer, and A. acid conjugates from rice leaves. Phy- Oxley. Dietary modification of poten- tochemistry 2004; 65(9): 1291–1298. PLANTAGO OVATA 419

12 Plantago ovata Forsk.

Common Names Ashwagolam India Lisn al kalb Arabic countries Babka Poland Obeko Japan Barhanj Arabic countries Plantago United States Bidr qtn Arabic countries Plantain United States Blond psyllium Arabic countries Psillo indiano Germany Buzar qatona Arabic countries Qurayta Arabic countries Ch-chientzu China Rebla Arabic countries Common plantain Arabic countries Spangur India Hab zargah Arabic countries Spogel Iran Isphghol India Warak sabun masasah Arabic countries

BOTANICAL DESCRIPTION protruded stamina, ovary free with one or Plantago ovata is a stemless, soft, hairy an- two cells, containing one or more ovules. nual herb of the PLANTAGINACEAE The style capillar and terminated by a single family that grows to a height of 30–45 cm. subulate stigma. The fruit is a small The leaves are 7.5–23 cm long, 0.5–1 cm pyxidium covered by the persistent corolla broad, narrowly linear, linear lanceolate or and enclosed in capsules that open at matu- filiform, opposite, finely acuminate entire or rity. They are composed of a proper integu- distantly toothed, attenuated at the base ment which covers a fleshy endosperm at and usually three-nerved. The root system the center of which is a cylindrical axile and has a well-developed taproot with few fi- a homotype embryo, ovoid-oblong or boat- brous secondary roots. A number of flower- shaped, smooth and yellowish brown, acute ing shoots arise from the base of the plant. at one end 2–3 mm long, pale-green brown The flower spikes turn reddish brown at rip- with a darker elongated spot on the convex ening, the lower leaves dry, and the upper side. On the concave side, the hilium is cov- leaves yellow. Plants flower approx 60 days ered with the remains of a thin white mem- after planting. Flowers are numerous, small, brane. It has no odor or taste, but the and white, in ovoid or cylindrical spikes herbage is demulcent, bitter, and somewhat 1.3–3.8 cm long, bracts 4 mm long and astringent. Seeds are hard, translucent, broad. The corolla gives attachment to four boat-shaped structure, up to 8 mm long and

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 419 420 MEDICINAL PLANTS OF THE WORLD

1 mm broad. The surface is glossy and shin- sociated with bile secretion abnormalities. ing, with a pinkish brown color. There is an Mucilage of the dried seed is used externally oval spot in the center of convex (dorsal) as an emollient. Seedcoat of the dried seed surface. On the concave (ventral) surface is is taken orally as a bulk laxative. Acetic acid a deep furrow is seen with a hilum that ap- extract of the dried seed is used externally pears as a red spot in the center. for rheumatoid arthritis and gout. Infusion ORIGIN AND DISTRIBUTION of the dried seed is taken orally for urinary tract inflammationsPO005. Plantago ovata originated from Europe to Spain. Leaf is taken orally by infusion for Southern Mediterranean to Eastern Asia coldPO045 (India, Iraq, Iran, Spain, and Canary Is- Thailand. Hot water extract of the dried lands). It is produced commercially in sev- seed husks is taken orally as a demulcent and eral European countries, Pakistan, and for diarrheaPO061. India. Seed produced from Plantago ovata is known in trading circles as white or blonde CHEMICAL CONSTITUENTS psyllium, Indian Plantago, or Isabgol; the (ppm unless otherwise indicated) common name in India for Plantago ovata, Alanine, (DL): SdPO062 comes from the Persian words “isap” and Amyrin, D: SdPO073 PO073 “ghol” which mean horse ear, which is de- Amyrin, E: Sd Asparagine, l, (–): SdPO062 scriptive of the shape of the seed. India Aucubin glucoside: SdPO073 dominates the world market in the produc- Campesterol: SdPO073 tion and export of psyllium. In India, Plan- Cystine, l: SdPO062 tago ovata is cultivated mainly in North Docosance, N: Sd CtPO004 Gujarat as a “Rabi” or post-rainy season Dotriacontane, iso: Sd CtPO004 PO004 crop. An important environmental require- Dotriacontane, N: Sd Ct PO004 ment of this crop is a dry open place. Psyl- Eicosane, N: Sd Ct Fixed oil (Plantago ovata): Endosperm 8.8%PO070 lium research and field trials in the United Fructose: SdPO073 States have been conducted mainly in Ari- Glucose: SdPO073 zona and Washington. A major cultural Glutamic acid: SdPO062 problem limiting psyllium production in the Glycine: SdPO062 upper midwest is the shattering characteris- Heneicosane, N: Sd CtPO004 Hentriacontane, iso: Sd CtPO004 tic of the mature crop. Some success has PO004 been achieved by crossbreeding high-yield- Hentriacontane, N: Sd Ct Heptacosane, N: Sd CtPO004 ing Indian varieties with varieties that are Heptadecane, iso: Sd CtPO004 more shatter-tolerant. Heptadecane, N: Sd CtPO004 PO004 TRADITIONAL MEDICINAL USES Hexacosane, N: Sd Ct Hexadecane, ante-iso: Sd CtPO004 India. Decoction of dried seeds is taken Hexadecane, iso: Sd CtPO004 orally for diarrheaPO030 and as a demul- Hexadecane, N: Sd CtPO004 centPO052. Seeds are taken externally as an Indicaine: SdPO073 emollient poultice, for constipations, and Leucine, nor, (DL): SdPO062 PO070 PO004 for gastric complaintsPO052. Linoleic acid: Sd oil 53.4% , Sd Ct PO004 Iran. Water extract of the dried seed is ad- Linolenic acid: Sd Ct Luteolin: LfPO102 ministered externally for its inflammatory Lysine, l: SdPO062 and emollient effects. Mixed with coconut Myristic acid: Sd CtPO004 juice, it is used as a diuretic. Dried seeds are Nonacosane, iso: Sd CtPO004 taken orally for diarrhea and indigestion as- Nonacosane, N: Sd CtPO004 PLANTAGO OVATA 421

Nonadecane, N: Sd CtPO004 prepared a laxative containing Plantago Octadecane, ante-iso: Sd CtPO004 ovata seeds twice daily (Plantaben) pre- Octadecane, iso: Sd CtPO004 PO004 scribed to her paralytic mother. Methacho- Octadecane, N: Sd Ct line inhalation test revealed mild bronchial Octadec-cis-12-enoic acid, 9-oxo: Sd oilPO049 hyperresponsiveness (PC = 1.5 mg/mL), Oleic acid: Sd oilPO070, Sd CtPO004 20 Palmitic acid: Sd CtPO004 which elicited an isolated early asthmatic Pentacosane, iso: Sd CtPO004 responsePO086. Two years after initiating regu- Pentacosane, N: Sd CtPO004 lar psyllium-containing laxative use, a 40- Plantago ovata mucilage: Sd huskPO060 year-old woman suffered with pruritic Plantagonine: SdPO073 macular, an urticarial rash involving the PO002 Planteose: Sd entire body including the palms, soles, and Ricinoleic acid, iso: Sd oilPO049 oropharynx sparing only the face. There was Sitosterol, E: SdPO073 Stearic acid: Sd CtPO004 an associated sensation of chest and throat Stigmasterol: SdPO073 tightness and lip swelling. The signs and Sucrose: SdPO073 symptoms resolved on discontinuation of Tetracosane, N: Sd CtPO004 the psyllium and occurred immediately af- Triacontane, N: Sd CtPO004 ter the patient initiated a challenge test. PO004 Tricosane, N: Sd Ct The total serum IgE was elevated, and the PO004 Tritriacontane, iso: Sd Ct modified radioallergosorbent test (RAST) Tritriacontane, N: Sd CtPO004 Tyrosine: SdPO062 for psyllium-specific IgE was positive (Plan- PO093 Valine, (DL): SdPO062 tago ovata antigen) . Anaphylactic response. Dried seeds, ad- PHARMACOLOGICAL ACTIVITIES ministered orally to female adults, produced AND CLINICAL TRIALS wheezing, throat and chest tightness, urti- Abortifacient effect. Dried seeds, adminis- caria, itching, nasal congestion, and vomit- tered intravaginally to pregnant women, ing after ingestion of the psylliumPO021. A were activePO063. The seedcoat, administered severe anaphylactic reaction was produced intrauterine to pregnant women at a dose of by the ingestion of psyllium, a major con- 350 g/person, was activePO059. stituent of several bulk laxatives. The hy- Absorption effect. Dried seed husks, ad- persensitivity was confirmed by skin testing ministered orally to adults at a dose of 3.5 g/ and RASTPO101. person, decreased the bioavailability of Anti-artherosclerotic effect. Husks, ad- carbamazepinePO044. ministered to African green monkeys at a Allergenic activity. Fiber of the dried seed, concentration of 10% of diet, were active. administered orally to female adults, was The monkeys were fed a high cholesterol active. Total serum immunoglobulin (Ig) E dietPO025. was elevated in a 40-year-old woman with Antibacterial activity. Water extract of the allergic cutaneous and respiratory symp- dried seed, on agar plate at concentration of toms associated with chronic psyllium 10 mg/mL, was inactive on Corynebacterium ingestionPO037. Dried seedcoat, administered diphtheriae, Diplococcus pneumoniae, Staphylo- orally to adults, was active. A 60-year-old coccus aureus, and Streptococcus viridans and female suffered an anaphylactic reaction produced weak activity on Streptococcus after ingestion of a psyllium-containing pyogenesPO057. cerealPO054. Skin prick result from psyllium Antidiabetic activity. Dietary psyllium fi- powder and specific IgE antibodies were ber, administered to patients with type 2 positive in a 31-year-old atopic woman who diabetes at three doses of 5 g each daily be- 422 MEDICINAL PLANTS OF THE WORLD fore meals, produced no significant changes adults with hypercholesterolemia at a dose in patient’s weight. Fasting plasma glucose, of 10.2 g/day, was activePO014. Husks, admin- total cholesterol, low-density lipoprotein istered to male rats at a dose of 10% of diet, (LDL) cholesterol, and triglyceride levels reduced total cholesterol and increased showed a reduction (p < 0.05), whereas HDL-cholesterol levels in animals fed a high-density lipoprotein (HDL) cholesterol high-cholesterol dietPO009. The husk, admin- increased significantly (p < 0.01) after the istered orally to 25 children of both sexes treatment. The 125 subjects were given a 6- with hypercholesterolemia at a dose of 58 g/ week period of diet counseling, followed by day for 6 weeks, was active on the blood. a 6-week of treatment periodPO079. Significant reduction in total and LDL cho- Antidiarrheal activity. Ethanol extract lesterol levels was noted during the treat- (50%) of the dried seed, administered to ment periodPO010. The seed, administered to guinea pigs and rabbits at a dose of 300 mg/ male rats at a dose of 10% of diet, reduced kg, was inactive on the ileum vs Escherichia total cholesterol and increased HDL choles- coli-enterotoxin-induced diarrheaPO030. The terol levels in animals fed a high-cholesterol fiber, administered intragastrically to 10 dietPO009. The seed, administered orally to 28 calves with diarrhea at a dose of 18.89 g/L, adults of both sexes with mild hypercholes- was equivocal, and breath hydrogen was de- terolemia at a dose of 8.06 g/day for 3 creasedPO034. Seedcoat, administered orally to months, was active. After the treatment, human adults at a dose of 30 g/day, was serum total cholesterol, LDL cholesterol, activePO028. and artherogenic index significantly de- Antigalactogogue effect. Dried kernel, ad- creased, but the level of HDL cholesterol, ministered to cows at a concentration of triglyceride, and urea nitrogen was not 50% of diet, was inactivePO066. affectedPO015. Husk, administered orally to Antihypercholesterolemic activity. Seeds, adults of both sexes at a dose of 3 g/day, was administered orally to 20 adults with mild active on the blood. A meta-analysis was hypercholesterolemia at a dose of 5.1 g/day done to determine the effect of consump- for 40 days, reduced LDL cholesterol by 8% tion of psyllium-enriched cereal products on and total cholesterol by 6%PO022. Dried seed blood total cholesterol, LDL and HDL cho- fiber, in the ration of Syrian hamster at a lesterol levels to estimate the magnitude of dose of 7.5% of diet, was activePO038. Dried the effect among 404 adults with mild to seed fiber, administered orally to adults at a moderate hypercholesterolemia who con- dose of 10.2 g/day, was activePO040. Dried seed sumed a low-fat diet. Female subjects were fiber, administered orally to 50 healthy chil- divided into two groups to provide a rough dren 2 to 11 years of age at a dose of 6.4 g/ estimate of the effect of menopausal status day for 12 weeks, was activePO042. The hydro- (premenopausal < 50 years, postmenopausal phobic colloid of the dried seed, adminis- > 50 years) on blood lipids. The meta-analy- tered in the ration of sea quails at a dose of sis indicated that subjects who consumed a 10% of diet, was active vs diet-inducing psyllium cereal had lower total cholesterol hypercholesterolemiaPO019. The seed hull, and LDL cholesterol concentrations (differ- administered in the ration of genetically ences of 0.31 mmol/L [5%] on 0.35 mmol/L diabetic mice at a dose of 2.5% of diet for 18 [9%], respectively) than subjects who in- weeks, was active. Total cholesterol was gested a control cereal. HDL cholesterol lower, and HDL-cholesterol higher in psyl- concentrations were unaffected. There was lium-fed than in placebo-fed animalsPO051. no effect of sex, age, or menopausal status The seed hull, administered orally to 286 on blood lipids. The results indicated that PLANTAGO OVATA 423

consuming a psyllium-enriched cereal as Antihypocholesterolemic activity. CHCl3/ part of a low-fat diet improves the blood MeOH (9:1) extract of the husks, adminis- lipid profile on hypercholesterolemic adults tered orally to nine patients with primary over that which can be achieved with a low- hypercholesterolemia at a dose of 10.2 g/ fat diet alonePO011. Seed oil, administered by day, produced a decrease in total cholesterol gastric intubation to cholesterol fed rabbits and LDL levelsPO026. Husks, administered in at a dose of 5 mL/animal, was activePO071. the ration of African green monkeys at a Seedcoat, administered orally to nine adults concentration of 10% of diet, were active. with hyperlipoproteinemia at a dose of 30 g/ Plasma cholesterol concentrations were re- day for 11 days, decreased serum and LDL duced by decreasing LDL synthesisPO020. cholesterol. The treatment increased HDL Monkeys fed the high-cholesterol diet cholesterol precursors and fecal elimination showed a 39% decrease in serum chol- of cholesterol and bile acidsPO050. esterolPO025. Dried husks fiber, administered Antihyperglycemic activity. The seed orally to adults of both sexes at doses of hull, administered to genetically diabetic 13.7% of diet, was activePO032. mice at a dose of 2.5% of diet for 18 weeks, Antileukemic activity. Aucubin, in com- produced higher levels of insulin than in the bination with caffeic acid, chlorogenic acid, control and placebo groupPO051. Psyllium de- ferulic acid, p-coumaric acid, and vanillic creased the amount of dialyzable glucose acid, exhibited weak antileukemic activity when added at a concentration of 20% to in (inhibitory concentration [IC]50 26–56 Pg/ vitro mix of bran cereal and human saliva. mL, international system of units 2–11) on Bran, administered orally to adults at a dose human leukemia and lymphoma cell lines. of 10% of diet, lowered the glycemic index Water-insoluble compounds, such as tri- of a bran cereal meal when taken just before terpenoids (oleanolic acid and ursolic acid), or concurrently with meal in both diabetic monotepene (linalool), and flavonoid and normal volunteersPO056. (luteolin) produced strong activityPO077. Antihyperlipemic activity. The seed hull, Anti-nematodal activity. Water extract of administered to genetically diabetic mice at the dried seed, at various concentrations, a dose of 2.5% of diet for 18 weeks, was was active on Meloidogyne incognitaPO064. inactivePO051. Husks and seeds, administered Anti-yeast activity. Ethanol (80%) extract in ration of male rats at a dose of 10%, were of the dried entire plant, on agar plate at a active on the liver and reduced the lipid lev- concentration of 1 mg/mL, was inactive on els in animals fed a high-cholesterol dietPO009. Candida albicansPO065. Seedcoat, administered orally to nine adults Appetite suppressant. Dried seeds powder, with hyperlipoproteinemia at a dose of 30 g/ administered orally to adults at a dose of 20 day for 11 days, decreased serum cholesterol, g/person 3 hours before feeding, produced a lowered LDL, and slightly increased HDL. significant increase in sense of fullness and Serum triglycerides were unchanged. Cho- a decrease in fat consumptionPO043. lesterol precursors and fecal elimination of Bile acid synthesis stimulation. Fiber, ad- cholesterol and bile acids were increasedPO050. ministered in ration of male rats at a dose of Antihypertriglyceridemic effect. Fiber of 5% of the diet, produced a higher total bile the fresh seed husks, administered orally to acid pool size compared to rats fed cellulose. adults of both sexes at a dose of 7 g/day, was It also lowered the hydrophobicity of the active. Triglyceride level continued to drop bile acid poolPO036. 90 days after treatment was discontinued. Bile secretion increase. Dried seeds, ad- Results were significant at p < 0.01 levelPO039. ministered orally to 20 male adults with 424 MEDICINAL PLANTS OF THE WORLD mild hypercholesterolemia at a dose of 5.1 reducing serum cholesterol, that this cho- g/day for 40 days, were activePO022. Fiber, ad- lesterol-lowering effect is not mediated by ministered in the ration of male rats at a increased fecal bile acid losses, and in- dose of 5% of diet, was activePO036. creased ileal losses of bile acids may be com- Carcinogenesis inhibition. Fiber, admin- pensated for by enhanced reabsorption into istered orally to male rats at a concentration the colonPO007. Fiber, administered to Syrian of 4%, was active. Wheat bran and psyllium hamsters at a dose of 7.5% of diet, was ac- (1:1), at a total level of 18% dietary fiber, tive. Major effect was exerted at the level of offered the highest protection against colon LDL-cholesterol production. Minor effect tumor developmentPO069. resulted from an increase in receptor-medi- Cervical dilator. Isaptent, prepared from ated LDL clearance by the tissuesPO038. Husk, granulated Plantago ovata seed husk, admin- administered orally to adults of both sexes istered as a cervical dilator to 804 women with hyperlipidemia at a dose of 11.9 g/day, between 15 and 45 years of age, achieved produced lowered total, LDL, and HDL satisfactory dilatation in 94% of the cases. cholesterolPO047. Short-term dietary fibers, The cervical dilatation bore no relation- Plantago ovata, and guar gum preparations ship to age, parity, and gestation period of decreased serum cholesterol, mainly LDL the subjects. There was no apparent dam- cholesterol, as compared to low-fiber or age to the cervix, and the vaginal flora re- nonviscous high-fiber periods, through en- mained unchanged in the randomly selected hancing cholesterol elimination as fecal bile subjectsPO059. acids. These changes were associated with Cholesterol absorption inhibition. Fiber, significant increases in serum levels of cho- administered in ration of male hamsters at a lesterol precursors, whereas that of concentration of 7.5% of diet, was inact- cholestanol was decreasedPO099. ivePO033. Seeds, administered orally to 20 Chronic constipation. Seeds, administered male adults with mild hypercholesterolemia orally to 149 patients, ages 18–81 years with at a dose of 5.1 g/day for 40 days, were chronic constipation at a dose of 15–30 g/ activePO022. day for at least 6 weeks, produced improve- Cholesterol level decrease. The husks and ment or symptom-free in 85% of the pa- seeds were administered orally to six normal tients. Eight percent of patients with slow adult males and five adult males with ileo- transit and 63% of patients with a disorder stomy and six normal adult males and four of defecation did not respond to dietary adult males with ileostomy, respectively, at fiberPO089. A double-blind study comprising a dose of 10 g/day for 3 weeks. The husk had 20 patients with chronic constipation, of no effect on cholesterol or triglyceride con- whom 10 had associated irritable bowel syn- centrations in either normal or ileostomy drome, was conducted. All of the patients subjects. Total and HDL cholesterol con- receiving Plantago had good results against centrations were reduced on average by 6.4 one in the placebo group. Frequency of and 9.3%, respectively, in normal group af- stools increased from 2.5 r 1 vs 8 r 2.2 stool ter seed supplementation. No effect on fe- per week, p < 0.001 for paired data. Fecal cal bile acid excretion in the normal weight increase and colonic transit time de- subjects was found after both regimens. Ileo- crease was observed in the treated groupPO096. stomy bile acids were increased (on average Cocarcinogenic activity. Seeds, adminis- 25%) after seed supplementation, whereas tered in ration of rats at a dose of 20%, pro- no effect on cholesterol concentrations was duced an increased incidence of colon found. These results suggest that psyllium tumors induced with 1, 2-dimethyl hydan- seed may be more effective than the husk in toin in male rats only. A mixture of pure PLANTAGO OVATA 425 compounds was used to obtain the reported lon. The treatment, in patients resected for effectPO067. Bran, administered to rats at a colorectal cancer, increased the intake of concentration of 4% of the diet, was active fiber by 17.9 r 0.8 g/day from basal levels of vs N-methynitroso-induced carcinogenesis 19.22 r 1.7 g/day. Fecal samples were ob- in the breast. Greatest effect was obtained tained on eight occasions, twice before with coadministration of wheat branPO013. treatment and thrice during and thrice after Colonic tumor. Seeds, administered in a treatment. One month of fiber therapy in- fiber supplemented diet at a concentration creased fecal concentration of butyrate by of 5% of the diet to rats with trinitrobenzen- 42 r 12% (from 13.2 r 1.2 to 19.3 r 3 esulfonic acid-induced colitis, indicated mmol/L), acetate by 25 r 6%, propionate that dietary fiber supplementation facili- by 28 r 9%, and total short chain fatty acids tated recovery from intestinal insult. This by 25 r 6%. Concentrations were increased was evidenced both histologically by a pres- during the 3-month fiber treatment but re- ervation of intestinal cytoarchitecture and versed to pretreatment levels within 1–2 biochemically by a significant reduction in months. After cessation of fiber supplemen- colonic meloperoxidase activity and by res- tation, the relative concentration (ratio) of toration of colonic glutathione levels. The butyrate was not altered owing to a simulta- intestinal content of fiber-fed colitic rats neous increase in acetate and propionate. showed significantly higher production of Fecal pH decreased initially but was normal- short-chain fatty acids, mainly butyrate and ized after 2 months of fiber supplements. propionatePO075. Seeds, administered to 20 Fiber therapy increased the 24-hour produc- patients resected for colorectal cancer at a tions of butyrate by 47 r 10% and acetate dose of 20 g/day for 3 months, increased fe- by 50 r 7% in 16.6% fecal homogenates cal concentrations of butyrate by 42 r 12% with added Plantago ovata seed. Short-chain from 13.2 r 1.2 to 19.3 r 3 mmol/L, acetate fatty acid productions returned to pretreat- by 25 r 6%, propionate by 28 r 9%, and ment levels after discontinuation of addi- total short-chain fatty acids by 25 r 6%. tional fiber intake. Oral intake of Plantago Concentrations were increased during the ovata seeds adapted the colonic flora to in- 3-month fiber treatment but reversed to pre- crease the production of butyrate and ac- treatment levels within 1 to 2 months after etate from this fiber and increased fecal cessation of fiber supplementation. The concentration of butyrate by 42% in relative concentration of butyrate was not patients resected for colonic cancer. The altered owing to a simultaneous increase in effects depended on continuity of the acetate and propionate. Fecal pH decreased treatmentPO008. Husk, administered orally to initially but was normalized after 2 months adults of both sexes at a dose of 7.4 g/day, of fiber supplements. Fiber therapy in- was active in a double-blind, randomized creased the 24-hour productions of butyrate crossover study with 14 healthy volunteers, by 47 r 10% (p < 0.0001) and acetate by 50 to evaluate the effect of psyllium on post- r 7% (p < 0.0001) in 16.6% fecal homo- prandial serum glucose, triglycerides and in- genates with added Plantago ovata seeds sulin levels, gastric fullness, hunger feeling, (20 mg/mL), but short-chain fatty acid pro- and food intake. Gastric emptying was mea- ductions returned to pretreatment levels af- sured using a standard double-radiolabeled ter discontinuation of additional fiber 450-kcal meal and feelings by visual ana- intakesPO083. logical scales. No delay in the gastric emp- Colorectal effects. Seed, administered tying of the solid and liquid phases of the orally to 20 patients of both sexes at a dose meal was observed. After the meal, hunger of 20 g/day for 3 months, was active on co- feelings and energy intake were significantly 426 MEDICINAL PLANTS OF THE WORLD lower during the psyllium session than dur- hour postmeal between Plantago and pla- ing the placebo session (13% and 17%, re- cebo and also Plantago and water. Total fat spectively, p < 0.05). Postprandial increase intake was significantly lower in grams per in serum glucose, triglycerides, and insulin day and as a percentage of energy on the day levels was less with psyllium than with pla- of the meal after Plantago compared with cebo (p < 0.05). Psyllium reduced hunger waterPO091. feelings and energy intake in normal volun- Esophageal obstruction. A case was re- teers at reasonable dose and without requir- ported of a 41-year-old woman with chest ing mixing with the meal. It does not act by pain and regurgitation after swallowing a slowing the gastric emptying of hydro- tablespoonful of Plantago ovata in granules. soluble nutrients but by increase in the time She kept the granules in her mouth for a few allowed for intestinal absorption, as sug- seconds before swallowing with 250 mL of gested by the flattening of the postprandial water. Flexible endoscopy revealed a con- serum glucose, insulin, and triglyceride sistent mass blocking the inferior esophagus. curvesPO016. Seeds and husks, administered to A mild hiatus hernia was subsequently dis- rats at doses of 100 to 200 g/kg, produced covered. Most of the cases that were re- elevated total acetate in the cecal content ported with this problem took the granules or feces, total fecal bile acid excretion was with insufficient liquidPO074. stimulated and E-glucuronidase (EC3.2.1.31) Ethinylestradiol pharmacokinetics. Seed, activity reduced. The seeds increased fecal at a concentration of 65% of the diet and fresh weight to 100%, fecal dry weight to seed cuticle at a concentration of 2.2%, ad- 50%, and fecal water content to 50%. The ministered orally at the same time with husks, at the high concentration only, had ethinylestradiol to rabbits, decreased be- such effect. Fecal bacterial mass as estimated tween 29% and 35% the extent of ethi- from the 2,6-diaminoplimelic acid output nylestradiol absorbed (represented by the was increased to the greatest extent by the pharmacokinetic parameters area under the seed-containing diet and by the high con- curve and the maximum plasma concen- centration of the husks. Length and weight tration) without affecting the rate of the of the small intestine were not greatly af- absorption process (represented by the fected by the seeds, but both variables in- time to reach maximum concentration and creased significantly in the large intestine. the absorption rate constant)PO088. Mucosal digestive enzyme activities were Food consumption reduction. Seed hull, inhibited to different degrees by both fibers administered to mice at a concentration of in the jejunum and occasionally activated 52.5% of diet, was inactive. No differences in the ileumPO097. in psyllium-fed and placebo-fed groups Digestibility. The effect of Plantago ovata and for normal and diabetic rats were seed containing supplement (Plantaginis detectedPO051. ovatae semen and testa) on appetite vari- Gallbladder effect. Seeds, administered ables and nutrient and energy intake in 17 orally to 20 adult males with mild hyperc- subjects was investigated. There were three holesterolemia at a dose of 5.1 g/day for 40 study periods of 3 days each in which the sub- days, reduced postprandial residual volume jects were given Plantago (20 g granules with and increased volume of bile emptiedPO022. 200 mL water), placebo (20 g granules with Gallstone prevention. Psyllium was inves- 200 mL water) or water 3 hours premeal and tigated in a double-blind clinical trial to the same dose immediately premeal. There compare the effect of rational diet plus was a significant difference in fullness at 1 ursodeoxycholic acid vs a rational diet PLANTAGO OVATA 427 supplemented with psyllium in obese sub- short-chain fatty acid as propionic acid in- jects undergoing a weight-reduction diet. creased and fecal pH was reduced. Values Patients with body mass index of 30 kg/m2 from pooled fecal samples indicated that or more and with normal gallbladder and approx 50% of the ingested ispaghula was biliary tree ultrasound were included. excreted by the 50-g ispaghula/kg diet Weight-reduction diet was individually cal- groupPO095. culated for each patient, according to his Gastric emptying time. Dried husk of the energy expenditure. Patients were randomly seed, administered orally to 12 healthy assigned to group I (diet with 750 mg adults at a dose of 10 g/person, delayed gas- ursodeoxycholic acid and fiber placebo) or tric emptying from the third hour after a group II (diet with 15 g of psyllium and meal. It increased satiety and decreased ursodeoxycholic acid placebo) for 2 months. hunger 6 hours after a mealPO024. Weight reduction was similar in both Gastrointestinal enzymes effect. Seed groups, gallstone disease was observed in and husk, incubated in vitro with gas- one patient of group I (5.5%) and two pa- trointestinal enzymes in buffer solutions at tients of group II (p > 0.05). All of the pa- concentrations of 1–5% for 10–30 min at tients with gallstone disease lost a minimum 37qC, had no effect on pepsin, trypsin, and of 4 kg during the study periodPO081. D-amylase, only stimulating effect on chy- Gastric digestibility. Ispaghula, mucilage motrypsin, lipase, and lactasePO098. from Plantago, administered orally to seven Glucose tolerance test. Psyllium mucilage, healthy subjects at a dose of 18 g/day for two administered to eight healthy volunteers at 15-day periods, indicated that whole gut doses of 10, 20, and 30 g of mucilage in 75 g transit time and gas excretion in breath and of glucose, produced a significant relation- flatus were not different during periods of ship between dose of psyllium mucilage and ispaghula and placebo ingestion. Fecal wet its attenuating effect of hyperglycemia. Se- and dry weights increased significantly dur- rum glucose levels were measured at 0, 30, ing ispaghula ingestion. Fecal short-chain 60, 120, and 180 minutes. Maximum peak fatty acid concentrations and the molar pro- of glucose at 30 minutes and the area under portions of propionic and acetic acids also a curve of glucose were significantly lower increased. Most of the ispaghula had in the test with 20 and 30 g of mucilage than reached the cecum 4 hours after ingestion the test with 0 and 10 gPO084. in an intact highly polymerized form. Dur- Glycemic index. Psyllium, administered to ing ispaghula ingestion, the increase in the 12 patients with noninsulin-dependent dia- fecal output of neutral sugars was accounted betes mellitus and 10 healthy volunteers, for by the fecal excretion of arabinose and reduced the glycemic index of carbohydrate xylose in an intact highly polymerized food. Each subject was evaluated after three formPO092. Ispaghula, administered at doses of meal tests with an intake of 90 g of white 5, 15, or 50 g/kg to rats on a basal diet of 45 bread (50 g of carbohydrates). In one test, g nonstarch polysaccharides/kg for 28 days, the subjects were also given 15 g of psyllium increased stool dry weight and apparent wet mucilage and in another 200 mg of acarbose. weight. Fecal water-holding capacity Only bread was ingested in the control (amount of water held per gram dry fecal group. Serum glucose and insulin concen- material at 0.2 mPa) was unchanged. Fecal trations were measured every 30 minutes short-chain fatty acids concentration did from 0–180 minutes. In the noninsulin-de- not change, but short-chain fatty acid out- pendent diabetes mellitus patients, area-un- put increased. The molar proportion of der-the-curve (AUC)-glucose in the test 428 MEDICINAL PLANTS OF THE WORLD with acarbose (1.9 r 0.7 mmol/L) and with glutinating antibody titer in primary re- psyllium (4.3 r 1.2 mmol/L) was signifi- sponse. Intraperitoneal injection of 0.25 g/ cantly lower than in the control test (7.4 r kg of the extract to mice prior to immuniza- 1.5 mmol/L). The glycemic index of bread tion with sheep red blood cells resulted in a plus acarbose was 26 r 13 and of bread plus significant decrease in hemagglutinating psyllium 59 r 10. AUC-insulin and insulin antibody titre. Oral and intraperitoneal ad- index behaved similarly. In healthy indi- ministration of 0.25 and 0.5 g/kg resulted in viduals, AUC-glucose and glycemic index an increase in white blood cells and spleen did not significantly change with the treat- leukocyte counts. The spleen weight also ments; however, insulinic index with increased with intraperitoneal injection acarbose was 17 r 16 and with psyllium was (0.25 and 0.5 g/kg) and oral administration 68 r 15PO080. of 0.5 g/kg of Plantago ovata. Results suggest Hepatic encephalopathy. Psyllium, ad- that Plantago ovata can suppress the humoral ministered to eight patients with diabetes immune responses, especially in primary with chronic portal systemic encephalopa- immune responsePO078. thy, produced a significant increase in the Hypercholesterolemic activity. Fiber of number of bowel movements. In this cross- the fresh seed husks, administered orally over study, for one group, a meat protein adults of both sexes at a dose of 7 g/day, was diet was consumed and neomycin plus laxa- active. Results were significant at p < 0.05 tives was given. The other group received levelPO039. Psyllium, administered orally to 14 vegetable protein supplemented with psyl- subjects with polygenic hypercholester- lium fiber to reach 35 g of fiber per day. At olemia at a dose of 3.4 g three times daily the end of the experimental period, fasting before meals, produced a reduction of 8% in glucose levels were 204 r 86 mg% in the total cholesterol and 11% in LDL choles- meat protein diet group and 127 r 8 mg% terol. The subjects with secondary in the vegetable protein diet group. In all dyslipidemias were excluded from this study. cases, fasting glucose levels decreased at the The subjects were given an isocaloric diet, end of the vegetable diet period, regardless with less than 10% of the calories provided of the previous treatment. An improvement as saturated fats, polyunsaturated:saturated of greater than or equal to 25 mg% of fast- relation greater than 1 and daily intake of ing glucose levels was observed in seven of less than 300 mg of cholesterol. The study the eight patients after the vegetable pro- was divided in two stages: The first, from tein diet and in no case after the meat pro- week –6 to 0, evaluated exclusively the re- tein diet (p < 0.0078). The parameters of sponse to diet, and the second, from week 0 encephalography were comparable at the to 12, evaluated the response to psyllium. end of both of meat protein diet and the No significant changes in triglycerides and vegetable protein dietPO105. HDL cholesterol were observedPO104. 3-Hydroxy-3-methylglutaryl coenzyme Hypocholesterolemic activity. Fiber, ad- A reductase inhibition. Husks, admin- ministered orally to males with hyperlipi- istered to African green monkeys at a con- demia, produced a 5.7% decrease in LDL centration of 10% of diet, were active. The cholesterol level. Fiber, administered orally monkeys were fed a high cholesterol to healthy adults of both sexes at a dose of dietPO025. 15 g/person, was inactivePO027. Husks, admin- Water extract of the plant, administered istered in ration of adults at a dose of 114 g/ orally to rabbits at a dose of 0.5 g/kg, pro- day for 6 weeks, decreased the total choles- duced a significant decrease in anti-hemag- terol and LDL cholesterol levelsPO018. Fiber, PLANTAGO OVATA 429 administered in ration of male hamsters at a decreased the number of bleeding episodes. dose 7.5% of diet, enhanced the loss of ste- During the 15 days of treatment, the aver- rol by the liverPO033. Fiber, administered age number of bleeding episodes was 4.8 r orally to human adults at a dose of 20 g/per- 3.8 vs 6.4 r 3 for the control group. During son, increased fecal fat loss and decreased the following 15 days, it decreased to 3.1 r fat digestibility coefficient in healthy 2.7 vs 5.5 r 3.2 (p < 0.05) in the control volunteersPO035. Seed hull, administered to group, and in the last 10 days of treatment a mice at a dose of 2.5% of diet, was inactive. further reduction to 1.1 r 1.4 was found vs Aside from a transient decrease at 4 and 10 5.5 r 2.9 (p < 0.01). The number of con- weeks of an 18-week feeding period, total gested hemorrhoid cushions diminished cholesterol was similar in psyllium-fed and from 2.6 r 1 to 1.6 r 2.2 after fiber treat- placebo-fed animals. HDL level was similar ment (p < 0.01), and no differences were in the two groupsPO051. Fiber of the fresh seed found in the control group. In the fiber husks, administered orally to adults of both group, hemorrhoids bled on contact in 5 out sexes at a dose of 7 g/day, produced a drop in of 22 patients before treatment and in none LDL and total cholesterol levels. The levels after treatment, no differences were found continued to decrease 90 days after treat- in the control groupPO082. ment stoppedPO039. Seed oil, administered Laxative effect. Seed hull, taken orally by orally to rabbits at a dose of 5 mL/animal, adults at a dose of 7 g/person, increased was activePO001. Administration by gastric weekly fecal mass without influencing tran- intubation was inactivePO071. sit time or frequencyPO023. Seedcoat, admin- Hypoglycemic activity. Seed administered istered orally to 80 patients at a dose of 6.4 orally to 18 patients with noninsulin-depen- g/person three times daily, was active in a dent diabetes at a dose of 13.6 g/day in two blinded placebo controlled study of efficacy equal doses lowered glucose level by 14 % of extract in treatment of irritable bowel after breakfast and 20% after dinnerPO055. syndromePO048. Water extract of the dried Seed hull, administered to mice at a dose of kernel, administered orally to 40-year-old 2.5% of the diet for 18 weeks, produced a adults of both sexes, was activePO058. Seed transient decrease in 10 weeks in psyllium- powder, administered orally to adults of fed animals relative to placebo-fed ani- both sexes, was active. Biological activity malsPO051. reported has been patentedPO006. Dried seeds, Hypolipidemic activity. Seed hull, admin- administered orally to adults at a dose of 0.5 istered to mice at a dose of 2.5% of diet for g/person, were active. Placing the seeds in 18 weeks, was inactivePO051. The husk, ad- water increased their volume, 90% alcohol ministered orally to male Hartley guinea produced a decrease in volume to normal pigs at doses of 7.5 or 10 g/100 g of Plantago seed size, and linseed oil had no effect on ovata for 4 weeks, exerted a hypolipidemic volume. The seed mucilage remained in gel effect by affecting bile acid absorption and form and is considered preferable to the altering hepatic cholesterol metabolismPO076. solid form because it is more easily Insulin release inhibition. Seed adminis- digestedPO072. Dried seed powder, adminis- tered orally to 18 patients with noninsulin- tered orally to 35 patients with chronic dependent diabetes at a dose of 13.6 g/day constipation at a dose of 50 mg/person, lowered insulin levels by 17%PO055. was active in a controlled, double-blind Internal bleeding hemorrhoids. Fiber, ad- studyPO012. Fiber, administered orally to ministered orally to 50 patients with bleed- adults, was active. Psyllium fiber and ing internal hemorrhoids for 15 days, sennosides were prepared into a wafer to be 430 MEDICINAL PLANTS OF THE WORLD used as a laxative. Biological activity re- Toxic effect. Dried kernel of the seed, ad- ported has been patentedPO029. Mixture of the ministered to cows at a dose of 50% of diet, Plantago ovata and Cassia senna fibers, taken was inactivePO066. orally by adults at a dose of 10 mL/person, Ulcerative colitis. Plantago ovata seeds, ad- were active for constipationPO031. Fiber, ad- ministered orally to 105 patients with ulcer- ministered orally to adults of both sexes at a ative colitis in remission at a dose of 10 g dose of 30 g, was inactive vs loperamide-in- twice daily, produced a 40% (14 of 35 pa- duced constipation on healthy volunteers. tients) failure rate after 12 months. The pa- No effect on colon transit was seen. There tients were randomized into groups that also was an increase in stool weightPO041. received mesalamine (500 mg twice daily) Lipid metabolism effect. Fiber of the fresh and Plantago ovata seeds plus mesalamine at seed husk, administered orally to adults of the same dose. The primary efficacy was both sexes at a dose of 7 g/day, was active. maintenance of remission for 12 months. Of LDL/HDL ratio dropped during treatment the 105 patients, 102 were included in the and for 90 days thereafter. Results were sig- final analysis. After the 12-month treat- nificant at p < 0.05 levelPO039. ment period, the failure rate was 35% (13 of 37) in the mesalamine group and 30% (9 of Sterol metabolism. Psyllium husk, admin- istered orally to six normal subjects and five 30) in the Plantago ovata plus mesalamine group. Probability of continued remission subjects with ileostomy at a dose of 10 g/day was similar (Mantel-Cox test, p = 0.67; in- for 3 weeks and psyllium seeds administered tent-to-treat analysis). A significant in- to six normal subjects and four subjects with crease in fecal butyrate levels (p = 0.018) ileostomy at a dose of 10 g/day, indicated was observed after Plantago ovata seed that psyllium seed might be more effective administrationPO087. than the husk in reducing serum choles- Weight increase. Seed hull, administered terol. The cholesterol-lowering effect is not in ration of mice at a concentration of 2.5% mediated by increased fecal bile acid losses, of diet for 18 weeks, was active. No differ- and increased ileal losses of bile acids might ences in psyllium-fed and placebo-fed be compensated for by enhanced reabsorp- groups in both diabetic and normal animals tion in the colon. The husk had no effect were foundPO051. on cholesterol or triglyceride concentra- Weight loss. Mucilage, administered orally tions in either normal or ileostomy subjects. to human adults at a dose of 3 g/person, was Total and HDL cholesterol concentrations active. Twenty-eight obese women were di- were reduced on average by 6.4 and 9.3%, vided into two groups and given mucilage respectively, in the normal group after seed twice daily in conjunction with an 800- supplementation. No effect on fecal bile calorie hypoglucidic diet, or diet only, in a acid excretion in the normal subjects was crossover design. Weight loss was similar for found after both regimes. Ileostomy bile ac- both groups in the first period. In the sec- ids were increased (on average 25%) after ond period, the group given mucilage lost seed supplementation, whereas no effect on more weight than the diet-only group, indi- cholesterol concentrations was foundPO090. cating that the weight-reducing effect of Taurocholic acid adsorption. Husk and mucilage only becomes important as com- seed, inoculated with human fecal culture pliance with the diet decreases owing to and incubated with taurocholic acid, pro- timePO053. duced 53% incorporation if taurocholic acid Wound healing. Husk mucopolysaccha- for the husk and 59% for the seedPO090. rides, administered as a sachet (Askina Cav- PLANTAGO OVATA 431 ity) or in a hydrocolloid mixture (Askina acids of Plantago ovata seeds. Phy- Hydro), produced a gradual and sustained tochemistry 1969; 8(10): 2077–2081. absorbency over 7-day period, amounting to PO005 Zagari, A. Medicinal plants. Vol. 4, 5th ed, Tehran University Publica- four to six times their weight in water. Ad- tions, No 1810/4, Tehran, Iran, 1992; herence of wound bacteria to the muco- 4: 969. polysaccharides started after 2 hours and was PO006 Sander, E. H. Psylium-hydrocolloid more pronounced after 3 hours. Semi-quan- gum compositions and fiber supple- titative measurements of bacterial adher- ments. Paten-Can Pat Appl-2,100,295 ence used centrifugation and subsequent 1994; 17 p. PO007 Gelissen, C., B. Brodie, and M. A. optical density determinations of superna- Eastwood. Effect of Plantago ovata tant. These confirmed the strong adherence (psyllium) husk and seeds on sterol potential of psyllium particles. Lactic acid metabolism: studies in normal and dehydrogenase staining of pretreated cul- ileostomy subjects, Amer J Clin Nutr tured human skin explants did not reveal 1994; 59(2): 395–400. PO008 Nordgaard, I., H. Hove, M. R. Clausen, toxicity of the mucopolysaccharides derived and P. B. Mortensen. Colonic produc- from psyllium husk. Langerhans’ cell migra- tion of butyrate in patients with previ- tion from the epidermis was negligible, and ous colonic cancer during long-term interleukin-1 E expression in the explants treatment with dietary fiber (Plantago was not significant, supporting the low al- ovata seeds). Scand J Gastroenterol lergenic potential of psyllium. The charac- 1996; 31(10): 1011–1020. PO009 Kritschevsky, D., S. A. Tepper, and D. teristics of mucopolysaccharides granulate M. Klurfeld. Influence of psyllium derived from husk in Askina Cavity (sa- preparations on plasma and liver lipids chet) and Askina Hydro (hydrocolloid mix- of cholesterol-fed plants. Artery 1995; ture) related to fluid absorption, bacterial 21(6): 303–311. adherence, biocompatibility, stimulation of PO010 Davidson, M. H., L. D. Dugan, J. H. macrophages, irritancy response, and Burns, D. Sugimoto, K. Story, and K. Drennan. A psyllium-enriched cereal allergenicity showed an optimal profile, sup- for treatment of hypercholesterolemia porting the good clinical performancePO085. in children: a controlled, double blind, crossover study. Amer J Clin Nutr REFERENCES 1996; 63(1): 96–102. PO001 Siddiqui, H. H., K. K. Kapur, and C. K. PO011 Olson, B. H., S. M. Anderson, M. P. Atal. Indian seeds oils. Effect of Plan- Becker, et al. 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PO014 Davidson, M. H., K. C. Maki, J. C. function caused by feeding ispaghula Kong, et al. Long-term effects of con- husk and polydextrose. Aliment suming food containing psyllium seed Pharmacol Ther 1988; 2(6): 513–519. husk on serum lipids in subjects with PO024 Bergmann, J. F., O. Chassany, A. Petit, hypercholesterolemia. Amer J Clin R. Triki, C. Caulin, and J. M. Segre- Nutr 1998; 67(3): 367–376. staa. Correlation between echographic PO015 Segawa, K., T. Kataoka, and Y. Fukuo. gastric emptying and appetite: Influ- Cholesterol-lowering effects of psyl- ence of psyllium. Gut 1992; 33(8): lium seed associated with urea metabo- 1042–1043. lism. Biol Pharm Bull 1998; 21(2): PO025 Mc Call, M. R., T. Mehta, C. W. Leath- 184–187. ers, and D. M. Foster. Psyllium husk I. PO016 Riguad, D., F. Paycha, A. Muelemans, Effect on plasma lipoprotein, choles- M. Merrouche, and M. Mignon. Effect terol metabolism, and artherosclerosis of psyllium on gastric emptying, hun- in African green monkeys. Amer J ger feeling, and food intake in nor- Clin Nutr 1992; 56(2): 376–384. mal volunteers: a double-blind study. PO026 Smith, M. A., and A. A. Aso. Com- European J Clin Nutr 1998; 52(4): parison of psyllium hydrophilic 239–245. mucilloid and bile salt binding resin PO017 Arlian, L. G., D. L. Vyszenski-Noher, therapy for hypercholesterolemia. A. T. Lawrence, K. R. Schrotel, and H. Abstr Endocrine Society 144th Annual L. Ritz. Antigenic and allergenic an- Meeting June 1992; 62. alysis of psyllium seed components. J PO027 Hopewell, R., R. Yeater, and I. Ullrich. Allergy Clin Immunol 1992; 89(4): Soluble fiber: Effect on carbohydrate 866–876. and lipid metabolism. Progress Food PO018 Anderson J. W., S. Riddell-Mason, N. Nutr Sci 1993; 17(2): 159–182. J. Gustafson, S. F. Smith, and M. PO028 Eherer, A. J., A. Santa, A. Carol, J. Mackey. Cholesterol-lowering effects of Porter, and J. S. Fordtran. Effect of psyllium-enriched cereal as an adjunct psyllium, calcium polycarbophil, and to a prudent diet in the treatment of wheat bran on secretory diarrhea in- mild to moderate hypercholesterolemia. duced by phenolphthalein. Gastroen- Amer J Clin Nutr 1992; 56(1): 93–98. terology 1993; 104(4): 1007–1012. PO019 Day, C. E. Activity of psyllium hydro- PO029 Colliopoulos, J. Psyllium-based laxa- philic colloid for reducing serum chol- tive compositions. Patent-US-5,232, esterol in sea quail fed diet supplemented 699 1993; 6 p. with cholesterol. Artery 1991; 18(3): PO030 Gupta, S., J. N. S. Yadava, and J. S. 163–167. Tandon. Antisecretory (antidiarrheal) PO020 Mc Call, M. R., T. Mehta, C. W. activity of Indian medicinal plants Leathers, and D. M. Foster. Psyllium against Escherichia coli enterotoxin-in- husk II. Effect on the metabolism of duced secretion in rabbit and Guinea apoliprotein B in African green mon- pig ileal loop models. Int J Pharmacog keys. Amer J Clin Nutr 1992; 56(2): 1993; 31(3): 198–204. 385–393. PO031 Passmore, A. P., K. Wilson-Davies, C. PO021 James, J. M., S. K. Cooke, A. Barnett, Stoker, and M. E. Scott. Chronic con- and H. A. Sampson. Anaphylactic re- stipation in long stay elderly patients: actions to a psyllium-containing ce- a comparison of lactulose and a senna- real. J Allergy Clin Immunol 1991; fiber combination. Brit Med J 1993; 88(3): 402–408. 307(6907): 769–771. PO022 Everson, G. T., B. P. Daggy, C. Mc PO032 Wolever, T., D. Jenkins, S. Mueller, et Kinley, and J. A. Story. Effect of psyl- al. Method of administration influ- lium hydrophilic mucilloid on LDL- ences the serum cholesterol lowering cholesterol and bile acid synthesis in effect of psyllium. Amer J Clin Nutr hypercholesterolemic men. J Lipid Res 1994; 59(5): 1055–1059. 1992; 33(8): 1183–1192. PO033 Turley, S.D., B. P. Daggy, and J. M. PO023 Tomlin, J., and N. W. Read. A com- Dietschy. Psyllium augments the cho- parative study of the effects on colon lesterol-lowering action of cholestyr- PLANTAGO OVATA 433

amine in hamsters by enhancing sterol PO045 Martinez-Lirola, M. J., M. R. Gonzalez- loss from the liver. Gastroenterology Tejero, and J. Molero-Mesa. Ethnobo- 1994; 107(2): 444–452. tanical resources in the province of PO034 Naylor, J. M. and T. Lieber. Effect of Almeria, Spain: Campos de Nijar. psyllium on plasma concentration of Econ Bot 1996; 50(1): 40–56. glucose, breath hydrogen concentra- PO046 Arjmandi, B. H., E. Sohn, S. Juma, S. tion, and fecal composition in calves R. Murthy, and B. P. Daggy. Native with diarrhea treated orally with elec- and partially hydrolyzed psyllium has trolyte solutions. Amer J Vet Res comparable effects on cholesterol me- 1995; 56(1): 56–59. tabolism in rats. J Nutr 1997; 127(3): PO035 Ganji, V. and C. V. Kies. Psyllium 463–469. husk fiber supplementation to soybean PO047 Jenkins, D., T. Wolever, E. Vidgen, et and coconut oil diets of humans: effect al. Effect of psyllium in hypercholester- on rat digestibility and fecal fatty acid olemia at two monounsaturated fatty excretion. Eur J Clin Nutr 1994; acid intakes. Amer J Clin Nutr 1997; 48(8): 595–597. 65(5): 1524–1533. PO036 Matheson, H. B. and J. A. Story. Di- PO048 Prior, A., and P. J. Whorwell. Double etary psylium hydrocolloid and pectin blind study of Ispaghula in irritable increase bile acid pool size and change bowel syndrome. Gut 1987; 28: 1510– bile acid composition in rats. J Nutr 1513. 1994; 124(8): 1161–1165. PO049 Jamal, S., I. Ahmad, R. Agarwal, M. PO037 Freeman, G. L. Psyllium hypersensitiv- Ahamad, and S. M. Osman. A novel ity. Ann Allergy 1994; 73(6): 490–492. oxo fatty acid in Plantago ovata seed oil. PO038 Turley, S. D., and J. M. Dietschy. Phytochemistry 1987; 26(11): 3067– Mechanisms of LDL-cholesterol lower- 3069. ing action of psyllium hydrophilic PO050 Miettinen, T. A., and S. Tarpila. Se- mucilloid in the hamster. Biochim rum lipids and cholesterol metabolism Biophys Acta 1995; 1255(2): 177–184. during guar gum, Plantago ovata and PO039 Gupta, B. R., C. G. Agrawal, G. P. high fiber treatments. Clinica Chim Singh, and A. Ghatak. Lipid-lowering Acta 1989; 183: 253–262. efficacy of psyllium hydrophilic mucil- PO051 Watters, K., and P. Blaisdell. Reduc- loid in non insulin dependent diabetes tion of glycemic and lipid levels in DB/ mellitus with hyperlipidaemia. Indian DB diabetic mice by psyllium plant J Med Res 1994; 100(5): 237–241. fiber. Diabetes 1989; 38(12): 1528– PO040 Chan, E. K., and D J. Schroeder. Psyl- 1533. lium in hypercholesterolemia. Ann PO052 Shah, G. L. and G. V. Gopal. Ethno- Pharmacother 1995; 29(6): 625–627. medical notes from the tribal inhabit- PO041 Ewe, K., B. Uberschaer, and A. G. ants of the north Gujarat (India). J Press. Influence of senna, fiber, and Econ Taxon Botany 1985; 6(1): 193–201. fiber+senna on colonic transit in PO053 Enzi, G., E. M. Inelmen, and G. lopermaide-induced constipation. Crepaldi. Effect of a hydrophilic muci- Pharmacology 1993; 47(1): 242–248. lage in the treatment of obese patients. PO042 Williams, C. L., M. Bollella, A. Spark, Pharmacotherapeutica 1980; 2(7): and D. Puder. Soluble fiber enhances 421–428. the hypercholesterolemic effect of the PO054 Lantner, R. R., B. R. Espiritu, P. step I diet in childhood. J Amer Coll Zumerchik, and M. C. Tobin. Anaphy- Nutr 1995; 14(3): 251–257. laxis following ingestion of a psyllium- PO043 Turnbull, W. H., and H. G. Thomas. containing cereal. JAMA 1990; 264(19): The effect of a Plantago ovata seed con- 2534–2536. taining preparation of appetite vari- PO055 Pastors, J. G., P. W. Blaisdell, T. K. ables, nutrient, and energy intake. Int Balm, C. M. Asplin, and S. L. Pohl. J Obesity 1995; 19(5): 338–342. Psyllium fiber reduces rise in postpran- PO044 Etman, M. A. Effect of a bulk forming dial glucose and insulin concentrations laxative on the bioavailability of car- in patients with non-insulin–depen- bamazepine in man. Drug Dev Ind dent diabetes. Amer J Clin Nutr 1991; Pharm 1995; 21(16): 1901–190. 53(6): 1431–1435. 434 MEDICINAL PLANTS OF THE WORLD

PO056 Wolever, T. M. S., V. Vuksan, H. the concentrate mixture of milk cows. Eshuis, et al. Effect of method of ad- Gujarat Agr Univ Res 1983; 9(1): ministration of psyllium on glycemic 33–36. response and carbohydrate digestibil- PO067 Toth, B. Effect of Metamucil on tumor ity. J Amer Coll Nutr 1991; 10(4): formation by 1,2-dimethylhydrazine 364–371. dihydrochloride in mice. Food Chem PO057 Naovi, S. A. H., M. S. Y. Khan, and S. Toxicol 1984; 22(7): 573–578. B. Vohora. Anti-bacterial, anti-fungal PO068 Dooley, D. P., M. Rhodes, and D. and anthelmintic investigations on In- Drehner. Psyllium worm. Amer J dian medicinal plants. Fitoterapia Gastroenterol 1993; 88(1): 153–154. 1991; 62(3): 221–228. PO069 Alabaster, O., Z. C. Tang, A. Frost, PO058 Ricci, P. D., and R. Angeli. Plantago and N. Shivapurkar. Potential syner- ovata and defecation disorders in the gism between wheat bran and psyllium: aged. Effects of the administration of enhanced inhibition of colon cancer. powdered Plantago ovata on defecation Cancer Lett 1993; 75(1): 53–58. disorders in the aged. Clin Ter 1978; PO070 Atal, C. K., K. K. Kapoor, and H. H. 86: 434–439. Siddiqui. Studies on Indian seed oils. PO059 Khanna, N. M., J. P. S. Sarin, R. C. Part I. Preliminary screening of li- Nandi, et al. Isaptent—a new cervical noleic acid rich oils. Indian J Phar- dilator. Contraception 1980; 21: 29–40. macy 1964; 26; 163–164. PO060 Sandhu, J. S., G. J. Hudson, and J. F. PO071 Siddiqui, H. H., K. K. Kapoor, and C. Kennedy. The gel nature and structure K. Atal. Studies on Indian seed oils. of the carbohydrate of Ispaghula husk. Part II. Effect of Plantago ovata embryo Carbohydr Res 1981; 93: 247–259. oil on raised serum cholesterol levels PO061 Jewvachdamrongkul, Y., T. Decha- in rabbits. Indian J Pharmacy 1964; tiwongtse, D. Pecharaply, J. Bansiddhi, 26: 1663–1664. and P. Kanchanapee. Identification PO072 Wasicky, B. Investigations of the seeds of some Thai medicinal plants. Ma- of Plantago ovata, P. psyllium, and P. hidol Univ J Pharm Sci 1982; 9(3): major variety cruenta as laxatives. 65–73. Planta Med 1961; 9: 232–244. PO062 Patel, R. B., C. G. Rana, M. R. Patel, PO073 Balbaa, S. I., M. S. Karawaya, and M. H. K. Dhyani, and H. V. Chauhan. S. Afifi. Pharmacognostical study of Chromatographic screening of proteins the seeds of certain Plantago species of seeds of Plantago ovata Forsk. Indian growing in Egypt. UAR J Pharm Sci Drugs Pharm Ind 1981; 16: 3–5. 1971; 12(1): 35–52. PO063 Roy, P. Mid trimester abortion by slow PO074 Salguero Molpeceres O., M. C. Seijas dilatation with Isapgol tents (Dilexc). Ruiz-Coello, J. Hernandez-Nunez, D. Patna J Med 1982; 56(5): 95–97. Caballos Villar, L. Diaz Picazo, and L. PO064 Vijayalakshimi, K., S. D. Mishra, and Ayerbe Garcia-Monzon. Esophageal S. K. Prasad. Nematocidal properties obstruction caused by dietary fiber of some indigenous plant materials from Plantago ovata, a complication against second stage juveniles of Mel- preventable by adequate information. oidogyne incognita (koffoid and white) Gastroenterologia y Hepatologia chitwood. Indian J Entomol 1979; 2003; 26(4): 248–250. 41(4): 326–331. PO075 Rodriguez-Cabezaz, M. E., J. Galvez, PO065 Al–Shamma, A., and L. A. Mitscher. M. D. Lorente, et al. Dietary fiber Comprehensive survey of indigenous down-regulates colonic tumor necrosis Iraqi plants for potential economic factor alpha and nitric oxide produc- value. I. Screening results of 327 spe- tion in trinitrobenzenesulfonic acid– cies for alkaloids and antimicrobial induced colitis rats. J Nutr 2002; agents. J Nat Prod 1979; 42: 633–642. 132(11): 3263–3271. PO066 Shukla, P. C., M. C. Desai, L. P. PO076 Romero, A. L., K. L. West, T. Zern, Purohit, and H. B. Desai. Use of and M. L. Fernandez. The seeds from Isabgul (Plantago ovata Forsk.) gola in Plantago ovata lower plasma lipids by PLANTAGO OVATA 435

altering hepatic ad bile acid metabo- Drugs Under Exp Clin Res 2001; lism in guinea pigs. J Nutr 2002; 27(5–6): 165–175. 132(6): 1194–1198. PO086 Aleman, A. M., S. Quirce, C. Bombin, PO077 Chiang, L. C., W. Chiang, M. Y. and J. Sastre. Asthma related to inha- Chiang, L. T. Ng, and C. C. Lin. Anti- lation of Plantago ovata. Med Clin leukemic activity of selected natural 2001; 116(1): 20–22. products in Taiwan. Amer J Chin Med PO087 Fernandez-Banares, F., J. Hinojosa, J. 2003; 31(1): 37–46. L. Sanchez-Lombrana, et al. Random- PO078 Rezaeipoor, R., S. Saednia, and M. ized clinical trial of Plantago ovata seeds Kamalinejad. The effect of Plantago (dietary fiber) as compared with ovata on humoral immune responses in mesalamine in maintaining remission experimental animals. J Ethnopharma- in ulcerative colitis. Spanish Group for col 2000; 72(1–2): 283–286. the Study of Crohn’s Disease and Ul- PO079 Rodriguez-Moran, M., F. Guerrero- cerative Colitis (GETECCU). Amer J Romero, and G. Lazcano-Burciaga. Gastroenterol 1999; 94(2): 427–433. Lipid- and glucose-lowering efficacy of PO088 Fernanzed, N., M. J. Diez, M. T. Teran, Plantago psyllium in type II diabetes. J J. J. Garcia, A. P. Calle, and M. Sierra. Diabet Complic 1998; 12(5): 273–278. Influence of two commercial fibers in PO080 Frati-Munari, A. C., W. Benitez Pinto, the pharmacokinetics of ethinyl- C. Raul Ariza Andraca, and M. estradiol in rabbits. J Pharmacol Exp Casarrubias. Lowering glycemic index Therap 1998; 286; 870–874. of food by acarbose and Plantago psyl- PO089 Voderholzer, W.A., W. Schatke, B. E. lium mucilage. Arch Med Res 1998; Muhldorfer, A. G. Klauser, B. Birkner, 29(2): 137–141. and S. A. Muller-Lissner. Clinical re- sponse to dietary fiber treatment of PO081 Moran, S., M. Uribe, M. E. Prado, et chronic constipation. Amer J Gastro- al. Effects of fiber administration in the enterol 1997; 92(1): 95–98. prevention of gallstones in obese pa- PO090 Gelissen, I. C., and M. A. Eastwood. tients on a reducing diet. A clinical Taurocholic acid adsorption during trial. Revista de Gastroenterologia de non-starch polysaccharide fermenta- Mexico 1997; 62(4): 266–272. tion: an in vitro study. Brit J Nutr PO082 Perez-Miranda, M., A. Gomez- 1995; 74(2): 221–228. Cedenilla, T. Leon-Colombo, J. PO091 Turnbull, W. H., and H. G. Thomas. Pajares, and J. Mate-Jimenez. Effect of The effect of a Plantago ovata seed con- fiber supplements on internal bleeding taining preparation on appetite vari- hemorrhoids. Hepato-Gastroener ables, nutrient and energy intake. Int J 1996; 43(12): 1504–1507. Obesity Rel Metab Disord 1995; PO083 Nordgaard, I., H. Howe, M. R. 19(5): 338–342. Clausen, and P. B. Mortensen. Colonic PO092 Marteau, P., B. Flourie, C. Cherbut, et production of butyrate in patients with al. Digestibility and bulking effect of previous colonic cancer during long- ispaghula husk in healthy humans. Gut term treatment with dietary fiber. 1994; 35(12): 1747–1752. Scand J Gastroenter 1996; 31(10): PO093 Freeman, G. L. Psyllium hypersensitiv- 1011–1020. ity. Ann Allergy 1994; 73(6): 490–492. PO084 Frati-Munai, A. C., M. A. Flores- PO094 Gelissen, I. C., B. Brodie, and M. A. Garduno, R. Ariza-Andraca, S. Islas- Eastwood. Effect of Plantago ovata Andrade, and A. Chavez-Negrete. (psyllium) husk and seeds on sterol Effect of different doses of Plantago metabolism: studies in normal and psyllium mucilage on the glucose toler- ileostomy subjects. Amer J Clin Nutr ance test. Archivos de Investigacion 1994; 59(2): 395–400. Medica 1989; 20(2): 147–152. PO095 Edwards, C. A., J. Bowen, W. G. PO085 Westerhof, W., P. K. Das, E. Mid- Brydon, and M. A. Eastwood. The ef- dlelkoop, J. Verschoor, L. Storey, and fect of ispaghula on rat caecal fermen- C. Regnier. Mucopolysaccharides from tation and stool output. Brit J Nutr psyllium involved in wound healing. 1992; 68(2): 473–482. 436 MEDICINAL PLANTS OF THE WORLD

PO096 Tomas-Ridicci, M., R. Anon, M. PO101 Suhonen, R., I. Kantola, and F. Minguez, A. Zaragoza, J. Ballester, and Bjorksten. Anaphylactic shock due to A. Benages. The efficacy of Plantago ingestion of psyllium laxative. Allergy ovata as a regulator of intestinal tran- 1983; 38(5): 363–365. sit. A double-blind study compared PO102 Harborne, J. B., and C. A. Williams. to placebo. Revista Espanola de Comparative biochemistry of flavonoids. Enfermedades Digestivas 1992; 82(1): XIII. 6-Hydroxyluteolin and scutellarein 17–22. as phyletic markers in higher plants. PO097 Leng-Peschlow, E. Plantago ovata seeds Phytochemistry 1971; 10: 367–378. as dietary fiber supplement: physiologi- PO103 Machado, L., O. Zetterstrom, and E. cal and metabolic effects in rats. Br J Fagerberg. Occupational allergy in Nutr 1991; 66(2): 331–349. nurses to a bulk laxative. Allergy 1979; PO098 Leng-Peschlow, E. Interference of di- 34(1): 51–55. etary fibers with gastrointestinal en- PO104 Lerman Garber, I., M. Lagunas, J. C. zymes in vitro. Digestion 1989; 44(4): Sierra Perez, et al. The effect of psyl- 200–210. lium plantago in slightly to moderately PO099 Miettinen, T. A. and S. Tarpila. Serum hypercholesterolemic patients. Ar- lipids and cholesterol metabolism dur- chives del Instituto de Cardiologia de ing guar gum, Plantago ovata and high Mexico 1990; 606): 535–539. fiber treatments. Clin Chim Acta PO105 Uribe, M., M. Dibildox, S. Malpica, et 1989; 183; 253–262. al. Beneficial effect of vegetable pro- PO100 Faber, P., and A. Strenge–Hesse. Rel- tein diet supplemented with psyllium evance of rhein excretion into breast plantago in patients with hepatic en- milk. Pharmacology 1988; 1(Suppl cephalopathy and diabetes mellitus. 36): 212–220. Gastroenterology 1985; 88(4): 901–907. SACCHARUM OFFICINARUM 437

13 Saccharum officinarum L.

Common Names ’O:yz Laos Harilik suhkruroog Estonia Aankha India Havupunkit Finland Ak Pakistan Hong gan zhe China Ampeu Cambodia Iikh India Azucar, cane de Canary Islands Ikhhu Pakistan Azucar, cane de Guatemala Kaneh Israel Bagasse China Kansha Japan Cana comun Spain Khand Pakistan Cana de assucar Portugal Ko Hawaii Cana de azucar Canary Islands Kushiar Pakistan Cana de azucar Guatemala Mia Vietnam Cana de azucar Mexico Moba Tanzania Cana de azucar Spain Naishekar Iran Cana dulce Canary Islands Noble cane United States Cana dulce Spain Oi daeng Thailand Canaduz Spain Oi Thailand Canamiel Spain Qasab al sukkar Arabic countries Cane, sugar India Qasab es sukkar Arabic countries Canna da zucchero Italy Saccar Nepal Canna mele Italy Sahacar Nepal Canne de sucre France Sahachar Nepal Cay mia Vietnam Sakhara India Cha’ncat Mexico Sakharnyi trostnik Russia Cukornad Hungary kul’turnyi Cukrova trtina Czech Republic Sakharnyi trostnik Russia Dulce, cana Canary Islands lekarstvennyi Gan zhe China Satou kibi Japan Ganiesi Nicaragua Shecerna trska Croatia Ganna Nepal Shecerna trska Serbia Ganna Pakistan Sladkornitrs Slovenia Gannaa India Sockerror Sweden Gannaa Pakistan Sokeriruoko Finland Gendari Pakistan Sugar cane Barbados Guo zhe China Sugar cane Guyana

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 437 438 MEDICINAL PLANTS OF THE WORLD

Sugar cane India Tebu Indonesia Sugar cane Indonesia Tebu Malaysia Sugar cane Iran Tiwu Sudan Sugar cane Jamaica To pi’avare Rarotonga Sugar cane Tanzania Ton oi Thailand Sugar cane Trinidad Tubo Philippines Sugarcane Hawaii Tue Papua-New Guinea Sugarcane, blue ribbon United States Ukha India Suikerriet Netherlands Ukhu Nepal Sukkerroer Denmark Usa India Sukkerror Norway Uuka India Teboe Indonesia Zuckerrohr Germany Tebu telur Malaysia

BOTANICAL DESCRIPTION ORIGIN AND DISTRIBUTION Saccharum officinarum is a tropical perennial Native to Old World tropics, probably New grass of the GRAMINEAE family. It is 3–4 Guinea. It is cultivated for the sugar-rich m tall, approx 5 cm in diameter, with un- stems or canes in the most parts of South- branched stems, which have many nodes east Asia, Africa, India, South America, and short conspicuous internodes filled with China, islands of the Pacific and Caribbean, solid, juicy pulp. Each stem produces its own and other tropical regions. root system. Two types of roots develop: the TRADITIONAL MEDICINAL USES first type, from the primordia of the cutting Brazil. Hot water extract of the fresh leaf is after planting, are thin and branched, and taken orally to treat hypertension or induce the second type, from the primordia of the diuresisSO113. tillers, which are thick, fleshy, and less Canary Islands. Hot water extract of the branched. With age, all roots become fresh fruit juice is taken orally for cystitis brown, shrivel, and die. Leaves are up to 1.5 and hot water extract of the fresh stem is m long, falling from the lower stems when used ophthalmically for conjunctivitisSO121. they wither. Each leaf consists of linear-lan- Guatemala. Hot water extract of the dried ceolate blade, up to 10 cm wide in the base, leaf is taken orally for renal inflammation narrowing into sheath clasping the stem, and as a diureticSO118. Hot water extract of sharp serrate on the margin and siliceous. the dried stalk is used externally for skin dis- The midrib is prominent and broad, white eases and irritations, mouth lesions, stoma- and concave on the upper surface, and green titis, dermatitis, and inflammationsSO119. below. Flowers are clustered in large, dense, Hawaii. Water extract of the shoot is taken feathery, ovoid, terminal panicles up to 1 m orally for asthmaSO129. or more, with many fragile, jointed India. Decoction of the juice, 2–3 g Di- branches. Spikelets are paired; one is pedi- ospyros melanoxylon gum and water are cellate and the other sessile, with silver silky boiled and taken orally three times daily for hairs spreading from the base, twice as long 3 days for typhoid. No food is taken during as the body of spikelet. Both spikelets are treatment. Juice is mixed with Ficus religiosa two-flowered: the lower empty, and the up- roots and made into pills the size of small per bisexual. Glumes are equal, mostly peas. Pills are taken mornings and evenings chartaceous, lemma of upper floret is awn- for 3 days for malariaSO117. Ten grams of 3- less. The seeds are ovate, yellowish-brown, year-old fresh stem and 0.5 g of sulfur are approx 1 mm long, dry one-seeded fruits. mixed thoroughly, made into pills the size SACCHARUM OFFICINARUM 439 of a peanut, and taken orally. Three pills 3-Hydroxy-1-(4-hydroxy-3-methoxyphenyl)-2- daily are taken by women for approx 40 days [4-(3-hydroxy-1-(E)-propenyl)-2,6- to produce permanent sterilitySO122. dimethoxyphenoxy] propyl- -D-glucopyranoside: PlSO044 Indonesia. Extract of the plant is used as an E SO079 3-Hydroxy-4,5-dimethoxyphenyl-E-D- abortifacient . A 4–5 cm long piece of glucopyranoside: PlSO044 black cane stalk is pounded with half of a 4-(E-D-glucopyranosyloxy)-3,5- young pineapple, ragi (rice, garlic, Alpinia dimethoxyphenyl-propanone: PlSO004 galangal, cinnamon, ginger, and Capsicum 4-[(Erythro) 2,3-dihydro-3(hydroxymethyl)-5- annuum) and diluted with water. The ex- (3-hydropropyl)-7-methoxy-2- tract is taken twice daily as an abortifa- benzofuranyl]-2,6-dimethoxyphenyl-E- SO004 cientSO110. D-glucopyranoside: Pl Mexico. Ethanol (95%) extract of the stem 4-[Ethane-2-[3-(4-hydroxy-3-methoxyphenyl)- 2-propen]oxy]-2,6-dimethoxyphenyl- -D- is used as a mouthwash for toothaches. The E glucopyranoside: PlSO044 extract is rubbed on affected area of nettle 4-[Ethane-2-[3-(4-hydroxy-3-methoxyphenyl)- SO111 stings . 2-propen]oxy]-2-methoxyphenyl-E-D- Nepal. Hot water extract of the stem is glucopyranoside: PlSO044 taken orally by men as an aphrodisiacSO078. 9-O-E-D-xylopyranoside of icariol A2: PlSO004 Pakistan. Juice of the stem is taken orally in Abscisic acid: StSO091 SO019 large quantities as an anaphrodisiacSO079. D-Galactosidase: Immature Stalk SO019 Papua-New Guinea. Fresh stem is chewed D-Mannosidase: Immature Stalk Apigenin, 5-7-dimethyl: 4'-O- -D-glucoside: for diarrhea and vomiting sicknessSO100. E LfSO102 Rarotonga. Juice of the fresh stem is taken Apigenin, 5-O-methyl: FlSO104 SO125 orally to treat bronchitis . Apigenin: StSO128 Saudi Arabia. Boiled molasses is used to Arabinose: StSO101 sterilize woundsSO124. Arundoin: Lf waxSO096 Taiwan. Decoction of the dried root is Benzoic acid: StSO086 taken orally to treat diabetes mellitusSO126. E-D-fructfuranosyl-D-D-(6-syringyl)- SO044 Tanzania. Decoction of the dried stems of glucopyranoside: Pl sugar cane and Pachystela msolo is taken E-D-fructfuranosyl-D-D-(6-vanilloyl)- glucopyranoside: PlSO044 orally as a galactogogueSO114. E-Galactosidase: Immature StalkSO019 CHEMICAL CONSTITUENTS E-Glucosidase: Immature StalkSO019 (ppm unless otherwise indicated) E-N-acetylglucosaminidase: Immature SO019 2-[4-(3-Hydroxy-1-propenyl)-2,6- Stalk SO018 dimethoxyphenoxy]-3-hydroxy-3-(4-hy- E-xylosidase: Immature Stalk Calcium: Pl JuSO087 droxy-3,5-dimethoxyphenyl)propyl-E-D- SO093 SO085 glucopyranoside: PlSO004 Campesterol: Bract , St SO086 3-[5-(Threo) 2,3-dihydro-2-(4-hydroxy-3- Coumarin: St SO096 methoxyphenyl)-3-hydroxymethyl-7- Cylindrin: Lf wax methoxybenzofuranyl]-propanoic acid: Dehydrodiconiferyl alcohol-9'-E-D- SO044 PlSO004 glucopyranoside: Pl SO043 3-Hydroxy-1-(4-hydroxy-3,5- Dotriacontanoic acid: Wax dimethoxyphenyl)-2-[4-(3-hydroxy-1-(E)- Feruloyl-D-L-arabinofuranosyl(phenyl- propenyl)-2,6-dimethoxyphenoxy]propyl-E- propanoid-1-3)-O-E-D-xylopyranosyl(1-4)- D D-glucopyranoside: PlSO044 -xylopyranose, 3-Hydroxy-1-(4-hydroxy-3-methoxyphenyl)-2- O-E-D-xylopyranosyl(1-4)-O-(5-O-trans): SO095 [4-(3-hydroxy-1-(E)-propenyl)-2- St Flavone, 5-7-dimethoxy-3'-O- -D-glucoside: methoxyphenoxy]propyl-E-D-glucopyranoside: E SO088 PlSO044 St 440 MEDICINAL PLANTS OF THE WORLD

Flavone,3'-4'-5-7-tetrahydroxy-3-6-dimethoxy: Sucrose: StSO086 FlSO104 Sugar, invert: StSO084 Flavone,7-hyroxy-5-methoxy: 3'-O-E-D-galac- Sulfur inorganic: Pl JuSO087 toside: StSO088 Swertiajaponin: StSO128 Fructose: StSO101 Swertisin: StSO108 Galactose: StSO101 Taraxerol methyl ether: Lf waxSO096 Gibberellin A-1: StSO091 Tetracontanoic acid: WaxSO043 Gibberellin A-19: StSO091 Traicontanoic acid: WaxSO043 Gibberellin A-20: StSO091 Tricin: StSO128 Gibberellin A-29: StSO091 Tricin-7-glucoside sulfate: StSO128 Gibberellin A-3: StSO091 Tricin-7-glucoside: StSO108 Glucose: StSO101 Tricin-7-O-(2''-O-rhamnosyl)-galacturonide: Invertase: Immature StalkSO019 StSO108 Lupeol, O-methyl: Lf waxSO096 Tricin-7-O-E-D-glucopyranoside: PlSO092 Luteolin: StSO128 Tricin-7-rhamnosyl-galacturonide: StSO128 Melibiose: Immature StalkSO019 Vanilloyl-1-O-E-D-glucoside: RtSO083 Mg inorganic: Pl JuSO087 Vicenin: PlSO092 Octacosanoid acid: WaxSO043 Xylopyranose, D, O-(5-O-feruloyl-D-L- Octacosanol: WaxSO016 arabinofuranosyl)-(1-3)-O-E-D- O-Nitrophenyl-E-D-xylopyrosinase: Immature Xylopyranosyl-(1-4): StSO107 StalkSO018 Xylose: StSO101 Orientin, 3'-7-dimethyl ether: StSO108 Orientin, iso, 3'-7-dimethoxy: PlSO092 PHARMACOLOGICAL ACTIVITIES Orientin, iso, 3'-7-dimethyl ether: StSO108 AND CLINICAL TRIALS Orientin, iso: StSO128 Abortifacient effect. Ethanol (50%) ex- Orientin: StSO128 tract of the dried leaf, administered intra- Peonidin-3-O-E-D-galactoside: StSO089 gastrically to rats at a dose of 200 mg/kg, was Phenyl-O-D-glucoside, 3-4-6-trimethohy: activeSO112. StSO082 Acetylcholine release. Policosanol pro- Phenyl-O-D-glucoside, 3-4-dimethoxy: StSO082 Phosphorus inorganic: Pl JuSO087 duced some interactions in the modulation Phytosterol: Bract 0.36-0.43%SO093 of the acetylcholine (ACh) release at the P-Nitrophenyl-E-D-xylopyrosinase: Immature mouse neuromuscular junction. Polico- StalkSO018 sanol enhanced to a small extent either the Potassium inorganic: Fr Ju (unripe)SO103, Pl spontaneous or the evoked ACh release. JuSO087 An increase in the rate of the conforma- Protein (Saccharum officinarum): Bagasse (press tional change induced at the nicotinic mud) 40.0%SO081 SO019 receptor-channel complex by ACh was also Raffinose: Immature Stalk SO053 Saccharan A: StSO099, StalkSO094 observed . Saccharan B: StSO099, StalkSO094 Allergenic effect. Twenty-two children Saccharan C: StSO099, StalkSO094 with asthma aged from 7 to 14 years old, and Saccharan D: StSO099, StalkSO094 12 “normal” control children aged from 8 to Saccharan E: StSO099, StalkSO094 13 years were submitted to nonspecific Saccharan F: StSO099, StalkSO094 bronchoprovocation test with metacholine Saccharum officinarum glucan B-O: SO115 before and during the sugar cane burning. Bagasse The metacholine concentrations used were Schaftoside, iso: StSO128 Schaftoside: StSO128 0.025, 0.25, 1, 2.5, 10, and 25 mg/mL. The Sitosterol, E: StSO085, BractSO093 results were expressed as concentration of Stachyose: Immature StalkSO019 metacholine that induces a fall of 20% or Stigmasterol: StSO085, BractSO093 more in the forced expiratory volume in the SACCHARUM OFFICINARUM 441

first second (FEV1; PC20). The PC20 average tions, applied intradermally into human for children with asthma was significantly skin, produced localized wheals and ery- lower than the control group, before (asth- thema reactions. The glucans were active matic children [A] = 3.68, control children on intradermal injection into both dextran- [C] = 25.62 mg/mL) and during the burning sensitive and dextran-resistant rats and, like (A = 4.11, C = 25.25 mg/mL) (p < 0.05). dextrans, were active on subcutaneous in- There were no significant differences when jection into dextran-sensitive animalsSO072.

PC20 values before and during burning were Analgesic effect. FAM, a mixture of fatty compared in each group. The same was ob- acids from wax oil, in the hot-plate model served regarding FEV1, forced vital capac- and in the acetic acid-induced writhing test ity (FVC), and forced expiratory flux (FEF) in mice, produced analgesic propertiesSO005. between 25 and 75% of FVC (25–75%)SO028. Ethanol (95%) extracts of the fresh leaf, Specific immunoglobulin (Ig) E antibodies administered intragastrically to mice at a to sugar cane pollen were investigated in 74 dose of 1 g/kg, were active vs benzoyl perox- Okinawan children who suffered from aller- ide-induced writhing. Extract of the fresh gic disorders. Two (2.7%) with asthma of shoot was inactive. Both extracts were in- the 74 patients had specific IgE antibodies active vs tail flick response to hot waterSO120. to sugar cane pollen, house dust, and Antibacterial activity. Tincture of dried Dermatophagoides farinae. They had no his- stalk (extract of 10 g plant material in 100 tories of their symptoms being aggravated mL ethanol), on agar plate at a concentra- when sugar cane flowers bloomSO059. The in- tion of 30 PL/disc, was inactive on Pseudo- teraction of a complement activating glucan monas aeruginosa, Staphylococcus aureus, and from sugar cane (Bo) with Igs was studied. produced weak activity on Escherichia Bo precipitated a small fraction of IgG from coliSO119. human serum. In combination with this Antihepatotoxic activity. Water extract of fraction, it activated complement by the the dried stem (bagasse), administered in- classical pathway, not in its absence. The traperitoneally to mice at a dose of 25 mg/ results indicated that normal human serum kg, was active vs CCl4-induced hepato- contains natural antibodies against Bo, toxicitySO105. which form complement-activating im- Antihypercholesterolemic effect. Polico- mune complexes with Bo by binding it to sanol, administered orally to normocholes- their F(ab) region. The antibodies did not terolemic New Zealand rabbits at doses of cross-react with dextran, a glucan from bar- 5–200 mg/kg for 4 weeks, significantly re- ley, and surface constituents of Escherichia duced total cholesterol and low-density li- coliSO067. The immunostimulating polysac- poprotein cholesterol (LDL-C) serum levels charide (Bo) from sugar cane activated in a dose-dependent manner. Serum triglyc- complement in whole human and guinea eride (TG) levels of the treated and control pig serum in vitro by the classical pathway. animals were significantly different, but the Complement consumption was also demon- reduction observed was not dose-depen- strated in guinea pigs on iintravenous injec- dent. High-density lipoprotein cholesterol tion. Complement in sera from two severely (HDL-C) levels remained unchanged. The patients with hypogammaglobulinemia was results indicated that the reduction in total not activated by polysaccharide but was cholesterol values induced by policosanol made reactive by the addition of purified was mainly mediated through a decrease in human IgGSO68. Three glucan contaminants LDL-C levelsSO016. Policosanol was adminis- of crude cane sugar and invert sugar solu- tered to patients who were obese (body mass 442 MEDICINAL PLANTS OF THE WORLD index [BMI] Ն 30) with type II hypercho- lecular-weight aliphatic primary acids puri- lesterolemia at a dose of 5 mg once daily fied from sugar cane wax) was adminis- with the evening meal for 3 years. The treat- tered to rabbits fed a casein diet at doses of ment significantly lowered serum LDL-C (p 5, 50, and 100 mg/kg/day for 4 weeks. The < 0.01 vs placebo), the primary efficacy 50 and 100 mg doses significantly decreased variable (24.3%), and total cholesterol total cholesterol and LDL-C. TGs were not (15.8%) after 1 year of treatment. There was affected. At the completion of the study, an increase in HDL-C (21.9%). The effects HDL-C levels significantly increased at all were persistent during the trial. At the the doses assayed. D-003 inhibited de novo completion of the study, policosanol had synthesis of cholesterol, since the incorpo- 3 lowered LDL-C by 31.8% and total choles- ration of H2O into sterols in the liver and terol by 20.1%, whereas it markedly raised proximal small bowel was significantly de- HDL-C (24.6%). Thirty patients (18 place- pressed. D-003 significantly raised the rate bos and 12 policosanol) discontinued the of removal of [125I]-LDL from serum and sig- study: 15 (11 placebos and 4 policosanol) nificantly elevated [125I]-LDL binding activ- because of adverse events and 12 (9 place- ity to liver homogenatesSO025. Policosanol bos and 3 policosanol) because of serious was administered to older patients (60–80 adverse events (SAE), most vascular. Poli- years) with type II hypercholesterolemia at cosanol was safe and well tolerated, not im- a dose of 10 mg tablets once daily with the pairing significantly any safety indicator. evening meal for 8 weeks. The treatment Average body weight was slightly reduced was less effective than atorvastatin (10 mg/ during the study, indicating a general day) in reducing serum LDL-C and total acceptable compliance with dietary recom- cholesterol levels. Policosanol, but not mendations, but policosanol did not show atorvastatin, significantly increased serum any drug effect on body weightSO020. Poli- HDL-C levels, whereas both drugs similarly cosanol, administered to 239 patients with reduced atherogenic ratios and serum TGs. type 2 diabetes at a dose of 5 mg/day or pla- Policosanol was better tolerated than ator- cebo for 2 years, significantly reduced LDL- vastatin as revealed by patient withdrawal C (21.1%), total cholesterol (17.5%), and analysis and overall frequency of adverse TGs (16%) after 1 year. There was an in- eventsSO037. Policosanol was administered to crease in HDL-C levels (10.7%). The effects 56 postmenopausal women at a dose of 5 of the treatment persisted during the study. mg/day for 8 weeks and doubled to 10 mg/ At the completion of the study, policosanol day during the next 8 weeks. The treatment lowered LDL-C (29.5%), total cholesterol significantly decreased LDL-C, total choles- (21.9%), and TGs (16.9%) and elevated terol, the ratios of LDL-C to HDL-C, and HDL-C (12.4%). No significant changes on total cholesterol to HDL-C when compared lipid profile variables of the placebo group with baseline and placebo. HDL-C levels occurred during the study. The frequency of were significantly elevated by 7.4% at the serious adverse events, most vascular, in completion of the study. The drug was safe policosanol patients (6/119, 5%) was lower and well tolerated. No drug-related adverse than in respective placebo (26/120, 43.3%). effects were observed. Five patients taking No drug-related impairment of safety indi- placebo (17.9%) and 13 patients taking cators, particularly on glycemic control, was policosanol (46.4%) reported improve- observed. A reduction of systolic and dias- ments in habitual symptoms and health per- tolic blood pressures was observed in pa- ception during the studySO046. tients receiving policosanol compared with Antihyperglycemic activity. Ethanol placeboSO021. D-003 (a mixture of high-mo- (95%) extract of the dried leaf, adminis- SACCHARUM OFFICINARUM 443 tered intragastrically to rabbits at a dose of 1 pigs in a dose-dependent manner. Single g/kg, produced weak activity vs alloxan-in- doses of D-003 (5–500 mg/kg), administered duced hyperglycemia. The effect did not in- orally 2 hours before induction of arterial crease proportionally with the doseSO080. thrombosis, significantly inhibited the re- Ethanol (20%) extract of the fresh stem, ad- duction of rectal temperature. D-003 ad- ministered intragastrically to rats at a dose ministered at a single dose (50–200 mg/kg) of 60 mg/animal, was active vs glucose 2 hours before the experiment significantly administrationSO082. increased the bleeding time in a dose-de- Anti-implantation effect. Ethanol (50%) pendent manner. The time-course effects of extract of the dried leaf, administered D-003 on platelet aggregation, arterial intragastrically to hamsters at a dose of 100 thrombus formation, and bleeding time mg/kg, was activeSO112. showed no effect 0.5 hour after dosing, and Anti-inflammatory effect. FAM, adminis- maximal effects exhibited 1–2 hours after trated orally to rats, produced anti-inflam- treatment. There was no significant effect 4 matory activity in the cotton pellet hours after treatmentSO050. granuloma assay and in the carrageenin- Anti-yeast activity. Tincture of the dried induced pleurisy test. The effect was also stalk (extract of 10 g plant material in 100 produced in the peritoneal capillary perme- mL ethanol), on agar plate at a concentra- ability test in miceSO005. tion of 30 PL/disc, was inactive on Candida Anti-thrombotic activity. D-003, adminis- albicansSO119. tered orally to rats at a single dose of 200 Arterial blood pressure. Policosanol, ad- mg/kg, but not at 25 mg/kg, significantly in- ministered orally to spontaneously hyper- creased plasma levels of 6 keto PGF1-D lev- tensive rats (SHR) at doses of 25, 50, and els, a stable metabolite of prostacyclin 200 mg/kg, did not significantly change ar- PGI(2) from collagen-stimulated blood (4 terial pressure. Pretreatment with 200 mg/ Pg/mL) compared with control group. Lev- kg of policosanol significantly increased els of 6 keto PGF1-D levels determined af- propranolol-induced hypotensive effects. ter 10 days of oral treatment with both doses The effect of nifedipine remained un- of D-003 were significantly larger than the changed. The results indicated that controls. Single and repeated oral doses of policosanol did not antagonize the hypoten- D-003 significantly reduced the thrombox- sive effect of E-blockers, but it can increase ane TxB(2) plasma levels obtained from the hypotensive effect of E-blockers with- whole blood stimulated by collagen and the out modifying cardiac frequencySO012. weight of venous thrombus experimentally Arterial thrombosis. Policosanol, in the induced in rats. TxB(2)/6 keto PGF1-D venous thrombosis models at a concentra- ratio significantly decreased in animals tion of 25 mg/kg, significantly decreased the treated with D-003. D-003 at single doses thrombus weight, the protective effect per- (400 mg/kg but not 200 mg/kg) significantly sisting until 4 hours after its oral adminis- protected from death induced by en- tration and reduced rectal temperature dovenous infusion of collagen plus epineph- variation induced by arterial thrombosis. At rine in miceSO040. D-003, administered orally the same dose, policosanol increased 6-keto- to guinea pigs and rats at single or repeated PGF1-D serum levels in ratsSO015. doses of 25–200 mg/kg for 3 days, inhibited Atherosclerotic lesions protection. platelet aggregation induced by collagen Policosanol (with acacia gum as vehicle) (2.2 Pg/mL) and adenosine 5'-triphosphate was administered orally to male New (ADP) (2 Pmol/L) in rats, and collagen Zealand rabbits on a cholesterol-rich diet at (0.25 Pg/mL) induced aggregation in guinea doses of 25 or 200 mg/kg for 60 days. The 444 MEDICINAL PLANTS OF THE WORLD control animals developed marked hyperc- mins. The rats fed this diet did not exhibit holesterolemia, macroscopic lesions, and osteoporosis as the rats without sugar cane arterial intimal thickening. Intima thick- wax in the diet. The sugar cane wax, con- ness was significantly less (32.5 r 7 and 25.4 taining a long-chain carbohydrate with an r 4 PM) in hypercholesterolemic rabbits hydroxy radical, prevented the develop- treated with policosanol than in controls ment of osteoporosis via a nonestrogenic (57.6 r 9 PM). In most policosanol-treated mechanismSO033. animals, atherosclerotic lesions were not Carcinogenicity. Policosanol (Ateromix- present. In others, thickness of fatty streaks ol), administered orally to Swiss mice of had less foam cell layers than in controlsSO051. both sexes at doses of 50–500 mg/kg for 18 Policosanol, administered orally to 50 male months, produced no differences in daily Wistar rats at doses of 0.5, 2.5, 5, and 25 clinical observations, weight gain, food mg/kg daily for 8 days, produced a signifi- consumption, and mortality (survival analy- cant reduction of the atherosclerotic lesions sis) between groups. Histopathological in animals treated with lipofundinSO058. study indicated that the frequency of neo- Bone resorption inhibition. D-003 was ad- plastic (benign and malignant) lesions was ministered to ovariectomized or sham oper- similar in the control and policosanol- ated Sprague–Dawley female rats at doses of treated groups. No drug-related increase in 50 and 200 mg/kg/day for 3 months. The the occurrence of malignant or benign neo- treatment prevented a decrease in trabecu- plasm and no acceleration in tumor growth lar number and thickness and increases in in any specific group were observedSO057. trabecular separation, osteoclast number, Water extract of the stem, administered and surface compared with ovariectomized subcutaneously to female rats at a dose of 35 controls. D-003 prevented the bone loss and mg/animal for 77 weeks, was inactiveSO090. decreased bone resorption induced by ova- Cardiovascular disease prevention. Poli- riectomy. It failed to increase osteoblast sur- cosanols, administered at 5 to 20 mg/day, face compared with control ovariectomized decreased the risk of atheroma formation by ratsSO024. A polysaccharide fraction of Sac- reducing platelet aggregation, endothelial charum officinarum was administered to nor- damage, and foam cell formation in ani- mal rats and rats fed a high-sugar diet. mals. It lowered total cholesterol and LDL- Feeding the high-sugar diet induced an el- C levels by 13 to 23% and 19 to 31%, evation of serum glucose and significant respectively, while increasing HDL-C from accumulation of lipid peroxides in the serum 8 to 29%. Policosanols improved lipid pro- and liver. The accumulation of lipid perox- files by reducing hepatic cholesterol biosyn- ides was inhibited by combined feeding with thesis while enhancing LDL clearance. the polysaccharide fraction. Pathological When compared with statins, policosanols examination showed that endothelial cell exhibited comparable cholesterol-lowering swelling in the ascending aorta in one third effects at much smaller dosesSO029. of rats receiving the high-sugar diet control Carotid artery thickening effect. Poli- but no pathological change was observed in cosanol was administered to rabbits with all of the rats concurrently treated with the collars around the left carotid at doses of 5 polysaccharide fractionSO017. Sugar cane wax and 25 mg/kg for 7 and 15 days or 20 mg/kg was administered to rats fed a restricted, lovastatin for 15 days. There was a signifi- semipurified diet containing a 50%-reduced cant reduction in neointima in the treated level of carbohydrate and oil diet but nor- animals compared with controls. The reduc- mal levels of protein, minerals, and vita- tion in lovastatin-treated animals was sig- SACCHARUM OFFICINARUM 445 nificantly lower than in policosanol-treated lian gerbils at doses of 25, 50, and 200 mg/ groups. The reduction in smooth muscle cell kg, significantly reduced serum thrombox- proliferation observed in policosanol- ane B2 levels. The highest dose significantly treated rabbits was significantly larger increased 6-keto-PGF1-D. The results indi- than in lovastatin-treated animalsSO049. Poli- cated that policosanol, at 200 mg/kg, signifi- cosanol, administered orally to rabbits at cantly protected against cerebral ischemia doses of 5 and 25 mg/kg, prevented intimal induced by unilateral ligation of common thickening. Collars were placed around the carotid artery in Mongolian gerbils. Admin- left carotid for 15 days. To evaluate intimal istration of ineffective doses of policosanol thickening, the cross-sectional area of in- (25 mg/kg) and aspirin (30 mg/kg) signifi- tima and media were measured. Neointima cantly protected animals indicating a syner- was significantly reduced in policosanol- gism between themSO061. treated animals compared with controls. Cholesterol synthesis inhibition. D-003, The smooth muscle cell proliferation was in cultured fibroblasts at doses of 0.05-50 studied by the immunohistochemical detec- Pg/mL for 12 hours, inhibited cholesterol tion of proliferating cell nuclear antigen, biosynthesis from 14C-labeled acetate (33– and a significant reduction was observed in 68%) in a dose-dependent mannerSO046. policosanol-treated rabbitsSO054. Policosanol, in human lung fibroblasts for Cerebral ischemia. Policosanol, adminis- 48 hours before the experiment, produced a tered to Mongolian gerbils at a dose of 200 dose-dependent inhibition of 14C-acetate mg/kg immediately after unilateral carotid incorporation into total cholesterol. La- ligation and at 12- or 24-hour intervals for beled mevalonate incorporation was not in- 48 hours, significantly inhibited mortality hibited. LDL processing was markedly and clinical symptoms when compared with enhanced. LDL binding, internalization, controls. Lower dose (100 mg/kg) was not and degradation were significantly increased effective. Control animals showed swelling after policosanol treatment. Cholesterol (tissue vacuolization) and necrosis of neu- generation was not inhibited at the lowest rons in all areas of the brain studied (frontal dose of policosanol assayed, but LDL pro- cortex, hippocampus, striatum, and olfac- cessing was significantly increasedSO060. tory tubercle), showing a similar injury pro- Polysaccharide fraction of the dried stem, file. In the group treated with 200 mg/kg administered intraperitoneally to rats at a policosanol, swelling and necrosis were sig- dose of 40 mg/kg, was inactive vs high-sugar nificantly reduced when compared with the dietSO116. control group. In another experimental Chronotropic effect negative. Ethanol model, policosanol at a dose of 200 mg/kg (50%) extract of the fresh leaf, administered (n = 19) significantly reduced the edema intragastrically to rats at a dose of 40 mg/kg, compared with the control group, with a was activeSO113. cerebral water content identical to that of Coagulative effect. D-003, a mixture of ali- the sham-operated animals. The polico- phatic primary acid from sugar cane wax, sanol-treated group (n = 10) showed administered orally to beagle dogs at doses significantly higher cyclic adenosine of 200 or 400 mg/kg for 9 months, signifi- monophosphate (cAMP) levels (2.68 pmol/ cantly reduced total cholesterol, inhibited g of tissue) than the positive control (1.91 platelet aggregation, and increased bleeding pmol/g of tissue) and similar to those of time compared with levels in controls. Data nonligated gerbils (2.97 pmol/g of tissue)SO052. analyses of body weight gain, food consump- Policosanol, administered orally to Mongo- tion, clinical observations, the remaining 446 MEDICINAL PLANTS OF THE WORLD blood biochemistry, and hematology indi- filtrate were observed in the liver of 87.5% cators, including coagulation parameters of positive controls. D-003 dramatically (prothrombin time and kaolin-activated reduced both necrotic areas and inflamma- thromboplastin time), organ weight ratios, tory infiltrate and was present in only 12.5% and histopathological findings, showed no animals treated with 25 mg/kg of D-003 and trends with D-003 doses or significant dif- in none (0%) of the animals treated with ferences between treated animals and 100 mg/kgSO007. controlsSO001. Dental caries development influence. Cytotoxic activity. Fresh plant juice, in cell Two groups of sugar cane cutters and sisal SO109 culture was inactive, ED50 6.25% . Dried plant workers, with similar socioeco- retina, in cell culture at undiluted con- nomic backgrounds, had similar levels of centration was active on macrophagesSO106. fluoride in drinking water, consuming simi- D-003 at doses of 5 or 25 mg/kg for 18 hours, lar amounts of refined sugar per day but had significantly decreased the percentage of a significant difference in the number of turgent cells and hepatocytes with necrosis pieces of sugar cane chewed per day. Sugar and increased the percentage of normal cane cutters had significantly higher mean hepatocytes with respect to positive con- decayed missing teeth (DMT)/decayed trols in a dose-dependent manner. Necrotic missing surface (DMS) scores than sisal areas and inflammatory infiltrates were plant workers. Analysis of variance revealed observed in the liver of 90% positive (para- a weakly significant effect of sugar cane cetamol-treated) controls. D-003 dramati- chewing on the caries scores (p = 0.02 from cally reduced both necrotic areas and DMT and p = 0.05 for DMS). The results of inflammatory infiltrate and was present in the study indicated that sugar cane chewing 10% animals treated in the two experi- in large quantities for a long period has a mental series. There were no histological caries-promoting effect in populations with alterations in liver sections of negative con- a low-caries prevalenceSO063. trolsSO003. D-003 was administered to male Diabetogenic effect. Chromatographic Sprague–Dawley rats with acute hepatotox- fraction of the fresh stem, administered icity induced by intraperitoneal injection of intragastrically to rats at a dose of 1 g/kg, carbon tetrachloride (1 mL/kg). Treatment was active. The fraction inhibited the eleva- with D-003 at 25 or 100 mg/kg for 18 hours tion of serum TG, lipid peroxides, and insu- significantly decreased the percentage of lin of rats fed on a high-sugar diet for 61 ballooned cells and hepatocytes with lipidic daysSO127. inclusions. It increased the percentage of Diuretic activity. Decoction of the dried normal hepatocytes compared with that in leaf, administered nasogastrically to rats at positive controls in a dose-dependent man- a dose of 1 g/kg, was inactiveSO118. Ethanol ner. The percent inhibitions of the occur- (50%) extract of the fresh leaf, administered rence of ballooned cells and hepatocytes intragastrically to rats at a dose of 40 mL/kg, with lipids were marked (75 and 50%, re- was active. Five parts fresh plant material in spectively) with the high dose (100 mg/kg). 100 parts water/ethanol was usedSO098. The percentage of turgent hepatocytes was Esophageal motility. Forty healthy volun- significantly reduced compared with posi- teers (20 aged 20–30 years, 10 aged 50–60 tive controls, but this effect was not dose- years, and 10 aged 70–80 years) were sub- dependent. No histological alterations in mitted to esophageal manometry during 10 the liver sections of negative controls were swallows of water, 10 swallows of sugar cane found. Necrotic areas and inflammatory in- syrup, and 10 “dry” swallows. Basal pressure SACCHARUM OFFICINARUM 447 of the upper esophageal sphincter and the transit when measured by the carmine lower esophageal sphincter, amplitude, du- marker technique. Daily supplements of ba- ration and velocity of contraction, and the gasse increased the total daily excretion of duration of the lower esophageal sphincter fecal bacteria, but there were no changes in relaxation were measured. Water and sugar bacteria excreted per gram of feces. The cane syrup did not differ regarding quanti- composition of the bacterial flora showed no tative contraction parameters, but sugar change. There was increased excretion of cane syrup led to a higher incidence of syn- fecal acid sterols on the bagasse supplement, chronous contractions. The three age but this failed to occur with bran. No groups had similar amplitude and velocity changes attributable to fiber supplements of con-tractile waves. The oldest group had occurred in the plasma TGs or choles- markedly more frequent synchronous con- terolSO073. tractions and failures of contraction after Glutamate–oxaloacetate–transaminase both water and sugar cane syrup swallows. inhibition. Polysaccharide fraction of the This was associated with a high incidence dried stem, administered intraperitoneally of scintigraphic transit abnormalities in to rats at a dose of 40 mg/kg, was active vs this groupSO055. high-sugar dietSO116. Fecal steroid and lipid excretion. Fiber Glutamate–oxaloacetate–transaminase supplements from sugar cane residue (ba- stimulation. Polysaccharide fraction of the gasse), administered to volunteers for 12 dried stem, administered intragastrically to weeks, increased stool weights and stool fat rats at a dose of 1 g/kg, was active vs high- excretion. Bagasse increased the daily loss sugar dietSO116. of acid steroids and decreased transit time Glutamate–pyruvate–transaminase inhi- without alteration in fecal flora. The in- bition. Polysaccharide fraction of the dried creased excretion of bile acids and fatty ac- stem, administered intraperitoneally to rats ids failed to lower the plasma cholesterol at a dose of 40 mg/kg, was inactiveSO116. and TGs after 12 weeksSO076. Glutamate–pyruvate–transaminase Foam-cell formation. Policosanol was ad- stimulation. Polysaccharide fraction of the ministered to 18 Wistar rats with carrag- dried stem, administered intragastrically to eenan-induced granulomas at doses of 2.5 or rats at a dose of 1 g/kg, was active vs high- 25 mg/kg for 20 days. The treatment pro- sugar dietSO116. duced a significant reduction of the foam- Growth-promoting effect. Sugar cane cell formation in granulomas (extravascular extract, administered orally to 1-week-old medium)SO056. chicken at a dose of 500 mg/kg/day for 3 or Gastrointestinal effect. Sugar-cane fiber 6 days, produced significantly higher body (bagasse) was administered to normal am- weight and gain in body weight/day and a bulant volunteers at a dose of 10.5 g of ba- lower food conversion ratio within the gasse containing 5.1 g of crude fiber to a growing period of 6 weeks than physio- normal diet containing 3.7 g of crude dietary logical saline-administered control chic- fiber daily for 9 months. The treatment kensSO038. A black phenolic-carbohydrate raised the mean fecal weight from 88.3 r 6.4 complex (nonsugar, nondialyzable compo- g to 139.7 r 10.2 g/day (p < 0.005). There nents of cane molasses fractions), adminis- was a significant rise in fecal solids and fecal tered to male weanling rats at a dose of water, although the percentage of water in 0.03% of diet, significantly increased the the stools remained unchanged. Bagasse growth rate above that of rats fed the basal supplements accelerated gastrointestinal diet alone. The alkaline cleaved, non- 448 MEDICINAL PLANTS OF THE WORLD dialyzable-free hemicellulose stimulated rabbits at a dose of 100 mg/kg at 48 hour growth when incorporated into rat diets at intervals for 4 weeks, produced no effect on the 0.03% levels. Acid hydrolysis of the food intake and body weight. Plasma LDL complex yielded an insoluble product iden- increased and plasma TG levels decreased tified as lignin and represented 18–20% of in all groups. The results did not confirm the entire complexSO074. a hypocholesterolemic effect of polico- Hemoglobin effect. Molasses, adminis- sanolSO022. tered to 40 male weaning rats, 21 days of Hypoglycemic activity. Ethanol (95%) ex- age, at a dose of 12.5% molasses in casein tract of the dried leaf, administered intra- diet with 10.14% protein, produced a small gastrically to rabbits at a dose of 1 g/kg, but not significant increase in hemoglobin produced weak activitySO080. Juice of the levels compared to the control groupsSO048. dried stalk, administered intraperito- Hepatotoxicity. D-003 was administered to neally to mice at a dose of 200 mg/kg, was male Sprague–Dawley rats with liver dam- activeSO094. Polysaccharide fraction of the age induced by paracetamol orally at a dose dried stem, administered intraperitoneally of 600 mg/kg, or intraperitoneally at a dose to rats at a dose of 40 mg/kg, was inactive vs of 200 mg/kgSO003. high-sugar dietSO116. 3-Hydroxy-3-methylglutaryl coenzyme Hypolipemic activity. Polysaccharide frac- A reductase activity. Policosanol, in Vero tion of the dried stem, administered fibroblast cell culture at concentrations of intragastrically to rats at a dose of 1 g/kg, 0.5–50 Pg/mL, decreased in a dose-depen- was active vs high-sugar diet. Intraperito- dent manner, cholesterol biosynthesis from neal administration at a dose of 40 mg/kg [14C]-acetate and 3H-water, but not from was activeSO116. [14C]-mevalonate. There was no evidence Hypotensive activity. Ethanol (50%) ex- for a competitive or noncompetitive inhibi- tract of the fresh leaf, administered tion of 3-hydroxy-3-methylglutaryl coen- intragastrically to rats at a dose of 40 mL/kg, zyme A (HMG-CoA) reductase activity. was activeSO113. Treatment of intact cells with policosanol Immunostimulating effect. Sugar cane ex- in the presence of lipid-depleted medium tract, administrated orally to 3-week-old produced a suppressive effect on enzyme chickens at a dose of 500 mg/kg/day for 3 activity, indicating a modulatory effect of days before or after irradiation, enhanced policosanol on reductase activitySO009. both primary and secondary immune re- Policosanol downregulated cellular expres- sponses in chickens immunized with sheep sion of HMG-CoA reductase and, thus, has red blood cells and Brucella abortus. Cell- the potential to suppress isoprenylation re- mediated immunity was measured by de- actions much like statins do. Policosanol did layed-type hypersensitivity to human not directly inhibit HMG-CoA reductase, J-globulinSO002. Sugar cane extract, adminis- and even in high concentrations, it failed to tered orally to 2- or 10-month-old chickens downregulate this enzyme by more than at a dose of 500 mg/kg/day for 3 days before 50%, thus likely accounting for the safety of immunized with sheep red blood cells, Bru- policosanolSO041. cella abortus, and Salmonella enteritidis organ- Hypocholesterolemic activity. A mixture isms, produced significantly increased and of high molecular-weight primary aliphatic prolonged antibody responses to these anti- alcohols from sugar cane (Lesstanol, pro- gens, compared with control chickens. vided by Johnson & Barana), administered Chickens treated with extract revealed en- intragastrically to normocholesterolemic hanced delayed type hypersensitivity re- SACCHARUM OFFICINARUM 449 sponses to human J globulinSO036. Sugar cane Lipid metabolism. Polysaccharide fraction extract, in chicken polymorphonuclear of the dried stem, administered intragastri- cell culture of the peripheral blood at doses cally to rats at a dose of 1 g/kg daily for 14 of 250–1 mg/mL for 24 hours, significantly weeks, was active vs high-sugar diet. The increased the phagocytosisSO038. Water ex- effect was measured in the liver. Intraperi- tract of the dried stem, administered intra- toneal administration at doses of 20 and 40 gastrically to mice at a dose of 200 mg/kg, mg/kg for 14 weeks was active. The higher prolonged the survival time of animals irra- dose produced an increase of liver phos- diated by deep X-ray. Intraperitoneal ad- pholipidsSO116. Sugar cane carbohydrate was ministration to mice, at a dose of 25 mg/kg, administered to rats at doses: a. starch increased spleen weight and antagonized (54%) + cane sugar (0%); b. starch (44%) + the immunosuppressive actions of predniso- cane sugar (10%); c. starch (10%) + cane lone and cyclophosphamide. Intraperito- sugar (44%); and d. only cane sugar (54%) neal administration to mice at a dose of 25 for 8 weeks. The beneficial effect of the un- mg/kg, prolonged the survival time of ani- saturated fat in lowering the serum choles- mals irradiated by deep X-ray and was inac- terol level was nullified by an excess of cane tive on graft vs host reaction modelSO105. sugar in the diet. In the liver, there was an Immunosuppression prevention. Sugar increase of 40–50% of cholesterol, as the cane extract was administered orally to 3- cane sugar level in the diet was raised, irre- week-old inbred chickens at a dose of 500 spective of the type of dietary fatSO075. D-003 mg/kg/day for 3 days before or after injec- was administered orally to normocholes- tion of cyclophosphamide; on the last day, terolemic rabbits at doses of 5 mg/kg/day the chickens were immunized intravenously alone or with fluvastatin at 5 mg/kg/day with sheep red blood cells (SRBC) and Bru- each for 30 days. D-003 produced a decrease cella abortus. The treatment produced a sig- of LDL-C by 81.5% (p < 0.01) and the com- nificant increase in body weight, gain in bined therapy reduced LDL-C values by body weight per day, relative weight of the 75.9%. D-003 and combined therapy sig- bursa of Fabricius, and antibody responses nificantly lowered serum total cholesterol to SRBC and Brucella abortus than un- by 48.4% (p < 0.01) and 45.3%, respec- treated control chickens. There were signifi- tively, compared to controls. The responses cantly higher values in body weight, gain in of LDL-C and total cholesterol to combined body weight per day, and relative bursal therapy were statistically similar but less weight, and antibody responses to both an- pronounced than those reached by D-003 tigens, when compared to chickens treated alone. D-003 and combined therapy in- with cyclophosphamide alone. In histologi- creased HDL-C 21.5% and 19%, respec- cal examination, chickens that were given tively; the changes were significant vs the the extract showed a typical bursa with well- control. Combined therapy, but not D-003 constituted follicles, and chickens treated alone, lowered TGs (13.0%, p < 0.05 vs con- with extract and cyclophosphamide showed trol). The effects of combined therapy on a well-reconstituted bursa with almost nor- HDL-C were similar to those of D-003 mal structureSO023. alone. All groups showed similar food con- Insulin antagonist. Ethanol (20%) extract sumption and body weight gain, health sta- of the fresh stem, administered intragastri- tus being unaffected by the treatmentsSO027. cally to rats at a dose of 60 mg/animal, was Octa-6, a policosanol mixture from sugar active vs glucose administration. Insulin el- cane wax, was administered orally to 50 evation was inhibitedSO082H13208. male golden Syrian hamsters at a dose of 25 450 MEDICINAL PLANTS OF THE WORLD mg/kg body weight for 4 weeks. The treat- significant decrease in thiobarbituric acid ment produced no difference between Octa- reactive substance generation. In all the sys- 6 and Ricewax (a policosanol mixture from tems, the maximum effect was attained at rice wax, 50 mg/kg BW) treatments in any 50 mg/kg. There was a parallel attenuation of the lipid parameters measured, and both in the reduction of lysine amino groups and had similar levels of TG, total cholesterol, a significant reduction of carbonyl content and HDL-C as the control. Octa-6, but not after oxidation of lipoprotein samplesSO043. Ricewax increased non-HDL-C as com- Policosanol, administered to patients with pared with the controlSO032. type II hypercholesterolemia at doses of 20 Lipoprotein oxidation inhibition. Polico- mg/day or 40 mg/day, did not produce sig- sanol was administered orally to rats at nificant additional cholesterol-lowering ef- doses of 250–500 mg/kg/day for up to 4 ficacy at higher dose over the 20 mg/day weeks. There was no change in choles- doseSO045. terol, TGs, and phospholipid content of li- Metabolic effect. A case of 22 infants with poprotein very low-density lipoprotein + acute diarrhea was studied. Eleven infants LDL fractions. Policosanol significantly pro- aged 4–10 months were given nasogastric longed the lag time and reduced the propa- infusion, and 11 infants aged 5–17 months gation rate of diene generation and received intravenous fluid. The absorption thiobarbituric acid-reactive substances con- of nasogastric infusion fluid was remarkable tent. Policosanol increased lysine reactivity as was observed by the amount of stool loss, in Cu2+-treated lipoprotein fractionsSO011. weight gain, reduction of serum specific Policosanol, administered orally to rats at gravity, and urea nitrogen. Biochemical doses of 100 and 250 mg/kg for up to 4 study showed high incidence of hyper- weeks, produced a partial prevention of rat natremia. Nasogastric infusion fluid con- in vitro microsomal lipid peroxidation. The taining a table salt and cane sugar provided formation of thiobarbituric acid-reactive effective volume. Electrolyte imbalance and substances in microsomes isolated from metabolic acidosis were gradually corrected treated rats was significantly decreased by at a similar rate to bicarbonate-containing about 50%, when peroxidation was initiated solution. Balance study indicated that by Fe3+/ADP/nicontinamide adenine di- nasogastric infusion retained less nitrogen nucleotide phosphate (NADPH), Fe2+/ and sodium during the course of treatment ascorbate, and CCl4/NADPH-generating as compared to intravenous infusion. All of system. Oral administration of policosanol the infants recovered from diarrheal disease in rats provided a partial inhibition of once dehydration was corrected without lipid peroxidationSO013. D-003, administered complicationsSO071. orally to rats at doses of 0.5, 5, 50, and 100 Migraine. Sixty patients with migraine mg/kg for 4 weeks, produced at doses 5, 50, completed elimination diets after a 5-day and 100 mg/kg significant inhibition of cop- period of withdrawal from their normal diet. per-mediated conjugated-diene generation Fifty-two (87%) of the patients had been in a concentration-dependent manner. D- using oral contraceptive steroids, tobacco, 003 increased lag phase by 53.1, 115.3, and and/or ergotamine for an average of 3 years, 119.3%, respectively, and decreased the rate 22 years, and 7.4 years, respectively. The of conjugate-diene generation by 16.6, 21.5, foods causing reactions were wheat (78%), and 19.6%, respectively. D-003 inhibited orange (65%), eggs (45%), tea and coffee azo-compound-initiated and macrophage- (40% each), chocolate and milk (37% mediated lipid peroxidation as judged by the each), beef (35%), and corn, cane sugar, SACCHARUM OFFICINARUM 451 and yeast (33% each). When averages of 10 both sexes at doses of 250, 500, and 1000 common foods were avoided, there was a mg/kg/day for 6 months, significantly inhib- dramatic fall in the number of headaches ited platelet aggregation. Bleeding time was per month, 85% of patients becoming head- increased after 3 months of treatment with ache-free. The 25% of patients with hyper- D-003. The increase was maintained for 6 tension became normotensiveSO070. months and was reversible after washout. Myocardial necrosis inhibition. D-003 Coagulation factors, such as prothrombin was administered orally to rats with isoprot- time and kaolin-activated thromboplastin- erenol-induced myocardial necrosis at single time, which were determined in eight male (25–400 mg/kg) or repeated doses of 5–200 animals from each group, were unaffected. mg/kg. Single doses dose-dependently de- Data analyses of body weight gain, food con- creased necrosis area, percent of infarct area, sumption, clinical observations, blood bio- and the presence of polymorphonuclear chemistry, hematology, organ weight ratios, cells (PMNs) in myocardial tissue, but only and histopathological findings did not show the reductions induced by 200 and 400 mg/ trends related to D-003 dose or significant kg were significant. D-003 administered re- differences between control and treated peatedly for 10 days decreased all myocar- groups. The highest studied dose of D-003 dial necrosis indicators in a dose-dependent (1 mg/kg/day) represented a nontoxic dose level in the chronic toxicity study in manner, with results effective from 25 mg/ ratsSO008. Policosanol, administered orally to kg to the highest dose tested, indicating that rats at doses of 5–20 mg/kg, inhibited the the repeated dose scheme was more effec- decrease in circulating platelet counts and tive to prevent the damageSO031. collagen-induced malondialdehyde concen- Four locally Ophthalmic surgical swabs. tration in plasma. Policosanol (25 mg/kg) available plant materials have been studied inhibited the clotted whole-blood throm- and adapted for use as suitable surgical swabs boxane B2 formation. Administration of for various ophthalmic surgical procedures. 50–200 mg/kg, in a single dose, inhibited Corn, millet and sugar cane stems, and the ADP-induced platelet aggregation in plate- banana leaf frond provided cheap, easily let-rich plasma, whereas a lower dose (25 available, and suitable materials for use as mg/kg) did not change responses to ADP alternative surgical swabs to the much used significantly, but rats treated with this dose SO064 and tested German Spontex swabs . for 4 weeks showed a significant inhibition Platelet aggregation. Policosanol, in pa- of platelet aggregation in PRP when a tients with type II hypercholesterolemia and submaximal ADP concentration was ad- positive pleiotropic properties (inhibition of ministeredSO062. platelet aggregation and lipid peroxidation), Postprandial glycemic response reduc- reduced thromboxane A(2) and malondi- tion. Sugar cane bioflavonoid was admin- aldehyde (MDA) serum levels. In rats, the istered to 10 healthy, nonsmoking, nor- percentage of inhibition of adenosine mal-weight young adults with normal diphosphate-induced aggregation (preincu- glucose tolerance at doses of 15, 50, or 100 bation with nitroprusside) was higher in mg of bioflavonoid. The treatment pro- platelet-rich plasma of policosanol-treated duced no significant differences among the animals than in control animals. Pretreat- mean glycemic index (GI) values of the ment with single doses of policosanol three extract test meals. The bioflavonoid significantly increased the nitroprusside-in- extract effectively reduced the GI value of a duced hypotensive effectSO006. D-003, admin- high-GI starchy meal by up to 37% without istered orally to Sprague–Dawley rats of any apparent side effectsSO026. 452 MEDICINAL PLANTS OF THE WORLD

Serum and liver cholesterol influence. D-003 showed prostacyclin PGI(2) levels Partially purified Okinawan sugar cane wax significantly larger than those of positive and fatty alcohol, administered to Wistar and negative controls and a dose-related rats at a dose of 0.5% of diet, significantly effectSO030. lowered the concentrations of serum and Toxicity. D-003, a mixture of higher ali- liver cholesterol in the rats. There were no phatic primary acids purified from sugar significant differences observed in phospho- cane wax, administered to Wistar rats at a lipid and TG levels either in serum or liver dose of 2000 mg/kg, was investigated ac- among the experimental groups. No signi- cording to the Acute Toxic Class (ATC) ficant differences in the amount of feces method (an alternative for the classical LD50 excreted by the three experimental diet test). The results obtained in this study de- groups and no significant differences in the fined D-003 oral acute toxicity as unclassi- excretion of cholesterol were foundSO066. fied. D-003, administered orally to rats of Okinawan sugar cane rind, administered to both sexes at doses of 50, 200, and 1250 mg/ Wistar rats, produced no significant differ- kg for 90 days, produced no evidence of ences in the food intakes and the liver treatment-related toxicity. Data analysis weight between the rats fed sugar cane rind of body weight gain, food consumption, and other groups. The addition of 1% cho- clinical observations, blood biochemical, lesterol to the diet produced a significant hematology, organ weight ratios, and histo- increase in body weight gain but the supple- pathological findings did not produce sig- mentation of sugar cane rind (2%) showed nificant differences between control and an effect on weight control of rats. The se- treated groups. The results indicated that D- rum cholesterol and TG levels of the rats 003 orally administered to rats was safe and given sugar cane rind were lowered signifi- that no drug-related toxicity was detected cantly. The lipid levels in the liver were al- even at the highest doses investigated in most the same when compared with the both acute (200 mg/kg) and subchronic control groups. The amount of feces ex- (1205 mg/kg) studiesSO010. D-003 was admin- creted by the rats fed with sugar cane rind istered intragastrically to CEN/NMRI mice was approx 37% more than that of the con- (6–8 animals per sex per group) at doses of trol group, and the fecal excretion of neu- 5, 50, or 500 mg/kg for 90 days. The treat- tral sterols was significantly higherSO069. ment did not increase the frequency of Spinal cord ischemia. D-003, administered micronucleated polychromatic erythrocytes to New Zealand rabbits at doses of 25 and evaluated only in female mice or the ratio 200 mg/kg for 10 days, significantly in- of polychromatic to normochromatic eryth- creased the mean scores reached 4 hours af- rocytes, compared with the controls. D-003 ter reperfusion, although no dose relation did not change the sperm count or the fre- was observed. Twenty-four hours after quency of all types of abnormal head shapes, reperfusion, no deaths occurred in both compared with the controls. D-003, admin- sham and D-003 treated groups; meanwhile, istered to mice of both sexes at a dose of 2 g/ in positive controls, the mortality rate was kg for 6 days, produced no cytotoxic and 38.5%. In addition, 100% of sham, 69% and genotoxic effects. D-003, administered 77% of rabbits treated with D-003 at 25 and intragastrically to five male Sprague–Dawley 200 mg/kg, respectively, did not show histo- rats at a dose of 1.25 g/kg for 90 days, pro- pathological changes. One hundred percent duced no single-strand breaks or alkali- of positive control animals showed severe labile site induction on DNA in liver cells damage. Animals treated with both doses of using Comet assaySO034. D-003 (suspended in SACCHARUM OFFICINARUM 453

1% acacia gum solution), administered tected. Eight of treated rats (six males and intragastrically to rats at doses of 5, 100, and two females) died during the study, five of 1000 g/kg/day on days 6 through 15 of ges- them (four males and one female) from tation, produced no evidence of maternal or among those receiving the highest dose developmental toxicity. Maternal clinical (5000 mg/kg). All deaths were related to signs of toxicity were not observed, and the gavage manipulation of higher dosesSO035. analysis of initial body weight and the body Voluntary ethanol intake effect. SKV, an weight gain during the treatment period Ayurvedic formula produced by the fermen- were comparable among the groups treated tation of cane sugar with raisins and 12 with D-003 and control. D-003 produced no herbal ingredients, decreased the voluntary adverse effects on reproductive performance ethanol ingestion in the rats and increased or on embryonic or fetal development, food intake. Electrocardiogram and electro- including visceral and skeletal examina- encephalogram studies in alcoholic rats tionSO039. D-003, in the neutral red (NR) showed cardiac depression; augmentation of assay and in the Ames test at doses up to 1 frequency and amplitude of the D, ', and I mg/mL for up to 72 hours, produced no cy- waves; and weakness in the E waves. The totoxic evidences. D-003 (5–5000 Pg/ changes were reversed during SKV-induced plate) did not increase the frequency of voluntary alcohol restriction. The involve- reverse mutations in the Ames test in both ment in the electrocardiogram and electro- alternatives with or without S9 mix meta- encephalogram wave patterns was associated bolic activation and a preincubation with improvement in blood glucose and stepSO042. Policosanol, administered intragas- plasma protein levels and reduction in J- trically to 24 beagle dogs (12 males and 12 glutamyl transpeptidase activitiesSO065. females) at doses of 30 and 180 mg/kg daily Weight loss. Polysaccharide fraction of the for 52 weeks, produced no mortality in any dried stem, administered intragastrically to group. Policosanol was well tolerated, and rats at a dose of 1 g/kg daily for 14 weeks, no toxic symptoms were observed. All was inactive vs high-sugar diet. Intraperito- groups showed similar weight gain and food neal administration at doses of 20 and 40 consumption. Lipid profile determinations mg/kg for 14 weeks was activeSO116. showed that policosanol decreased total REFERENCES cholesterol by approx 20% from 8 to 52 SO001 Gamez, R., R. Mas, M. Noa, et al. Ef- weeks. TGs and HDL-C were not changed fects of chronic administration of D- significantly. No blood biochemistry or 003, a mixture of sugar cane wax high histopathological disturbances were ob- molecular acids, in beagle dogs. Drugs servedSO014. Policosanol, administered orally Exp Clin Res 2004; 30(2): 75–88. to Sprague–Dawley rats at doses of 50, 500, SO002 Amer, S., K.J. Na, M. El-Abasy, M. 2500, or 5000 mg/kg for 6 months, produced Motobu, Y. Koyama, K. Koge, and Y. Hirota. Immunostimulating effects of no significant differences in blood biochem- sugar cane extract on X-ray radiation istry, hematology, organ weight ratios, and induced immunosuppression in the histopathological findings compared with chicken. Int Immunopharmacol 2004; controls, nor any tendency with the dose. 4(1): 71–77. Body weight gain and food consumption in SO003 Mendoza, S., M. Noa, R. Mas, and N. the groups receiving 2500 or 5000 mg/kg Mendoza. Effect of D-003, a mixture of high molecular weight primary acids tended to be lower than in the control from sugar cane wax, on paracetamol- group, but difference was not significant. No induced liver damage in rats. Int J Tis- drug-related toxicity symptoms were de- sue React 2003; 25(3): 91–98. 454 MEDICINAL PLANTS OF THE WORLD

SO004 Takara, K., D. Matsui, K. Wada, T. SO014 Mesa, A. R., R. Mas, M. Noa, et al. Ichiba, I. Chinen, and Y. Nakasone. Toxicity of policosanol in beagle dogs: New phenolic compounds from one-year study. Toxicol Lett 1994; Kokuto, non-centrifuged cane sugar. 73(2): 81–90. Biosci Biotechnol Biochem 2003; SO015 Carbajal, D., M. L. Arruzazabala, R. 67(2): 376–379. Mas, V. Molina, and S.Valdes. Effect of SO005 Ledon, N., A. Casaco, V. Rodriguez, et policosanol on experimental thrombo- al. Anti-inflammatory and analgesic sis models. Prostaglandins Leukot Es- effects of a mixture of fatty acids iso- sent Fatty Acids 1994; 50(5): 249–251. lated and purified from sugar cane wax SO016 Arruzazabala, M. L., D. Carbajal, R. oil. Planta Med 2003; 69(4): 367–369. Mas, V. Molina, S. Valdes, and A. La- SO006 Arruzazabala, M.L., D. Carbajal D, R. guna. Cholesterol-lowering effects of Mas R, S. Valdes, and V. Molina V. policosanol in rabbits. Biol Res 1994; Pharmacological interaction between 27(3-4): 205–208. Policosanol and nitroprusside in rats. J SO017 Hikino, H., M. Takahashi, C. Konno, Med Food 2001; 4(2): 67–70. A. Ishimori, T. Kawamura, and T. SO007 Noa, M., S. Mendoza, R. Mas, and N. Namiki. Effect of glycans of Saccharum Mendoza. Effect of D-003, a mixture of officinarum on carbohydrate and lipid high molecular weight primary acids metabolism of rats. J Ethnopharmacol from sugar cane wax, on CL4C-in- 1985; 14(2–3): 261–268. duced liver acute injury in rats. Drugs SO018 Chinen, I., K. Oouchi, H. Tamaki, and Exp Clin Res 2002; 28(5): 177–183. N. Fukuda. Purification and properties SO008 Gamez, R., R. Mas, M. Noa, et al. Six- of thermostable beta-xylosidase from month toxicity study of oral adminis- immature stalks of Saccharum officin- tration of D-003 in Sprague Dawley arum L. (sugar cane). J Biochem (To- rats. Drugs R D 2002; 3(6): 375–386. kyo) 1982; 92(6): 1873–1881. SO009 Menendez, R., A.M. Amor, I. Rodeiro, SO019 Chinen, I., T. Nakamura, and N. et al. Policosanol modulates HMG- Fukuda. Purification and properties of CoA reductase activity in cultured fi- alpha-galactosidase from immature broblasts. Arch Med Res 200; 32(1): stalks of Saccharum officinarum (sugar 8–12. cane). J Biochem (Tokyo) 1981; 90(5): SO010 Gamez, R., R. Mas, M. Noa, et al. 1453–1461. Acute and oral subchronic toxicity of SO020 Mas, R., G. Castano, J. Fernandez, et D-003 in rats. Toxicol Lett 2000; al. Long-term effects of policosanol on 118(1-2): 31–41. obese patients with Type II hypercho- SO011 Menendez, R., V. Fraga, A.M. Amor, lesterolemia. Asia Pacific J Clin Nutr R.M. Gonzalez, and R. Mas. Oral ad- 2004; 13(Suppl): S102. ministration of policosanol inhibits in SO021 Mas, R., G. Castano, J. Fernandez, et vitro copper ion-induced rat lipo- al. Long- term effects of policosanol on protein peroxidation. Physiol Behav older patients with Type 2 diabetes. 1999; 67(1): 1–7. Asia Pacific J Clin Nutr 2004; SO012 Molina Cuevas, V., M.L. Arruzazabala, 13(Suppl): S101. D. Carbajal Quintana, R. Mas Ferreiro, SO022 Murphy, K. J., D. A. Saint, and P. R. and S. Valdes Garcia. Effect of poli- Howe. Lack of effect of sugar cane and cosanol on arterial blood pressure in sunflower seed policosanols on plasma rats. Study of the pharmacological in- cholesterol in rabbits. Asia Pacific J teraction with nifedipine and propra- Clin Nutr 2004; 13(Suppl): S69. nolol. Arch Med Res 1998; 29(1): SO023 El-Abasy, M., M. Motobu, K. 21–24. Nakamura, K. Koge, T. Onodera, O. SO013 Fraga, V., R. Menendez, A.M. Amor, Vainio, P. Toivanen, and Y. Hirota. R.M. Gonzalez, S. Jimenez, and R. Preventive and therapeutic effects of Mas. Effect of policosanol on in vitro sugar cane extract on cyclophospha- and in vivo rat liver microsomal lipid mide-induced immunosuppression in peroxidation. Arch Med Res 1997; chickens. Int Immunopharmacol 2004; 28(3): 355–360. 4(8): 983–990. SACCHARUM OFFICINARUM 455

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peroxidation by the oral administra- cerebral ischemia in Mongolian ger- tion of D-003, a mixture of very long- bils. Braz J Med Biol Res 1999; 32(10): chain saturated fatty acids. Can J 1269–1276. Physiol Pharmacol 2002; 80(1): 13–21. SO053 Re, L., S. Barocci, C. Capitani, et al. SO044 Takara, K., D. Matsui, K. Wada, T. Effects of some natural extracts on the Ichiba, and Y. Nakasone. New antioxi- acetylcholine release at the mouse dative phenolic glycosides isolated neuromuscular junction. Pharmacol from Kokuto non-centrifuged cane Res 1999; 39(3): 239–245. sugar. Biosci Biotechnol Biochem SO054 Noa, M., R. Mas, and R. Mesa. Effect 2002; 66(1): 29–35. of policosanol on intimal thickening in SO045 Castano, G., R. Mas, L. Fernandez, J. rabbit cuffed carotid artery. Int J Car- Illnait, R. Gamez, and E. Alvarez. Ef- diol 1998; 67(2): 125–132. fects of policosanol 20 versus 40 mg/ SO055 Ferriolli, E., R. O. Dantas, R. B. day in the treatment of patients with Oliveira, and F. J. Braga. The influence type II hypercholesterolemia: a 6- of ageing on oesophageal motility after month double-blind study. Int J Clin ingestion of liquids with different vis- Pharmacol Res 2001; 21(1): 43–57. cosities. Eur J Gastroenterol Hepatol SO046 Mirkin, A., R. Mas, M. Martinto, et al. 1996; 8(8): 793–798. Efficacy and tolerability of policosanol SO056 Noa, M., M. C. de la Rosa, and R. Mas. in hypercholesterolemic postmeno- Effect of policosanol on foam-cell for- pausal women. Int J Clin Pharmacol mation in carrageenan-induced granu- Res 2001; 21(1): 31–41. lomas in rats. J Pharm Pharmacol SO047 Menendez, R., R. Mas, A. M. Amor, I. 1996; 48(3): 306–309. Rodeiros, R. M. Gonzalez, and J. L. SO057 Aleman, C. L., M. N. Puig, E. C. Elias, Alfonso. Inhibition of cholesterol bio- et al. Carcinogenicity of policosanol in mice: an 18-month study. Food Chem synthesis in cultured fibroblasts by D- Toxicol 1995; 33(7): 573–578. 003, a mixture of very long chain SO058 Noa, M., R. Mas, M. C. de la Rosa, and saturated fatty acids. Pharmacol Res J. Magraner. Effect of policosanol on 2001; 44(4): 299–304. lipofundin-induced atherosclerotic le- SO048 Costa, M. J., L. H. Moraes, F. M. Bion, sions in rats. J Pharm Pharmacol 1995; M. A. Rivera, L. S. Moura, and M. L. 47(4): 289–291. Conceicao. Efficacy evaluation of the SO059 Agata, H., N. Kondo, A. Yomo, et al. molasses supplementation in normal Sensitization to sugar cane pollen in Arch Latinoam and depleted rats diet. Okinawan allergic children. Asian Pa- Nutr 2000; 50(4): 341–345. cific J Allergy Immunol 1994; 12(2): SO049 Noa, M., R. Mas, and R. Mesa. A com- 151–154. parative study of policosanol vs SO060 Menendez, R., S. I. Fernandez, A. Del lovastatin on intimal thickening in Rio, et al. Policosanol inhibits choles- rabbit cuffed carotid artery. Pharmacol terol biosynthesis and enhances low Res 2001; 43(1): 31–37. density lipoprotein processing in cul- SO050 Molina, V., M. L. Arruzazabala, D. tured human fibroblasts. Biol Res Carbajal, R. Mas, and S. Valdes. 1994; 27(3–4): 199–203. Antiplatelet and antithrombotic effect SO061 Arruzazabala, M. L., V. Molina, D. of D-003. Pharmacol Res 2000; 42(2): Carbajal, S. Valdes, and R. Mas. Effect 137–143. of policosanol on cerebral ischemia in SO051 Arruzazabala, M. L., M. Noa, R. Mongolian gerbils: role of prostacyclin Menendez, R. Mas, D. Carbajal, S. and thromboxane A2. Prostaglandins Valdes, and V. Molina. Protective ef- Leuko Essent Fatty Acids 1993; 49(3): fect of policosanol on atherosclerotic 695–697. lesions in rabbits with exogenous hy- SO062 Arruzazabala, M. L., D. Carbajal, R. percholesterolemia. Braz J Med Biol Mas, M. Garcia, and V. Fraga. Effects Res 2000; 33(7): 835–840. of Policosanol on platelet aggrega- SO052 Molina, V., M. L. Arruzazabala, D. tion in rats. Thromb Res 1993; 69(3): Carbajal, et al. Effect of policosanol on 321–327. SACCHARUM OFFICINARUM 457

SO063 Frencken, J. E., P. Rugarabamu, and J. SO074 Fahey, G. C., J. E. Williams, and G.A. Mulder. The effect of sugar cane chew- McLaren. Influence of molasses lig- ing on the development of dental nin-hemicellulose fractions in rat caries. J Dent Res 1989; 68(6): nutrition. J Nutr 1976; 106(10): 1102–1104. 1447–1451. SO064 Oji, E. O. Locally available plant ma- SO075 Dumaswala, U. J., R. U. Dumaswala, terials for use as ophthalmic surgical and A. Venkataraman. The relative swabs. Ann R Coll Surg Engl 1986; effect of dietary fats and carbohydrates 68(6): 307–309. on lipid metabolism in the albino rat. SO065 Shanmugasundaram, E. R., and K. R. 1: Ital J Biochem 1976; 25(4): 289– Shanmugasundaram. An Indian herbal 303. formula (SKV) for controlling volun- SO076 Walters, R. L., I. M. Baird, P. S. tary ethanol intake in rats with Davies, et al. Effects of two types of di- chronic alcoholism. J Ethnophar- etary fibre on faecal steroid and lipid macol 1986; 17(2): 171–182. excretion. Br Med J 1975; 2(5970): SO066 Sho, H., I. Chinen, and N. Fukuda. 536–538. Effects of Okinawan sugar cane wax SO077 Suwal, P. N. Medicinal plants of and fatty alcohol on serum and liver Nepal. Ministry of Forests, Department lipids in the rat. J Nutr Sci Vitaminol of Medicinal Plants, Thapathali, (Tokyo) 1984; 30(6): 553–559. Kathmandu, Nepal 1970. SO067 Li, X. Y., R. Nolte, and W. Vogt. Natu- SO078 Couvee. Compilation of herbs, plants, ral antibodies against a polysaccha- crops supposed to be effective in vari- ride (Bo) from sugar cane mediate its ous complaints and illness. J Sci Res complement-activating effect. Immu- 1952; 1S: 1. nobiology 1983; 164(2): 110–117. SO079 Ahmad, Y.S. A note on the plants of SO068 Li, X., and W. Vogt. Activation of the medicinal value found in Pakistan. classical complement pathway by a Government of Pakistan Press, polysaccharide from sugar cane. Immu- Karachi, 1957. nopharmacology 1982; 5(1): 31–38. SO080 Lin, Y. C., J. T. Huang and H. C. Hsiu. SO069 Sho, H., I. Chinen, K. Uchihara, and Studies on the hypoglycemic activity N. Fukuda. Effects of Okinawan sugar of the medicinal herbs. Formosan Med cane rind on serum and liver choles- Assoc 1964; 63(8): 400–404. terol and triglyceride levels in the rat. SO081 Pongpan, A., W. Avirutnant, and P. J Nutr Sci Vitaminol (Tokyo) 1981; Chumsri. Some Thai plants as sub- 27(5): 463–470. strates for microbial protein produc- SO070 Grant, E.C. Food allergies and mi- tion. Mahidol Univ J Pharm Sci 1983; graine. Lancet 1979; 1(8123): 966–969. 10(1): 15–18. SO071 Varavithya, W., P. Posayanond, K. SO082 Kimura, Y., H. Okua, N. Shoji, T. Tontisirin, L. Chernjitra, and C. Taemto, and S. Arichi. Effects of non- Kashemsant. Oral hydration in in- sugar fraction in black sugar on lipid fantile diarrhoea. Southeast Asian J and carbohydrate metabolism. Part II. Trop Med Public Health 1978; 9(3): New compounds inhibiting elevation 414–419. of plasma insulin. Planta Med 1984; SO072 West, G. B. Glucans and dextrans in 1984(5): 469–473. rats and man. Int Arch Allergy Appl SO083 Yadava, V. S., and K. Misra. Vanilloyl- Immunol 1978; 56(4): 380–382. 1-O-beta-D-glucoside acetate from the SO073 Baird, I. M., R. L. Walters, P. S. roots of Saccharum officinarum. Indian Davies, M. J. Hill, B. S. Drasar, and D. J Chem Ser B 1989; 28(1): 875–877. A. Southgate. The effects of two di- SO084 Morita, I., S. Morishita, T. Tatsumi, etary fiber supplements on gastro- and S. Kako. Invert sugar having high intestinal transit, stool weight and inversion. Patent-Japan Kokai-74 frequency, and bacterial flora, and 134,852 1974. fecal bile acids in normal subjects. Me- SO085 Doepke, W., and U. Hess. Obtaining tabolism 1977; 26(2): 117–128. phytosterol mixtures from oil fraction 458 MEDICINAL PLANTS OF THE WORLD

sof sugar cane waxes. Patent-Ger SO097 Seetharam, K. A., and J.S. Pasricha. (East) 1974; 104,513. Condiments and contact dermatitis of SO086 Ferber, L., and F. G. Carpenter. Plant the finger-tips. Indian J Dermatol pigments as colorants in cane sugar. Venerol Leprol 1987; 53(6): 325–328. US Agr Res Serv South Reg ARS SO098 De A Ribeiro, R., F. Barros, M. Mar- 1975; 51: 23. garida, et al. Acute diuretic effects in SO087 Da Gloria, N. A., and A. A. Rodella. conscious rats produced by some me- Inorganic quantitative analysis of sugar dicinal plants used in the state of cane juice, vinasse, and molasses. I. Cal- Sao Paulo, Brasil. J Ethnopharmacol cium, magnesium, potassium, sulfur and 1988; 24(1): 19–29. phosphorus determination in single ex- SO099 Takagi, S. Isolation of polysaccharides tract. An Esc Super Agr Luiz Dr as pharmaceuticals from sugarcane and Queiroz Univ Sao Paulo 1972; 29: 5. its molasses. Patent-Japan Kokai Tok- SO088 Dubey, R. C., and K. Misra. Flavonoids kyo Koho-61 83,130 1986; 13 pp. of sugar cane. J Indian Chem Soc SO100 Holdsworth, D., and T. Rali. A survey 1974; 51: 653. of medicinal plants of the southern SO089 Misra, K. and R. C. Dubey. Anthocya- Highlands, Papua New Guinea. Int J nin of sugarcane. Curr Sci 1974; 43: Crude Drug Res 1989; 27(1): 1–8. 544A. SO101 Vicente, C., J. L. Mateos, M. M. SO090 Kapadia, G. J., E. B. Chung, B. Ghosh, Pedrosa, and M.E. Legaz. High-perfor- et al. Carcinogenicity of some folk me- mance liquid chromatographic deter- dicinal herbs in rats. J Nat Cancer Inst mination of sugars and polyols in 1978; 60: 683–686. extracts of lichens and sugarcane SO091 Kuhnie, J. A., P. H. Moore, W. F. juice. J Chromatogr 1991; 553(1/2): Haddon, and M. M. Fitch. Identifica- 271–283. tion of gibberellins from sugar cane SO102 Misra, C. S., and K. Misra. Dimethyl plants. J Plant Growth Regul 1983; apigenin 4'-O-beta-D-glucopyranoside 2(1): 59–71. from Saccharum officinarum leaves. SO092 Patron, N. H., P. Smith, and T. J. Curr Sci 1978; 47: 152. Mabry. Identification of flavonoid SO103 Irvine, J. E. Variation of non-sucrose compounds in HPLC separation of solids in sugarcane. I. Potassium. Sugar sugar cane colorants. Int Sugar J 1985; J 1978; 41(5): 28–30. 87(1043): 213–215. SO104 Misra, K., and C. S. Misra. Flavonoids SO093 Goswami, P. C., H. D. Singh, and J. N. of Saccharum officinarum flowers. In- Baruah. Isolation of phytosterols from dian J Chem Ser B 1979; 18: 88. sugarcane press mud and microbial SO105 Jin, Y. N., H. Z. Liang, C. Y. Cao, Z. conversion of the phytosterols to 17- W. Wang, R. S. Shu, and X. Y. Li. Im- ketosteroids. Curr Sci 1984; 53917): munological activity of bagasse 917–919. polysaccharides. Chung-Kuo Yao Li SO094 Taahashi, M., C. Konno, and H. Hsueh Pao 1981; 2: 269–275. Hikino. Isolation and hypoglycemic SO106 Bhattacharjee, J. W., R. P. Saxena, and activity of saccharin A, B, C, D, E, and S.H. Zaidi. Experimental studies on F, glycans of Saccharum officinarum the toxicity of bagasse. Environ Res stalks. Planta Med 1985; 1985(3): 1980; 23: 68–76. 258–260. SO107 Kato, A., J. Azuma, and T. Koshijima. SO095 Kato, A., J. I. Azuma, and T. A new feruloylated trisaccharide from Koshijima. Isolation and identification bagasse. Chem Lett 1983; 1983(1): of a new feruloylated tetrasaccharide 137–140. from bagasse lignin-carbohydrate com- SO108 Mabry, T. J., Y. L. Liu, J. Pearce, et al. plex containing phenolic acid. Agr New flavonoids from sugarcane (Sac- Biol Chem 1987; 51(6): 1691–1693. charum). J Nat Prod 1984; 47(1): SO096 Smith, R. M., and M. Martin-Smith. 127–130. Triterpen methyl ethers in leaf waxes SO109 Achamaas, G., and R. Thawornset. of Saccharum and related genera. Phy- Phytochemical and anticancer screen- tochemistry 1978; 17(8): 1307–1312. ing of Schefflera leucantha and Saccha- SACCHARUM OFFICINARUM 459

rum officinarum. Undergraduate Spe- popularly used in Guatemala for the cial Project Report 1980; 69 pp. treatment of dermatomucosal dis- SO110 Hirschhorn, H. H. Botanical remedies eases. J Ethnopharmacol 1987; 20(3): of the former Dutch East Indies (Indo- 223–237. nesia). I. Eumycetes, Pteridpohyta, SO120 Costa, M., L. C. di Stasi, M. Kirizawa, Gymnospermae, Angiospermae (Mono- S. L. J. Mendacolli, C. Gomez, and G. cotyledons only). J Ethnopharmacol Trolin. Screening in mice of some me- 1983; 7(2): 123–156. dicinal plants used for analgesic pur- SO111 Martinez, M. A. Medicinal plants used poses in the state of Sao Paulo. J in a Totonac community of the Sierra Ethnopharmacol 1989; 27(1/2): 25–33. Norte del Puebla: Tuzamapan de SO121 Darias, V., L. Bravo, R. Rabanal, C. Galeana, Puebla, Mexico. J Ethno- Sanchez Mateo, R. M. Gonzalez Luis, pharmacol 1984; 11(2): 203–221. and A. M. Hernandez Perez. New con- SO112 Aswal, B. S., D. S. Bahakuni, A. K. tribution to the ethnopharmacological Goel, K. Kar, B. N. Mehrotra, and K.C. study of the Canary Islands. J Mukherjee. Screening of Indian plants Ethnopharmacol 1989; 25(1): 77–92. for biological activity: part X. Indian J SO122 Vedavathy, S., K. N. Rao, M. Rajaiah, Exp Biol 1984; 22(6): 312–332. and N. Nagaraju. Folklore information SO113 De A Ribeiro, R., M. M. R. Fiuza de from Ryalaseema region, Andhra Melo, F. de Baroz, C. Gomes, and G. Pradesh for family planning and birth Troln. Acute antihypertensive effect control. Int J Pharmacog 1991; 29(2): in conscious rats produced by some 113–116. medicinal plants used in the state of SO123 Aleman, C. L., R. Mas, C. Hernandez, Sao Paulo. J Ethnopharmacol 1986; I. Rodeiro, E. Cerejido, M. Noa, A. 15(3): 261–269. Capote, R. Menedez, A. Amor, V. SO114 Hedberg, I., O. Hedberg, P. J. Madati, Fraga, V. Sotolongo, and S. Jimenez. A K. E. Mshigeni, E. N. Mshiu, and G. 12-month study of policosanol oral Samuelsson. Inventory of plants used toxicity in Sprague Dawley rats. in traditional medicine in Tanzania. Toxicol Lett 1994; 70(1): 77–87. Part III. Plants of the families Papillion- SO124 Seabrook, W. B. adventures in Arabia aceae-Vitaceae. J Ethnopharmacol among the Bedouins, Druses, Whirling 1983; 9(2/3): 237–260. Dervishes & Yezidee devil worshipers. SO115 Li, X., B. Damerau, and W. Vogt. In- Blue Ribbon Book, New York 1927; fluence of a bagasse glucan (B-O) on 99–105 leukocyte aggregation and accumula- SO125 Holdsworth, D. K. Traditional medici- tion. Chung-Kuo Yao Li Hsueh Pao nal plants of Rarotonga, Cook Islands. 1985; 6(2): 137–140. Part II. Int J Pharmacog 1991; 29(1): SO116 Hikino, H., M. Takahashi, C. Konno, 71–79. A. Ishimori, T. Kawamura, and T. SO126 Lin, C. C. Crude drugs used for the Namiki. Effect of glycans of Saccharum treatment of diabetes mellitus in Tai- officinarum on carbohydrate and lipid wan. Amer J Chin Med 1992; 20(3/4): metabolism of rats. J Ethnopharmacol 269–279. 1985; 14(2/3): 261–268. SO127 Kimura, Y., H. Okuda, and S. Arichi. SO117 Anis, M., and M. Iqbal. Antipyretic Effects of non-sugar fraction in black utility of some Indian plants in tradi- sugar on lipid and carbohydrate me- tional medicine. Fitoterapia 1986; tabolism: part I. Planta Med 1984; 57(1): 52–55. 1984(4): 465–468 SO118 Caceres, A., L. M. Giron, and A. M. SO128 McGhie, T. Analysis of sugarcane fla- Martinez. Diuretic activity of plants vonoids by capillary zone electro- used for the treatment of urinary ail- phoresis. J Chromatogr 1993; 534(1): ments in Guatemala. J Ethno- 107–112. pharmacol 1987; 19(3): 233–245. SO129 Hope, B. E., D. G. Massey, and G. SO119 Caceres, A., L. M. Giron, S. R. Massey-Fournier. Hawaiian Materia Alvarado, and M.F. Torres. Screening Medica for asthma. Hawaiian Med J of antimicrobial activity of plants 1993; 52(6): 160–166. SERENOA REPENS 461

14 Serenoa repens (Bantam) Small

Common Names American United States Palmetta Della Florida Italy dwarf palm tree Palmetto de la sierra Spain Cabbage palm United States Palmetto fan palm United States Chou palmiste France Palmetto, dark United States Corifa del Malabar Italy Palmier nain France Grote waaier palm Netherlands Palmier pitic Romania Ju zhong lu China Palmito Portugal Kaapiopalmu Finland Palmito Spain Karlikova palma Ukraine Sabal du Mexique France Karlikovaya palma Russia Sabal du Texas France Kis legyezopalma Hungary Sabal United States Niska palma Bulgaria Sagepalme Germany Palma enana Spain Sagepalmefruchte Germany Americana Sagpalmetto Sweden Palma nana Italy Saw palmetto United Kingdom Palma sabal Spain Saw palmetto United States Palmeen The Isle of Man (Manx) Serenoa palmu Finland Palmet Netherlands Solfjaderspalm Sweden

BOTANICAL DESCRIPTION zomes. The bright-green, fan-shaped ever- The saw palmetto is a creeping, horizontal green leaves are approx 1 m wide, with 15 periennial of the PALMAE family. Saw pal- to 30 divisions that are roundish in outline metto usually grows as a small shrub to a and are borne on slender stalks edged with height of 0.6–2.1 m. Occasionally, it grows spines. The white, small flowers are borne as a small tree with erect or oblique stems, on stalked panicles that grow from the leaf 6–7.5 m tall. In its procumbent form, saw axils. The flower spike is thickly hairy and palmetto branches form a tangled mass, considerably shorter than the leaves. The with the root crown projecting above to petioles are armed with sharp spines, giving support the foliage. The stem systems run saw palmetto its common name. The fruit is parallel to the soil surface, eventually a fleshy, elipsoid drupe, 1.2–2.5 cm long, branching beneath the substrate to form rhi- one-seeded, which is green or yellow before

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 461 462 MEDICINAL PLANTS OF THE WORLD ripening but becomes reddish brown or Eicosenoic acid: FrSR100 blackish brown as it matures. Farnesol: FrSR105 Geraniol, geranyl: Fr 16SR120 ORIGIN AND DISTRIBUTION Geranyl-geraniol: FrSR105 This palm is native to the southeastern Glycerol: Sd oilSR080 United States, from Florida to North Caro- Hexacosan-1-ol: Fr 170SR117 lina. It grows in coastal dune areas and in- Hexatriaconta-2-cis-6-cis-10-cis-14-cis-18-cis- land pine woodlands, often forming dense, 22-trans-26-trans-30-trans-34-trans-nonaen- 1-ol,3-7-11-15-19-23-31-35-nonamethyl: impenetrable thickets in the understory of Fr 19SR120 pines, such as slash pine (Pinus elliottii) and Lauric acid: FrSR130, Fr Pu, SdSR113 longleaf pine (Pinus palustris). Laurin, 1-mono: FrSR034 SR101 SR113 TRADITIONAL MEDICINAL USES Linoleic acid: Fr , Sd Linolenic acid: Fr Pu, SdSR113 Germany. The fruit is taken orally as a Lupen-3-one: FrSR124 source of estrogenSR077. Lupeol: FrSR120 North America. Hot water extract of the Mannitol: Sd oilSR080 fruit is taken orally as a sedativeSR127. Myristic acid ethyl ester: FrSR112 United States. Hot water extract of the Myristic acid: FrSR100, SdSR113 SR034 fruit is taken orally for prostate inflam- Myristin, 1-mono: Fr SR117 SR123 Octacosan-1-ol: Fr 0.46% mation and for benign prostatic hyper- SR106 SR113 SR098,SR109 Oleic acid: Fr , Sd plasia . Fluid extract of the fruit is Palmitic acid: Fr 9.5%SR117, SdSR113 SR126 taken orally for dysmenorrhea . Hot wa- Palmitoleic acid: FrSR100 ter extract of the fruit is used to treat colds Phytol: FrSR120 and for irritated throat. A teaspoon of ber- Populnin: FrSR121 ries in a cup of boiling water is cooled and Quercitrin, iso: FrSR121 taken 1 or 2 cups a daySR128. Rhoifolin: FrSR121 Rutin: FrSR121 CHEMICAL CONSTITUENTS Serenoa polyprenol 2: Fr 5SR120 (ppm unless otherwise indicated) Serenoa polyprenol 3: Fr 35SR120 1-Monolaurin: Dried FrSR034 Serenoa polysaccharide: FrSR074 1-Monomyristin: Dried FrSR034 Serenoa triacylglycerols: Fr Pu, SdSR113 Anthranilic acid: FrSR078 Sitosterol, E, 6-O-caprinoyl-E-D-glucoside: Arachic acid: FrSR100 FrSR121 Campesterol: FrSR124 Sitosterol, E, 6-O-lauryl-E-D-glucoside: FrSR121 Capric acid: Fr Pu, SdSR113, Sd oilSR080 Sitosterol, E, 6-O-myristyl-E-D-glucoside: FrSR121 Caprinic acid: FrSR120 Sitosterol, E, diglucoside: FrSR121 Caproic acid ethyl ester: FrSR112 Sitosterol, E, laurate: FrSR121 Caproic acid: Sd oilSR080, Fr 1.5%SR117 Sitosterol, E, myristate: FrSR121 Caprylic acid ethyl ester: FrSR112 Sitosterol, E, palmitate: FrSR121 Caprylic acid: FrSR100, Sd oilSR100 Sitosterol, E: FrSR124 Carotene: Sd oilSR080 Stearic acid: Fr 1.8%SR117 Coumaric acid, para: Fr Ju (unriped)SR104 Sterols (3): Mesocarp, EpicarpSR079 Cycloartenol, 24-methylene: FrSR105 Stigmasterol acetate: FrSR105 Cycloartenol: FrSR105 Stigmasterol: FrSR124 Daucosterol: Fr 47SR077 Tetracosan-1-ol: Fr 40SR117 Decanoid acid: FrSR120 Triacontan-1-ol: FrSR123 Dotriaconta-2-cis-6-cis-10-cis-14-cis-18-trans- Tridecanoid acid: FrSR101 22-trans-26-trans-octaen-1-ol,3-7-11-15-19- Undecanoid acid: FrSR130 23-27-31-octamethyl: Fr 270SR120 Valerianic acid ethyl ester: FrSR112 SERENOA REPENS 463

PHARMACOLOGICAL ACTIVITIES extract, in 11 different tissue specimens, re- AND CLINICAL TRIALS duced the mean uptake of DHT and T by Adaptation to resistance training. AN- 40.9% and 41.9%, respectively, in all tissue DRO-6 mixture, containing 300 mg andros- specimensSR044. Lipidic extract, in human tenedione, 150 mg dehydroepiandrosterone, foreskin fibroblasts, was incubated with [3H] 750 mg Tribulus terrestris, 625 mg chrysin, T or [3H] DHT at different dilutions (5.7– 300 mg indole-3-carbinol, and 540 mg saw 28.6 U/mL. One unit was defined as the palmetto, administered daily to 10 young amount of extract required to inhibit 50% men 3 days/week for 8 weeks, did not in- of the specific binding (inhibitory concen- 3 crease serum testosterone (T) concentra- tration [IC]50) of [ H]1881 to rat prostate tions, reduced the estrogenic effect of cytosol. A dilution of 28.6 U/mL signifi- androstenedione, and did not augment the cantly altered the formation of DHT and adaptations to resistance trainingSR062. strongly inhibited 3-ketosteroid reductase- D-Adrenoreceptor blocking. Lipid frac- mediated conversion of DHT to 5-D-an- tion of the dried fruit was active. The bio- drostane-3 D, 17-E-diol. Dilution of 7.1 U/ logical activity has been patentedSR100. mL extract resulted in 50% inhibition of the Extract of the dried fruit, administered to binding of 2 u 10–9 M [3H]DHT to its recep- male adults at a concentration of 125 Pg/ tor. Sucrose gradient centrifugation of the mL, inhibited 3H-prozosin binding to cloned radioactive cell lysate of fibroblasts demon- human prostatic adrenoreceptorsSR063. strated that 28.6 U/mL extract abolished Androgenic effect. Extract, administered 70% of the 3.6 S receptor-complex radioac- to patients with benign prostatic hyperpla- tive peak. The results indicated that the sia (BPH) at a dose of 320 mg/day for 3 extract inhibited 5-D-reductase, 3-ketos- months, produced a statistically significant teroid reductase and receptor binding of reduction of dihydrotestosterone (DHT) androgensSR046. Permixon, administered to (2363 r 553 pg/g tissue, p < 0.001) and epi- rats with [3H]methyltrienolone as a ligand dermal growth factor (6.98 r 2.48 ng/g tis- at a concentration of 5 nM, inhibited com- sue, p < 0.01) and increased T values (1023 petitively the binding to the cytosolic recep- r 101 pg/g tissue, p < 0.001) mainly in the tor of the rat prostateSR047. Saw palmetto periurethral region of the BPH tissue. The herbal blend, administered to men with biochemical effects were similar to those symptomatic BPH for 6 months, reduced the obtained with finasteride. This enlargement prostatic tissue DHT levels by 32% from is responsible for urinary obstruction with 6.49 to 4.40 ng/g in the saw palmetto group respect to the subcapsular regionSR030. (p < 0.005), with no significant change in Permixon, in the prostatic cell lines LNCaP the placebo groupSR058. A 24-year-old woman and PC3, respectively, responsive and unre- with androgenetic alopecia who became sponsive to androgen stimulation, induced sensitized to topical minoxidil after using an a double proliferative/differentiative effect extemporaneous preparation of minoxidil in LNCaP cell line not observed in PC3 4% with retinoic acid in a propylene glycol cells. In PC3 cells cotransfected with wild- base, subsequently became sensitized to saw type androgen receptors and catalase re- palmetto, a topical herbal extract com- porter genes under the control of an monly promoted for hair-loss treatmentSR012. androgen-responsive element, the extract The liposterolic extract of Serenoa repens inhibited androgen-induced catalase (LSESr) and E-sitosterol, administered to transcriptionSR036. Permixon, the liposterolic healthy males between the ages of 23 and 464 MEDICINAL PLANTS OF THE WORLD

64 years, with mild-to-moderate androge- adults inhibited uptake of DHT in foreskin, netic alopecia, produced a highly positive uterus, and vaginal skinSR044 and was active SR046 response to treatment. The blinded investi- on fibroblasts, IC50 7.1 U/mL . Ethanol gative staff assessment report indicated that (95%) extract of the dried fruit, adminis- 60% of the study subjects dosed with the tered intragastrically to rats at a concentra- active study formulation were rated as im- tion of 300 mg/mL, reduced the weight of proved at the final visitSR018. Extract of the the ventral prostate or seminal vesicle in dried fruit, administered intragastrically to castrated rats after administration of ex- male rats at a dose of 300 mg/day, inhibited ogenous TSR089. the decrease in prostate weight induced by Anticrustacean activity. Ethanol (95%) castrationSR117. Lipid fraction in cell culture extract of the dried fruit produced weak was active on fibroblasts of human skin and activity on Artemia salina, lethal concentra- SR108 SR034 the prostate gland . Hexane extract of tion (LC)50 31.5 Pg/mL . the dried fruit, administered intragastrically Anti-edematous activity. Ethanol (95%) to rats at a dose of 1.8 g/day, was inactive vs extract of the dried fruit, administered T- and DHT-stimulated prostate growth in externally to mice at a concentration of castrated ratsSR084. 500 Pg, reduced croton oil ear edema by Androgenic receptor-binding activity. 42%SR089. Hexane extract of the dried fruit Ethanol (95%) extract of the dried fruit, at (PA-109), administered intragastrically to a concentration of 100 Pg/mL, was inactive rats at a dose of 5 g/kg, was active vs dext- vs displacement of DHT from rat prostate ran-induced pedal enemaSR088. androgen receptors. Administration to rats Anti-estrogenic activity. Serenoa repens produced weak activity vs 3H-methyltrieno- extract, administered to 35 patients with lone binding to cytosolic androgen recep- benign prostatic hypertrophy at a dose of tors in the ventral prostate of castrated rats, 160 mg twice daily for 3 months, produced SR089 IC50 1 mg/mL . Ethanol (95%) extract of negative result of nuclear fraction of estro- the dried fruit, in cell culture, was inactive gen receptors for high-affinity low-capacity on human skinSR110. Steroid fraction of the binding and the low-affinity high-capacity extract, administred to rats, was active on binding classes in 17 cases and cytosolic SR103 prostate gland, IC50 0.33 mg/mL . Etha- fraction of estrogen receptors in 6 of 18 nol (95%) extract of the dried fruit, admin- cases. Both estrogen receptors were detected istered to male rats, was inactive vs binding in all 15 samples examined, but in the of labeled DHT to the rat prostatic andro- treated group, nuclear fraction of estrogen gen receptorSR084. Hexane extract of the receptors were significantly (p < 0.01) lower dried fruit, administered to adults, reduced than in the untreated group. The cytosolic DHT binding to receptor in cultured geni- fraction of estrogen receptors remained al- SR082 tal skin fibroblasts, IC50 7.1 U/mL . most unchanged. Similar results were ob- Premixon, a liposterolic extract of the plant, tained for progesterone receptors: the inhibited competitively the binding of DHT nuclear fraction of the treated group pros- to the cytosolic receptor of the rat tatic samples was significantly (p < 0.01) prostateSR047. lower than that of the untreated groupSR043. Anti-androgenic effect. Sterol fraction of The fruit, taken orally by 35 adults with the dried fruit, in cell culture, was active on BPH at a dose of 160 mg/person, three times CA-PC3 and reduced androgen-induced re- a day for 3 months, suppressed expression of porter gene expression in transcriptional as- nuclear estrogen receptors and androgen SR036 SR043 say; IC50 50 Pg/mL . Administration to receptors . Hexane extract of the dried SERENOA REPENS 465 fruit, administered intragastrically to 35 enzymes of the arachidonic acid pathways. adults at a dose of 320 mg/day for 3 months, Results indicated that CO- and 5-LO-inhib- inhibited nuclear estrogen receptors in pro- iting principle of the extract SG 291 must static tissue samplesSR114. be localized in the acidic lipophilic fraction. Anti-inflammatory activity. Ethanol (95%) The CO and 5-LO inhibitory effects is an extract of the fruit, administered by gastric explanation for the in vivo observed an- intubation to guinea pigs at a dose of 5 g/kg, tiphlogistic and antiedematous activity of was active vs carrageenan-induced pedal the lipophilic extract SG 291SR042. Hexane edemaSR121. Hexane extract, administered by extract of the dried fruit, administered gastric intubation to guinea pigs at a dose of intragastrically to guinea pigs at a dose of 1 mL/kg, was active vs ultraviolet (UV)-in- 1 mL/kg, was active vs UV-induced duced erythema. The treatment was effec- erythema for up to 5 hours of exposure. A tive for up to 5 hours of exposure. A dose of dose of 5 mL/kg was effective after 7 hours 5 mL/kg was protective against UV after exposure. A dose of 5 mL/kg was active erythema after 7 hours of exposure. A dose vs dextran-induced generalized edema, his- of 3 mL/kg, administered to mice, was ac- tamine-induced papules, and IgE-dependent tive vs centrifugation-induced tail edema. passive cutaneous anaphylaxis in adrenalec- The extract was administered for 5 days tomized rats. A dose of 10 mg/kg was active before induction. A dose of 10 mL/kg, ad- vs histamine-induced cutaneous capillary ministered to rats, was active vs histamine- permeability increase, dextran- and 48/80- induced cutaneous capillary permeability induced papules, and IgE-dependent passive increase. The effect peaked in 3 hours. cutaneous anaphylaxis and inactive vs There was no significant activity after 24 bradykinin- and serotonin-induced papules. hours, and the activity was highly dose- Administration to mice at a dose of 3 mL/kg dependent. The dose was also active vs was active vs centrifugation-induced tail serotonin-, bradykinin-, 48/80-, and dex- edema. The extract was given for 5 days trose-induced papules, and immunoglobulin before inductionSR125. Ethanol extract of the (Ig) E-dependent passive cutaneous ana- dried fruit, administered intragastrically to phylaxis. The extract was given 30 minutes rats at a dose of 5 g/kgSR121, and water extract, before induction. A dose of 5 mL/kg, admin- administered intravenously at a dose of 0.3 istered to rats by gastric intubation, was ac- mg/kgSR074, were active vs carrageenan- tive vs dextran-induced generalized edema, induced pedal edema. histamine-induced papules in adrenalecto- Antioxidant activity. Ether extract of the mized rats, and IgE-dependent passive cuta- dried fruit, administered externally to neous anaphylaxis in adrenalectomized adults as an ingredient in cosmetic, was ratsSR125. The extract, SG 291 (Talso, Talso active. The biological activity has been uno) from the fruits, produced dual inhibi- patentedSR122. tion of the cyclo-oxygenase (IC50 28.1 Pg/ Antiphlogistic activity. Water extract of mL) and 5-lipoxygenase pathway (IC50 18 the fruit and an acidic polysaccharide pro- Pg/mL). Fraction A (acid lipophilic com- duced strong antiphlogistic activity. The pounds) inhibited the biosynthesis of cyclo- polysaccharide had an average molecular oxygenase (CO) and 5-lipoxygenase (5-LO) weight (MW) of 100,000 and contained as metabolites in the same intensity as the main sugar components galactose (38.4%), native extract, SG 291. The fractions B and arabinose (18.7%), and uronic acid (14%)SR074. C (fatty alcohols and sterols), and E-sito- Apoptosis induction. Permixon, in the sterol produced no inhibitory effect on both stroma and epithelium of normal prostate 466 MEDICINAL PLANTS OF THE WORLD and of BPH tissues from patients treated (41%) of the patients opted to continue with or without Permixon, produced cell therapySR050. numbers and proliferative indices higher in Cell-growth effect. Saw palmetto berry ex- BPH than in normal prostates. Apoptosis tract, in prostatic 267B-1, BRFF-41T, and values were similar. In normal prostates, LNCaP cell lines for 3 days, inhibited pro- there was no significant difference between liferation, IC50 20–30 nL/mL of medium for apoptotic and proliferative indices. In the 267B-1 and BRFF-41T and approx 10-fold BPH-treated group, Permixon significantly more for the LNCaP cell line. The effect on inhibited proliferation and induced cell the cell lines was not irreversible. Concen- death in both epithelium and stromaSR024. tration of 200 nL extract equivalent/mL in- Permixon, in cultures of fibroblast and hibited normal prostate cells by 20–25%. epithelial cells from the prostate, epididy- Growth of other nonprostatic cancer cell mis, testes, kidney, skin, and breast at a lines, i.e., Jurkat and HT-29 was affected by concentration of 10 Pg/mL, produced no approx 50 and 40%, respectively. Adminis- changes in the morphology of prostate cells, tration of the extract and DHT to LNCaP including accumulation of lipid in the cyto- cells decreased significantly the IC50 con- plasm and damage to the nuclear and mito- centration compared to LNCaP cells grown chondrial membranes. Permixon increased in the presence of serum and extract. The the apoptotic index for prostate epithelial reduced cellular growth after treatment of cells by 35 and 12% in the prostate stromal/ the cell lines with the extract may relate to fibroblast. A lesser apoptotic effect was decreased expression of Cox-2 and may re- found in skin fibroblast (3%). None of the sult from changes observed in the expression other primary cultures showed any increase of Bcl-2. Expression of Cox-1 under similar in apoptosis compared with the controlsSR025. conditions was not affected because of its Aromatase inhibition. Ether extract of the constitutive expressionSR053. dried fruit, administered to adults at con- Cell proliferation effect. Permixon, in bi- centrations of 91 and 132 Pg/mL, produced opsies of human prostate, did not affect weak activity on microsomesSR089. basal prostate cell proliferation, with the Calcium ion release inhibition. Hexane exception of two prostate specimens in extract of the dried fruit, in cell culture at a which a significant inhibition of basal pro- concentration of 10 Pg/mL, was active vs liferation was observed with the highest prolactin-induced calcium ion increase in concentration (30 Pg/mL) and inhibited Chinese hamster ovary cellsSR021. basic fibroblast growth factor (b-FGF)-in- Category III prostatitis/chronic pelvic duced proliferation of human prostate cell pain syndrome. Extract, administered to cultures. This effect was significant for the men 24 to 58 years old (mean age 43.2), di- highest concentration of Permixon. In some agnosed with category III prostatitis (CP)/ prostate samples, a similar inhibition was chronic pelvic pain syndrome (CPPS), at a also noted with lower concentrations. Un- dose of 325 mg daily for 1 year, produced no saturated fatty acids ranging from 1 to 30 ng/ appreciable long-term improvement. There mL did not affect the basal prostate cell pro- was a decrease of mean total National Insti- liferation; a slight increase in cell prolifera- tutes of Health Chronic Prostatitis Symp- tion was noted in one prostate specimen. tom Index score from from 24.7 to 24.6 in Doses of 1, 10, or 30 Pg/mL markedly inhib- the saw palmetto arm (p = 0.41). There were ited the b-FGF-induced cell proliferation to three cases of headache in the saw palmetto the basal value. Lupenone, hexacosanol, group. At the end of the trial, 13 of 32 and the unsaponified fraction of Permixon SERENOA REPENS 467 markedly inhibited the b-FGF-induced death. Myristoleic acid had been identified cell proliferation, whereas a minimal ef- as one of the cytotoxic components in the fect on basal cell proliferation was noted. extract. The cell death exhibited apoptotic b-FGF induced a 2.5-fold increase in hu- and necrotic nuclear morphology. Cell man prostate cell proliferation; the glan- death was also partially associated with dular epithelium was mainly affected, caspase activationSR022. The extract, in hu- minimal labeling being recorded in the man urological cancer cell lines, PC-3, other regions of the prostate. Similar results LNCaP, and SKRC-1, at concentrations of were observed with epidermal growth factor 1–10 Pg/mL, effectively suppressed the in- (EGF), although the increase in cell pro- vasion activity of PC-3 cells into Matrigel, liferation was not recorded in some cases. whereas that of LNCaP and SKRC-1 cells Lovastatin antagonized both the basal pro- was unaffected by the extract. The extract liferation and the growth factor-stimulated did not affect the viability, adhesion ability, proliferation of human prostate epithe- or motility of the cell lines. Urokinase plas- lium. Geraniol and farnesol increased cell minogen activator (uPA) was more strongly proliferation only in some prostate speci- expressed on the membrane fraction of mens, this effect being antagonized by PC-3 cells than that of LNCaP or SKRC-1 lovastatinSR032. cells. The purified uPA activity was inhib- Coagulative effect. Permixon, adminis- ited by the extract from Serenoa repens in a tered to 108 patients at a dose of 320 mg/ dose-dependent manner, indicating that the day for at least 8 weeks before the procedure suppression of PC-3 cell invasion by the ex- of transurethral resection of prostate, pro- tract is based on an inhibition of the uPA duced significantly lower bleeding than in activity, which is necessary for tumor cell the control (124 vs 287 mL, respectively), invasionSR023. The compounds (1-mono- and the need of transfusion decreased re- laurin and 1-monomyristin) fractionated markably. The duration of postoperative from ethanol extract (95%) of the pow- catheterization (3 vs 5 days, respectively) dered, dried berries, produced moderate and the evaluated hematological parameters biological activities in the brine shrimp le- (red cells 4.5 vs 4 million, hemoglobin 13.4 thality test and against renal (A-498) and vs 11.9 g, hematocrit 40 vs 35%) were sig- pancreatic (PACA-2) human tumor cells. nificantly lower than in the control Borderline cytotoxicity was exhibited groupSR001. against human prostatic (PC-3) cellsSR034. Cyclo-oxygenase inhibition. Ethanol Hexane extract of the dried fruit, in cell cul- (95%) extract of the dried fruit, adminis- ture at a concentration of 100 Pg/mL, was tered to sheep, was active on microsomes, inactive on Chinese hamster ovary cellsSR021. SR089 IC50 28.1 Pg/mL . Diuretic activity. Fruit, administered in the Cytochrome P450 2D6 and 3A4 activi- ration of mice, combined with tomato fruit, ties. Saw palmetto extract, administered to promoted urination. The biological activity healthy volunteers (six men and six women) has been patentedSR097. for 14 days at generally recommended doses, DNA content in prostate epithelial cells. did not alter the disposition of coad- Saw palmetto herbal blend, administered to ministered dextromethorphan and alpra- 20 men with symptomatic BPH, mean age zolam primarily dependent on the CYP2D6 65 years and International Prostate Symp- or CYP3A4 pathways for eliminationSR004. tom Score (IPSS) 18 for 6 months, produced Cytotoxic activity. Extract from saw pal- no significant change from baseline in the metto, in LNCaP cell culture, produced cell nuclear morphometric descriptors (e.g., size, 468 MEDICINAL PLANTS OF THE WORLD shape, DNA content, and textural features). and quality-of-life score both decreased After 6 months, 25 of the 60 nuclear mor- significantly from baseline in the active phometric descriptors were significantly dif- treatment group (26.8% and 18.2%, respec- ferent compared with baseline. The tively, p < 0.001). There were also improve- multivariate model had an area under the ments in prostate volume (2.7%) and receiver operating characteristic curve of maximum detrusor pressure (5.2%) in the 94% and an accuracy of 85%. Results indi- Permixon group. Three patients receiving cated that treatment appeared to alter the Permixon experienced gastrointestinal DNA chromatin structure and organization disturbances but these did not lead to in prostate epithelial cellsSR052. withdrawal or require additional therapy. Drug–dietary supplement interaction. A In patients with mild/moderate BPH, survey was conducted on dietary supple- Permixon treatment reduced intravesical ment use in 458 veteran outpatients cur- obstruction and produced a rapid improve- rently taking prescription medications. ment in urodynamic parameters and symp- Self-reported dietary supplement use was toms. The drug was well toleratedSR010. cross-referenced with each patient’s pre- Estradiol/T-induced prostate enlarge- scription medication list, and potential in- ment. The LSESr was administered to rats: teractions were identified from several shams treated with LSESr (sham rats), cas- tertiary sources and medical literature trated animals treated with estradiol, cas- searches. A total of 197 patients (43%) were trated animals treated with T, castrated currently taking at least one dietary supple- animals treated with estradiol/T, and cas- ment with prescription medication(s). The trated treated with LSESr for 3 months. A most common products included vitamins significant increase of the weight of pros- and minerals, garlic, Ginkgo biloba, saw pal- tates in the estradiol/T-treated castrated rats metto, and ginseng. Among these, 89 (45%) was observed in comparison with sham- had a potential for drug-dietary supplement operated rats. The increase reached a maxi- interactions of any significance. Most of mum in 30 days and remained at a plateau these interactions (n = 84 [94%]) were not or slightly declined thereafter. The increase serious based on limited available evidence, of prostate total weight induced by the hor- giving an incidence of 6% (5/89) of poten- mone treatment was inhibited by the ad- tially severe interactions among patients ministration of LSESr. The weight was taking interacting drugs and dietary supple- significantly lower at days 60 and 90 for the ments and 3% (5/197) among patients tak- dorsal and lateral regions of the prostate. ing coincident dietary supplements and The weight of the ventral region of the pros- medicationsSR048. tate was significantly lower after 30 and 60 Early urodynamic effect. Permixon was days treatment with LSESrSR037. administered to 75 patients with lower uri- Estrogenic effect. Hexane extract of the nary tract symptoms resulting from mild-to- fruit, at a concentration of 5 nM, inhibited moderate BPH (mean IPSS 8.2), aged the binding of mibolerone and methyl- 52–78 years, at a dose of 160 mg twice daily trienolone to androgen receptorsSR087. for 9 weeks. Maximum urinary flow rate in- Fertility effect. Tetrahydrofuran extract of creased 6% (p < 0.001), and there was a re- the fruit, administered orally to hamster at a duction in detrusor pressure at maximum concentration of 9 mg/mL, reduced sperm flow (12.8%, p < 0.001), opening detrusor penetrationSR115. Zona-free hamster oocytes, pressure (12.6%, p < 0.001), and residual pretreated with 0.6 mg/mL of St. John’s wort urine volume (12.6%, p < 0.05). The IPSS at a concentration of 0.06 mg/mL, resulted SERENOA REPENS 469 in zero penetration after incubation with 200 Pg/mL. The extract was active on pros- Serenoa repens extract for 1 hour. Sperm ex- tate epithelial cells isolated from BPH tis- posed to 0.6 mg/mL of St. John’s wort re- sue, IC50 40 Pg/mL, fibroblasts isolated from sulted in DNA denaturation and mutation adenocarcinoma, IC50 70 Pg/mL, and pros- of the BRCA1 exon 11 geneSR028. tate epithelial cells isolated from adenocar- SR038 Follicle-stimulating hormone release cinoma tissue, IC50 90 Pg/mL . inhibition. Extract of the dried fruit, admin- Hydroxysteroid(3-D) dehydrogenase istered orally to male adults at a dose of 160 inhibition. Sterol fraction of the dried fruit, mg/person twice daily for 30 days, was administered to adults at a concentration of inactiveSR045. 5.7 U/mL, was active on fibroblastsSR046. Gene expression inhibition. Hexane ex- Immunostimulant activity. Polysaccharide tract of the fruit, taken orally by male adults fraction of the fruit, administered intraperi- at a dose of 320 mg/day, significantly re- toneally to mice at a dose of 10 mg/animal, duced nuclear estrogen and androgen recep- was active vs clearance of colloidal tors in the prostateSR087. carbonSR066. The treatment increased serum Growth inhibition. Fruit, administered to androstenedione concentrations after 2, 5, immature rats at a dose of 50% of the diet and 8 weeks (p < 0.05), while serum con- for 75 days, produced uniform retardation in centrations of free and total T were un- skeletal and organ development. Growth changed. Serum estradiol was elevated at of suckling rats whose dam received the weeks 2, 5, and 8 in ANDRO-6 (p < 0.05). berries was depressed. Adult rats were not Serum estrone was elevated at weeks 5 and affected by the dietSR081. 8 (p < 0.05). Muscle strength was also in- Hair stimulant effect. Hexane extract of creased (p < 0.05). The acute effect of one- the dried fruit, administered externally to third of the daily dose of ANDRO-6 was adults, was active. Biological activity has studied in 10 men (23 r 4 years). Serum been patented. This patent claims useful- androstenedione concentrations were ness for alopeciaSR096. elevated (p < 0.05) from 150 to 360 min- Hepatotoxic activity. Ether extract of the utes after ingestion, and serum free or dried fruit, administered orally to male total T concentrations were unchangedSR062. adults at a dose of 320 mg/day, was active Water-soluble, acidic branched-chain het- on the liverSR094. eroglycanes isolated from the water or alka- Hormonal effects. A commercial product, line-water extracts produced significant PC-SPES, composed of Chrysantemum immunostimulating activitiesSR066,SR067. morifolium, Ganoderma lucidum, Glycyrrhiza Insulin-like growth factor 1 signaling glabra, Isatis indigotica, Panax pseudoginseng, suppression. Saw palmetto extract, in the Rabdosia rubescens, Scutellaria baicalensis, P69 prostate epithelial cell line at a concen- and Serenoa repens was tested in hormone- tration of 150 Pg/mL for 24 hours, decreased insensitive cell lines LNCAP-BCL-2, PC- insulin-like growth factor-I (IGF-1)-in- 3, and DU-145 at variable concentrations. duced proliferation of P69 cells and induced LNCAP, the only hormone-sensitive cell cleavage of the enzyme poly(adenosine 5'- line, was affected by the lowest dose of PC- diphosphate [ADP]-ribose)polymerase, an SPES testedSR119. index of apoptosis. Treatment of serum- Hydroxysteroid(17-E) dehydrogenase starved P69 cells with 150 Pg/mL for 6 inhibition. Hexane extract of the dried hours, reduced IGF-1-induced phosphoryla- fruit, administered to adult males, was active tion of Akt and Akt activity. The extract on fibroblasts isolated from BPH tissue, IC50 reduced IGF-1-induced phosphorylation of 470 MEDICINAL PLANTS OF THE WORLD the adapter protein insulin receptor sub- mg/day or tamsulosin 0.4 mg/day for 12 strate-1 and decreased downstream effects months, decreased total IPSS by 7.8 with of Akt activation, including increased Permixon and 5.8 with tamsulosin (p = cyclin D1 levels and phosphorylation of gly- 0.051). The irritative symptoms improved cogen synthase kinase-3 and p70(s6k). significantly more (p = 0.049) with There was no effect on IGF-1-induced phos- Permixon (–2.9 vs –1.9 than tamsulosin). phorylation of MAPK, IGF-1 receptor, or The superiority of Permixon in reducing Shc. Treatment of starved cells with the irritative symptoms appeared as soon as extract alone induced phosphorylation month 3 and was maintained up to month the proapoptotic kinase/c-Jun N-terminal 12 (p = 0.03)NT002. Fifty men with previously kinaseSR049. untreated LUTS and a IPSS greater than or Intraoperative hemorrhage. A case was equal to 10 were treated with a commer- reported of severe intraoperative hemor- cially available extract at a dose of 160 mg rhage in a patient who was taking saw pal- twice daily for 6 months. The mean IPSS metto. His bleeding time, which was improved from 19.5 r 5.5 to 12.5 r 7.0 (p < prolonged, normalized a few days after he 0.001) among the 46 men who completed discontinued saw palmetto treatmentSR057. the study. An improvement in symptom Leukotriene B4 production inhibition. score of 50% or greater after treatment for The lipidic extract (LESSr), in calcium 2, 4, and 6 months was noted in 21% (10 of ionophore A23187-stimulated human poly- 48), 30% (14 of 47), and 46% (21 of 46) of morphonuclear neutrophils at a concentra- the patients, respectively. There was no sig- tion of 5 Pg/mL, significantly inhibited the nificant change in peak urinary flow rate, production of the 5-lipoxygenase metabo- postvoid residual urine volume, detrusor lites 5-HETE, 20-COOH LTB4, LTB4, and pressure at peak flow, and mean serum pros- 20-OH LTB4. This effect of LESSr was also tate-specific antigen (PSA) levelSR031. Saw observed in the presence of exogenous palmetto extract, administered to 85 men arachidonic acid (20 Pg/mL) and when 45 years of age or older, with IPSS greater formyl-methionyl-leucyl-phenylalanine was than or equal to 8, for 6 months, produced a used as the antagonist, indicating that inhi- decrease of the mean symptom score from bition of LTB4 production by the extract 16.7 to 12.3 in the saw palmetto group, com- was unrelated to phospholipase A2 block- pared with 15.8 to 13.6 in the placebo group ade and independent of the stimulating (p = 0.038). The quality-of-life score im- agentSR033. proved to a greater degree in the saw pal- Lipoxygenase (platelet) inhibition. Hex- metto group, but this difference was not ane extract of the dried fruit, administered statistically significant. No change occurred to rats at a concentration of 700 mg/mL, had in the sexual function questionnaire results no effect on arachidonic acid transforma- in either group. The peak flow rate in- tionSR125. creased by 1 mL/s and 1.4 mL/s in the saw Lipoxygenase 5 inhibition. Extract of the palmetto and placebo groups, respectively (p dried fruit, in cell culture, was active on = 0.73)SR054. SR129 platelets, IC50 18 Pg/mL . Lymphohistiocytic adenoma activity. Low urinary tract symptoms. Permixon, The lipidosterolic extract of saw palmetto, administered to 685 patients with BPH with in cells infiltrating the adenoma (lympho- IPSS greater than or equal to 10 and 124 cyte T, lymphocyte B, and macrophages patients with severe low urinary tract symp- with a high proportion of lymphocyte T), toms (LUTS) (IPSS >19) at a dose of 320 modified the inflammatory process. Many of SERENOA REPENS 471 the inflammatory markers, such as lympho- tract, administered orally to healthy males quines (interleukin [IL]-1, IL-2, IL-4, IL-6, at a dose of 320 mg, produced plasma level and IL-13) and some growth factors (EGF, concentration-time profile almost identical transforming growth factor [TGF]-D, inter- with reference preparation dose (160 mg). feron [IFN]-J, TGF-E) were elevated in the The ratio of area under the curve (AUC) adenoma tissueSR016. (extent of absorption) was 1.026 (90% con- Mast cell accumulation. Permixon, ad- fidence interval 0.992–1.062). The ratio of ministered to adult Wistar rats at a dose of Cmax (rate of absorption) was 0.982 (90% 100 mg/kg body weight every second day for confidence interval 0.930–1.038). The dif-

90 days, produced significant changes with ference of Tmax was 0 hours (90% confidence acinar epithelium becoming flat or low interval from 0 to 0.25 hour)SR086. cuboidal in the central region of ventral Phospholipase A2 inhibition. The extract prostate. In the same region, mean mast cell on the pancreas, inhibited the hydrolysis of number per optical field in the control, low- diplamitoyl-phosphatidylcholine by Naja dose and high-dose groups were, respec- naja pancreas phosphatase A2, IC50 54 Pg/ tively, 4.7 r 0.7, 3.4 r 1 and 2.4 r 0.6, mL. The extract inhibited the hydrolysis of showing a dose-dependent, statistically sig- diplamitoyl-phosphatidylcholine on the pig nificant decrease. Administration of pancreas, IC50 35 Pg/mL. Hexane extract, in Permixon significantly reduced mast cell cell culture, was inactive on cultured pros- accumulation and provoked epithelium at- tatic cellsSR083. rophy within the central area of the rat ven- Potassium channel blocking activity. tral prostateSR017. Hexane extract, in Chinese hamster ovary Mutagenic activity. Tetrahydrofuran ex- cells overexpressing the prolactin receptor tract of the fruit, at a concentration of 9 at a concentration of 30 Pg/mL, was mg/mL, was inactive on Gambusia affinis activeSR021. spermSR115. Prolactin receptor signal transduction. Phagocytosis rate increase. Polysaccha- The lipidosterolic extract, in Chinese ham- ride fraction of the fruit, administered to ster ovary cells, reduced the basal activity of adults at a concentration of 10 Pg/mL, was a K+ channel and of protein kinase (PK) C. active on polymorphonuclear leukocytesSR067. Pretreatment of the cells with the extract Pharmacokinetics. Hexane extract of the for 6–36 hours abolished the effects of pro- fruit, administered rectally to 12 healthy lactin on Ca2+, K+ conductance and PKC. male adults at a dose of 640 mg, produced The results indicated that the extract can bioavailability similar to that observed for block prolactin-induced prostate growth by the oral formulations. Extract, administered inhibiting several steps of prolactin recep- orally to healthy males at a dose of 320 mg tor signal transductionSR021. (1 u 320 mg capsule, new formulation; or 2 Prostaglandin inhibition. Ethanol (95%) u 160 mg, reference preparation) for 1 extract of the dried fruit, at variable con- month, produced a rapid absorption with a centrations, was activeSR121. peak time (Tmax) of 1.5–1.58 hour and peak Prostate cancer effect. Saw palmetto, vi- plasma level (Cmax) of 2.54–2.67 Pg/mL. The tamin E, and selenium supplements were area under the curve value ranged from 7.99 used by 26.5% of the questioned men diag- to 8.42 Pg/hour/mL. The plasma concentra- nosed with prostate cancerSR051. PC-SPES, tion-time profile of both preparation was an herbal mixture of chrysanthemum, isatis, nearly identical. Both preparations can be licorice, Ganoderma lucidum, Panax pseudo- considered as bioequivalentSR099. Hexane ex- ginseng, Rabdosia rubescens, saw palmetto, 472 MEDICINAL PLANTS OF THE WORLD and Scutellaria was administered to two pa- Prostate-specific gene expression and tients with hormone-refractory prostate proliferation. PC-SPEC ethanol extract, a cancer with metastatic disease. treatment multi-herbal mixture, in androgen-depen- with total androgen blockade progressing to dent LNCaP cell culture at concentrations an androgen-independent status, decreased of 1 or 5 PL/mL for 72 hours, produced a the PSA value for both patients from an ini- 72–80% reduction in cell growth and a simi- tial value of 100 and 386 ng/mL to 24 and lar decrease in cell viability by the higher 114 ng/mL after 1 year and 4 months, re- concentration. These results contrasted spectively, remaining stable. No gyneco- with cells incubated with same concentra- mastia or hot flashes were observed in these tion of individual herbal extract, which patients and the treatment was well toler- supressed growth in the order: Dendranthema ated. PC-SPES has shown a strong estro- morifolium Tzvel (85.2% reduction) greater genic in vitro and in vivo activity as an than Panax pseudoginseng (80.9%) greater alternative tool in the management of pros- than Glycyrrhiza uralensis Fisch (73%) tate cancer patients. The results indicated greater than Rabdosia rubescens Hara that PC-SPES might have some potential (70.8%) greater than Scutellaria baicalensis activity against hormone-independent pros- Georgi (66.5%) greater than Ganoderma tate cancersSR061. An extract of saw palmetto, lucidum Karst (63.5%) greater than Isatis administered to 20 mature male dogs with indgotica Fort (50.0%) greater than Serenoa benign prostatic hyperplasia, at doses of repens (14.5%). Serenoa repens lowered in- 1500 mg/day or 300 mg/day for 91 days, did tracellular and secreted PSA levelSR020. not affect prostatic weight, prostatic vol- Prostatic adenoma. Permixon (PA 109), ume, or prostatic histologic scores, libido, admininistered for 1 month to 110 patients semen characteristics, radiographs of the with a prostatic adenoma, produced a caudal portion of the abdomen, prostatic greater effect in nocturia, urinary output, ultrasonographs, or serum T concentrations. postmicturitional residue and subjective Results of complete blood cell counts, serum criterias: dysuria, patients’ opinions than biochemical analyses or urinalysis, and placebo, especially in the objective criteria. body weights did not change during treat- In a supplementary study of 47 patients, mentSR026. with a mean follow-up of 14.5 months and Prostate hypertophy. Permixon, adminis- over 2.5 years in some cases, permixon pro- tered to 30 patients at a dose of 320 mg/day duced good effect for micturitional disorders for 30 days, produced significant differences associated with nonsurgical adenomas of the in the number of voidings, strangury, maxi- prostateSR076. The extract, administered to 22 mum and mean flow, and residual urine patients at a dose of 320 mg/day for 60 days, compared to placebo groupSR071. The extract, produced significant differences for volume administered to 40 patients with moderate voided, maximum and mean urine flow, dys- BPH at a dose of 160 mg twice daily for 3 uria, and nocturia compared with placebo months, produced significant improvements group. There were no side effectsSR070. in the number of daytime voidings, noc- Prostatic hyperplasia. Permixon was ad- turia, incomplete voidings, dysuria, and ministered to 4280 patients during 14 clini- urine retention. Transrectal and superpubic cal trials. The trials were of different sizes ultrasound indicated the residual urine con- (22–1100 patients) and duration (21–720 tent dropped from 110 mL at the beginning days). Permixon produced a significant im- of the study to 45 mL at the end. There was provement in peak flow rate and reduction no significant change in the size of the pros- in nocturia above placebo, and a five-point tate in either groupSR072. reduction in the IPSSSR003. Permixon, ad- SERENOA REPENS 473 ministered orally to patients with BPH at a maintained up to 24 monthsSR008. Libeprosta, dose of 160 mg twice daily for 3 months, the lipidosterolic extract of Serenoa repens, produced a decrease in the number of administered to 100 male outpatients with lymphocytes B as compared to control LUTS suggestive of BPH, at doses of two 80 (Permixon-treated 58.2 r 53.7 and control mg tablets twice daily or two 80-mg tablets 91.4 r 44.1). Tumor necrosis factor-D and three times daily, significantly reduced the IL-1E were dramatically lower in the Per- IPSS mean total score from baseline values mixon-treated group. Other parameters did (p < 0.001) by the both regimens. Significant not show significant changes. IPSS in the improvements from baseline also occurred Permixon-treated group was significantly in quality-of-life scores, maximum and reduced (p < 0.006) from 20 r 5.9 to 14.9 r mean urinary flow rates, and residual urine 3.8SR005. Serenoa repens extract, at a dose of volume (p < 0.05). The decrease in residual 320 mg for 12 weeks, was administered to urine with both regimens was highly signifi- 100 men aged under 80 years with BPH cant (p < 0.001). No significant differences symptoms and a maximum urinary flow rate in efficacy were noted between the two dose of 5–15 mL/s for a voiding volume of 150 groups. No treatment-related complications mL. The extract produced no significant dif- or clinical adverse events occurredSR009. Saw ference in the IPSS, peak urinary flow rate palmetto, in combination with tamsulosin or for the Rosen International Index of (TAM), and TAM alone were evaluated in Erectile Function questionnaireSR007. Hexane patients with IPSS greater than or equal to extract of the fruit, taken orally by male 13 and a maximum urinary flow rate 7–15 adults at a dose of 320 mg/day, was active in mL/second. A dose of 160 mg of saw pal- a 3-year prospective multicenter study that metto/TAM (SR/TAM) or 0.4 mg of TAM evaluated the use of the extract in treating were administered twice daily for 52 weeks. 435 patients. Symptomatic improvement There was no statistically significant differ- included a 50% reduction in residual urine ence between the two groups for the major and a 6.1 mL/second increase in peak urine end points and the secondary end points. flow. The deterioration rate was signifi- For the major end points total IPSS between cantly lower in the treated patientsSR111. The the baseline value and the final evaluation extract, administered to male rats, inhib- were TAM –5.2, TAM/SR –6 (p = 0.286). ited estradiol/T-induced prostate enlarge- For the secondary end points, changes in the mentSR087. Permixon, administered to 155 voiding scores (p = 0.239), filling scores (p men with BPH at a dose of 160 mg twice = 0.475) of IPSS, maximum urinary flow daily for 2 years, produced a significant rate (p = 0.564), percentage of respondents improvement of IPSS and quality of life according to the IPSS (p = 0.361), improve- from baseline at each evaluation time point. ment in quality of life (p = 0.091)SR013. At the end of the study and at each evalua- Permixon, administered to men with symp- tion, maximum urinary flow also improved tomatic BPH at doses of 320 mg per day (N significantly. Prostate size decreased. Sexual = 350) or TAM 0.4 mg per day (N = 354) function remained stable during the first for 1 year, produced a decrease of IPSS by year of treatment and significantly im- 4.4 and no differences in either irritative or proved (p = 0.001) during the second year. obstructive symptom improvements. The PSA was not affected, and no changes in increase in maximum urinary flow rate was plasma hormone levels were observed. Nine similar in both treatment groups (1.8 mL/ patients reported 10 adverse events, none second Permixon, 1.9 mL/second TAM). related to treatment. Improvements in effi- Serum prostate-specific and antigen re- cacy parameters began at 6 months and were mained stable, whereas prostate volume de- 474 MEDICINAL PLANTS OF THE WORLD creased slightly in the Permixon-treated Chinese hamster ovary cells overexpressing patients. The two compounds were well the prolactin receptor, was activeSR021. tolerated; however, ejaculation disorders Protein synthesis stimulation. Sterol frac- occurred more frequently in the TAM tion of the extract, in cell culture at a con- groupSR014. Preparations of saw palmetto, ad- centration of 25 Pg/mL, produced weak ministered to 3139 men in 21 randomized activity on CA-LNCAP. A concentration trials lasting 4–48 weeks, improved urinary of 50 Pg/mL was active on CA-PC3SR036. symptom scores, symptoms, and flow mea- PSA production inhibition. Ethanol (70%) sures compared with the placebo. Compared extract of PC-SPES (a Chinese herb combi- with finasteride, Serenoa repens produced nation of chrysanthemum, dyers woad, lico- similar improvements in urinary symptom rice, reishi, san-qi ginseng, rabdosia, saw scores and peak urine flow. Adverse effects palmetto, and baikal skullcap), in cultured resulting from Serenoa repens were mild and prostate cancer cell line at variable doses for infrequent. Withdrawal rates in the men 24 hours, produced a significant effect in assigned to placebo, Serenoa repens or supressing cell growth in all the cell finasteride were 7%, 9%, and 11%, re- linesSR119. spectivelySR015. Permixon, administered to 26 Radioactivity distribution. The N-hexane patients with prostatic hyperplasia (total lipido/sterolic extract (LSESr) supple- PSA < 4 ng/mL) before meal with a small mented with [14C]-labeled oleic or lauric ac- quantity of water at a total daily dose of 320 ids or E-sitosterol was administered orally to mg twice daily for 5 years, significantly re- rats. The highest level of radioactivity up- duced the disease symptoms and improved take was LSESr supplemented with [14C]-la- quality of life. Five years of treatment de- beled oleic acid. Ratios of radioactivity in creased mean IPSS by 8.8 r 0.18 (75.5%), tissues compared to plasma showed an up- quality of life by 1.31 r 0.08 (53.3%), and take of radioactivity greater in prostate as size of the prostate by 10.81 r 0.55 cm3 compared with other genital organs, i.e., the (29.8%). Neither the symptoms nor quality seminal vesicles or to other organs such as of life became worse for these five years. The liverSR035. size of the prostate reduced in 16 patients, Rectal bioavailability and pharmacoki- was unchanged in 9 patients, and increased netics. Serenoa repens extract, administered in 1 patient. Maximal urinary flow rate in- rectally to 12 healthy male volunteers at a creased by 35%. Residual urine increased dose of 640 mg/person, produced the mean during the treatment in one patient. maximum concentration in plasma of nearly Permixon intolerance was not observedSR019. 2.60 Pg/mL approx 3 hours after adminis- Prostatic hypoplasia. The extract of saw tration, with mean value for the area under palmetto, crushed whole berry derived from the curve AUC 10 Pg/hour/mL. The saw palmetto fruit, or a combination of the bioavailability and pharmacokinetic profile saw palmetto extract and cernitin, adminis- were similar to those observed after oral ad- tered to castrated rats receiving T, decreased ministration. Tmax occurred approx 1 hour the size of the prostate to roughly the same later, and plasma concentration 8 hours af- size as in the noncastrated rats, a size that ter drug administration was still quantified. was significantly smaller than castrated rats The drug tolerability was good, and no ad- treated with T in the same manner (p < verse effect was observedSR068. Serenoa repens 0.01). Both nutraceuticals generally de- capsules, administered orally at a dose of 160 creased body weightSR006. mg four times daily or rectally 640 mg daily Protein kinase C inhibition. Hexane ex- for 30 days to 60 patients with BPH, pro- tract, at a concentration of 30 Pg/mL on duced no significant differences in diminu- SERENOA REPENS 475 tion of scores assigned to dysuria, tion to male adults at a dose of 320 mg/day pollakiuria, prostate dimension, and mictu- was inactive on serumSR084. Hexane extract rition residue between the two groupsSR069. of the fruit, administered orally to male Reductase, 5-D inhibition. Permixon was adult at a dose of 160 mg/day, was inactive evaluated in cultures of fibroblast and epi- on serumSR041. Lipid fraction of the extract, thelial cells from the prostate, epididymis, in cell culture was active on human prostate testes, kidney, skin, and breast at a concen- cancer cell line DU-145; administered tration of 10 Pg/mL. The extract inhibited orally to adults at a dose of 320 mg/person/ 5-DR type I and II isoenzymes activity in day for 3 months, was inactiveSR108. prostate cells, but other cells showed no in- Respiration inhibition (cellular)-state 4. hibition of 5-DR activitySR025. Saw palmetto Extract of the fruit, in cell culture, was ac- SR129 extract, in pig prostatic tissue, inhibited 5- tive on platelets. IC50 28.1 Pg/mL . D-reductase enzyme, which catalyzes the Serum PSA. PC-SPES, a Chinese herb com- conversion of T into DHT in prostatic mi- bination of chrysanthemum, dyers woad, crosomes of growing pigs. Peaks for the 5-D- licorice, reishi, san-qi ginseng, rabdosia, saw reductase activity were found at pH 5.5 and palmetto, and baikal skullcap, produced 8, which indicates the presence of both type positive results. The respondents experi- 1 and type 2 isozymes. Kinetic parameters of enced a decline in serum PSA, most to the porcine 5-D-reductase in the presence of undetectable range. Of these patients, 88% Serenoa repens extracts revealed uncom- maintained a low PSA concentration, petitive, noncompetitive, and mixed types whereas 12% had a rise from nadir. In a sec- of inhibitionsSR029. Ethanol (95%) extract of ond study, 93% of the respondents with the fruit, administered to adults at a con- positive results and only 7% reporting a rise centration of 500 Pg/mL, was active on in PSA after the initial lowering with PC- prostate glands when assayed in epithelium SPES was found. There were some side and stroma of BPH tissueSR106. Fixed oil of effectsSR060. the fruit, administered orally to male adults Serum sex hormones effect. DION (300 at a dose of 320 mg/day, was activeSR116. mg androstenedione, 150 mg dehydro- Hexane extract of the fruit, at concentra- epiandrosterone, 540 mg saw palmetto, 300 tions of 50 and 100 mg/L, was active. A con- mg indole-3-carbinol, 625 mg chrysin, 750 centration of 20 mg/L was inactiveSR101. mg Tribulus terrestris), administered daily to Ether extract of the dried fruit, at concen- healthy 30- to 59-year-old men for 28 days, trations of 59 and 71 Pg/mL, produced weak produced no change in serum concentra- activitySR089. Hexane extract of the dried tions of total T and PSA. DION increased fruit, was active on reductase type 1 and 2, the concentrations of serum androstenedi- SR039 IC50 4.0 and 7 Pg/mL, respectively . one (342%), free T (38%), DHT (71%), Permixon, administered to adults at a dose and estradiol (103%). Serum high-density of 10 Pg/mL, was active on prostate lipoprotein (HDL) cholesterol concentra- SR075 gland . CO2 extract of the dried fruit was tions were reduced by 5 mg/dL in DION (p active, minimum inhibtory concentration < 0.05). Increases in serum free T (r2 = 1:500SR102. Hexane extract of the fruit 0.01), androstenedione (r2 = 0.01), DHT (r2 (Permixon), in cell culture was active vs = 0.03), or estradiol (r2 = 0.07) concentra- cocultures of prostatic epithelial cells and tions in DION were not related to age. The fibroblastsSR118. Hexane extract of the fruit, ingestion of androstenedione combined administered to male adults, was activeSR082. with herbal products increased serum-free T Administration of the extract to male rats concentrations in older men, but herbal was active, IC50 5.6 Pg/mL. Oral administra- products did not prevent the conversion of 476 MEDICINAL PLANTS OF THE WORLD ingested androstenedione to estradiol and rats, at a concentration of 0.33 mg/mL, was DHTSR055. Nutritional supplement (AND- active vs contractions of ductus differens HB) containing 300 mg androstenediol, induced by electrical stimulationSR085. 480 mg saw palmetto, 450 mg indole-3- Spasmolytic activity. Lipidic extract of the carbinol, 300 mg chrysin, 1500 mg J-lino- fruit relaxed vanadate-induced contractions lenic acid and 1350 mg Tribulus terrestris, on rat uterus incubated in a calcium-free administrated per day to the men stratified solution, effective concentration (EC)50 = into age groups: 30 year olds, 40 year olds, 11.41 r 1.38 Pg/mL. The effect was not and 50 year olds for 28 days, produced no modified by 3 PM concentration of in- difference in basal serum total T, estradiol, domethacin, EC50 = 8.77 r 1.28 vs 11.41 r and PSA concentrations between age 1.38 Pg/mL, and 5 Pg/mL concentration of groups. Basal serum-free T concentrations actinomycin D, EC50 = 8.23 r 2.19 vs 11.41 were higher (p < 0.05) in the 30- (70.5 r r 1.38 Pg/mL. The inhibitor of intracellular 3.6 pmol/L) than in the 50-year-olds (50.8 calcium mobilization TMB-8 (0.1 mM), r 4.5 pmol/L). Basal serum androstenedione Na+/Ca2+ exchanger inhibitor amiloride (0.1 and DHT concentrations were significantly mM), calcium chelator BAPTA-AM (50 higher in the 30-year-olds than in the 40- mM), PKA inhibitor TPCK (10 PM), and or 50-year-olds. Basal serum hormone con- protein synthesis inhibitor cycloheximide centrations did not differ between the treat- (10 Pg/mL), significantly shifted to the right ment groups. Serum concentrations of total the dose-response curve of the extract (EC50 T and PSA were unchanged by supplemen- = 17.83 r 1.87 Pg/mL, 18.61 r 2.50 Pg/mL, tation. Ingestion of AND-HB resulted in 35.28 r 9.13 Pg/mL, 33.99 r 3.07 Pg/mL, increased (p < 0.05) serum androstenedione and 27.31 r 4.93 Pg/mL, respectively, vs (174%), free T (37%), DHT (57%) and 11.41 r 1.38 Pg/mL)SR064. Total lipidic (L) estradiol (86%) throughout the treatment and saponifiable (S) extracts of the fruit, at period. There was no relationship between concentrations of 0.1–1 mg/mL, relaxed the the increases in serum-free T, androstenedi- tonic norepinefrine-induced contraction on 2 one, DHT, or estradiol and age (r = 0.08, the rat aorta, EC50 0.53 r 0.05 mg/mL (L) 0.03, 0.05, and 0.02, respectively). Serum and 0.5 r 0.04 mg/mL (S), and by KCl on HDL cholesterol concentrations were re- rat uterus. The extracts, at concentrations duced (p < 0.05) by 0.14 mM/L in AND- of 0.3–1 mg/mL, antagonized the dose–re- HBSR056. Permixon, administered to healthy sponse curve of contractions induced by male volunteers aged 20–30 years at a dose acetylcholine on urinary bladder. DL-Pro- of 80 mg twice a day for 1 week, produced pranolol (1 PM) but not the inactive (R)- no effect on the serum DHT level. No sig- (+)-propranolol (1 PM), potentiated the nificant difference was found between extracts relaxant effect by lowering the EC50 finasteride and Permixon with respect to 0.35 r 0.2 vs 0.20 r 0.01 mg/mL (L) and serum T, except on days 3 and 6, respec- 0.43 r 0.02 vs 0.19 r 0.02 mg/mL, p < 0.01, tively (p Յ 0.05). The corresponding serum (S). Cycloheximide, at a concentration of T levels remained within the normal 10 Pg/mL, antagonized the effect of saw pal- rangesSR041. metto extracts. Actinomycin D (5 Pg/mL) Smooth muscle relaxant activity. Hexane significantly (p Յ 0.01) antagonized the ef- extract of the dried fruit, administered to fect of the total lipidic extract without guinea pigs at a concentration of 0.15 mg/ modifying the effect of the saponifiable ex- mL, was active on bladder and ileum vs KCl- tract. The relaxant effect of both extracts induced contractionsSR085. Administration to was not modified by the tyrosine kinase in- SERENOA REPENS 477 hibitor genistein (10 PM) or the ornithine reductions of supine blood pressure, they did decarboxylase inhibitor D-difluoromethyl- not affect blood pressure during orthostatic ornithine (10 mM)SR065. Ethanol (95%) ex- stress testing and did not alter heart rate tract of the fruit, administered to guinea pigs under either conditions. Plasma catechola- at a concentration of 0.15 mg/mL, was ac- mines remained largely unalteredSR059. The tive on the bladder and ileum vs KCl-in- extracts of saw palmetto inhibited radio- duced contractions. Administration to rats ligand binding to human D1-adrenoceptors at a concentration of 0.3 mg/mL, was active and antagonist-induced [3H]inositol phos- on vas deferens vs norepinephrine-induced phate formation. Saturation binding experi- contractionsSR109. ments in the presence of a single saw Sperm motility inhibition. Saw palmetto palmetto extract concentration indicated a (Permixon, Sabal serrulatum), incubated noncompetitive antagonism. The relation- with washed sperm at a concentration of 0.6 ship between active concentrations in vitro mg/mL for 24 and 48 hours, inhibited sperm and recommended therapeutic doses for the motilitySR027. saw palmetto extracts was slightly lower Testosterone effects. A liposterolic extract than that for several chemically defined D of Serenoa repens was administered to 20 1-adrenoceptor antagonistsSR063. N-hexane men aged 50 to 75 years with BPH at a dose lipid/sterol extract inhibition of a type 1 5- of 160 mg twice daily for 30 days. The ex- D-R expressed in a baculovirus-directed-in- tract produced no changes in plasma levels sect cell system was noncompetitive. When of T, FSH, and luteinizing hormone. The expressed in terms of recommended thera- results indicated that Serenoa extract, which peutic doses, was threefold greater for the is useful in the treatment of BPH, does not n-hexane lipid/sterol extract than for finas- act via systemic changes of hormone terideSR040. levelsSR045. Thromboxane A2 synthesis inhibition. Testosterone metabolism. The lipido-ste- Ethanol (95%) extract of the dried fruit, rol extract (LSESr, Permixon) was studied administered to rats, was active on leuko- in primary cultures of epithelial cells and fi- cytes vs A23187 stimulation, IC50 15.2 Pg/ broblasts separated from benign prostate mLSR089. hypertrophy and prostate cancer tissues. Toxic effect. Ethanol (95%) extract of the The extract inhibited the formation of the dried fruit, administered to adult males at a T metabolites androstenedione G 4 and 5 D- dose of 320 mg/day, was inactiveSR091, SR095. DHT SR038. The lipophilic extracts of fruits Ether extract of the fruit, administered inhibited T 5P-reductase (EC 1.3.99.5) orally to male adults at a dose of 320 mg/ (5PR). For fatty acid-like 5PR inhibition a day, was inactiveSR090,SR093,SR031. Ether extract strongly polar end-group and a molecular of the fruit, administered orally with Urtica skeleton allowing nonpolar interactions dioica to male adults at a dose of 320 mg/day with the enzyme were required. The result for 24 weeks, was inactiveSR092. Hexane ex- indicated that 5PR activity in prostatic tis- tract of the fruit, administered orally to male sue may be influenced by the lipid environ- adults at a dose of 320 mg/day, was inact- mentSR073. Three different saw palmetto iveSR076,SR107. extract preparations, administered to 12 Type 1 and 2 5-D-reductase activity. The healthy young men at a dose of 320 mg daily lipidosterolic extract of seeds was investi- for 8 days, did not result in D1-adrenoceptor gated in the baculovirus-directed insect cell subtype occupancy in the radioreceptor as- expression system Sf9 expressing the corre- say. Although the extracts produced minor sponding type 1 and type 2 human genes. 478 MEDICINAL PLANTS OF THE WORLD

The extract produced an inhibition of 5- benign prostatic hyperplasia. BJU Int DR1 and 5-DR2 activities in the presence of 2004; 93(6): 751–756. free fatty (oleic, lauric, linoleic, and myris- SR004 Markowitz, J. S., J. L. Donovan, C. L. Devane, et al. Multiple doses of saw tic) acids only. Esterified fatty acids, palmetto (Serenoa repens) did not alter alcohols, and sterols assayed were inactive. cytochrome P450 2D6 and 3A4 activ- A specificity of the fatty acids in 5-DR1 or ity in normal volunteers. Clin Pharma- 5-DR2 inhibition has been found. Palmitic col Ther 2003; 74(6): 536–542. and stearic acids were inactive on the two SR005 Vela Navarrete, R., J. V. Garcia Cardoso, A. Barat, F. Manzarbeitia, isoforms. Lauric acid was active on 5-DR1 and A. Lopez Farre. BPH and inflam-

(IC50 = 17 r 3 Pg/mL) and 5-DR2 (IC50 = 19 mation: pharmacological effects of r 9 Pg/mL). The inhibitory activity of Permixon on histological and molecu- myristic acid was evaluated on 5-DR2 only lar inflammatory markers. Results of a and found active on this isoform (IC = 4 double blind pilot clinical assay. Eur 50 r Urol 2003; 44(5): 549–555. SR011 2 Pg/mL) . LSESr markedly inhibited SR006 Talpur, N., B. Echard, D. Bagchi, M. both isozymes (Ki [type 1] = 8.4 nM and 7.2 Bagchi, and H. G. Preuss. Comparison

Pg/mL, respectively; Ki [type 2] = 7.4 nM of Saw Palmetto (extract and whole and 4.9 Pg/mL, respectively). Results indi- berry) and Cernitin on prostate growth cated that LSESr displayed non-competitive in rats. Mol Cell Biochem 2003; 250(1–2): 21–26. inhibition of the type 1 isozyme and SR007 Willetts, K. E., M. S. Clements, S. uncompetitive inhibition of the type 2 Champion, S. Ehsman, and J. A. Eden. isozymeSR039. Serenoa repens extract for benign pros- Vasoconstriction activity. Fruit, adminis- tate hyperplasia: a randomized con- tered to immature rats at a dose of 50% of trolled trial. BJU Int 2003; 92(3): 267–270. the diet for 75 days after weaning, resulted SR008 Pytel, Y. A., A. Vinarov, N. Lopatkin, in peripheral vasoconstriction leading to A. Sivkov, L. Gorilovsky, and J. P. gangrene in the extremities within 40 Raynaud. Long-term clinical and bio- days, and the loss of whole limbs in some logic effects of the lipidosterolic ex- casesSR081. tract of Serenoa repens in patients with symptomatic benign prostatic hyper- Weight loss. Fruit, administered to rats at a plasia. Adv Ther 2002; 19(6): 297–306. dose of 50% of the diet for 75 days, was SR009 Giannakopoulos, X., D. Baltogiannis, inactiveSR081. D. Giannakis, et al. The lipidosterolic extract of Serenoa repens in the treat- REFERENCES ment of benign prostatic hyperplasia: a SR001 Pecoraro, S., A. Annecchiarico, M. C. comparison of two dosage regimens. Gambardella, and G. Sepe. Efficacy of Adv Ther 2002; 19(6): 285–296. pretreatment with Serenoa repens on SR010 Al-Shukri, S. H., P. Deschaseaux, I. V. bleeding associated with transurethral Kuzmin, and R. R. Amdiy. Early resection of prostate. Minerva Urol urodynamic effects of the lipido-ste- Nefrol 2004; 56(1): 73–78. rolic extract of Serenoa repens (Per- SR002 Debruyne, F., P. Boyle, F. Calais Da mixon®) in patients with lower urinary Silva, et al. Evaluation of the clinical tract symptoms due to benign prostatic benefit of permixon and tamsulosin in hyperplasia. Prostate Cancer Prostatic severe BPH patients-PERMAL study Dis 2000; 3(3): 195–199. subset analysis. Eur Urol 2004; 45(6): SR011 Raynaud, J. P., H. Cousse, and P. M. 773–779. Martin. Inhibition of type 1 and type 2 SR003 Boyle, P., C. Robertson, F. Lowe, and 5alpha-reductase activity by free fatty C. Roehrborn. Updated meta-analysis acids, active ingredients of Permixon. of clinical trials of Serenoa repens ex- J Steroid Biochem Mol Biol 2002; tract in the treatment of symptomatic 82(2–3): 233–239. SERENOA REPENS 479

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Sport Nutr Exerc Metab 2000; 10(3): SR072 Mattei, F. M., M. Capone, and A. 340–359. Acconcia. Serenoa repens extract in the SR063 Goepel, M., U. Hecker, S. Krege, H. medical treatment of benign pros- Rubben, and M. C. Michel. Saw tatic hypertrophy. Urologia 1988; 55: palmetto extracts potently and non- 547–552. competitively inhibit human alpha1- SR073 Niederprüm, H. J., H. U. Schweikert, adrenoceptors in vitro. Prostate 1999; and K. S. Zänker. Testosterone 5P-re- 38(3): 208–215. ductase inhibition by free fatty acids SR064 Gutierrez, M., A. Hidalgo, and B. from Sabal serrulata fruits. Phytomedi- Cantabrana. Spasmolytic activity of a cine 1994; 1: 127–133. lipidic extract from Sabal serrulata SR074 Wagner, H., and H. Flachsbarth. A fruits: further study of the mechanisms new antiphlogistic principle from underlying this activity. Planta Med Sabal serrulata. I. Planta Med 1981; 41: 1996; 62(6): 507–511. 244–251. SR065 Gutierrez, M., M. J. Garcia de Boto, B. SR075 Bayne, C. W., F. Donnelly, M. Ross, Cantabrana, and A. Hidalgo. Mecha- and F. K. Habib. Serenoa repens (Per- nisms involved in the spasmolytic ef- mixon): 5-alpha-reductase types I and fect of extracts from Sabal serrulata fruit II inhibitor-new evidence in a cocul- on smooth muscle. Gen Pharmacol ture model of BPH. Prostate 1999; 1996; 27(1): 171–176. 40(4): 232–241. SR066 Wagner, H., A. Proksch, I. Riess- SR076 Champault, G., A. M. Bonnard, J. Maurer, et al. Immunostimulant action Cauquil, and J. C. Patel. Medical treat- of polysaccharides (heteroglycans) ment of the prostatic adenoma. A con- from higher plants. Preliminary com- trolled test of PA 109 vs placebo in 110 munication. Arzneimittelforschung patients. J Ann Urol (Paris) 1984; 6: 1984; 34(6): 659–661. 407–410. SR067 Wagner, H., A. Proksch, I. Riess- SR077 Schoepflin, G., H. Timpler, and R. Maurer, et al. Immunostimulating Hansel. Beta sitosterol as an active action of polysaccharides (hetero- principle of sabal fruit. Planta Med glycans) from higher plants. Arznei- 1966; 14(4): 403–407. mittelforschung 1985; 35(7): SR078 Hansel, R., G. Schoepflin, and H. 1069–1075. Timpler. The occurrence of anthranilic SR068 De Bernardi Di Valserra, M., and A. acid in sabal fruit (Serenoa repens). S.Tripodi. Rectal bioavailability and Planta Med 1966; 14(3): 261–265. pharmacokinetics in healthy volun- SR079 Hansel, R., H. Timpler, and G. Scho- teers of Serenoa repens new formula- epflin. Thin-layer chromatography of tion. Arch Med Interna (Italy) 1994; sabal (saw palmetto) fruit. Planta Med 46(2): 77–86. 1964; 12(2): 169–172. SR069 Roveda, S., and P. Colombo. Clinical SR080 Griebel, C., and E. Bames. A palm fruit controlled trial on therapeutical employed for imparting aroma to bioequivalence and tolerability of Ser- brandy. Z Nahr-Genussm 1916; 1916: enoa repens oral capsules 160 mg or rec- 282–290. tal capsules 640 mg. Arch Med Interna SR081 Feurt, S. D., and L. E. Fox. A note on (Italy) 1994; 46(2): 61–75. the effects of feeding saw palmetto ber- SR070 Boccafoschi, C., and Annoscia, S. ries, Serenoa repens (Bartram) small, to Comparison of Serenoa repens extract rats. J Amer Pharm Ass Sci Ed 1954; with placebo by controlled clinical 43: 636–638. trial in patients with prostatic adeno- SR082 Sultan, C., A. Terraza, E. Carilla, M. matosis. Urologia 1983; 50: 1257–1268. Briley, and B. Descomps. Antiandro- SR071 Emili, E., M. Lo Cigno, and U. genic effects of Permixon: in vitro stud- Petrone. Clinical trial of a new drug ies. Acta Urol Ital 1987; 1(4): 23. for treating hypertrophy of the pros- SR083 Ragab, A., J. Ragab, A. Delhon, et al. tate (Permixon). Urologia 1983; 50: Effects of Permixon on phospholipase 1042–1048. A2 activity and on arachidonic acid SERENOA REPENS 483

metabolism in cultured prostatic cells. in the treatment of benign prostatic Acta Urol Ital 1987; 1987 (1): 23–24. hyperplasia (BPH). Urologe 1996; 36 SR084 Rhodes, L., R. L. Primka, C. Berman, B: 292–300. et al. Comparison of finasteride SR093 Schneider, H. J., E. Honold, and T. (Proscar), a 5-alpha reductase inhibi- Masuhr. Treatment of benign prostatic tor, and various commercial plant ex- hyperplasia. Results of a surveillance tracts in in vitro and in vivo 5-alpha study in the practices of urological spe- reductase inhibition. Prostate 1993; cialists using a combined plant-based 22: 43–51. preparation (Sabal extract WS 1473 SR085 Odenthal, K. P., and H.W. Rauwald. and Urtica extract WS 1031). Fortschr Lipophilic extract from Sabal serrulata Med 1995; 113(3): 37–40. inhibits contractions in smooth muscu- SR094 Hamid, S., S. Rojter, and H. Vierling. lar tissue. Akt Urol 1996; 27: 152–158. Protracted cholestatic hepatitis after SR086 De Bernardi Di Valserra, M., A. S. the use of prostate. Ann Intern Med Tripodi, S. Contos, and R. Germogli. 1997; 127(2): 169–170. Serenoa repens capsules; a bioequiva- SR095 Schneider, H. J., and A. Uysal. lence study. Acta Toxicol Ter 1994; Internationaler prostate-symptomen- 15(1): 21–39. score (I-PSS) im klinischen alltag. SR087 Nemecz, G. Saw palmetto berries of Urologe 1994; 34: 443–447. this scrubby palm tree of the south- SR096 Barr, E. I. A composition for the treat- eastern U.S. may be an answer to ment of androgenic alopecia and hirsut- symptoms associated with an enlarged ism. Patent-PCT Int Appl-98 33,472 prostate. US Pharmacist 1998; 23(1): 198; 21 pp. 97–102. SR097 Hirakoshi, J., K. Ishinabe, K. Yatagai, SR088 Stenger, A., J. P. Tarayre, E. Carilla, et I. Hanada, and H. Iwaki. Urination al. Pharmacologic and biochemical promoters containing saw-palmetto study of an hexane extract of Serenoa extracts and lycopene. Patent-Japan repens B (PA 109). Gaz Med France Kokai Tokkyo Koho-10 158,182 1998; 1982; 89(17): 2041–2048. 4 pp. SR089 Koch, E., and W. S. Arzneimitel. Phar- SR098 Marandola, P., H. Jallous, E. macology and modes of action of ex- Bombardelli, and P. Morazzoni. Main tracts of palmetto fruit (Sabal fructus), phytoderivaties in the management of stinging nettle roots (Urticae radix) benign prostatic hyperplasia. and pumpkin seed (Cucurbitae peponis Fitoterapia 1997; 68(3): 195–204. semen) in the treatment of benign pro- SR099 Bombardelli, E., and P. Morazzoni. Ser- static hyperplasia. Phytopharm Forsch enoa repens (Bartram) J.K. Small. Klin Anwend, D. Loew, N. Rietbrock, Fitoterapia 1997; 68(2): 99–133. (eds.), Verlag Dietrich Steinkopf, SR100 Salinero, R., A. Miguel, A. Sevilla Darmstadt 1995; 1995: 57–79. Toral, et al. Extracts of Sabal serrulata SR090 Ziegler, H., and U. Holscher. Efficacy as adrenergic antagonists and inflam- of saw palmetto fruit special extract mation inhibitors. Patent-Eur Pat WS 1473 in patients with alken stage Appl-527,101 1993: 8 pp. I-II benign prostatic hyperplasia-open SR101 Niederprum, H. J., H. U. Schweikert, multicentre study. Jatros Urol 1998; and K. S. Zanker. Testosterone 5-al- 14: 34–43. pha-reductase inhibition by free fatty SR091 Derakhshani, P., H. Geerke, K. J. acids from Sabal serrulata fruits. Bohnert, and U. Engelmann. Phytomedicine 1994; 1(2): 127–133. Beeinflussung des internationalen SR102 Hagenlocher, M., G. Romalo, and H. prostate-symptomen-score unter der U. Schweikert. Specific inhibition of therapie mit sagepalmenfruchteextrakt 5-alpha reductase by a new extract of bei taglicher einmalgabe. Urologe Sabal serrulata. Akt Urol 1993; 24: 1997; 37: 384–391. 146–149. SR092 Metzker, H., and U. Holscher. Efficacy SR103 Briley, M., E. Carilla, and F. Furan. of a combined Sabal-Urtica preparation Permixon, a new treatment for benign 484 MEDICINAL PLANTS OF THE WORLD

prostatic hyperplasia, acts directly at SR114 Caponera, M., G. D’Eramo, G. P. the cytosolic androgen receptor in rat Flammia, et al. Antiestrogenic activity prostate. Br J Pharmacol 1983; 79: 327. of Serenoa repens in patients with SR104 De Swaef, S. I., J. O. de Beer, and A. J. BPH. Acta Urol Ital 1992; 1992(4): Vlietinck. Quantitative determination 271–272. of P-coumaric acid in Echinacea pur- SR115 Ondrizek, R. R., P. J. Chen, W. C. purea press juice and urgenin. A vali- Patton, and A. King. An alternative dated method. J Liq Chromatogr medicine study of herbal effects on 1994; 17(19): 4169–4183. penetration of zonea-free hamster oo- SR105 Jommi, G., L. Verotta, and M. J. cytes and the integrity of sperm deox- Magistretti. Alcohols isolated from li- yribonucleic acid. Fertil Steril 1999; pophilic Serenoa repens extracts and 71(3): 517–522. their use for the treatment of prostate SR116 Sawaya, M. E. Novel agents for the pathologies. Patent-Eur Pat Appl- treatment of alopecia. Semin Cutane- 287,000 1988; 9 pp. ous Med Surg 1998; 17(4): 276–283. SR106 Weisser, H., S. Tunn, B. Behnke, and SR117 Cristoni, A., P. Morazzoni, and E. M. Krieg. Effects of the Sabal serrulata Bombardelli. Chemical and pharmaco- extract IDS 89 and its subfractions on logical study on hypercritical CO2 ex- 5alpha-reductase activity in human tracts of Serenoa repens. Fitoterapia benign prostatic hyperplasia. Prostate 1997; 68(4): 355–358. 1996; 28(5): 300–306. SR118 Bayne, C. W., E. S. Grant, K. SR107 Champault, G., J. C. Patel, and A. M. Chapman, and F. K. Habib. Character- Bonnard. A double-blind trial of an ization of a new co-culture model for extract of the plant Serenoa repens in BPH which expresses 5 alpha-reduc- benign prostatic hyperplasia. Br J Clin tase types I and II: the effects of Pharmacol 1984; 18: 461–462. Permixon on DHT formation. J Urol SR108 Lowe, F. C., and J. C. Ku. Phyto- 1999; 157: 755. therapy in treatment of benign pros- SR119 de la Talle, A., O. R. Hayek, R. tatic hyperplasia: a critical review. Buttyan, E. Bagiella, M. Murchardt, Urology 1996; 48(1): 12–20. and A. E. Katz. Effects of a phy- SR109 Odenthal, K. P. Phytotherapy of be- totherapeutic agent, PC-SPES, on nign prostatic hyperplasia (BPH) with prostate cancer; a preliminary investi- Cucurbita, Hypoxis, Pygeum, Urtica gation on human cell lines and pa- and Sabal serrulata (Serenoa repens). tients. BJU Int 1999; 84(7): 845–850. Phytother Res 1996; 10: S141–S143. SR120 Jommi, G., L. Verotta, P. Gariboldi, SR110 Duker, E. M., and L. Kopanski. Inhibi- and B. Gabetta. Constituents of the li- tion of 5-alpha-reductase activity by pophilic extract of the fruits of Serenoa extracts from Sabal serrulata. Planta repens (Bart.) Small. Gazz Cim Ital Med 1989; 55(6): 587. 1988; 118(12): 823–826. SR111 Bach, D. and L. Ebeling. Long-term SR121 Hiermann, A. About contents of sabal drug treatment of benign prostatic fruits and their anti-inflammatory ef- hyperplasia-results of a prospective, 3- fect. Arch Pharm (Weiheim) 1989; year multicenter study using sabal ex- 322(2): 111–114. tract IDS 89. Phytomedicine 1996; SR122 Hatinguais, P. and R. Belle. Stable, 3(2): 105–111. deodorized antiprostatic extract of SR112 von Kloss, P. Steam vaporizable con- Sabal serrulatum. Patent-Fr Demande- stituents of pressed juice of Sabal 2,480,754 1981; 5 pp. serrulata (Roem et. Schult). Arch- SR123 Hatinguais, P. H., R. Belle, Y. Basso, J. P. neimforsch 1966; 16(1): 95–96. Ribet, M. Bauer, and J. L. Pousset. SR113 Wajda-Dobos, J. P., M. Farines, J. Composition of the hexane extract from Soulier, and H. Cousse. Comparative Serenoa repens fruit. Trav Soc Pharm study of the lipid fraction of pulp (Montpeiller) 1981; 41: 253–262. and seeds of Serenoa repens (Palma- SR124 Anon. Prostatitis inhibitors from Sabal ceae). Ol Corps Gras Lipides 1996; serrulatum fruits. Patent-Japan Kokkai 3(2): 136–139. Tokkyo Koho-58 67,625 1983; 3 pp. SERENOA REPENS 485

SR125 Tarayre, J. P., A. Delhon, H. Laures- SR129 Breu, W., M. Hagenlocher, K. Redl, G. sergues, et al. Anti-edematous action of Tittel, F. Stadler, and H. Wagner. a hexane extract from Serenoa repens Antiphlogistic activity of an extract Bartr. Drupes. Ann Pharm Fr 1983; from Sabal serrulata fruits prepared by 41(6): 559–570. supercritical carbon dioxide/in vitro SR126 Novitch, M., and R. S. Schweiker. inhibition of the cyclooxygenase and Orally administered menstrual drug 5-lipoxygenase metabolism. Arzneim- producs for over-the-counter human forsch 1992; 42(4): 547–551. use, establishment of a monograph. Fed SR130 de Swaef, S. I., and A. J. Vlietinck. Regist 1982; 47: 55,076–55,101. Simultaneous quantification of lauric SR127 Dragendorff, G. Die heilpflanzen der acid and ethyl laureate in Sabal serru- verschiedenen volker und zeiten, Enke, lata by capillary gas chromatography Stuttgart 1898; 885 pp. and derivatisation with trimethyl sul- SR128 Anon. The herbalist. Hammond Book phoniumhydroxide. J Chromatogr A Company, Hammond, Indiana 1931; 1996; 719(2): 479–482. 400 pp. SESAMUM INDICUM 487

15 Sesamum indicum L.

Common Names Acchellu India Sesam Germany Ajonjoli Spain Sesam Spain Ashadital India Sesam Sweden Bariktil India Sesame France Bijan Malaysia Sesame United Kingdom Chaam-kkae Korea Sesame United States Cycam Bulgaria Sesamfre Iceland Dee la Thailand Sesami Greece Ellu India Sesamkruid Netherlands Gergelim Brazil Sesamo Italy Gingelly United Kingdom Sesamo Portugal Goma Japan Sesamo Spain Harilik seesam Estonia Sesamzaad Netherlands Hei chih ma China Sezam indicky Slovakia Karuthellu India Sezam Croatia Khasa India Sezam Czech Republic Kkae Korea Sezam Poland Koba Japan Sezam Russia Konjed Iran Sezam Ukraine Kunzhut Russia Sezama seklas Latvia Kunzuut Estonia Sezama Slovenia Linga Philippines Sezamas Lithuania Man nga Laos Sezamo Spain Mittho-tel India Shooshma Armenia Moa China Shooshmayi good Armenia Mua chi China Shumshum Israel Nga Laos Sim-sim Arabic countries Ngaa Thailand Sim-sim Netherlands Nuvvulu India Suom Finland Rasi India Susam Albania Sasim Arabic countries Susam Bulgaria Seesami Finland Susam Turkey Semsem United Kingdom Susan Romenia Sesam Denmark Sven Sweden

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 487 488 MEDICINAL PLANTS OF THE WORLD

Szezam Hungary Tisi India Szezammag Hungary Ufuta Mozambique Szezammag Israel Ufuta Tanzania Tal India Vanglo Germany Teel France Vung Vietnam Til India Wijen Indonesia Til Pakistan Yallu India Tila India Zelzlane Arabic countries Till France Zi ma zi China

BOTANICAL DESCRIPTION sity within the several hundred varieties of Sesame is an erect annual (or occasionally, sesame. However, the sesame varieties are a perennial) of the PEDALIACEAE family usually divided into two types: shattering that grows to a height of 0.5–1.5 m, depend- and nonshattering. On ripening, sesame ing on the variety and the growing condi- capsules split, releasing the seed (hence the tions. Some varieties are highly branched, phrase, “open sesame”). Because of this whereas others are unbranched. Leaves, shattering characteristic, sesame has been 7.5–12.5 cm, simple or, when variable, with grown primarily on small plots that are upper ones narrowly oblong, middle ones harvested by hand. The discovery of an ovate and toothed and the lower ones lo- indehiscent (nonshattering) mutant by bate or pedatisect. Flowers are white, pink, Langham in 1943 began the work toward or mauve-pink with dark markings, borne in development of a high-yielding, shatter- racemes in the leak axils. The fruit is capsu- resistant variety. Although researchers lar, oblong-quadrangular, slightly com- have made significant progress in sesame pressed, deeply four grooved, 1.5–5 cm long. breeding, harvest losses resulting from Seeds are black, brown, or white, 2.5–3 mm shattering continue to limit domestic pro- long and approx 1.5 mm wide. In general, duction. the unbranched varieties mature earlier. At ORIGIN AND DISTRIBUTION maturity, leaves and stems tend to change Sesamum indicum L. is one of the oldest cul- from green to yellow to red. The leaves will tivated plants in the world. It was a highly begin to fall off the plants. The bell-shaped prized oil crop of Babylon and Assyria at white to pale-rose flowers begin to develop least 4000 years ago. Today, India and in the leaf axils 6–8 weeks after planting, China are the world’s largest producers of and this continues for several weeks. Mul- sesame, followed by Myanmar, Sudan, tiple flowering is favored by opposite leaves. Mexico, Nigeria, Venezuela, Turkey, Uganda, Initiation of flowering is sensitive to photo- and Ethiopia. period and varies among varieties. Sesame is normally self-pollinated, although cross- TRADITIONAL MEDICINAL USES pollination by insects is common. The fruit Arabic countries. Dried seeds are used ex- contains 50–100 or more seeds. The seeds ternally in the form of a plaster as a contra- mature 4–6 weeks after fertilization. The ceptive in Unani medicine. The seed oil is growth of sesame is indeterminant; that is, applied on the glans penis before coitus to the plant continues to produce leaves, prevent conceptionSI111. flowers, and capsules as long as the weather China. Hot water extract of seed is taken permits. The lighter colored seeds are con- orally for impotenceSI028. Seed oil is taken sidered higher quality. There is great diver- orally for tuberculosisSI035. SESAMUM INDICUM 489

Cuba. Seed oil is taken orally as a galacto- Iran. Oil of dried seeds is taken orally for its gogueSI138. laxative effectSI045. Europe. Seed oil taken orally is used as an Ivory Coast. The juice of new leaves is emmenagogueSI025. drunk to expel placentaSI034. Haiti. Decoction of dried seeds is taken Jordan. Seed oil is taken orally to induce orally for asthmaSI122. lactation and as an antitussiveSI075. India. The seed oil is taken orally as a Malaysia. Hot water extract of seeds is purgativeSI139. A mixture of dried fruits of taken orally as an emmenagogue and in a Sesamum indicum, Clerodendrum indicum, large dose as an abortifacientSI038. Seed oil is Moringa pterygosperma, and Piper nigrum is taken orally as an emmenagogue and used mixed with crude sugar and taken orally for by males as a tonic for sexual neuras- 20 days to produce sterilitySI103. Leaves are theniaSI032. ground with jaggary and taken orally with Mexico. Seeds, ground and mixed with coconut milk to treat rabiesSI062. Infusion of masa, are eaten for increasing milk flow in the leaf is taken once a day for controlling nursing mothersSI031. diabetesSI069. Decoction of 25–30 dried Morocco. Seeds are eaten as a hypnotic and leaves is given once a day for 6 months to stimulant and taken by females as a stimu- control diabetesSI093. Extract of the seed is lant for lactationSI077. taken orally as an abortifacient and an Mozambique. Juice of the entire plant is emmenagogueSI029. Hot water extract of the taken orally as an aphrodisiacSI079. Hot water seed is taken orally as an emmena- extract of the seed is taken orally as emme- gogueSI036,SI136 and an abortiveSI136. Hot water nagogue and abortifacientSI079. extract of the dried seed is taken orally as an Nepal. Seed oil smeared around umbilicus abortifacientSI123, an emmenagogueSI123, a and 3–5 mL placed inside the ostium is used tonic, a diuretic, and an aphrodisiac; to as an abortifacientSI070. promote hair growth; for ulcers, piles, eye Pakistan. Seeds are taken orally as an diseases, and biliousness; and as a galacto- emmenagogueSI026. gogueSI126. Dried seeds when taken orally Peru. Hot water extract of the dried bark is have an abortifacient effect in an over- taken orally for dislocations, chest pains, doseSI107. Olive oil extract of Terminalia and contusionsSI125. arjuna, Aglaia roxburghiana, Jasminum Saudi Arabia. Hot water extract of dried officinalis, Indigofera tinctoria, Tinspora cordi- plant was used as a contraceptive in the folia, Pterocarpus marsupium, Eclipta alba, 13th centurySI137. Pandanus tectorius, Oroxylum indicum, South Africa. Hot water extract of aerial Valeriana hardwickii, Terminalia chebula, parts is taken orally by the Bantu as an Termianlia bellerica, Emblica officinalis, aphrodisiacSI036. Hot water extract of leaves Punica granatum, Nelumbium speciosum, and is taken orally by the Transvaal Sotho as a Sesamum indicum is used externally to pre- remedy for malariaSI036. vent premature graying of hairSI127. Paste of South Korea. Hot water extract of seed is Bridelia scandens prepared in Sesamum taken orally to induce menstruationSI130. indicum oil is applied externally for wounds Hot water extract of dried seed is taken caused by dog bitesSI115. Fresh seed oil is used orally as an abortifacient and emmen- for eye diseases. A decoction of the leaf of agogueSI119. Gymnema silvestre is heated with sesame United States. Dried seeds are eaten as an seed oil until an emulsion is formed and emmenagogueSI110. Hot water extract of the then used as a drop for the eyes several times seed oil is taken orally to promote menstru- a daySI113. ationSI037. 490 MEDICINAL PLANTS OF THE WORLD

Vietnam. The seed oil is taken orally as an Nepetin: LfSI141 emmenagogueSI033. Obtusifoliol: Sd oilSI061 Oleic acid: Sd oilSI050 CHEMICAL CONSTITUENTS Oxalic acid: SdSI063 (ppm unless otherwise indicated) Palmitic acid: Sd oilSI050 Amyrin,D: Sd oilSI061 Palmitoleic acid: Sd oil <0.5%SI067 Amyrin, E: Sd oilSI061 Pedaliin: Lf 0.3%SI142 Anthraquinone, 2-(4-methyl-pent-3-enyl): Pinoresinol 4'-O-E-D-glucopyranosyl (1-2)-E- Hairy Rt Cult 29SI042 D-glucopyranoside: Sd 42SI152 Anthraquinone, 2-(4-methyl-penta-1-3- Pinoresinol 4'-O-E-D-glucopyranosyl (1-6)-E- dienyl): Hairy Rt Cult 18SI042 D-glucopyranoside: Sd 20.6SI152 Arachidonic acid: Sd oil <1%SI067 Pinoresinol glycoside: SdSI078 Arginine: Sd cake 3.9%SI040 Pinoresinol, (+): Sd 17.9SI078 Asarinin, (+): Sd oilSI112 Pinoresinol: Sd 162.5SI043 Avenasterol, 5-dehydro: Sd oilSI061 Pinoresinol-4'-O-E-D-glucopyranosyl (1-2)-O- Avenasterol, 7-dehydro: Sd oilSI061 (E-D-glucopyranosyl (1-6))-E-D- Behenic acid: Sd oil <0.5%SI067 glucopyranoside, (+): Sd 52.2SI156 Bicyclo(3.3.0)-octane, 3-7-dioxa, 2-(3-4- Piperitol, (+): Sd 1.5SI151 methylenedioxy-phenyl)-6-(4-hydroxy-3- Planteose: SdSI104 methoxy-phenyl): SdSI059 Protecatechuic acid: Lf, FrSI132 Caffeic acid: Lf, FrSI132 Protein: LfSI102, Sd 29.5%SI132 Campesterol: Sd oilSI061 Sesamin analog: Sd 16SI120, Sd oil 0.17%SI128, Campneoside I: Pl 330.9SI044 Call Tiss 4807.6SI051, RtSI131, PodSI151 Campneoside II: Pl 49.5SI044 Sesamin, (+): Call Tiss 4903.8SI059 Cholesterol: Sd oilSI061 Sesamin, epi, (+): Sd 1.5SI151 Cistanoside F: Pl 217.1SI044 Sesamin, epi: SdSI097 Citrostadienol: Sd oilSI061 Sesamin: PlSI047, Sd oilSI096, SdSI097 Coumaric acid, ortho: Lf, FrSI132 Sesaminol diglucoside: PlSI047 Coumaric acid, para: Lf, FrSI132 Sesaminol, epi: SdSI097 Cycloartanol, 24-methylene: Sd oilSI061 Sesaminol: SdSI053 Cycloartenol, 24-methylene: Sd oilSI067 Sesaminol-2'-O-E-D-glucopyranoside: Cycloartenol: Sd oilSI061 Sd 111.2SI043 Cycloeucalenol: Sd oilSI061 Sesaminol-2'-O-E-D-glucopyranosyl(1-2)-O- Diacetyl: Sd oilSI067 [E-D-glucopyranosyl(1-6)]-E-D- Esculentic acid: Call TissSI072, PlSI052 glucopyranoside: Sd 237.5SI043 Fatty acids: Sd oilSI153 Sesaminol-2'-O-E-D-glucopyranosyl(1-2)-O-E- Ferulic acid, trans: Sd 5.4–40SI151,SI120 D-glucopyranoside: Sd 1422.5SI043 Ferulic acid: Lf, FrSI132 Sesaminone, epi, (+): Pod, Sd 0.78SI151 Fucosterol, iso: Sd oilSI067 Sesamol: Sd oilSI108 Gadoleic acid: Sd oil <0.5%SI067 Sesamolin: SdSI068, PlSI047, StSI131 Gentisic acid: LfSI132 Sesamolin analog: Sd 48SI120 Globulin, D: SdSI089 Sesamolin, (+): Call Tiss 1.01SI051, Pod, Sd Glyoxal, methyl: Sd oilSI067 217.9SI151 Glyoxal: Sd oilSI067 Sesamolinol: SdSI041 Gramisterol: Sd oilSI061 Sesamolinol, (+): 1.9SI151 Kobusin, (+): Sd 1.1SI151 Sesamum compound 10: Pl 59.2SI044 Linoleic acid: Sd oilSI050 Sesamum compound 11: Pl 76.4SI044 Linolenic acid, D: Sd oilSI086 Sesamum compound 7: Pl 21.1SI044 Linolenic acid, J: Sd oilSI086 Sesamum compound 8: Pl 23SI044 Linolenic acid: Sd oil <1%SI067 Sesamum compound 9: Pl 26.4SI044 Myristic acid: Sd oilSI067 Simplexoside aglycone: Sd 16-86.2SI120,SI043 Naphthazarin-2-3-epoxide, 2-iso-propenyl: Sitosterol, E: Sd oilSI112 Hairy Rt Cult 550SI042 SOP-1: Sd oilSI153 SESAMUM INDICUM 491

SOP-2: Sd oilSI153 Allergenic activity. Seed oil, applied exter- SOP-3: Sd oilSI153 nally on adults at various concentrations, SI144 Squalene: Sd oil was activeSI143. Oral administration to female Stearic acid: Sd oilSI086 SI061 adults at a dose of 10 g/person produced Stigmast-7-en-3-E-ol: Sd oil SI048 Stigmasterol: Sd oilSI061 strong activity . The seeds, administered Sucrose: SdSI104 by inhalation to male adults, induced aller- Tannic acid: SdSI063 gic reaction. One adult developed occupa- Tocopherol, D: Sd oilSI039 tional hypersensitivity to sesame seeds. This Tocopherol, E: Sd oilSI067 was confirmed by skin prick testSI082. Inhala- Tocopherol, G: Sd oilSI067 tion of seeds by adults induced asthma, SI117 Tocopherol, J: Sd oil 60-70 rhinitis, and urticariaSI066. The seeds, admin- Urs-12-en-28-oic acid, 3- -(cis-para- E istered orally to male adults at a dose of 2 coumaroyl-oxy)-2-D-23-dihydroxy: PlSI052 Urs-12-en-28-oic acid, 3-E-(trans-para- mg/day, induced allergic reaction. The seed coumaroyl-oxy)-2-D-23-dihydroxy: PlSI052, produced generalized urticaria in a male Call TissSI072 adultSI080. The seed, administered orally to Vanillic acid: LfSI132 female adults at a dose of 10 g/person, in- Verbascoside: Call TissSI074, Pl 388.09SI044 duced anaphylaxisSI048. In 9070 investigated SI044 Verbascoside, decaffeoyl: Pl 201.4 infants and young children (0–2 years old), PHARMACOLOGICAL ACTIVITIES the overall prevalence of clinically relevant AND CLINICAL TRIALS immunoglobulin (Ig) E-mediated reactions Abortifacient effect. Ethanol (50 and among these patients was estimated at 1.2% 100%) extracts of the dried seed, adminis- (104/9070). Anaphylaxis was the present- SI005 tered intragastrically to pregnant rats at a ing symptom in 6/78 (7.7%) cases . Seed dose of 200 mg/kg, was inactiveSI087,SI135. Ac- oil, applied externally to adults, was inac- etone extract of the dried seed, on agar plate tive. It was applied to skin, hair, nails, eyes, at a concentration of 0.2 g/plate, was active and mucous membranes without irrita- SI067 on Salmonella typhimurium TA98 and tion . Seed oil applied as patch test to SI096 TA100 vs aflatoxin B1-induced mutagen- adults produced dermatitis . Seeds, ad- esis, Aspergillus ochraceous extract-induced ministered orally to female adults, induced SI048 mutagenesis, and Aspergillus versicolor ex- sesame seed anaphylaxis . The seed in- tract-induced mutagenesisSI101. gested by adults produced a severe allergic SI065 Acyl-coenzyme A inhibition. Cholesterol reactions in sensitized individuals . acyl-transferase inhibitor CP-105,191 dis- D-Tocopherol effect. The seed, adminis- solved in sesame oil was investigated in fed tered in the ration of male rats at a dose of and fasted dogs. Systemic availability of CP- 20% of low D-tocopherol diet for 8 weeks, 105,191 area-under-the-curve (AUC) was produced an increase of D-tocopherol in the three- to fourfold higher in fed dogs than in blood and tissue. Results were significant at fasted dogs when 50-mg doses were admin- p < 0.01SI046. istered as aqueous suspension. When CP- Anaphylactic response. Seed oil, adminis- 105,191 was partially dissolved in 20 mL tered periodontally to adults, was effective. sesame oil, the availability of CP-105,191 A 46-year-old male developed recurrent re- was increased by a factor of 2. Plasma AUCs action to sesame seed oil. The symptoms were similar for fed and fasted dogs after the were chills, shakiness, cramps, vomiting, fe- 12.5-mg dose completely dissolved in cal incontinence, fainting, flushing, and sesame oil, indicating that the increased pruritic welts. Skin test revealed a four-plus availability of drug when administered with multitest response and a marginally positive food is related to the presence of lipidSI019. rast. Significant histamine release was also 492 MEDICINAL PLANTS OF THE WORLD notedSI058. Seeds, administered orally to fe- ene chloride extract of the dried leaf, on male adults, induced anaphylaxisSI048. The agar plate at a concentration of 100 Pg/ seed, administered orally to female adults, plate, was inactive on Cladosporium cucu- induced anaphylaxis. In a double-blind, pla- merinum. Methanol and methylene chloride cebo-controlled case study of a patient with extracts of the dried root, at a concentra- celiac challenged with sesame seeds, it was tion of 100.0 Pg/plate, were active on Cla- indicated that sesame can induce non-IgE- dosporium cucumerinumSI071. Seed oil, on agar mediated anaphylaxisSI084. Ten allergic plate at an undiluted dose, was inactive on patients had positive IgE antibodies and Trichophyton mentagrophytes and Trichophy- skin-prick test to food-containing sesa- ton rubrumSI129. meSI002. Four patients with anaphylaxis, Antihemolytic activity. The seed, admin- angioedemia, or urticaria after ingestion of istered in the ration of male rats at a dose of sesame seed or sesame oil-containing prod- 5% of diet, was active on red blood cells ucts were studied for anti-sesame seed ex- (RBCs) vs low D-tocopherol diet. Results tract IgE by the radioallergosorbent test. were significant at p < 0.01SI046. Three of four were be positiveSI023. Antihypercholesterolemic activity. Seed Antibacterial activity. Ethanol extract of oil, administered by gastric intubation to the shade-dried seed, on agar plate at a con- rabbits at a dose of 1 g/kg, was activeSI149. centration of 2.5 mg/disc, was inactive on Antihypertensive effect. Sesame oil lignan Escherichia coli, Proteus mirabilis, Pseudomo- sesamin, in two-kidney, one-clip (2K,1C) nas aeruginosa, Staphylococcus aureus, and renal hypertensive rats fed a sesamin-con- Staphylococcus epidermidisSI088. Seed oil, on taining (1% w/w) diet, was investigated. agar plate at an undiluted dose, was inactive The hypertension was markedly reduced, on Bacillus subtilis, Escherichia coli, Salmo- but the sesame diet ameliorated the vascu- nella typhosa, Staphylococcus aureus, and lar hypotrophy. Results indicated that Vibrio choleraeSI129. The seeds, on agar plate, sesamin is useful as prophylactic treatment were active on Bacillus subtilis, Escherichia to combat the development of renal hyper- coli, Pseudomonas cichorii, and Salmonella tension and cardiac hypertrophySI017. typhimuriumSI083. Pretreatment of mice with Anti-implantation effect. Ethanol extract sesame extract significantly reduced the of the dried seed, administered intragastri- lethality of bacterial infection, possibly cally to female rats at a dose of 200 mg/kg, because of its host-mediated action. No was inactive vs early pregnancySI087. apparent acute toxicity was detected in mice Anti-inflammatory effect. Sesame oil, by oral administration of 10 g/kg of the present in the injectable gold preparation extractSI009. “Auromyose,” was administered at a dose of Anticrustacean activity. Methylene chlo- 18 g/daily for 12 weeks to 11 healthy male ride extracts of the dried leaf and root, at a volunteers. Tumor necrosis factor (TNF)-D, concentration of 500 ppm, were inactive on prostaglandin (PG)-E2, and leukotriene Artemia salina. The assay system was in- production levels did not indicate any sta- tended to predict for antitumor activity. tistically significant changes. This result did Methanol extract of the dried root, at a con- not suggest antiinflammatory effect of centration of 500 ppm, was inactive on sesame oil as present in injectable gold Artemia salinaSI071. Ethanol extract of the preparations used in the treatment of rheu- shade-dried seed was inactive on Artemia matoid arthritisSI013. salinaSI088. Anti-irradiation effect. Methanol extract Antifungal activity. Seed oil on agar plate of the dried seed, administered intraperito- was inactive on Aspergillus nigerSI129. Methyl- neally to mice at a dose of 1 g/kg, was inac- SESAMUM INDICUM 493 tive vs soft X-ray irradiation at lethal Anti-yeast activity. Ethanol extract of the doseSI154. shade-dried seed, on agar plate at a concen- Antimutagenic activity. Ethanol (70%) tration of 2.5 mg/disc, was inactive on Can- extract of the dried aerial parts, on agar dida albicansSI088. Undiluted seed oil on agar plate, was inactive on Escherichia coli PQ37 plate was inactive on Candida albicans and vs mitomycin-induced mutagenesis, assessed Saccharomyces cerevisiaeSI129. by the SOS-chromotest methodSI095. Apoptosis induction. The exposure of hu- Antioxidant activity. Hexane and metha- man lymphoid leukemia Molt 4B cells to nol extracts of the dried seed, tested on sesamolin, a component of sesame seed, pro- lard at a concentration of 0.06 %, were duced growth inhibition and the induction SI116 inactive . Seed oil, at undiluted concen- of apoptosisSI010. SI117 tration, was active . Acetone extract of Carcinogenic activity. Seed oil, in the the seed, at a concentration of 0.2 mg/kg, ration of rats at a dose of 2% of diet, was was active. Linoleic acid was used as a sub- active on squamous cell carcinoma of the SI120 strate in this test . fore stomach. Seed oil, administered intrap- Antitoxic effect. Sesame oil, adiministered eritoneally to mice at a dose of 0.5 mL/ani- to male Wistar rats, ameliorated hepatic and mal, was inactive. Pulmonary adenomas in renal damage in a dose-dependent manner offsprings did not occur with increased and increased survival in lipopolysaccha- incidence. Seed oil, administered subcuta- ride-treated rats. It decreased lipid peroxide neously to mice at a dose of 0.2 mL/kg dosed concentration in serum but not in liver and daily, was inactive. Increased incidence of kidney. Serum nitrite production was unaf- mammary adenocarcinoma was observedSI067. fected by sesame oil ingestion, and the ac- tivity of xanthine oxidase was reduced in Cholesterol level and metabolism. Sesame oil, administered to male Wistar rats the lipopolysaccharide-challenged ratsSI004. in the diet at concentrations of 12 or 24% Anti-tumor activity. Water extract of the dried seed, administered intragastrically to for 4 weeks, produced significantly lower mice at a dose of 50 mg/animal daily for 5 liver cholesterol and liver lipid levels, serum days, was active on CA-Ehrlich-ascites, total cholesterol, and low-density lipopro- 18% increase in life-span. Intraperitoneal tein (LDL) cholesterol in rats fed the 24% administration was active on Dalton’s diet. The high degree of unsaturation (85%) lyphoma and CA-Ehrlich-ascites, 19 and of sesame oil and the presence of linoleic SI016 39% increase in life-span, respectivelySI094. acid could be an important factor . Seed oil, administered to rats intraperito- Sesamin, administered to rats in the diet at neally with 1,2,5,6-dibenzanthracene or re- a concentration of 0.5% sesame oil for 4 tene, was active on sarcomaSI150. weeks, reduced the concentration of serum Antiviral activity. Ethanol (80%) extract and liver cholesterol significantly, irrespec- of the dried leaf, in cell culture at a concen- tive of the presence or absence of choles- tration of 0.2 mL/well, was equivocal on terol in the diet. Sesamin inhibited micellar poliovirus; inactive on herpes virus, measles, solubility of cholesterol but not bile acids. and Semliki Forest virus and produced It did not bound taurocholate nor affected weak activity on coxsackie virus SI076. Pre- the absorption of fatty acids. Only a mar- treatment of mice with sesame extract ginal proportion (ca 0.15%) of sesamin ad- failed to reduce the cytophatic effect of ministered intragastrically was recovered in human immunodeficiency virus 1 (HIV-1) the lymph. There was significant reduction infection in MT-4 cells. No apparent acute in the activity of liver microsomal 3-hy- toxicity was detected in mice with oral droxy-3-methylglutaryl coenzyme A (HMG- administration of 10 g/kg of the extractSI009. CoA) reductase, but the activity of hepatic 494 MEDICINAL PLANTS OF THE WORLD cholesterol 7 D-hydroxylase and alcohol de- a concentration of 100.0 Pg/mL, was active hydrogenase remained unaffectedSI021. on CA-colon-CACO-2, CA-human-colon- Chromotropic effect negative. Methanol CO-115, and human colon cancer cell line (70%) extract of the seed, administered to HT29SI100. Seed oil, in cell culture at a con- guinea pigs at a concentration of 100 Pg/mL, centration of 300 Pg/mL, was inactive on was active on the atrium. The extract, ad- melanoma-NHEM and melanoma-SK- ministered intravenously to rats at dose of MEL-2SI055. Water extract of the dried seed 10 mg/kg, produced atropine abolished was active on Leuk-P815. Tumor-toxic ac- effectSI057. tivity was evaluated by culturing mastocy- Corticosteroid type activity. Seed oil, ad- toma P815 cells with macrophage cells and ministered parenterally to pregnant rats, was measured the incorporation of 3H-thimidine active. The survival time of adrenalecto- radioactivitySI099. Ethanol (100%) extract of mized pregnant rats and their subsequent lit- the shade dried seed, in cell culture at vari- ters was increasedSI148. ous concentrations, was inactive on CA- Cytotoxic activity. Ethanol (90%) extract A549, CA-mammary-MCF-7, and human of the dried entire plant, in cell culture at a colon cancer cell line DLD-1SI088. concentration of 0.25 mg/mL,was active on Dermatitis improvement. Seed oil, ap- human lymphocytes; Vero cells, effective plied externally twice daily for 2 years to 35 dose (ED)50 0.36 mg/mL; Chinese hamster adults with dermatitic lesions, was acitve. ovary cells, ED50 0.44 mg/mL; and Dalton’s The effect was seen only with polymer- SI091 SI067 lyphoma, ED50 1.2 mg/mL . Methylene ized oil . chloride extract of the dried leaf, in cell cul- DNA synthesis inhibition. Ethanol (90%) ture, produced weak activity on CA-colon- extract of the dried entire plant, at a con- SI091 SW 480, inhibitory concentration (IC)50 6.1 centration of 0.25 mg/mL, was active . Pg/mL. A concentration of 500 ppm was Early antigen viral induction stimulation. inactive on CA-human-colon-CO-115SI071. Ether extract of the seed, in cell culture at Methylene chloride extract of the dried concentration of 0.1 mg/mL, was inactive root, in cell culture at a concentration of on lymphoma-RAJ1SI105. 500 ppm, was inactive on CA-human-co- Embryotoxic effect. Benzene and petro- lon-CO-115 and active on CA-colon-SW leum ether extracts of the dried seed, admin-

480, IC50 3.6 Pg/mL. Methanol extract of istered by gastric intubation to pregnant rats the dried root, in cell culture at a con- at a dose of 150 mg/kg, were inactiveSI109. centration of 500 ppm, was inactive on Ethanol (50%) extract of the seed, adminis- CA-colon-SW 480 and CA-human-colon- tered orally to female rats at a dose of 200 CO-115SI071. Ethanol (50%) extract of the mg/kg, was inactiveSI135. seed, in cell culture, was inactive on CA- Estrogenic effect. Seed oil, applied subcu- SI027 9KB, ED50 greater than 20 Pg/mL . Water taneously to ovariectomized mice, was extract of the dried seed, in cell culture at a inactiveSI134. The plant, administered orally concentration of 500.0 Pg/mL, produced to immature female rats at a dose of 2 g/kg, weak activity on CA-mammary-microal- was activeSI090. veolarSI098. Water extract of the dried seed, Fatty acid oxidation. Seeds, administered in cell culture at a concentration of 500 Pg/ orally to rats at a dose of 200 g/kg, increased mL, was inactive on CA-JTC-26SI054. Seed hepatic mitochondrial and the peroxiso- oil, in cell culture at concentrations of mal fatty acid oxidation rateSI003. 0.01% and 0.1%, was inactive on the rat fi- Glucosidase inhibition. Ethyl acetate and broblasts. A concentration of 1% produced water soluble fractions of the seed were in- weak activitySI140. Seed oil, in cell culture at active on the intestineSI085. SESAMUM INDICUM 495

Glutamate–oxaloacetate–transaminase Hypocholesterolemic activity. Extract of inhibition. Seed oil, administered to mice the dried entire plant, administered to rats at a concentration of 0.6% of diet, was ac- at a dose of 30% of diet, was activeSI121. tive. Biological activity reported has been Lignan fraction of the seed, administered in patentedSI064. the ration of 4-week-old rats at a dose of Glutamate–pyruvate–transaminase inhi- 0.2% of the diet for 3 weeks, was active. Di- bition. The seed and seed oil, administered etary fat sources were safflower and primrose to mice at a concentration of 0.6% of diet, oilsSI097. were active. Biological activity reported has Hypoglyceridemic activity. Lignan frac- been patentedSI064. tion of the seed, administered to 4-week-old Generally recognized as safe status. Ap- rats at a dose of 0.2% of diet for 3 weeks, was proved by the US Food and Drug Adminis- active. Dietary fat sources were safflower tration in 1996 (sect. 582.10) as a flavoring and primrose oilsSI097. agentSI155. Hypophospholipidemic activity. Lignan Hair-stimulant effect. Ethanol (50%) ex- fraction of the seed administered to 4-week- tract of the dried seed, applied externally to old rats at a dose of 0.2% of diet for 3 weeks, mice at a dose of 0.33 g/mL for 10 days, was was active. Dietary fat sources were saf- activeSI092. flower and primrose oilsSI097. Hemotoxic activity. Seed oil, adiminis- Hypotensive effect. Methanol (70%) ex- tered orally to human adults, produced tract of the seed, administered intravenously thrombocytosis in children. the effect was to rats at dose of 3 mg/kg, was active. The inactivated by ultraviolet radiationSI146. effect was inhibited by pretreatment with Hypercholesterolemic activity. Seed oil, atropineSI057. administered by gastric intubation to rabbits Immunoglobulin level. The effect of at a dose of 0.4 g/kg, was inactiveSI149. Male sesaminol and sesamin on the ethanol-in- Wistar rats fed 12 or 24% sesame oil in the duced immune indices were examined in diet for 4 weeks were investigated. The rats rats given a low (10%)-casein diet. Sesa- on the 24% sesame oil diet had significantly minol decreased splenic leukotriene B4 pro- lower lymphatic cholesterol and fatty duction, whereas sesamin increased the acidsSI020. plasma PGE2 concentration. A significant Hyperglycemic activity. Extract of the IgG-elevating effect of these lignans was dried entire plant, administered to rats at a observed. The concentration of plasma IgE dose 30% of diet, was activeSI121. Seed oil, was not influencedSI015. adiministered orally to adults at a dose of 60 Inflammation induction. Seed oil, applied g/person, produced weak activitySI147. Hot externally as a patch test to human adults at water extract (4%) or methanol eluent frac- a dose of 0.032 mL/person, was inactiveSI147. tion (0.7%) of the defatted seed, adminis- Inotropic effect negatve. Methanol (70%) tered orally to genetically diabetic 5 weeks extract of the seed, administered to guinea old male KK-Ay-mice, had a reductive ef- pigs at dose of 100 Pg/mL, was active on the fect on the plasma glucose concentration. atrium. The effect was abolished by atro- The effect is suggested to be casused by the pineSI057. delayed glucose absorptionSI001. Insecticide activity. Seed oil, applied ex- Hyperlipidemic activity. Seed oil, adimin- ternally on cattle at a concentration of istered orally to adults at a dose of 60 g/per- 0.7%, was active. It was used as a delousing son, was activeSI147. Seed oil, administered by agentSI067. gastric intubation to rabbits at a dose of 0.4 Interleukin induction. Water extract of g/kg, was activeSI149. the dried seed produced weak activity. 496 MEDICINAL PLANTS OF THE WORLD

Interleukin (IL)-1 activity was measured by reactions of dimethylaminopyrine and the IL-1 dependent growth of a T-helper hexobarbitalSI067. cell lineSI099. Moluscicidal activity. Methylene chloride Larvicidal activity. Methylene chloride ex- extract of the dried leaf, at a concentration tract of the dried leaf, at a concentration of of 400 ppm, was inactive on Biomphalaria 500 ppm, was inactive on Aedes aegypti. glabrata. Methylene chloride and methanol Methylene chloride extract of the dried root extracts of the dried root were also inact- was active on Aedes aegypti, lethal concen- iveSI071. tration (LC)100 12.5 Pg/mL. The methanol Monoamine oxidase activity increase. extract was inactiveSI071. Seed oil, in cell culture, was active on as- Lipid metabolism effect. Lignan fraction trocytes vs chlorgyline-induced monoam- of the seed, administered to 4-week-old rats ine oxidase (MAO) inhibition, IC50 9077 at a dose of 0.2% of diet for 3 weeks, was ppm SI081. active. Dietary fat source, were evening Mutagenic activity. Water extract of the primrose and safflower oils. Proportion of plant, on agar plate at a concentration of dihomo-J-linolenate increased in response 100 mg/plate, was inactive on pig kidney- to reduction of G-5-desaturase activity and LLC-PK-1 cells and trophoblastic cells of the proportion of docosapentaenoate de- placenta. The effect was the same with or creased in liver phosphatidylcholine. Liver without metabolic activationSI106. Acetone phospholipid level decreased vs control. extract of the dried seed, on agar plate at a Lignan fraction of the seed administered to concentration of 0.2 Pg/plate, was inactive 4-week-old rats at a dose of 0.2% of diet for on Salmonella typhimurium TA100 and 3 weeks, was active. The dietary fat source TA98. Metabolic activation had no effect was evening primrose and safflower oils. on the resultsSI101. Ethanol extract of the Liver phospholipid level decreased vs con- shade dried seed, on agar plate at various trol. With the dietary fat source evening concentrations, was inactive on Salmonella primrose oil, fecal excretion of neutral ste- typhimurium T1530SI088. Seed oil, on agar roids increased and microbial transforma- plate, was inactive on Salmonella typhi- tion of cholesterol to coprostanol decreased. murium TA100 and TA98SI067. Chloroform/ The specific activity of liver microsomal G- methanol extract (2:1), on agar plate at a 5 and G-6 desaturases were decreased and concentration of 10 mg/plate, was inactive increased, respectively. Lignan fraction of on Salmonella typhimurium TA100 and the seed, administered to 4-week-old rats at TA98. The effect was the same with or a dose of 0.2% of diet for 3 weeks, was inac- without metabolic activationSI106. Mice fed tive. The production of thromboxane A2 diets containing various levels of sesame oil (TXA-2) by platelets and PGI-2 by the for 8 weeks were investigated. Aflatoxin B1- aorta was not influenced whether dietary fat induced chromosomal aberrations in bone was evening primrose oil or safflower oilSI097. narrow cells were statistically higher in mice Lipid peroxide formation inhibition. The fed 9 and 12% sesame oil than those fed 3% seed, administered to male rats at a dose of sesame oil. The data suggested that the me- 5% of diet, was active in liver vs low-alpha- tabolism of a mutagen could be influenced tocopherol diet. Results were significant at by the dietary lipid intake of the test p < 0.01 levelSI046. animalsSI022. Metabolism. Seed oil, administered intrap- Nasal mucosal effect. Pure sesame oil eritoneally to mice at a dose of 160 mg/kg, (Nozoil) was tested in 79 subjects with na- produced a decrease in the hydroxylation sal mucosa dryness. Half of them received SESAMUM INDICUM 497 pure sesame oil for 2 weeks followed by enty six percent of the patients were cured, isotonic sodium chloride solution (ISCS) 16% showed a partial response, and 8% did for 2 weeks. The other half received ISCS not improveSI118. for 2 weeks, followed by pure sesame oil for Pharmacokinetics. Seed oil, administered 2 weeks. Nasal mucosal dryness improved intramuscularly to dogs at a dose of 1 mL/kg significantly when pure sesame oil was used labeled glyceryl trioleate injected with the compared with ISCS (p < 0.001). The im- oil, was distributed primarily to iliac nodes, provement in nasal stuffiness was also bet- heart, liver, and lungsSI067. ter with pure sesame oil (p < 0.001) as was Phytotoxic effect. Ethanol (95%) extract improvement in nasal crusts (p < 0.001). of the dried seed oil, at a concentration of Eight of 10 subjects reported that their na- 500 ppm, was inactive. The biological ac- sal symptoms had improved with pure tivity reported has been patentedSI114. sesame oil compared with 3 of 10 for ISCS Prostaglandin induction. Seed oil, admin- (p < 0.001). Adverse events were few and istered subcutaneously to rats at a dose of temporarySI006. Twenty patients with dryness 1 g/day for 14 days, stimulated PGI-2 syn- of the nose, and 20 patients who had previ- thesis in the thoracic aortaSI124. ously undergone nasal irradiation were in- Pyruvate kinase inhibition. The seed, ad- vestigated. For the 20 days, the patients ministered to male rats at a dose of 5% of sprayed sesame oil into each nostril three diet, was active in plasma vs low-D-toco- times a day, the nasal problems decreased pherol diet. Results were significant at p < significantly. The greatest effect was exerted 0.05 levelSI046. on dryness and the side effects from using Quil-A saponin toxicity. Mice fed Quil-A- sesame oil were few in number and mildSI011. supplemented diet (a saponin that emulsi- Nematocidal activity. Ethanol (95%) ex- fies fats and potentiates the immune tract of the seed oil, at a concentration of responses) showed higher level of docosa- 500 ppm, was active. Petroleum ether ex- pentaenoic acid in the liver. These changes tract of the seed oil, at a concentration of were associated with a significant reduction 500 ppm, completely controlled rootknot in in the plasma PGE1 and PGE2 and grape, tomato, and sugar beet without phy- thrombohane-B2 levels in response to an totoxicity. The biological activity reported intraperitoneal injection of a lethal dose of has been patented. The seed oil was also ac- lipopolysaccharide endotoxin, LD50 20 mg/ tive and the biological activity has been kg. The data suggest that sesame seed oil and patentedSI114. Quil A, when present in the diet, exerted Neuromuscular blocking activity. Decoc- cumulative effects that resulted in a de- tion of the seed oil, administered orally to crease in the levels of dienoic eicosanoids adults of both sexes at a dose of 4.6 g/per- with a reduction in IL-1 E and a con- son, was active. A mixture of Piper longum, commitant elevation in the levels of IL-10 Zingiber officinale, Piper cubeba, Curcuma that were associated with a marked increase zedoaria, Juniperus communis, Cichorium survival in miceSI014. intybus, Mentha arvensis, Commiphora Radical scavenging effect. Seed oil, in cell mukul, and Sesamum indicum was given. culture, was active on astrocytes vs perox- SI081 Twenty five patients with laquwa (spastic ide radical scavenging, IC50 27461 ppm . facial paralysis) were treated with this mix- Spasmogenic activity. Methanol (70%) ture in divided doses of 4.6 g in 24 hours. extract of the seed, administered to guinea Six grams of a decoction of Lavendula pigs at a dose of 1 mg/mL, was active on the stoechas was also given in some cases. Sev- uterus and ileum. The effect was abolished 498 MEDICINAL PLANTS OF THE WORLD by atropine. Methanol (70%) extract of the oil into the pectoral area for muscle au- seed, administered to rats at dose of 1 mg/ gumentation. Excision revealed a cyst filled mL, was active on uterus (estrogen)SI057. with oily material, surrounded by granulo- Steroidogenic activity. Seed oil, applied matous tissueSI012. Miniature swine fed bro- externally to rats, produced 3-oxosteroid minated sesame oil at dietary levels of 5, 25, level increased on the treated skinSI067. 50, or 500 mg/kg of body weight for 17 Teratogenic activity. Seed oil, adminis- weeks showed decreased growth rate and tered intragastrically to rats at a dose of 4 food intake at the high dose of sesame oil. mL/animal for 6–10 days of gestation, was Marked elevations in LDH, SGOT, and inactiveSI067. SGPT values were seen at the highest dose Tocopherol level. Consumption of 5 mg of level, and these enzyme activities were in- J-tocopherol per day for a 3-day period from creased at the 50 mg/kg dose levelSI024. sesame seeds in nine subjects, significantly Toxicity assesment. Ethanol (50%) ex- elevated serum J-tocopherol levels (19.1% tract, administered intraperitoneally to SI027 increase, p = 0.03) and depressed plasma E- mice, produced LD50 500 mg/kg . tocopherol (34% decrease, p = 0.01). No Tumor-promotion inhibition. Methanol significant changes in baseline or post- extract of the dried entire plant, in cell cul- intervention plasma levels of cholesterol, ture at a concentration of 200 Pg/mL, was triglycerides, or carotenoids were foundSI007. active vs 12-O-hexadecanoylphorbol-13- In 40 investigated female students (mean acetate-induced Epstein–Barr virus acti- SI049 age 26 years) after 4 weeks of sesame oil-rich vation . diet, the J-tocopherol concentrations nor- Tyrosinase inhibition. Methanol (80%) malized to serum lipids increased signifi- extract of the dried entire plant at a con- cantly (p < 0.01), and the / -tocopherol centration of 100 Pg/mL produced weak D J SI049 ratios decreased significantly from baseline activity . concentrations (p < 0.05). The D-toco- White blood cell-macrophage stimulant. Water extract of the dried seed at a concen- pherol concentrations did not changeSI008. tration of 2 mg/mL was active on macro- Rats fed diets low in D-tocopherol and high phages. Nitrate formation was used as an in J-tocopherol, differed in content of index of the macrophage stimulating activ- sesamin (0.25, 0.5, 1, 2, or 4 g/kg) from ity to screen effective foodsSI099. sesame oil for 4 weeks. Sesamin-feeding in- Weight-gain inhibition. Seed oil adminis- creased J-tocopherol and J/D-tocopherol ra- tered subcutaneously to mice at a dose of tios in the plasma (p < 0.05), liver (p < 0.05 mL/animal was active. Brain weight 0.001), and lungs (p < 0.001). The increase also decreased after 210 days of dosingSI067. was not significant for D-tocopherol. Results suggest, that sesamin appears to spare J-to- REFERENCES copherol in rat plasma and tissues, and the SI001 Takeuchi, H., L. Y. Mooi, Y. Inagaki, effect persists in the presence of J-toco- and P. He. Hypoglycemic effect of a hot-water extract from defatted sesame pherol. 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lignans produce marked enhancement SI058 Chiu, J. T., and I. B. Haydik. Sesame of vitamin E activity in rats fed a low seed oil anaphylaxis. J Allergy Clin alpha-tocopherol diet. Lipids 1995; Immunol 1991; 88(3): 414–415. 30(11): 1019–1028. SI059 Mimura, M., Y. Takahara, A. Ichi- SI047 Kuriyama, K., K. Tsuchiya, and T. kawa, and T. Osawa. Lignan com- Murui. Generation of new lignan glu- pounds and their manufacture with cosides during germination of sesame Sesamum indicum. Patent-Japan Kokai seeds. Nippon Nogei Kagaku Kaishi Tokkyo Koho-36,207,389 1988; 5 pp. 1995; 69(6): 685–693. SI060 Murui, T., and A. Ide. Anticarcino- SI048 Stern, A., and B. Wuthrich. Non-IgE- genic glycosides with aglycones ex- mediated anaphylaxis to sesame. Al- tracted from sesame seeds. Patent-Japan lergy 1998; 53(3): 325–326. Kokai Tokkyo Koho-62,238,287 1987; SI049 Shin, N. H., K. S. Lee, S. H. Kang, K. 6 pp. R. Min, S. H. Lee, and Y. S. Kim. In- SI061 Kamal-Eldin, A., L. A. Appelquist, G. hibitory effect of herbal extracts of Yousif, and G. M. Iskander. Seed lipids DOPA oxidase activity of tyrosinase. of Sesamum indicum and related wild Nat Prod Sci 1997; 3(2): 111–121. species in Sudan. The sterols. J Sci SI050 Oezcan, M., and A. Akguel. Some Food Agr 1992; 59(3): 327–334. compositional characteristics of SI062 Reddy, M. B., K. R. Reddy, and M. N. sesame seeds and oil. Turk J Agr For Reddy. A survey of plant crude drugs 1995; 19(1): 59–65. of Anantapur District, Andhra Pra- SI051 Mimura, M., Y. Takahara, A. Ichi- desh, India. Int J Crude Drug Res kawa, and T. Osawa. Lignan com- 1989; 27(3): 145–155. pounds and their manufacture with SI063 Odumodu, C. U. Antinutrients con- Sesamum indicum. Patent-Japan Kokai tent of some locally available legumes Tokkyo Koho-63,207,389 1997; 5 pp. and cereals in Nigeria. Trop Geograph SI052 Okada, N., K. Takebayashi, A. Kawa- Med 1992; 44(3): 260–263. shima, and M. Niwano. A triterpene, its SI064 Shinmen, Y., K. Akimoto, S. Asami, manufacture, and cancer inhibitors con- et al. Dioxabicyclooctane derivatives taining triterpenes. Patent-Japan Kokai as liver function improvers. Patent-Eur Tokkyo Koho-06,329,590 1994; 9 pp. Pat Apl-409,654 1991; 13 pp. SI053 Kuryama, K., and T. Murui. Manufac- SI065 Kagi, M. K., and B. Wuthrich. Falafel ture of lignan glycosides and lignans burger anaphylaxis due to sesame from sesame seeds. Patent-Japan Kokai seed allergy. Ann Allergy 193; 71(2): Tokkyo Koho-07,145,066 1995; 10 pp. 127-129. SI054 Sato, A. Studies on anti-tumor activ- SI066 Keskinen, H., P. Ostman, E. Vaherj, et ity of crude drugs. III. The effect of al. A case of occupational asthma, decreasing resistance of cancer cell in rhinitis and urticaria due to sesame seed. long term in vitro screening test Clin Exp Allergy 1991; 21: 523–524. with aqueous extracts of some crude SI067 Anon. Final report on the safety assess- drugs. Yakugaku Zasshi 1990; 110(7): ment of sesame oil. J Amer Coll 490–497. Toxicol 1993; 12(3): 261–277. SI055 Smith, D. E., and J . W. Salerno. Selec- SI068 Kang, S. S., J. S. Kim, J. H. Jung, and Y. tive growth inhibition of a human ma- H. Kim. NMR assessments of two lignant melanoma cell line by sesame furofan lignans from sesame seeds. Arch oil in vitro. Prostaglandins Essent Fatty Pharm Res 1955; 18(5): 361–363. Acids 1992; 46(2):145–150. SI069 Anis, M., and M. Iqbal. Medicinal SI056 James, C., A. Williams-Akita, Y. A. K. plantlore of Aligard, India. Int J Rao, L. Chiarmonte, and A. T. Pharmacog 1994; 32(1): 59–64. Schneider. Sesame seed anaphylaxis. SI070 Bhattarai, N. K. Folk herbal remedies N Y J Med 1991; 91(10): 457–458. for gynaecological complaints in cen- SI057 Hassan Gilant, A. U., and K. Aftab. tral Nepal. Int J Pharmacog 1994; Presence of acetylcholine-like sub- 32(1): 13–26. stance (S) in Sesamum indicum. Arch SI071 Cepleanu, F., M. O. Hamburger, B. Pharm Res 1992; 15(1): 95–98. Sordat, et al. Screening of tropical me- 502 MEDICINAL PLANTS OF THE WORLD

dicinal plants for Molluscicidal, larvi- tional hypersensitivity to sesame seeds. cidal, fungicidal and cytotoxic activi- Allergy 1996; 51(1): 69–70. ties, and brine shrimp toxicity. Int J SI083 Kumar, S., G. D. Bagchi, and M. P. Pharmacog 1994; 32(3): 294–307. Darokar. Antibacterial activity ob- SI072 Okada, N., K. Takebayashi, J. Kawa- served in the seeds of some coprophil- shima, et al. Inhibition of Epstein-Barr ous plants. Int J Pharmacog 1997; virus (EBV) activation by triterpenes 35(3): 179–184. in Sesamum indicum L. callus. Shoku- SI084 Pajno, G. B., G. Passalacqua, G. butsu Soshiki Baiyo 1994; 11(2): Magazzu, G. Barberio, D. Vita, and G. 145–149. W. Canonica. Anaphylaxis to sesame. SI073 Johns, T., E. B. Mhoro, and P. Sanaya. Allergy 2000; 55(2): 199–201. Food plants and masticants of the SI085 Toda, M., J. Kawabata, and T. Kasai. Batemi of Ngorongoro district, Tanza- Alpha-glucosidase inhibitors from nia. Econ Bot 1996; 50(1): 115–121. glove (Syzygium aromaticum). Biosc SI074 Richaado, H., K. Janetsuto, G. Biotech Biochem 2000; 64(2): 294–298. Uiriamu, A. Kawashima, M. Niwano, SI086 Engler, M. M., and M. B. Engler. Di- and M. Mimura. A-2 inhibitors con- etary borage oil alters plasma, hepatic taining acteoside. Patent-Japan Kokai and vascular tissue fatty acid composi- Tokkyo Koho-07,223,964 1995; 7 pp. tion in spontaneously hypertensive SI075 Al-Khalil, S. A survey of plants used rats. Prostaglandins Leukotrienes in Jordanian traditional medicine. Int Essent Fatty Acids 1998; 59(1): 11–15. J Pharmacog 1995; 33(4): 317–323. SI087 Runnebaum, B., T. Rabe, L. Kiesel, SI076 Vlietinck, A. J., L. van Hoof, J. Totte, and A. O. Prakash. Biological evalua- et al. Screening of hundred Rwandese tion of some medicinal plants extracts medicinal plants for antimicrobial and for contraceptive efficacy in females. antiviral properties. J Ethnopharmacol Future aspects in contraception. Part 2. 1995; 46(1): 31–47. Female contraception, MTP Press, SI077 Bellakhdar, J., R. Claisse, J. Fleurentin, LTD, Boston, 1984, 115–128. and C. Younos. Repertory of standard SI088 Alkofahi, A., R. Batshoun, W. Owais, herbal drugs in the Moroccan pharma- and N. Najib. Biological activity of copoea. J Ethnopharmacol 1991; some Jordanian medicinal plant ex- 35(2): 123–143. tracts. Fitoterapia 1996; 67(5): 435–442. SI078 Kawagishi, S., T. Oosawa, and H. SI089 Prakash, V., and P. K. Nandi. Isolation Katsuzaki. Pinoresinol glycoside, and characterization of alpha-globulin sesame seed extract containing the gly- of sesame seed (Sesamum indicum). J coside, and its use for preventing oxi- Agr Food Chem 1978; 26(2): 320. dation of lipids. Patent-Japan Kokai SI090 Tewari, P. V., H. C. Mapa, and C. Tokkyo Koho-06,116,282 1994; 5 pp. Chaturvedi. Experimental study on es- SI079 Amico, A. Medicinal plants of south- trogenic activity of certain indigenous ern Zambesia. Fitoterapia 1977; 48: drugs. J Res Indian Med Yoga Home- 101–139. opathy 1976; 11: 7–12. SI080 Eberlein-Konig, B., F. Rueff, and B. SI091 Unnikrishnan, M. C., and R. Kuttan. Przybilla. Generalized urticaria caused Cytoxicity of extracts of spices to cul- by sesame seeds with negative prick tured cells. Nutr Cancer 1988; 11(4): test result and without demonstrable 251–257. specific IgE antibodies. J Allergy Clin SI092 Kubo, M., H. Matsuda, M. Fukui, and Immunol 1995; 94(4): 560–561. Y. Nakai. Development studies of cu- SI081 Mazzio, E. A., N. Harris, and K. F. A. ticle drugs from natural resources. I. Soliman. Food constituents attenuate Effects of crude drugs extracts on hair monoamine oxidase activity and per- growth in mice. Yakugaku Zasshi oxidase levels in C6 astrocyte cells. 1988; 108(10): 871–978. Planta Med 1998; 64(7): 603–606. SI093 Singh, V. K. and Z. A. Ali. Folk medi- SI082 Alday, E., G. Curiel, M. J. Lopez-Gil, cines of Aligarh (Uttar Pradesh), In- D. Carreno, and I. Moneo. Occupa- dia. Fitoterapia 1989; 60(6): 483–490. SESAMUM INDICUM 503

SI094 Unnikrishnan, M. C., and R. Kuttan. Imanaka. A short-term in vitro assay for Tumour reducing and nutricarcino- promoter substances using human genic activity of selected spices. Can- lymphoblastoid cells latently infected cer Lett 1990; 51(1): 85–89. with Epstein Barr virus. Cancer Lett SI095 Seo, J. S., Y. W. Lee, N. J. Suh, and I. 1981; 13: 29–37. M. Chang. Assay of antimutagenic ac- SI106 Rockwell, P., and I. Raw. A mutagenic tivities of vegetable plants. Korean J screening of various herbs, spices and Pharmacog 1990; 21(1): 88–91. food additives. Nutr Cancer 1979; 1: SI096 Neering, H., B. E. J. Vitanyl., K. E. 10–15. Malten, W. G. Van Ketel, and E. Van SI107 Oommachan, M., and S. S. Khan. Dijk. Allergens in sesame oil contact Plants in aid of family planning dermatitis. Acta Derm 1975; 55: 31–34. programme. Sci Life 1981; 1: 64–66. SI097 Sugano, M., T. Inoue, K. Koba, et al. SI108 Yoshida, M., and T. Kashimoto. Deter- Influence of sesame lignans on various mination of sesamolin, sesamin and lipid parameters in rats. Agr Biol sesamol in sesame oil by high-perfor- Chem 1990; 54(10): 2669–2673. mance liquid chromatography. SI098 Sato, A. Studies on anti-tumor activ- Shokuhin Eiseigaku Zasshi 1982; 23: ity of crude drugs. I. The effects of 142–148. aqueous extracts of some crude drugs SI109 Prakash, A. O., R. B. Gupta, and R. in short-term screening test. Yaku- Mathur. Effect of oral administration gaku Zasshi 1989; 109(6): 407–423. of forty-two indigenous plant extracts SI099 Vyas, S. P., and N. Sankhla. Role of on early and late pregnancy in albino bio-regulants in growth and productiv- rats. Probe 1978; 17(4): 315–323. ity of desert plants. II. Effect of mor- SI110 Krag, K. J. Plants used as contracep- phactins on growth flowering protein tives by the North American Indians, and phosphorus content in Sesamum an ethnobotanical study. Thesis BS indicum. Trans Indian Soc Desert Harvard University 196; 117 pp Technol Univ Cent Desert Stud 977; SI111 Razzack, H. M. A. The concept of 2: 246. birth control in Unani medical litera- SI100 Salerno, J. W., and D. E. Smith. The ture. Unpublished manuscript of the use of sesame oil and other vegetable author 1980; 64 pp. oils in the inhibiting of human colon SI112 Kato, Y., E. Ueda, T. Kyoko, A. Yukiyo cancer growth in vitro. Anticancer Res Nagaoka, S.Iwashita, S. Ninomiya, 1991; 11(1): 209–215. and N. Kato. Asarinin in sesame oil. SI101 Ruan, C. C., Y. Liang, J. L. Liu, W. S. Pharmazie 1980; 35(12): 808–809. Tu, and Z. H. Liu. Antimutagenic ef- SI113 Dixit, R. S., And H. C. Pandey. Plants fect of eight natural foods on moldy used as folk medicine in Jhansi and foods in a high liver cancer incidence Lalitpur sections of Bundelkhand, area. Mutat Res 1992; 279(1): 35–40. Uttar Pradesh. Int J Crude Drug Res SI102 Vyas, S. P., and N. Sankhla. Role of bio- 1984; 22(1): 47–51. regulants in growth and productivity of SI114 MC Brayer, B. W. Sesame nematocidal desert plants. II. Effect of morphactins composition. Patent-US-4,442,092 on growth flowering protein and phos- 1982; 4 pp. phorus content in Sesamum indicum. SI115 John, D. One hundred useful raw drugs Trans Indian Soc Desert Technol of the Kani tribes of Trivandrum For- Univ Cent Desert Stud 977; 2: 246. est Division, Kerala, India. Int J Crude SI103 Lal, S. D., and K. Lata. Plants used by Drug Res 1984; 22(1): 17–39. the Bhat community for regulating fer- SI116 Lee, C. Y., J. W. Chiou, and W. H. tility. Econ Bot 1980; 34: 273–275. Chang. Studies on the antioxidative SI104 Dey, P. M. Biosynthesis of planteose in activities of spices grown in Taiwan. Sesamum indicum. FEBS Lett 1980; (2). Chung-Kuo Nung Yeh Hua 114: 153–156. Hsueh Hui Chin 1982; 20(1/2): 61–66. SI105 Ito, Y., S. Yanase, J.Fujita, T. SI117 Fukuda, Y., T. Oosawa, and M. Harayama, M. Takashima, and H. Namiki. Antioxidants in sesame seed. 504 MEDICINAL PLANTS OF THE WORLD

Nippon Shokuhin Kogyo Gakkaishi SI129 Ray, P. G., and S. K. Majumdar. Anti- 1981; 28: 461–464. microbial activity of some Indian SI118 Siddiqui, N. A., and M. Z. Hasan. plants. Econ Bot 1976; 30: 317–320. Therapeutic response of Arab medi- SI130 Lee, E. B., H. S. Yun, and W. S. Woo. cines in cases of laquwa. Bull Islamic Plants and animals used for fertility Med 1981; 1: 366–374. regulation in Korea. Korean J Pharma- SI119 Woo, W. S., E. B. Lee, K. H. Shin, S. cog 1977; 8: 81–87. S. Kang, and H. J. Chi. A review of re- SI131 Nagabhushanan, A., M. Srinivasan, search on plants for fertility regulation and V. Subrahmanyan. Breakdown in Korea. Korean J Pharmacog 1981; and synthesis of sesamolin in the 12(3): 153–170. sesame seed (Sesamum indicum). J Sci SI120 Fukuda, Y., T. Osawa, M. Namiki and Ind Res-C 1956; 15: 283. T. Ozaki. Studies on antioxidative sub- SI132 Das, V. S., K. N. Rao, and J. V. Rao. stances in sesame seed. Agr Biol Chem Phenolic acids in some members of 1985; 49(2): 301–306. Pedaliaceae. Curr Sci 1966 35: 160. SI121 Singhal, P. C., and L. D. Joshi. Glyce- SI133 Lopez, C., V. L. Villegas, M. De La Paz, mic and cholesterolemic role of ginger J. Silva Lara, and P. Cattaneo. Sesa- and til. J Sci Res Pl Med 1983; 4(3): mum indicum seeds. II. Chemical com- 32–34. position of the extracted oil. An Asoc SI122 Weniger, B., M. Rouzier, R. Daguilh, Quim Argent 1974; 62; 301. D. Henrys, J. H. Henrys, and R. Anton. SI134 Vague, J., J. C. Garrigues, J. Berthet, Popular medicine of the central pla- and G. Favier. The oestrogenic effect teau of Haiti. 2. Ethnopharmacological of several plants oil. Ann Endocrinol inventory. J Ethnopharmacol 1986; 1959; 18: 745–751. 17(1): 13–30. SI135 Prakash, A. O., and R. Mathur. SI123 Kamboj, V. P. A review of Indian me- Screening of Indian plants for antifer- dicinal plants with interceptive activ- tility activity. Indian J Exp Biol 1976; ity. Indian J Med Res 1988; 1988(4): 14: 623–626. 336–355. SI136 Dragendorff, G. Die heilpflanzen der SI124 El-Tahir, K. E. H., E. A. Hamad, A. M. verschieden volker und zeiten, F. Ageel, M. A. A. Nasif, and E. A. Enke, Stuttgard. 1898; 885 pp. Gadkarim. Effects of sesame and cod SI137 Jochle, W. Biology and biochemistry of liver oils on prostacyclin synthesis by reproduction and contraception. the rat thoracic aorta. Arch Int Angew Chem Int Ed Engl 1962; 1: Pharmacodyn Ther 1988; 292(1): 537–549. 182–188. SI138 Roig Y., and J. T. Mesa. Plantas SI125 Ramirez, V. R., L. J. Mostacero, A. E. medicinales, aromaticas o venenosas de Garcia, et al. Vegetales empleados en Cuba, Ministerio de Agricultura, Re- medicina tradicional Norperuana. publica de Cuba, Havana. 1945; 872 pp. Banco Agrario del Peru, NACL Univ SI139 Nayar, S. L. Poisonous seeds of India. Trujillo, Trujillo, Peru, June, 1988; 54 pp. Part II. J Bombay Nat Hist Soc 1954 SI126 Singh, V. P., S. K. Sharma, and V. S. 52(2/3): 1–18. Khare. Medicinal plants from Ujjain SI140 Saito, K. Fibroblast cultures. Nippon district Madhya Pradesh. Part II. In- Yakugaku Zasshi 1936; 23: 1–5. dian Drugs Pharm Ind 1980; 1980(5): SI141 Harborne, J. B., and C. A. Willliams. 7–12. Comparative biochemistry of fla- SI127 Kumar, D. S., and Y. S. Prabhakar. On vonoids. XIII. 6-hydroxyluteolin and the ethnomedical significance of the scutellarein as phyletic markers in arjun tree, Terminalia arjuna (Roxb.) higher plants. Phytochemistry 1971; Wight and Arnot. J Ethnopharmacol 10: 367–378. 1987; 20(2): 173–190. SI142 Morita, N. The flavonoid of sesame SI128 Heiduschka, A. Unsaponifiable matter leaves. I. The structure of the glyco- of sesame oil. Orig Com 8th Intern side, pedalin. Chem Pharm Bull 1960; Congr Appl Chem 1912; 11: 13. 8: 59–65. SESAMUM INDICUM 505

SI143 Malten, K. E., J. P. Kuiper, and W. B. SI150 Pollia, J. A. 1,2,5,6-dibenzanthracene J. M. Van der Staak. Contact allergic on certain organs and a transplantable investigations in 100 patients with ul- rat sarcoma in animals of pure breed. cus cruris. Dermatologica 1973; Radiology 1937; 29: 683–694. 147(4): 241–254. SI151 Marchand, P. A., M. J. Kato, and N. SI144 Fitelson, J. The occurrence of squalene G. Lewis. (+)-Episesaminone, A in natural fats. J Ass Offic Agr Chem Sesamum indicum furofuran lignan. Iso- 1943; 26: 506–511 lation and hemisynthesis. J Nat Prod SI145 Diquattro, C., and T. Mercadante. 1997; 60 (11): 1189–1192. Reticuloendothelioses due to estrogens SI152 Katsuzaki, H., M. Kawasumi, S. Kawa- and sesame oil, their morphological kishi, and T. Osawa. Structure of novel identity. II. Sez Med 1955; 62: 171–188. antioxidative lignan glucosides iso- SI146 Schiff, E., and C. Hirscheberger. lated from sesame seed. Biosci Biotech Thrombocytosis produced by a hith- Biochem 1992; 56(12): 2087–2088. erto unknown substance the “fat- SI153 Chen, E. C. F., S. S. K. Tai, C. C. Peng, soluble T factor”. Amer J Dis Child and J. T. C. Tzen. Identification of 1937; 53: 32–38. three novel unique proteins in seed oil SI147 Kabelitz, G. Comparative studies on bodies of sesame. Plant Cell Physiol the behavior of the alimentary lipemia, 1998; 39(9): 935–941. cholesterol, and blood sugar after load- SI154 Ohta, S., N. Sakurai, T. Inoue and M. ing with one synthetic and two natural Shinoda. Studieson chemical protec- food fats. Arch Ges Physiol 1944; 247: tors against radiation. XXV. Radiopro- 593–599 tective activities of various crude SI148 Tobin, C. E. Effect of adrenalectomy drugs. Yakugaku Zasshi 1987; 107(1): on pregnancy and survival of untreated 70–75. and sesame oil-treated rats. Endocri- SI155 Anon. GRAS status of foods and food nology 1941; 28: 419–425. additives. Fed Regist 1976; 41: 38,644. SI149 Yanagisawa, F., K. Ogasawara, and K. SI156 Katsuzaki, H., S. Kawakishi, and T. Bushimata. Biochemical studies on Osawa. Structure of novel antioxidant plant oils. II. Hypocholesterolemic ac- lignan triglucoside isolated from tion. Tokyo Toritsu Eisei Kenkyusho sesame seed. Heterocycles 1993; Kenkyu Nempo 1967; 1967(19): 90–96 36(5): 933–936. ZINGIBER OFFICINALE 507

16 Zingiber officinale Roscoe.

Common Names Aale India Chitta Africa Ada India Chnay Cambodia Adarak India Djae Indonesia Adhu India Djahe Netherlands Adi India Dumber Croatia Adraka Pakistan Dumbier lekarstvy Slovakia Adruka India Dzhindzhifil Bulgaria Aduva Nepal Engifer Iceland Afifindi Ecuador Gamug Tibet Afu Africa Gan jinang China Agnimanth Nepal Gember Indonesia Ajenjibre Cuba Gember Netherlands Ajenjibre Mexico Gengibre Brazil Ajijilla Ecuador Gengibre Portugal Ajilla Ecuador Gengibre Spain Ajinibre Mexico Gengibre Venezuela Ajirinrin Ecuador Ghimbir Romania Akakur China Gin Myanmar Alha India Gingebre Mauritius Aliah Indonesia Gingebre Spain Alla India Gingebre Vietnam Allam India Gingembre France Ardak India Ginger Tanzania Ardakam India Ginger Brazil Arstniecibas ingvers Latvia Ginger China Asgumetakui Africa Ginger Greece Asunglasemtong India Ginger Guyana Atuja Malaysia Ginger India Baojiang China Ginger Jamaica Beuing Indonesia Ginger Japan Cay gung Vietnam Ginger Nepal Chapepnomen ba Ecuador Ginger Nicaragua Chiang China Ginger Philippines Chichambara Nicaragua Ginger Sri Lanka

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 507 508 MEDICINAL PLANTS OF THE WORLD

Ginger Taiwan Keong China Ginger United States Kerati Papua New Guinea Ginger Venezuela Khing Laos Gojabghbegh Armenia Khing Thailand Gung Vietnam Khing-daen Thailand Gyin sein Myanmar Khnehey Cambodia Gyin Myanmar Khnhei phlung Cambodia Gyomber Hungary Khuong Vietnam Halia bara Malaysia Khyen-seing Myanmar Halia Malaysia Kinkh Thailand Haliya merah Malaysia Kintoki Japan Haliya Indonesia Kion Peru Harilik ingver Estonia Konga Papua New Guinea Hli Papua New Guinea Kunyit terus Malaysia Imberias Lithuania Lahja Indonesia Imbir Poland Lao jiang China Imbir Russia Lei Admiralty Islands Imbyr Ukraine Lia Indonesia Inber Israel Luya Philippines Inbwer Germany Mtangwizi Tanzania Inchi India Myoga Japan Ingee India Nagara India Ingefara Sweden Ngesnges Papua New Guinea Ingefer Denmark Nkrabo Africa Ingefer Norway Nkrama Africa Inguru Japan Nkrawusa Africa Inguru Sri Lanka Oshoga Japan Ingver Croatia Palana Papua New Guinea Ingver Slovenia Pia di udi Ecuador Ingverijuur Estonia Pia nuni Ecuador Ingwer Germany Piperoriza Greece Ingwer Tanzania Quing jiang China Inkivaari Finland Rhizoma, zingiberis Japan Isiot Bulgaria Saeng gang Korea Jae Indonesia San geung China Jahe Indonesia Sang keong China Jahi Malaysia Sga smug Tibet Jamaica ginger United States Shen jiang China Jamveel Iran Shengijang China Janzabeil Sudan Shohkyoh Japan Jenegibre Venezuela Shokyo Japan Jengibre Cuba Shokyo Taiwan Jengibre Spain Shouga Japan Jenibre Guatemala Shoukyo Japan Jenjibre Ecuador Shoukyo Taiwan Jenjibre Nicaragua Shringaveran India Jeung China Shukku India Jiang China Shuntya India Jinjaa Japan Sinh khuong Vietnam Kai China Sinziminli Africa Kallamu India Skenjabil Morocco Kan chiang Vietnam Skenjbir Morocco Kanga Papua New Guinea Sman-sga Tibet ZINGIBER OFFICINALE 509

Sonth India Zanjabil Arabic countries Sringaaran India Zanjabil Iran Sunth India Zazvor Czech Republic Sunthi India Zazvor Slovakia Sutho Nepal Zencebil Turkey Tangauzi Tanzania Zencefil Turkey Tangawizi Tanzania Zenzero Italy Tertuyagas Ecuador Zenzevero Italy Tsinstsimin China Zi jiang China Tsintsimir China Zingiber Spain Wai Papua New Guinea Zingibil Oman Zangbil Israel Zinjabil Yemen Zangvil Israel Zinjibil Ethiopia Zanjabeel India Zinzam Mauritius Zanjabeel Saudi Arabia

BOTANICAL DESCRIPTION TRADITIONAL MEDICINAL USES Zingiber officinale is a perennial herb belong- Admiralty Islands. The rhizome is taken ing to the ZINGIBERACEAE family. The orally as a contraceptiveZO245. rhizome is horizontal, branched, fleshy, aro- Brazil. Hot water extract of the dried root matic, white or yellowish to brown. Stem is is used externally for bronchitis and rheu- leafy, thick, to 60 cm high. Leaves are matismZO253. pointed, narrowly or linear-lanceolate, China. Ash of the burned leaves of approx 20 cm long and 1.5–2 cm wide, Pongamia pinnata, Citrullus colocynthis, Piper clasping the stem by long sheaths. The in- retrofractum, Plumbago zeylanica, Zingiber florescences, rarely produced by cultivated officinale, and Piper longum, mixed with mo- plants, are separate, approx 20 cm high, lasses and rock salt, is taken orally to treat consisting of threefold flowers subtending abdominal diseases, anemia, and phantom with bracts and bracteoles. Bracts are ovate, tumorsZO280. For choleric diarrhea and chro- approx 2.5 cm long, closely pressed against nic fever, powdered Ferula asafoetida, Acorus each other, pale green. Calyx is short, three- calamus, Zingiber officinale, Cuminum, lobed. Corolla has two yellow-green, Terminalia chebula, Inula racemosa, and pointed segments and shorter, an oblong- Saussurea lappa, are taken orallyZO280. The ovate, dark-purple lip spotted and striped oils of Zingiber officinale, Saussurea lappa, with yellow. Each flower has only one short- Sansevieria roxburghiana, Curcuma longa, stalked, fertile stamen and solitary stigma. and Rubia cordifolia, mixed with salt butter- The fruit, which is rarely formed, is a dehis- milk, and rice, are massaged on the patient cent capsule containing relatively large for cold and coughZO280. For heaviness of the seeds. stomach, powdered Ferula asafoetida, Acorus ORIGIN AND DISTRIBUTION calamus, Zingiber officinale, Cuminum cymi- Native to southern Asia, it is widely distrib- num, Terminalia chebula, Inula racemosa, and uted through the tropics and subtropics. Saussurea lappa, are taken orally. For skin dis- Requires a rather hot, moist climate and eases, decoction of Tinospora cordifolia, rich, well-drained soil. It is now cultivated Cyperus rotundus, and Zingiber officinale, in Indonesia, Jamaica, Sri Lanka, and mixed with equal quantity of decoction of China. Aconitum heterophyllum, is taken orallyZO280. 510 MEDICINAL PLANTS OF THE WORLD

China. Decoction of the dried rhizome is Ecuador. Decoction of the rhizome is taken taken orally as an antiemeticZO133. Hot water orally for migraines, diarrhea, and stomach- extract of the rhizome, in combination with acheZO152. Prunus persica (Sd), Carthamus tinctorius England. Dried rhizome is taken in combi- (Fl), Angelica sinensis (Rt), Saliva miltiorrhiza nation with Mentha pulegium (essential oil), (Rt), Ligusticum wallichii (Rt, St), Gardenia Aloe vera, Ipomoea purga, Glycyrrhiza glabra, jasminoides (Fr), Sanguisorba officinalis (Rt), and Canella alba for amenorrheaZO302. Infu- Corydalis ambigua (Tu), Glycyrrhiza uralensis sion of the fresh rhizome is taken orally in (Rt), Commiphora myrrha (resin), Boswellia Chinese herbal formulations to reduce carteri (resin), Cyperus rotundus (Rh), Cit- nausea and vomiting during pregnancy. rus tangerina (fruit peel), Pyrola japonica The peeled young ginger rhizome is sim- (Lf), Agrimonia pilosa (Pl), Lonicera japon- mered with sweet malt vinegar for several ica (Pl), Panax sanchi (Rt), Codonopsis hoursZO297. pilosula (Rt), Astragalus membranaceus (Rt), Europe. Hot water extract of the fresh rhi- Atractylodes macrocephala (Rh), Curcumina zome is taken orally for delayed menstrua- aromatica (Rh), and Caesalpinia sappan tion and for all forms of motion sicknessZO300. (heartwood), and the scales of the Manis Fiji. Dried root, ground with Vitex negundo pentadactyla, is used to treat ectopic preg- leaves, is applied to the forehead for head- nancies. Dosing for up to 8 days produced a ache. For colds, seeds of Elettaria carda- pain relief, the tumors disappeared in 100% momum, Zingiber officinale rhizome, and of the cases, and bleeding stopped in 100% Piper nigrum seeds, are ground in water, of the casesZO355. Decoction of the fresh rhi- mixed with honey, and taken orallyZO266. zome is taken orally for excruciating head- Fresh rhizome juice, together with the juice ache. It is taken in combination with Evodia of Allium cepa, is taken orally to stop vomit- rutaecarpa, Zizyphus jujuba, and Panax ing. The fresh juice is taken with honey or ginsengZO174. Hot water extract of the rhizome sugar for coughs, colds, stomachache, and is taken orally to suppress or retard the men- asthmaZO266. Fresh root juice is administered strual cycleZO165. The dried root, mixed with as eardrop for earacheZO266. Campanumoea pilosula (Rt), Astragalus Greece. Wine extract of the rhizome, with hiroshimanus (Rh), Araliacordata (Rt), and pomegranate and oak gall, is used as a vagi- Paeonia albiflora (Rt), is administered nal spermicidal suppositoryZO065. intravaginally for leucorrhea with backache, Guatemala. Decoction of the rhizome is fever, and weak pulse in patients with vagi- taken orally for feverZO149. nal cancer. For menorrhagia in patients Honduras. Decoction of the rhizome is with vaginal cancer, the dried root, mixed taken orally for coldZO159. with Typha species (pollen) and Agrimonia India. Hot water extract of the dried rhi- pilosa (twig), is administered intravagin- zome is administered orally as a remedy for allyZO299. whooping coughZO242 and hemorrhoids in Cuba. Hot water extract of the rhizome is Ayurvedic medicineZO255. The rhizome, in taken orally as an emmenagogue and for its combination with 25 g each of Prunus stimulating and aphrodisiac properties by amygdalus and Pistacia vera, 10 g of Piper ni- menZO354. The fresh rhizome is taken orally grum, 100 g of Hedychium spicatum, and 200 as an antispasmodicZO154. g of Elastrus paniculatus, is taken orally for East Africa. The fresh root, with scrapings rheumatism. For dysentery and stomach- of Ocimum suave, is taken orally for in- ache, 250 g of dried rhizome is taken with flamed tonsils and anginaZO260. 500 g dried stem bark of Holarrhena anti- ZINGIBER OFFICINALE 511 dysenterica and 100 g of dried Piper nigrum, unripe pineapple and rag (rice, garlic, and powdered and mixed with butter oil into Alpinia galanga, aromatics, and spices such pills about the size of a pea. Two to three as cinnamon, ginger, Capsicum annuum), is pills are taken dailyZO256. Hot water extract diluted with water and taken twice daily. of the rhizome is taken orally for amenor- The rhizome juice is taken orally for colic rheaZO063. The decoction is taken orally for and used externally in the form of a poultice diabetesZO169, and paste mixed with salt is for swelling of rheumatic areas and on used externally as an antiveninZO148. The snakebiteZO241. dried root with leaves of Adhatoda vasica and Japan. Fresh rhizome is used externally to Piper nigrum and Piper longum, are powdered promote hair growthZO239. and administered orally to treat bronchitis. Malaysia. The rhizome, mixed with Piper The powder is sometimes mixed with nigrum and honey, is taken orally as an honeyZO119. The fresh rhizome is taken orally abortifacientZO064. Hot water extract of the with honey to treat ulcerative gingivitisZO119. rhizome is administered orally after child- Hot water extract of the fresh rhizome is birth and as an abortifacientZO071. administered subcutaneously to treat fila- Mauritius. Hot water extract of the dried riasisZO193. The fresh rhizome juice is admin- root is taken orally as an emmenagogueZO223. istered to pregnant women just before Mexico. Decoction of the entire plant is childbirth to ease delivery. The fresh rhi- taken orally with honey as an emmenagogue zome is eaten for tuberculosis and throat and to soothe colicZO132. Hot water extract of painZO246 and for stomachacheZO248. For ane- the rhizome is taken orally for stomach- mia, Tinospora cordifolia, alone, or in com- acheZO228. bination with Strobilanthes auriculatus Morocco. Rhizome is taken orally as a roots and the dried rhizome of Zingiber calefacientZO160. officinale, is made into a decoction and Nepal. Decoction of the rhizome, mixed taken orallyZO248. For digestive complaints, with Artemisia dubia, is taken orally as an the leaf juice of Piper betel and leaf juice of antipyretic. The juice is mixed with butter Zingiber officinale are taken orally. A decoc- and massaged on the chest and throat to tion of Andrographis paniculata, Ocimum cure cough. The juice is taken orally for sanctum, and Zingiber officinale is taken throat infectionZO168. Decoction of the rhi- orally for malaria. Rhizome, made into a zome, mixed with the Justicia adhatoda, is paste, is applied to the forehead for head- mixed in warm water and salt and then ache. For toothache, black pepper and gin- taken orally twice a day for 2–3 days to treat ger are used as a tooth powder; combined abdominal painZO155. with charcoal, freshens the mouth. For the Nicaragua. Decoction of the root is taken common cold, a decoction of coffee pre- orally by women during childbirth, as a di- pared with black pepper and ginger is taken gestive, and for coldsZO156. The rhizome is orally. To relieve swellings and boils, a paste taken orally for belly pain, fever, and gasZO151. of Zingiber officinale rhizome and Santalum Nigeria. The rhizome is taken orally as a album stem is applied to the affected blood purifier, febrifuge, carminative, and areaZO248. stimulant, and for malaria, stomachache, Indonesia. Hot water extract of the rhizome headache, and indigestionZO102. Water ex- is taken orally to aid in childbirthZO071. As an tract of the dried rhizome is taken orally to abortifacient, the rhizome, in combination treat malariaZO097 and schistosomiasisZO224. with cinnamon, Capsicum annuum, a piece Oman. Infusion of the rhizome is taken of black cane stalk pound with half of an orally as an expectorant and for bronchitis. 512 MEDICINAL PLANTS OF THE WORLD

The infusion is administered ophthalmically Sudan. Hot water extract of the dried rhi- for cataractZO116. zome is taken orally for colds, pneumonia, Papua New Guinea. Fresh rhizome juice is and rheumatismZO227. taken orally for colds and cough. The fresh Tanzania. Rhizome is pound with the root rhizome is chewed for malaria, stomach of Pteridium aquilinum, and the juice taken worms, and the temporary relief of orally as an aphrodisiac. Hot water extract toothacheZO191. The fresh rhizome is taken of the rhizome is taken orally as a galact- orally for pneumonia, tuberculosis, fever, agogueZO069,ZO070. and rheumatism and externally for topical Thailand. Hot water extract of the dried ulcersZO254. Hot water extract of the dried rhizome is taken orally as a carmina- root is taken orally for stomach com- tiveZO211,ZO212, an antiemetic, an anticolic, a plaintsZO254. The chewed rhizome and leaf are hypnotic, a cardiotonicZO212, an emmenag- used externally to treat knee pain and swal- ogue, and a stomachicZO213. The fresh rhi- lowed to treat coughZO134. The dried rhizome zome is taken orally as an antiemetic and a is chewed, and the juice applied externally gastrointestinal sedativeZO158. Hot water ex- for migraine and to treat stingray stingsZO277. tract of the fresh rhizome is taken orally for The juice is taken orally to treat vomiting fever, headache, and diarrhea and as an and stomachache. For head lice, the rhi- emmenagogue, a carminativeZO215, and an zome is mixed with bark of Galbulimima aromatic stimulantZO216. The powdered fresh belgraveana and leaves of Nicotiana tabacum rhizome, together with cloves, are mixed and the juice is applied externallyZO294. with water and rubbed on the body for the Peru. Hot water extract of the dried rhi- relief of rheumatismZO216. zome is taken orally as a carminativeZO288 and Trinidad. Hot water extract of the rhizome contraceptiveZO289. is taken orally for diabetesZO101,ZO103. Philippines. Hot water extract of the dried United States. Hot water extract of the root is taken orally by pregnant women to dried rhizome is taken orally as a carmina- minimize the pain of early laborZO261. tive in flatulent colic and when a warming Rodrigues Islands. Decoction of the rhi- effect is neededZO304. Wine extract of the zome juice, mixed with Citrus aurantifolia, is dried rhizome, together with Viburnum taken orally for pulmonary disorders. The opulus, Scutellaria lateriflora, Symplocarous juice, mixed with lemon juice, honey, and foetidus, and Syzygium aromaticum, is taken hot water extract of Cymbopogon citratus, is as an antispasmodicZO304. ZO153 taken orally for colds . Venezuela. Hot water extract of the rhi- Saudi Arabia. Hot water extract of the zome is taken orally to stimulate the men- dried rhizome is taken orally as a sto- strual flowZO090. machic, a diuretic, a carminative, and an Vietnam. Hot water extract of the rhizome ZO178,ZO184 antiemetic and used externally as an is taken orally as an emmenagogueZO066. ZO178 antiseptic, anesthetic, and astringent . Yemen. Hot water extract of the rhizome is South Korea. Hot water extract of the dried taken orally as an aphrodisiac and is used as rhizome is taken orally as an abortifa- an aromatic stimulantZO234. cientZO264. Hot water extract of the rhizome, together with Bupleurum falcatum, Scu- CHEMICAL CONSTITUENTS tellaria baicalensis, Panax ginseng, Glycyrrhiza (ppm unless otherwise indicated) glabra, Zizyphus jujuba, and Pinellia tuberosa, Acetaldehyde: RhZO305 is taken orally for tonsillitis, otitis media, Acetic acid: RhZO295 tuberculosis, common cold, liver disorders, Acetone: RhZO305 chills, fevers, and chest painsZO267. Aframodial: Sd 0.04%ZO082 ZINGIBER OFFICINALE 513

Angelicoidenol-2-O-E-D-glucopyranoside: Copaene, D: Rh EOZO293 Rh 14ZO084 Coumaric acid, para: Rh 19ZO226 Arginine: TuZO247 Cubebene, D: Rh EOZO121 Aromadendrene: Rh EOZO195 Curcumene, D: Rh EO 1.94%ZO140 Aromadendrene, allo: Rh EO 0.14%ZO290 Curcumin: RhZO130 Asparagine: Rh 0.05%ZO308 Curcumin, hexahydro: Rh 21.3ZO109 Aspartic acid: Aer, TuZO247 Curcumin, hexahydrodemethyl: RhZO179 Benzaldehyde: RhZO295 Cyclobutane, cis-1-2-bis-(trans-3-4-dimethoxy Benzaldehyde, 3-phenyl: Rh EOZO195 styryl): Rh 13.9ZO081 Benzaldehyde, 4-phenyl: Rh EOZO195 Cyclohexene, cis-3-(3-4-dimethoxy phenyl)- Bisabolene: Rh EOZO068 4-(trans-3-4-dimethoxy styryl): Rh 50.6ZO081 Bisabolene, E: Rh 17.2-30.0ZO131,ZO079, Rh EO Cyclohexene, trans-3-(2-4-5-trimethoxy 10.51%ZO140 phenyl)-4-(trans-3-4-dimethoxy styryl): Bisabolene, J: Rh EO 2.5%ZO122 Rh 13.9ZO081 Bisabolol, E: Rh EO 0.59%ZO290 Cyclohexene, trans-3-(3-4-dimethoxy phenyl)- Borneol: Rh EO 1.8%ZO290 4-(trans-3-4-dimethoxy styryl): Rh 55.8ZO081 Borneol acetate: Rh EO 0.21%ZO290 Cymen-8-ol, para: Rh EO 0.07%ZO290 Borneol methyl ethyl: RhZO144 Cymene, para: Rh EO 2.6%ZO290 Borneol, (+): Rh EOZO306 Cysteine: AerZO247 Borneol, 5-hydroxy-O-E-D-glucopyrano- Dec-trans-2-en-1-al: RhZO144 side: Rh 8.5ZO170 Deca-3-5-diene, 3-6-epoxy-1-(hydroxy-3- Borneol, iso: RhZO144 methoxy phenyl): RhZO080 Butyraldehyde, N: RhZO305 Decan-1-al: RhZO144 Cadinene, D: Rh EOZO195 Decane, 3(R)-5(S)-diacetoxy-1-(3-4-dime- Cadinene, G: Rh EO 0.13%ZO290 thoxy phenyl): RhZO077 Cadinol, D: Rh EOZO195 Decane, 3(R)-5(S)-diacetoxy-1-(4-hy- Caffeic acid: RhZO226 droxy-3-methoxy phenyl): Rh 41.8ZO077 Calamenene: Rh EOZO195 Decane, 3(R)-acetoxy-5(S)-hydroxy-1-(4- Camphene: Rh EO 12.6%ZO290 hydroxy-3-methoxy phenyl): Rh 53.1ZO077 Camphene hydrate: RhZO144 Decane, 5(S)-acetoxy-3(R)-hydroxy-1-(4- Camphor: Rh EO 0.12%ZO290 hydroxy-3-methoxy phenyl): Rh 15.8ZO077 Caprylic acid: Rh EOZO306 Diethyl sulfide: RhZO305 Capsaicin: RhZO311 Dodec-trans-2-en-1-al: RhZO144 Car-3-ene: Rh EOZO219 Elemene, E: Rh EO 0.3%ZO290 Caryophyllene: EOZO068 Elemol: Rh EO 0.38%ZO290 Caryophyllene, E: Rh EO 0.09%ZO290 Essential oil: Rh 0.08–0.21%ZO229 Cedorol: Rh EOZO195 Ethyl acetate: RhZO305 Cedrol, D: Rh EOZO121 Ethyl myristate: Rh EOZO195 Chavicol: Rh EOZO306 Eudesmol, E: Rh EO 0.93%ZO290 Chrysanthemin: RhZO129 Eudesmol, J: Rh EO 0.23%ZO290 Cineol, 1-8: Rh EO 2.6-10%ZO290,ZO229 Eugenol: Rh EOZO121 Cineol, 1-8, 2-hydroxy: RhZO295 Eugenol, iso: RhZO144 Citral: Rh EO 13.0%ZO067 Eugenol, iso methyl ether: Rh EO 0.08%ZO290 Citronellal: Rh EO 0.29%ZO290 Farnesal: Rh EO 0.20%ZO290 Citronellol: Rh EO 0.3-13.0%ZO290,ZO067 Farnesene: EOZO068 Citronellol acetate: Rh EOZO121 Farnesene, D: Rh EO 2.5%ZO290 Citronellyl acetate: Rh EOZO195 Farnesene, D trans-trans: RhZO201 514 MEDICINAL PLANTS OF THE WORLD

Farnesene, E: Rt EOZO225 Gingerol, 12: RhZO309 Farnesene, E trans: Rh EO 0.12%ZO290 Gingerol, 12, methyl: RhZO271 Farnesol: Rh EOZO121 Gingerol, 14: RhZO271 Fluoride: Rh 7.9ZO291 Gingerol, 16: RhZO309 Furan, 2-(2-3-epoxy-3-methyl-butyl)-3- Gingerol, 4: Rh EOZO310 methyl: RhZO144 Gingerol, 6: Rh 0.04%-0.71%ZO147,ZO233 Furan, 2-(3-methyl-2-butenyl)-3-methyl: Gingerol, 6, (+): RtZO109 RhZO144 Gingerol, 6, (S)(+): PlZO107 Furanogermenone: RhZO279 Gingerol, 6, 5-methoxy: RhZO135 Furfural: Rh EOZO290 Gingerol, 6, acetyl: Rh 6.6ZO109 Galanolactone: RhZO117 Gingerol, 6, methyl: RhZO271 Geranial: Rh EO 15.9-40.0% ZO290,ZO229 Gingerol, 7: RhZO309 Geranic acid, cis: RhZO295 Gingerol, 8: Rh 110-1069ZO079, ZO233 Geranic acid, trans: RhZO295 Gingerol, 8, methyl: RhZO271 Geraniol: Rh EO 0.69%ZO290 Gingerol, 9: RhZO309 Geraniol acetate: Rh EO 0.20%ZO290 Gingerol, dihydro: Rt EOZO225 Geraniol, E-D-glucopyranoside: Rh 15ZO170 Gingerol, methyl: EOZO068 Geranium: Rh 87-169ZO232,ZO236 Gingesulfonic acid, 6: Rh 13ZO084 Gingediol, 10: RhZO313 Glanolactone: Rh 120ZO198 Gingediol, 12: RhZO098 Glycine: Aer, TuZO247 Gingediol, 12, methyl: RhZO098 Guaiol: Rh EOZO195 Gingediol, 6: Rh 21-30ZO109,ZO079 Hept-4-en-3-one, 7-(3-4-dihydroxy-phe- Gingediol, 6, diacetate: Rh 3.3ZO109 nyl)-1-(4-hydroxy-3-methoxy-phenyl): Gingediol, 6, diacetate methyl ether: RhZO313 Rh 1.4ZO076 Gingediol, 6, methyl ether: RhZO313 Hept-5-en-1-al, 2-6-dimethyl: RhZO144 Gingediol, 8: RhZO313 Hept-5-en-2-ol, 6-methyl: RhZO295 Gingerdiol, 6: RhZO130 Hept-5-en-2-one, 6-methyl: Rh EOZO195 Gingerdione, 10-dihydro: Rh 6.3ZO109 Heptan-2-ol: Rh 0.27%ZO290 Gingerdione, 10: Rh 11ZO109 Heptan-2-ol-E - D -glucopyranoside: Gingerdione, 10, dehydro: RhZO180 Rh 71.6ZO170 Gingerdione, 6-10-dehydro: RtZO214 Heptan-2-one: Rh EO ZO290 Gingerdione, 6-10: RtZO214 Heptan-3-one, 5-hydroxy-1-(4-hydroxy-3- Gingerdione, 6: Rh 3.3-10ZO109,ZO079 5-dimethoxy-phenyl)-7-(4-hydroxy-3- Gingerdione, 6, dehydro: Rh 25.3ZO109,ZO124 methoxy-phenyl): Rh 0.52ZO076 Gingerdione, 6, dihydro: RhZO180 Heptan-3-one, 5-hydroxy-7-(4-hydroxy-3- Gingerenone A: Rh 118-136ZO074,ZO075 5-dimethoxy-phenyl)-1-(4-hydroxy-3- Gingerenone B: Rh 4.7ZO074 methoxy-phenyl): Rh 5.2ZO076 Gingerenone B, iso: Rh 4.7ZO074 Heptan-3-one, 5-hydroxy-7-(4-hydroxy- Gingerenone C: Rh 14.2ZO074 phenyl)-1-(4-hydroxy-3-methoxy-phenyl): Gingerglycolipid A: Rh 13ZO078,ZO084 Rh 5.2ZO076 Gingerglycolipid B: Rh 15ZO078 Heptane, 1-5-epoxy-3-epi-hydroxy-1-3-4- Gingerglycolipid C: Rh 14ZO078,ZO084 dihydroxy-5-methoxy-phenyl)-7-(4-hy- Gingerol: RhZO278 droxy-3-methoxy-phenyl): RhZO083 Gingerol methyl ether: RhZO313 Heptane, 1-5-epoxy-3-hydroxy-1-(3-4- Gingerol, 10: Rh 2.6-1862ZO109,ZO233 dihydroxy-5-methoxy-phenyl)-7-(4-hy- Gingerol, 10, methyl: RhZO271 droxy-3-methoxy-phenyl): RhZO083 ZINGIBER OFFICINALE 515

Heptane, 1-5-epoxy-3- hydroxy-1- (4-dihy- Lauric acid: Rh EO 900ZO290 droxy-3-5-dimethoxy-phenyl)-7-(4-hy- Leucine: TuZO247 droxy-3-methoxy-phenyl): RhZO083 Leucine, iso: TuZO247 Heptane, 2(R)-5(S)-dihydroxy-1-7-bis- (4-hy- Limonene: Rh EO 2.1%ZO290 droxy-3-methoxy-phenyl): Rh 0.00056%ZO076 Linalool: Rh EO 1–3%ZO229 Heptane, 2-2-4-trimethyl: Rh EOZO195 Linalool, oxide: RhZO295 Heptane, 3(S)-5(S)-diacetoxy-1-(4'-hy- Linalool, propionate: Rh EOZO121 droxy-3'-5'-dimethoxy-phenyl)-7-(4''-hy- Linalool, trans, oxide: Rh EOZO195 droxy-3'-methoxy-phenyl): Rh 20ZO079 Linalool-E-D-glucopyranoside: Rh 11.6ZO170 Heptane, 3(S)-5(S)-diacetoxy-1-7-bis-(3-4- Melatonin: RhZO295 dihydroxy-phenyl): Rh 15.7ZO076 Mentha-1-5-dien-7-ol, para: RhZO295 Heptane, 3(S)-5(S)-dihydroxy-1-(4'-hy- Mentha-2-8-dien-1-ol, para: RhZO295 droxy-3'-5'-dimethoxy-phenyl)-7-(4'-hy- Mentha-1-5-dien-8-ol, para: RhZO295 droxy-3'-methoxy-phenyl): Rh 2ZO079 Menthan-3-ol, 1-8-epoxy-para-glucopyra- Heptane, 3(S)-5(S)-dihydroxy-1-7-bis-(4-hy- noside: Rh 5.8ZO170 droxy-3- methoxy-phenyl):Rh 0.00053%ZO076 Menthol acetate: Rh EOZO195 Heptane, 3-5-diacetoxy-1-(4-hydroxy-3-5- Metha-1-8-dien-7-ol, para: RhZO295 dimethoxy-henyl)-7-(4-hydroxy-3- Methyl acetate: RhZO305 methoxy-phenyl): Rh 30.3ZO075 Methyl nonyl ketone: Rh EOZO195 Heptane, 3-5-diacetoxy-1-7-bis-(4-hydroxy- Muurolene, D: Rh EOZO195 3-methoxy-phenyl, MeSO: Rh 40.8ZO075 Muurolene, J: Rh EO 0.91%ZO290 Heptane, 3-5-diacetoxy-7-(3-4-dihydroxy- Myrcene: RhZO175, Rh EO 1.9%ZO290 phenyl)-1-(4-hydroxy-3-methoxy-phenyl): Myrcene, E: Rh EOZO195 Rh 3.5ZO076 Myrtenal: Rh EO 0.06%ZO290 Heptane, 3-acetoxy-1-5-epoxy-1- (3-4-dihy- Neral: Rh EO 8.10%-26.0%ZO290,ZO229 droxy-5-methoxy-phenyl)-7-(4-hydroxy-3- Nerol: Rh EOZO219 methoxy-phenyl): RhZO083 Nerol, oxide: RhZO295 Heptane, 3-epi-acetoxy-1-5-epoxy-1-(3-4- Nerol-E-D-glucopyranoside: Rh 0.2ZO170 dihydroxy-5-methoxy-phenyl)-7-(4-hy- Nerolidol: Rh EOZO121, RhZO295 droxy-3-methoxy-phenyl): RhZO083 Nerolidol, 9-oxo: Rh EOZO195 Heptane, N: RhZO305 Nerolidol, cis: Rh EOZO140 Heptane-3(S)-diol, 1-7-bis- (4-hydroxy-3- Nerolidol, trans: Rh EO 0.70%ZO290 methoxy-phenyl): Rh 4ZO079 Nonal-1-al: RhZO144 Heptenone, methyl: Rh EOZO306 Nonal-2-ol: RhZO295, Rh EO 0.2%ZO290 Hexan-1-al: Rh EO 700ZO290 Nonane, N: RhZO305 Hexan-1-ol: RhZO295 Nonanol, N: RhZO305 Hexan-3-ol, cis: Rh EOZO195 Nonanone, N: Rh EOZO229 Himachalene, E: Rh EOZO195 Nonyl aldehyde: Rh EOZO306 Humulene epoxide 1: RhZO145 Octan-1-ol acetate: RhZO144 Humulene epoxide 2: RhZO145 Oct-trans-2-en-1-al: RhZO144 Ionone, E: Rh EOZO195 Octa-2-6-diene-1-8-diol, 2-6-dimethyl: RhZO295 Juniper camphor: Rh EOZO195 Octa-3-7-diene-1-6-diol, 2-6-dimethyl: RhZO295 Labda-trans-12-ene-15-16-dial, 8-E-17-ep- Octa-3-cis-6-dien-1-al, 3-7-dimethyl: RhZO144 oxy: RhZO126 Octa-3-trans-6-dien-1-al, 3-7-dimethyl: RhZO144 Labda-trans-6(17)-12-diene-15-16-dial: Octa-trans-2-cis-6-dien-1-ol, 3-7-dimethyl- RhZO135 8-hydroxy, E-D-glucopyranoside: Rh 5.2ZO170 516 MEDICINAL PLANTS OF THE WORLD

Octa-trans-2-trans-6-dien-1-ol, 3-7-dimethyl- Shogaol, 10: Rh 73.5ZO147 8-hydroxy, E-D-glucopyranoside: Rh 10.1ZO170 Shogaol, 10, cis: RhZO269 Octan-1-al: Rh EO 800ZO290 Shogaol, 10, dehydro: Rh 0.031ZO085 Octan-2-ol: RhZO295 Shogaol, 10, methyl, anti: RhZO269 Octane, N: RhZO305 Shogaol, 10, methyl, syn: RhZO269 Octanol, N: RhZO295 Shogaol, 10, trans: RhZO269 Octen-2-al, trans: Rh EOZO195 Shogaol, 12, cis: RhZO269 Oxalic acid: Rt 0.50%ZO312 Shogaol, 12, trans: RhZO269 Paradol: RhZO313 Shogaol, 6: Rh 278.5-400ZO147,ZO198 Paradol, 6: RhZO177 Shogaol, 6, cis: RhZO269 Patchouli alcohol: Rh EOZO195 Shogaol, 6, methyl: RhZO098 Pentan-2-ol: RhZO295 Shogaol, 6, methyl, anti: RhZO269 Perilla aldehyde: Rh EOZO140 Shogaol, 6, methyl, syn: RhZO269 Perillen: Rh EOZO195 Shogaol, 6, trans: RhZO269 Perillene: RH EOZO114 Shogaol, 8: Rh 48-130ZO147 Phellandrene, D: Rh EO 0.40%ZO290 Shogaol, 8, cis: RhZO269 Phellandrene, E: Rh EO 5.70%ZO290 Shogaol, 8, dehydro: Rh 0.046ZO085 Pin-2-en-5-ol, RhZO144 Shogaol, 8, methyl, anti: RhZO269 Pinene, D: Rh EO 3.90%ZO290 Shogaol, 8, methyl, syn: RhZO269 Pinene, E: Rh EO 0.53%ZO290 Shogaol, 8, trans: RhZO269 Pipecolic acid: Rh 0.032%ZO308 Starch: Rh 12.3%ZO231 Propanol, N: RhZO305 Sulfide, ethyl iso-propyl: RhZO305 Propionaldehyde: RhZO305 Sulfide, methyl allyl: RhZO305 Protease: RhZO125 Terpine, 1-8, hydrate: RhZO295 Pulegole, iso, neo: Rh EOZO195 Terpinen-4-ol: RhZO144 Rose oxide, cis: RhZO144 Terpinene, D: Rh EO 0.07%ZO290 Rose oxide, trans: RhZO144 Terpinene, J: Rh EOZO195 Rosefuran: Rh EO 0.18%ZO290 Terpineol, 4: RhZO295 Sabinene: RhZO305 Terpineol, D: Rh EO1.00%ZO290 Santalol, E: Rh EO 16.20%ZO140 Terpinolene: Rh EO 0.18%ZO290 Selina-3-7(11)-diene: Rh EO 0.13%ZO290 Threonine: Aer, TuZO247 Selinen-4-ol, cis: RhZO295 Thujone, E: Rh EOZO195 Selinene, D: Rh EOZO195 Tricyclene: Rh EO 0.23%ZO290 Selinene, E: Rh EOZO195 Undecan-2-ol: Rh EO 0.05%ZO290 Serine: Aer, Tu ZO247 Undecan-2-one: Rh EOZO121 Sesquiabinene, cis, hydrate: Rh EOZO195 Undecanone, N: Rh EOZO229 Sesquiphellandrene: Rh EOZO195 Uridine: Rh 11ZO084 Sesquiphellandrene, E: Rh EOZO122 Valeraldehyde, iso: RhZO305 Sesquiphellandrol, E: RhZO175 Valine: Aer, TuZO247 Sesquiphellandrol, E, cis: Rh EOZO088 Xanthorrhizol: Rh EO 0.10%ZO290 Sesquiphellandrol, E, trans: Rh EO 0.72%ZO290 Ylangene, D: RhZO295 Sesquisabinene, cis, hydrate: RhZO089 Zerumbodienone: RhZO145 Sequiterpene hydrocarbon: Rh EOZO195 Zingerberone: EOZO068 Sesquithujene: RhZO089 Zingerone: RhZO176, Rt EOZO225 Shikimic acid: LfZO086 Zingibenene, D: Rh EO 9.2%ZO290 Shogaol: RhZO230 Zingiberene: Rh 0.06%ZO181, Rt EOZO087 ZINGIBER OFFICINALE 517

Zingiberene, D: Rh EO 44.26%ZO140 test (RAST), specific immunoglobulin (Ig) Zingiberenol: RhZO089 E antibodies could be demonstrated in the Zingiberine: RtZO173 serum. Leukocytes from a normal donor, af- Zingiberol: Rh EO 0.29%ZO140 ter passive sensitization with serum from the Zingiberone: Rh 0.04%ZO307 patient, released a substantial (t50%) amount of histamine on challenge with gin- PHARMACOLOGICAL ACTIVITIES ger indicating an IgE-mediated allergy to- AND CLINICAL TRIALS ward gingerZO058. Adrenocorticotropic hormone induc- Analgesic activity. Ethanol (80%) extract tion. Dried rhizome, in a mixture of 7 g of the rhizome, administered intragastri- Bupleurum falcatum, 5 g Pinellia ternata, 3 g cally to rats at a dose of 100 mg/kg, was Scutellaria baicalensis, 4 g Zingiber officinale, inactive vs writhing-induced by acetic acid 3 g Zizyphus inermis, 3 g Panax ginseng, and 2 injectionZO292. Hydroalcoholic extract of the g Glycyrrhiza glabra, increased plasma dried rhizome, administered intragastrically adrenocorticotropic hormone (ACTH) to mice at a dose of 200 mg/kg, was active vs level in plasma relative to controls. The in- hot-plate method, tail flick response to ra- crease was not found in adrenalectomized or diant heat, and capsaicin-induced algesia dexamethasone-treated animalsZO283. and produced weak activity vs acetic acid- Acyl-coenzyme A cholesterol acyltrans- induced writhing and formalin-induced ferase inhibition. Decoction of the dried algesiaZO093. Rhizome juice, administered rhizome, administered intragastrically to intragastrically to mice at a dose of 199.8 mice at a dose of 1.2 g/kg, inhibited the in- mg/animal, was active vs tail flick response corporation of oleic acid into cholesteryl to radiant heat. The activity produced was oleate. The study was conducted with pre- equivalent to 10 mg/kg body weight of scription know as shosaikoto, which consists aspirinZO110. Decoction of the dried rhizome, of Bupleurum falcatum Bupleurum falcatum administered intragastrically to mice at a (Rt), Scutellaria baicalensis Scutellaria baica- dose of 1.2 g/kg on days 1–7, was active vs lensis (Rt), Pinellia ternata (Tu), Zizyphus hot-plate method. A dose of 300 mg/kg on jujuba (Fr), Panax ginseng (Rt), and Gly- days 1–8 was active vs cold stress-induced cyrrhiza glabra (Rh)ZO111. hyperalgesia, and a dose of 100 mg/kg on Alanine aminotransferase inhibition. De- days 1–22 was active vs adjuvant-induced coction of dried rhizome, taken orally by hyperalgesia. A mixture of Cinnamomum human adults of both sexes at a dose of 7.5 cassia (Bk), Zingiber officinale (Rz), Glycyr- g/day for 6 months, was active on 80 pa- rhiza glabra (Rt), Zizyphus jujuba (Fr), Ephe- tients with hepatitis B antigen-positive dra sinica (St), Asarum species (Rt), and chronic hepatitis. The study was conducted Aconitum species (Rt) was usedZO199. Metha- with a prescription that consists of B.upleu- nol (50%) extract of the rhizome, adminis- rum falcatum Bupleurum falcatum (Rt), tered subcutaneously to mice at a dose of 10 Scutellaria baicalensis Scutellaria baicalensis g/kg, was active vs inhibition of acetic acid- (Rt), Pinellia ternata (Tu), Zizyphus jujuba induced writhing and inactive vs hot-plate (Fr), Panax ginseng (Rt), and Glycyrrhiza method. A dose of 3 g/kg was inactive vs glabra (Rh)ZO123. inhibition of acetic acid-induced writh- Allergenic effect. A food industry worker ingZO237. Water extract of the dried rhizome, developed asthma in inhalation of dust from in combination with Bupleurum falcatum, spices. Skin prick test from ginger was Scutellaria baicalensis, Paeonia alba, Rheum strongly positive. With radioallergosorbent tanguticum, Citrus aurantium, Pinellia ter- 518 MEDICINAL PLANTS OF THE WORLD nata, and Zizyphus inermis, administered by was immediately before and 16 hours after gastric intubation to mice at a dose of 200 challenge. The extract, in a mixture of mg/kg, was active vs acetic acid-induced Pinellia ternata (Tu), Bupleurum falcatum writhing and pressure pain threshold (Rt), Pachyma hoelen (Rt), Scutellaria testZO323. baicalensis (Rt), Panax ginseng (Rt), Glycyr- Anesthetic activity. Hot water extract of rhiza glabra (Rt), Zizyphus vulgaris (Fr), Mag- the rhizome, at a concentration of 1%, was nolia officinalis (Bk), and Perilla frutescens active on the sciatic nerveZO220. (Pl) in ratios 9:4:3:2:1.5:1.5:1.5:1.5:1.5:1, Angiotensin-ll inhibition. Methanol ex- was active vs type IV reaction with contact tract of the rhizome, at a concentration of dermatitis induced by picryl chloride and 200 Pg/mL, was inactive on rat liver inactive vs type I reaction induced by anti- membraneZO324. dinitrophenylated ascaris-IgE serum in 48 Anthelmintic activity. Saline extract of the hours homologous passive cutaneous ana- dried rhizome, at a concentration of 2.5%, phylaxis (PCA) in rats. The results were sig- was 100% effective on Anisakis species nificant to p < 0.05 level. A mixture of larvaeZO143. Bupleurum falcatum (Rt), Pinellia ternata Anti-5-hydroxytryptamine effects. Gala- (Tu), Scutellaria baicalensis (Rt), Panax gin- nolactone, a diterpenoid and one of the ac- seng (Rt), Glycyrrhiza glabra (Rt), Zizyphus tive constituents of ginger, was investigated vulgaris (Fr), and Zizyphus bulgaris (Rh) on the guinea pig ileum, rat stomach fun- (8:8:3:3:3:3:1), was inactive vs type IV re- dus, and rabbit aortic strips. In the guinea action with contact dermatitis induced by pig ileum, galanolactone inhibited contrac- picryl chloride and active vs type I reaction tile responses to 5-hydroxytryptamine with induced by antidinitrophenylated ascaris- a pIC50 value of 4.93. The concentration- IgE serum in 48 hours homologous PCA in response curve of 5-hydroxytryptamine was ratsZO240. shown as a biphasic curve, and galano- Anti-amoebic activity. Ethanol (80%) ex- lactone produced a selective shift to the tract of the dried rhizome was inactive on right of the second phase. In the same Entamoeba histolytica, minimum inhibitory preparations, the pIC50 value of galanolac- concentration (MIC) greater than 1 mg/ tone against the response to carbamyl- mLZO136. The extract, administered intragas- choline was 4.45. The inhibitory effect of trically to male hamsters at a dose of 800 galanolactone on the 5-hydroxytryptamine mg/kg, was active vs experimentally induced responses in the stomach fundus and aortic hepatic amebiasisZO105. A dose of 250 mg/kg, strips was less than that in the ileum. In ad- administered intragastrically to rats on days dition, in the thoracic aorta precontracted 1–5, produced weak activity and a dose of with 50 mM K+, the relaxing effect of 500 mg/kg was activeZO136. galanolactone was approx 10% of that of Anti-atherosclerotic activity. Ethanol papaverineZO039. (50%) extract of the dried rhizome, admin- Anti-allergenic activity. Hot water extract istered intragastrically to male rabbits at a of the of the dried rhizome, administered dose of 500 mg/kg, reduced atherogenic in- by gastric intubation to mice at a dose of 100 dex from 4.7 to 1.2 on the aortaZO091. mg/kg, was inactive vs type IV reaction with Antibacterial activity. Decoction of the contact dermatitis induced by picryl chlo- dried entire plant, on agar plate, was inac- ride and type I reaction induced by tive on Proteus vulgaris, Staphylococcus antidinitrophenylated ascaris-IgE serum in aureus, and Staphylococcus epidermidis; MIC 48 hours homologous PCA in rats. Dosing 125 mg/mL. Bacillus subtilis, Bordetella ZINGIBER OFFICINALE 519 bronchiseptica, Sarcina lutea, and Pseudomo- Yersinia enteroliticaZO325. Ethanol (90%) ex- nas aeruginosa; MIC 250 mg/mL. The decoc- tract of the dried rhizome, on agar plate at tion produced weak activity on Bacillus a concentration of 500 mg/disc, produced cereus and Micrococcus flavus; MIC 31.25 weak activity on Bacillus subtilis, Escheri- mg/mLZO287. The essential oil, on agar plate chia coli, Streptococcus aureus, and Strep- at room temperature, was active on Lactoba- tococcus faecalisZO318. Hot water extract of cillus acidophilus and inactive at 37qC. The the dried rhizome, on agar plate at a treatment was inactive on Bacillus cereus. concentration of 50 mg/disc, was inactive No difference was observed in antibacterial on Salmonella typhimurium TA100 and activity at room temperature (25–30qC) or TA98ZO326. at 37qC. Acetone extract of the dried leaf, Antibody formation enhancement. De- on agar plate, was active on Escherichia coli, coction of the dried rhizome, in cell culture Pseudomonas aeruginosa, Salmonella B, Sal- at a concentration of 100 Pg/mL, was active. monella typhi, Sarcina lutea, and Shigella Peripheral lymphocytes from eight patients flexneri and inactive on Salmonella newport, with chronic active hepatitis, four with Serratia marcescens, Staphylococcus albus, hepatits B e antigen (HbeAg) and four with and Staphylococcus aureus. Ethanol (95%) anti-Hbe, were cultured. Anti-hepatits B extract of the dried leaf on agar plate was cove (HBc) and anti-Hbe antibodies pro- inactive on Escherichia coli, Pseudomonas duced by HbcAg stimulation were en- aeruginosa, Salmonella B, Salmonella newport, hanced by the treatment, which consisted Salmonella typhi, Sarcina lutea, Serratia of Zingiber officinale (Rh), Bupleurum marcescens, Shigella flexneri, Staphylococcus falcatum (Rt), Scutellaria baicalensis (Rt), P. albus, and Staphylococcus aureus. The water ternata (Tu), Zizyphus jujuba (Fr), Panax gin- extract was active on Escherichia coli, Pseudo- seng (Rt), and Glycyrrhiza glabra (Rh)ZO108. monas aeruginosa, and Shigella flexneri and The decoction was also active on peripheral inactive on Salmonella B, Salmonella new- blood monocytes from healthy adults port, Salmonella typhi, Sarcinia lutea, Serratia treated with pokeweed mitogen. The treat- marcescens, Staphylococcus albus, and Staphy- ment enhanced plaque cell formation in re- lococcus aureusZO296. The leaf essential oil was sponse to sheep red blood cellsZO123. active on Staphylococcus aureus and inactive Anticathartic effect. Acetone extract of on Escherichia coli and Pseudomonas aeru- ginger, administered orally to rats at a dose ginosaZO222. Ethanol (80%) extract of the rhi- of 75 mg/kg, significantly inhibited 5-hy- zome, on agar plate at a concentration of 50 droxytryptamine-induced diarrhea. To Pg/disc was active on Bacillus anthracis, clarify the active constituents responsible, Bacillus subtilis, Escherichia coli (strains 7075 extract was fractionated into four frac- and BB), Proteus mirabilis, Pseudomonas tions by silica gel chromatography. Frac- aeruginosa, Salmonella typhi (strain H), tions two and three, which were effective, Staphylococcus aureus, Staphylococcus epider- were further purified and [6]-shogaol, [6]- midis, and Staphylococcus haemolyticusZO292. dehydrogingerdione, and [8]- and [10]- Decoction of the rhizome, on agar plate, was gingerol had an anticathartic action. [6] inactive on Streptococcus mutans, MIC 250 -shogaol was more potent than [6]-dehy- mg/mLZO189. Water extract of the rhizome, on drogingerdione and [8]- and [10]-ging- agar plate at a concentration of 5 mg/mL, erolZO041. was inactive on Helicobacter pyloriZO167. Anticholesterolemic activity. Ginger, ad- Powdered-dried rhizome, in broth culture at ministered orally to rats, significantly el- a concentration of 4.5%, was inactive on evated the activity of hepatic cholesterol-7 520 MEDICINAL PLANTS OF THE WORLD

D-hydroxylase, the rate-limiting enzyme of Anticonvulsant activity. Hot water extract bile acid biosynthesis. The results indicated of the rhizome, at a concentration of 0.15%, that ginger could stimulate the conversion was active vs inhibition of Metrazol-in- of cholesterol to bile acids, an important duced bursting of snail neuronsZO218. Decoc- pathway of elimination of cholesterol from tion of the dried rhizome, taken orally by the bodyZO040. Standardized ginger extracts human adults at a concentration of 4 g/per- were evaluated for their effects on the de- son, was active. The study involved 24 velopment of atherosclerosis in apolipo- patients with frequent uncontrollable epi- protein E (apo E)-deficient mice, in relation leptic seizures. The treatment resulted in six to plasma cholesterol levels and resistance cases that were well controlled (no seizure of the low-density lipoprotein (LDL) to oxi- 10 months), 13 that were improved (marked dation and aggregation. Sixty apo E-defi- decrease or grand mal was eliminated), and cient mice, 6 weeks of age, were divided into three that showed no effect. No patients had three groups of 20 each and administered their condition worsen. The treatment also via the drinking water the following treat- contained Bulleurum falcatum (Rt), Cinna- ment for 10 weeks: group 1, placebo (con- momum cassia (Bk), Paeonia albiflora (Rt), trol group); 1.1% alcohol; group 2, 25 Pg of Glycyrrhiza glabra var. glandulifera (Rt), ginger extract in 1.1% alcohol; and group 3, Panax ginseng (Rt), Scutellaria baicalensis 250 Pg of ginger extract in 1.1% alcohol. (Rt), Pinellia ternata (Tu), and Zizyphus Aortic atherosclerotic lesion areas were re- jujuba (Fr)ZO249. Water extract of the dried duced 44% (p < 0.01) in mice that con- rhizome, administered by gastric intubation sumed 250 Pg of extract/day. It also resulted to mice at a dose of 4 g/kg, was active vs in reductions (p < 0.01) in plasma triglycer- supramaximal electroshock-induced convul- ides and cholesterol by 27 and 29%, respec- sions and audiogenic seizures and inactive vs tively, in very low-density lipoprotein strychnine- and pentlenetetrazide-induced (VLDL) by 36 and 53%, respectively, and convulsions. The results significant were at p in LDL by 58 and 33%, respectively. These < 0.05 level. The extract was used in combi- results were associated with a 76% reduction nation with Glycyrrhiza glabra, Panax in cellular cholesterol biosynthesis rate in ginseng, Scutellaria baicalensis, Zizyphus peritoneal macrophages derived from the jujuba, Pinellia ternata, Bulleurum falcatum, apo E-deficient mice that consumed the Cinnamomum cassia, and Paeonia albifloraZO250. high dose. Peritoneal macrophages har- Decoction of Zingiber officinale, Glycyrrhiza vested from apo E-deficient mice after con- glabra, Panax ginseng, Scutellaria baicalensis, sumption of 25 or 250 Pg of the extract daily Zizyphus jujuba, Pinellia ternata, Bupleurum had a lower (p < 0.01) capacity to oxidize falcatum, Cinnamomum cassia, and Paeonia LDL (45 and 60%, respectively) and to take albiflora, administered intragastrically to up and degrade oxidized LDL (43 and 47%, mice at a dose of 1 mg/kgZO208 and intrave- respectively). Consumption of 250 Pg of nously to rats at a dose of 1 mg/kgZO210, was ac- ginger also reduced (p < 0.01) the basal level tive vs metrazole-induced convulsions. of LDL-associated lipid peroxides by 62%. Water extract of Bupleurum falcatum, Scutel- In parallel, a 33% inhibition (p < 0.01) in laria baicalensis, Paeonia alba, Rheum tangu- LDL aggregation (induced by vortexing) ticum, Citrus aurantium, Pinellia ternata, was obtainedZO015. Ethanol (50%) extract of Zingiber officinale, and Zizyphus inermis, ad- the dried rhizome, administered intragastri- ministered by gastric intubation to mice at cally to male rabbits at a dose of 500 mg/kg, a dose of 800 mg/kg, was inactive vs strych- reduced total cholesterol and LDL choles- nine- and picrotoxin-induced convulsions and terol in cholesterol-fed animalsZO091. active vs caffeine-induced convulsionsZO323. ZINGIBER OFFICINALE 521

Anticrustacean activity. Ethanol (95%) 36%, whereas the incidence of vomiting was extract of the dried rhizome was active on 17, 14, and 31% in groups receiving 0.5 and ZO028 Artemia salina, lethal dose (LD)50 100 Pg/ 1 g ginger, respectively . Water extract of mLZO327. the dried rhizome, administered intragastri- Antidiarrheal activity. Decoction of the cally to male rats at a dose of 50 mg/kg, was dried rhizome, taken orally by children, was active. The dose blocked the lithium chlo- active. Infantile diarrhea was treated with ride-induced conditioned place aversion, kexieding capsule composed of 5 plant ma- indicating antiemetic activity comparable terials, including roasted ginger, clove, and with metoclopramide. A mixture of 50% fruit peel of Punica granatum. Of the 234 ginger, 20% gingko, and 30% water was infants and 71 children treated, 281 (92%) usedZO142. Powdered-dried rhizome, taken were cured in 1–3 days and 9 (3%) were sig- orally by human adults at a dose of 1 g/per- nificantly improved. The total effective rate son, was active in a double-blind, placebo- was 95%ZO206. Water extract of the dried rhi- controlled study on nausea in 120 patients zome, administered by gastric intubation to undergoing gynecological laparoscopic mice at a dose of 0.5 mg/g, was active vs cas- same-day surgeryZO120. Rhizome, adminis- tor oil-induced diarrheaZO328. tered orally to female human adults at a dose Anti-edema activity. Methanol extract of of 1 g/day, was active in a crossover study in the rhizome, applied topically to mice at a 27 women suffering from hyperemesis dose of 2 mg/ear, was active vs 12-O- gravidarum. The patients received 250 mg tetradecanoyl-13-acetate-induced ear in- of ginger powder or placebo four times daily flammation. The inhibition ratio was for 4 days. Sickness was assessed using a nineZO118. symptom score. The results suggested a sig- Anti-emetic effect. Patients scheduled to nificantly (p < 0.05) greater symptomatic have gynecological diagnostic laparoscopy benefit after administration of ginger com- as day cases were randomly allocated into pared with placebo. In a randomized, placebo, droperidol, ginger, and ginger plus double-blind controlled clinical study, 60 droperidol groups to receive either 2 g of women received 1 g of rhizome per day. The ginger or 1.25 mg droperidol or both. There patients were allocated randomly to receive were no significant differences in the inci- ginger, 10 mg metoclopramide, or placebo dences of postoperative nausea, which were as a single dose given with preoperative 32, 20, 22, and 33%; and vomiting, which medication. The severity of postoperative were 35, 15, 25, and 25% in the four groups, nausea was assessed on a four-point scale. respectivelyZO025. In a double-blind, random- The incidence of nausea during the first 24 ized, controlled trial in 108 ASA 1 or 2 hours after surgery was 28%, 30%, and 51% patients undergoing gynecological laparo- in the ginger, metoclopramide, and placebo, scopic surgery under general anesthesia, the respectively. A statistically significant (p < efficacy of ginger for the prevention of post- 0.05) difference in favor of ginger compared operative nausea and vomiting was studied. with placebo was reported for the total num- The patients received oral placebo, ginger ber of incidents of nausea. In a study of 120 BP 0.5 g, or ginger BP 1 g, all with oral diaz- patients, the rhizome, metoclopramide, and epam premedication, 1 hour before surgery placebo were given 1 hour before surgery and were assessed at 3 hours postoperatively. and the incidence of nausea and vomiting The incidence of nausea and vomiting in- was 21%, 27%, and 41% in the ginger, creased slightly but not significantly with metoclopramide, and placebo groups, re- increasing dose of ginger. The incidence of spectively. Significantly fewer patients with moderate or severe nausea was 22, 33, and nausea were reported in the ginger group 522 MEDICINAL PLANTS OF THE WORLD compared with the placebo groupZO072. The Antihepatotoxic activity. Hot water ex- rhizome, taken orally by pregnant human tract of the rhizome, administered by gastric adults at a dose of 1 g/day in a double-blind intubation to rats at dosages of 100 and 400 randomized, crossover study, was more ef- mg/kg, was active vs CCl4-induced hepa- fective than placebo in diminishing or totoxicity. Methionine (100 mg/kg) was eliminating emesis during pregnancyZO329. added to the 100 mg/kg dose. The treatment Acetone extract of the dried rhizome, ad- also consisted of Bupleurum falcatum (Rt), ministered intragastrically to dogs of both Scutellaria baicalensis(Rt), Pinellia ternata sexes at a dose of 200 mg/kg, was active vs (Tu), Zizyphus jujuba (Fr), Panax ginseng cisplatin-induced emesis and inactive vs (Rt), and Glycyrrhiza glabra (Rh)ZO267. Etha- apomorphine-induced emesis. The water nol (50%) and water extracts of the dried extract was inactive vs cisplatin-induced rhizome, in cell culture at a concentration emesisZO330. of 1 mg/mL, were inactive on hepatocytes Antifungal activity. 6-Dehydrozingerone vs complement-mediated cytotoxicityZO190. isolated by steam distillation from fresh rhi- Hot water extract of the dried rhizome, ad- zome exhibited antifungal activity against ministered intragastrically to mice for 1

Rhizoctonia solani, effective concentration month, was active vs CCl4-induced hepato- ZO005 (EC)50 86.49 mg/L . The essential oil, on toxicity. The test agent consisted of 7 g agar plate, was active on Aspergillus niger at Bupleurum falcatum, 5 g Pinellia ternata, 3 g 37qC and inactive at room temperature. Scutellaria baicalensis, 2 g Glycyrrhiza glabra, The undiluted essential oil was active on 1 g Zingiber officinale, 3 g Panax ginseng, and Alternaria species, Aspergillus candidus, 3 g Zizyphus jujuba in 100 mL waterZO185. Hot Aspergillus flavus, Aspergillus fumigatus, water extract of the dried rhizome, adminis- Aspergillus nidulans, Aspergillus niger, Clado- tered intraperitoneally to rats at a dose of sporium herbarium, Cunninghamella echinu- 200 mg/kg, was active vs D-galactosamine- lata, Helminthosporium sacchari, Microsporum induced hepatotoxicity. A mixture of 5 g gypseum, Mucor mucedo, Penicillium digita- Bupleurum falcatum, 4 g Pinellia ternata, 3 g tum, Rhizopus nigricans, Trichophyton rubrum, Scutellaria baicalensis, 4 g Zingiber officinale, and Trichothecium roseum and inactive on 3 g Zizyphus inermis, 3 g Paeonia albiflora, 2 g Fusarium oxysporumZO113. Acetone and etha- Citrus aurantium, and 1 g Rheum species was nol (95%) extracts of the dried leaf, on agar used. A mixture of 7 g Bupleurum falcatum, plate at a concentration of 50%, were active 5 g Pinellia ternata, 3 g Scutellaria baicalensis, on Neurospora crassa. The water extract, at a 4 g Zingiber officinale, 3 g Zizyphus inermis, 3 concentration of 50%, was inactiveZO252. g Panax ginseng, and 2 g Glycyrrhiza glabra, Antigen expression. Decoction of the rhi- suppressed hyaline degeneration of liver in- zome, in cell culture at a concentration of duced by D-galactosamineZO282. Methanol 100 Pg/mL, was active on lymphocytes from extract of a mixture of Machilus and Alisma patients who were human immunodefi- species, Amomum xanthiodes, Bulboschoenus ciency virus (HIV)-positive asymptomatic maritimus, Artemisia iwayomogis, Atracty- and had acquired immunodeficiency syn- lodes japonica, Crataegus cuneata, Hordeum drome (AIDS). The study was conducted vulgare, Citrus sinensis, Polyporus umbellatus, with a prescription that contained Agastache rugosa, Raphanus sativus, Poncirus Bupleurum falcatum (Rt), Zingiber officinale trifoliatus, Curcuma zedoaria, Citrus auran- (Rh), Scutellaria baicalensis (Rt), Pinellia tium, Saussurea lappa, Glycyrrhiza glabra, ternata(Tu), Zizyphus jujuba (Fr), Panax gin- and Zingiber officinale, administered by gas- seng (Rt), and Glycyrrhiza glabra (Rh)ZO204. tric intubation to rabbits at a dose of 0.5 g/kg, ZINGIBER OFFICINALE 523

was active vs CCl4-induced hepatox- vs carrageenan-induced pedal edema and icityZO331. cotton pellet granuloma. A mixture of 8 g Antihypercholesterolemic activity. Oleo- Bupleurum species, 3 g Glycyrrhiza glabra, 3 resin, administered orally to rats, was active g Zizyphus jujuba, 1 g Zingiber officinale, 3 g vs cholesterol-primed animalsZO217. Ethanol Panax ginseng, 8 g Pinellia ternata, and 3 g (95%) extract of the dried rhizome, admin- Scutellaria baicalensis was usedZO259. Dried istered intragastrically to male rabbits at a rhizome in combination with Commiphora dose of 200 mg/kg, was active vs cholesterol- mukul, taken orally by 24 patients with fed animalsZO104. rheumatoid arthritis, produced complete Antihyperglycemic activity. Rhizome ash, relief in 8 patients and partial relief in 7 administered intragastrically to albino rats patientsZO243. Decoction of the dried rhi- at doses of 90 and 250 mg/kg, was inactive zome, administered intragastrically to rats at vs glucose tolerance tests (GTT)ZO169. a dose of 100 mg/kg on days 1–22, was Antihypothermic effect. Acetone extract inactive vs adjuvant-induced arthritis. The of ginger, administered orally to rats at a decoction was used in combination with dose of 100 mg/kg, inhibited 5-hydrox- Cinnamomum cassia (Bk), Glycyrrhiza glabra ytryptamine-induced hypothermia. The ac- (Rt), Zizyphus jujuba (Fr), Ephedra sinica tive constituent of the extract was further (St), Asiasarum species (Rt), and Aconitum examined. Four fractions were isolated by species (Rt)ZO199. Ethyl acetate extract of the column chromatography. Fractions 1 and 2 dried rhizome, applied externally to the produced significant activity. When frac- mouse at a dose of 20 PL/animal, produced tion 2 was further purified, [6]-shogaol was weak activity vs tetradecanoyl phorbol obtained. A dose of 10 mg/kg, administered acetate-induced acetate phospholipid orally, also produced inhibition of 5-hydrox- synthesis and 12-O-tetradecanoylphorbol- ytryptamine-induced hypothermiaZO041. 13-acetate-induced ear inflammation. The Anti-inflammatory effect. Powdered gin- hexane extract was equivocalZO095. Hot wa- ger was evaluated in 56 patients (28 with ter extract of the dried rhizome, at variable rheumatoid arthritis, 18 with osteoarthritis, concentrations, was inactive on the rat red and 10 with muscular discomfort). Among blood cell (RBC) vs resistance of heat- the patients with arthritis, more than 75% induced hemolysis. A mixture of 6 g experienced, to varying degrees, relief in Bupleurum falcatum, 4.7 g Pinellia ternata, pain and swelling. All the patients with 2.7 g Scutellaria baicalensis, 3.3 g Zingiber muscular discomfort experienced relief in officinale, and 2.7 g Zizyphus inermis was pain. None of the patients reported adverse used. The extract, administered by gastric effects during the period of ginger consump- intubation to rats at a concentration of 500 tion that ranged from 3 months to 2.5 mg/kg for 30 days, reduced swelling 23.2% yearsZO036. Ethanol (80%) extract of the rhi- on day 24 vs adjuvant-induced arthritis. zome, administered intragastrically to rats at Dosing at 1 hour before and 1 and 2 hours a dose of 50 mg/kg, was active vs edema-in- after was inactive vs carrageenan- and duced in the paw by carrageenan inject- dextran-induced pedal edema and inflam- ionZO292. Water extract of the rhizome, mation induced by paw immersion in hot administered intragastrically to rats at a dose water. A mixture of 6 g Bupleurum falcatum, of 2 g/kg was active vs formalin-induced 4 g Pinellia ternata, 3 g Scutellaria baicalensis, pedal edemaZO150. Hot water extract of the 4 g Zingiber officinale, 3 g Zizyphus inermis, 3 dried rhizome, administered by gastric intu- g Paeonia albiflora, 2 g Citrus aurantium, and bation to rats at a dose of 1 g/kg, was active 1 g Rheum species, administered by gastric 524 MEDICINAL PLANTS OF THE WORLD intubation at a dose of 500 mg/kg for 30 polamine and d-amphetamine for effective- days, reduced swelling 36% on day 24 vs ness in prevention of motion sickness. The adjuvant-induced arthritis. When adminis- subjects were given the medications 2 hours tered 1 hour before and 1 and 2 hours after before they were rotated in a chair until a immersion, reduced swelling by 12.5% vs symptom total short of vomiting was inflammation induced by paw immersion in reached. The three doses of ginger adminis- hot water, reduced swelling 22.1% after 5 tered were all at the placebo level of effi- hours after dextran injection vs dextran-in- cacy. Amitriptyline, ethopropazine, and duced pedal edema, and was active vs carra- trihexyphenidyl increased the tolerated geenan-induced pedal edema. A mixture of head movements, but the increase was not 5 g Bupleurum falcatum, 1.5 g Glycyrrhiza statistically significant. Significant levels of glabra, 2 g Zizyphus inermis, 2 g Zingiber protection were produced by dimenhydri- officinale, 2 g Panax ginseng, 4 g Pinellia ternata, nate, promethazine, scopolamine, and D- 2 g Cinnamomum cassia, 2 g Paeonia albiflora, amphetamine. Efficacy was greatest, as the and 2 g Scutellaria baicalensis, administered dose was increasedZO003. Powdered rhizome, by gastric intubation at a dose of 500 mg/kg taken orally by human adults at a dose of 1 1 hour before and 1 and 2 hours after injec- g/person, was active vs seasicknessZO284. A tion of dextran, reduced swelling 25.5% at dose of 940 mg/kg was active vs motion sick- 5 hours vs dextran-induced pedal edema and ness in 36 susceptible volunteersZO141. The 32.5% on day 24 vs adjuvant-induced arthri- ground rhizome, taken orally by 80 male tis. The treatment was inactive vs inflamma- adults at a dose of 1 g/day, was active. Those tion induced by paw immersion in hot water who received the powder suffered less sea- and carrageenan-induced pedal edema. A sickness compared with those who received mixture of 7 g Bupleurum falcatum, 2 g placebo. The difference was statistically sig- Glycyrrhiza glabra, 3 g Zizyphus inermis, 4 g nificant, p < 0.05, 4 hours after receiving the Zingiber officinale, 3 g Panax ginseng, 5 g treatmentZO072. Pinellia ternata, and 3 g Scutellaria baical- Antimutagenic activity. Aqueous high- ensis, administered by gastric intubation to speed supernatant of the plant juice, on agar rats at a dose of 500 mg/kg, was inactive vs plate at a concentration of 0.1 mL/plate, was adjuvant-induced arthritis, dextran- and active on Salmonella typhimurium TA98 vs carrageenan-induced pedal edema, and in- tryptophan pyrolysate mutagenicity. S9 mix flammation induced by paw immersion in was addedZO273. Infusion of the rhizome, on hot waterZO332. Hot water extract of the dried agar plate at a concentration of 100 PL/disc rhizome, administered intraperitoneally to was inactive on Salmonella typhimurium rats at doses of 100 and 200 mg/kg, were ac- TA100 and TA98 vs ethyl methanesul- tive vs carrageenan-induced pedal edema. fonate and 2-amino-anthracene-induced The effect was not seen in adrenalectomized mutagenicity, respectively. Metabolic acti- ratsZO333. Methanol extract of the dried rhi- vation was not required for activityZO161. zome, applied topically to mice at a dose of Anti-nauseant effect. The rhizome, taken 20 PL/animal, was active vs tetradeca- orally by pregnant women at a dose of 250 noyl phorbol acetate-induced acetate mg/person for 4 days, was active. Thirty phospholipid synthesis and 12-O-tetradeca- women participated in the double-blind noylphorbol-13-acetate-induced ear inflam- randomized crossover study of the efficacy mationZO095. of the powdered rhizome in hyperemesis Antimotion sickness effect. Ginger and gravidarum. Each participant swallowed a other medications were compared with sco- 250 mg capsule containing ginger or lactose ZINGIBER OFFICINALE 525 four times daily for the first 4 days of treat- of soybean lipoxygenase. Ginger, onion and ment. This was interrupted by a 2-day wash- ginger, and garlic and ginger produced cu- out period, and the alternative medication mulative inhibition of lipid peroxidation was given in the second 4-day period. Two this exhibiting their synergistic antioxidant scoring systems evaluated the severity and activity. The antioxidant activity of the relief of the symptoms before and after each extract were retained even after boiling for period. The scores indicated that 70.4% of 30 minutes at 100qC, indicating that the the participants indicated preference to the constituents were resistant to thermal period in which ginger was givenZO298. denaturationZO016. The effect of ginger (1%, Anti-nematodal activity. Water extract of w/w) on exposure of rats to subchronic the rhizome, at a concentration of 10 mg/ malathion (O,O-dimethyl-S-1,2,bisethoxy- mL, was inactive on Toxocara canis. The carbonyl-ethyl phosphorodithioate) was methanol extract, at a concentration of 1 evaluated. Administration of malathion (20 mg/mL, was activeZO209. ppm) for 4 weeks increased the malondi- Anti-neurotoxic activity. Hot water ex- aldehyde levels in serum, activities of super- tract of the dried rhizome at a concentra- oxide dismutase, catalase, and glutathione tion of 75 Pg/mL, was active vs cytochalasin peroxidase in erythrocytes and glutathione B-induced neurite distortionZO281. reductase and glutathione S-transferase in Anti-osteoarthritic effect. Ginger extract serum. It decreased the glutathione level in was compared to placebo and ibuprofen in whole blood. Concomitant dietary feeding patients with osteoarthritis of the hip and of ginger significantly attenuated mal- knee in a controlled, double-blind, double- athion-induced lipid peroxidation and dummy, crossover study with a washout pe- oxidative stress in the rats. The results indi- riod of 1 week followed by three treatment cated the possible involvement of free radi- periods in a randomized sequence, each of 3 cals in organophosphate-induced toxicity weeks’ duration. The ranking of efficacy of and highlighted the protective action of the three treatment periods were ibuprofen gingerZO017. Ginger (1% w/w) significantly more than ginger extract greater than pla- lowered lipid peroxidation by maintaining cebo for visual analogue scale of pain (Fried- the activities of the antioxidant enzymes man test: 24.65, p < 0.00001) and the superoxide dismutase, catalase, and glu- Lequesne-index (Friedman test: 20.76, p < tathione peroxidase in rats. The blood glu- 0.00005). In the crossover study, no signifi- tathione content was significantly increased cant difference between placebo and ginger in ginger-fed rats. Similar effects were also extract could be demonstrated (Siegel- observed after natural antioxidant ascor-bic Castellan test), whereas explorative tests of acid (100 mg/kg, body weight) treat- differences in the first treatment period mentZO010. The glucosides, 1-(4-O-E-D-glu- showed a better effect of both ibuprofen and copyranosyl-3-methoxyphenyl)-3,5-dihy- ginger extract than placebo (p < 0.05). droxydecane and 5-O-E-D-glucopyranosyl- There were no serious adverse events re- 3-hydroxy-1-(4-hydroxy-3-methoxy- ported during the periods with active phenyl)decane, incubated with acetone, medicationsZO020. were hydrolyzed to 6-gingerdiol. Their anti- Antioxidant effect. Alcohol (50%) extract oxidative activities were investigated and of the ginger produced significant effect on compared to that of their aglycon, 6- enzymatic lipid peroxidation. The extract gingerdiol, by a linoleic acid model system dose-dependently inhibited oxidation of and by their 1,1-diphenyl-2-picrylhydrazyl fatty acid and linoleic acid in the presence (DPPH) radical-scavenging ability. 1-(4-O- 526 MEDICINAL PLANTS OF THE WORLD

E-D-glucopyranosyl-3-methoxyphenyl)-3,5- injectionZO292. Water extract of a mixture of dihydroxydecane did not indicate any Bupleurum falcatum, Scutellaria baicalensis, activity, 5-O-E-D-glucopyranosyl-3-hydroxy- Paeonia alba, Rheum tanguticum, Citrus 1-(4-hydroxy-3-methoxyphenyl)decane had aurantium, Pinellia ternata, Zingiber officinale, as strong activity as the aglycon in both and Zizyphus inermis, administered by gas- measurementsZO019. Amrita Bindu, a salt- tric intubation to mice and rabbits at a dose spice mixture, with pepper and ginger being of 200 mg/kg, was active vs typhoid vaccine- the main ingredients, was investigated for induced pyrexiaZO323. its effect in maintaining antioxidant defense Anti-radiation effect. Methanol extract of systems in blood and liver when exposed to the dried rhizome, administered intraperito- a carcinogenic nitrosamine, N-methyl-N'- neally to mice at a dose of 400 mg/kg, was nitrosoguanidine (MNNG). The mixture inactive vs soft X-ray irradiation at lethal prevented MNNG-induced depletion of the doseZO334. antioxidant enzymes and the scavenger Anti-rheumatic effect. Ginger oil, admin- antioxidants glutathione and vitamins A, istered orally at a dose of 33 mg/kg to male C, and E. It provides protection against Sprague–Dawley rats with arthritis induced free radical- and reactive oxygen species- in the knee and paw by injecting 0.05 mL of induced tissue lipid peroxidation and the fine suspension of dead Mycobacterium tu- resultant tissue degenerationZO030. Polyun- berculosis bacilli in liquid paraffin (5 mg/mL, saturated fatty acids are vulnerable to per- produced a significant suppression of both oxidative attack. Protecting from peroxida- paw and joint swellingZO029. Hot water ex- tion is essential to use their beneficial effects tract of the dried rhizome, administered in health and in preventing disease. The an- intragastrically to female mice at a dose of tioxidants vitamin E, t-butylhydroxy tolu- 20 mg/mL, was active in influenza virus-in- ene, and t-butylhydroxy anisole inhibited fected animalsZO099. ascorbate/Fe2+-induced lipid peroxidation in Antischistosomal activity. Hot water ex- rat liver microsomes. Zingerone from gin- tract of the dried rhizome, taken orally by ger-inhibited lipid peroxidation at high human adults at variable dosage levels, was concentrations (>150 PM). The inhibition active. A mixture of Rehmannia glutinosa was not affected by the addition of high Fe2+ (Rt), Dioscorea batatas (Tu), Dolichos lablab concentrationZO037. Aqueous high-speed su- (Sd), Glycyrrhiza uralensis (Rt), Zingiber pernatant of the rhizome, at a concentration officinale (Rh), Evodiarutae carpa (Fr), of 0.04 mL and hot water extract and juice Atractylodes macrocephala (Rh), and Panax at concentration of 0.02 mL, was activeZO073. ginseng (Rt) was usedZO301. Methanol extract of the rhizome, adminis- Antispasmodic activity. Ethanol (95%) tered intragastrically to mice at a dose of extract of the dried rhizome, at a concentra- 0.16 g/kg, was active vs ethanol-induced tion of 200 Pg/mL, was active on the guinea lipid peroxidation in the mouse liverZO182. pig ileum vs histamine- and barium-induced Antioxytocic effect. Water extract of the contractions. The water extract was active dried rhizome, at a concentration of 0.01 g/ vs barium-induced contractions and inac- mL, produced weak activity on the rat uterus tive vs histamine-induced contractionsZO335. vs oxytocin-induced contractionsZO328. The hot water extract, at a concentration of Antipyretic activity. Ethanol (80%) ex- 1 mg/mL, was active vs barium- and acetyl- tract of the rhizome, administered intra- choline (ACh)-induced contractions. A gastrically to rats at a dose of 100 mg/kg, was concentration of 3 mg/mL was active vs his- active vs hyperthermia induced by yeast tamine-induced contractions and on the vas ZINGIBER OFFICINALE 527 deferens vs norepinephrine-induced con- baicalensis, Zizyphus jujuba, Panax ginseng, tractionsZO336. Water extract of the dried rhi- and Glycyrrhiza glabra on days 1 to 10, were zome, in combination with Pinellia ternata, inactiveZO268. Ethanol (95%) extract of the Citrus aurantium, Pachyma hoelen, and dried rhizome, administered intraperito- Glycyrrhiza glabra, at a concentration of 0.01 neally to mice at a dose of 100 mg/kg, was g/mL, was active on the guinea pig ileum inactive on Sarcoma 180 (ASC)ZO194. Etha- and rabbit small intestine vs ACh- and nol (90%) extract of the dried rhizome, ad- barium-induced contractionsZO328. Water ministered intraperitoneally to mice at a extract of a mixture of Bupleurum falcatum, dose of 500 mg/kg, was inactive on CA- Scutellaria baicalensis, Paeonia alba, Rheum Ehrlich ascites, Sarcoma 180 (ASC), and tanguticum, Citrus aurantium, Pinellia ter- Leuk-SN36ZO318. nata, Zingiber officinale, and Zizyphus inermis, Anti-ulcer effect. Acetone extract of gin- administered to mice at a concentration of ger, administered orally to rats with HCl/ 1–5 mg/mL, was active vs histamine-in- ethanol-induced gastric ulcers at a dose of 1 duced contractions. A concentration of 10 g/kg, significantly inhibited gastric lesions mg/mL was active vs barium- and ACh- by 97.5%. Zingiberene and 6-gingerol, at a induced contractionsZO323. dose of 100 mg/kg, also inhibited gastric Anti-tumor activity. Ginger rhizome was lesions by 53.6 and 54.5%, respectivelyZO050. investigated for antitumor promoter activ- Decoctions of dried and roasted ginger were ity using the short-term assay of inhibition investigated on four experimental gastric of 12-O-tetradecanoyl phorbol-13-acetate ulcer models. The decoction was adminis- (TPA)-induced Epstein-Barr virus early an- tered orally at a dose of 4.5 g/kg to rats. The tigen (EBV-EA) in Raji cells. The inhibi- roasted ginger had a significant inhibiting tion of TPA-induced EBV-EA was detected tendency on three gastric ulcer models, ex- using the indirect immunofluorescence as- cept the indomethacin-induced model. The say (IFA) and Western blot technique. The dried ginger had no such effectsZO042. The indirect IFA detected the expression/inhi- rhizome, administered to rats at a dose of bition of EBV-EA-D (diffused EA), whereas 150 mg/kg, produced 57.5% inhibition of the Western blot technique detected the gastric ulcers induced by HCl and ethanol. expression/inhibition of both EBV-EA-D The acetone/ethanol extract, at a dose of and EA-R (restricted EA). The rhizome 500 mg/kg, produced 91.9% inhibition. Bu- possesses inhibitory activity toward EBV tanol extract, at a dose of 285 mg/kg, pro- activation, induced by TPA. The cytotox- duced 12.4% inhibition and water extract icity assay was conducted to determine the at a dose of 640 mg/kg, produced 45.8% toxicity of the rhizome extractZO023. Water inhibitionZO079. Acetone and methanol ex- extract of Zingiber officinale, Bupleurum tracts of the dried rhizome, administered falcatum, Pinellia ternata, Scutellaria bai- intragastrically to rats at a dose of 1 g/kg, calensis, Zizyphus jujuba, Panax ginseng, and were active vs HCl/ethanol-induced ulcers. Glycyrrhiza glabra, administered by gastric Chromatographic fraction of the dried rhi- intubation to mice at a dose of 300 mg/kg, zome, administered intragastrically to rats at was active on Leuk-L1210. Cytarabine or a dose of 40 mg/kg, was active vs HCl/etha- 5-fluorouracil was also administered. Water nol-induced ulcersZO181. Hot water extract of extract of the dried rhizome, adminis- the dried rhizome, administered by gastric tered intraperitoneally at doses of 100 and intubation to mice at a dose of 1.766 g/kg, 300 mg/kg, in combination with Bupleu- was inactive vs stress induced ulcersZO337. rum falcatum, Pinellia ternata, Scutellaria Methanol (50%) extract of the dried rhi- 528 MEDICINAL PLANTS OF THE WORLD zome, administered by gastric intubation to Virus (Manheim 57), poliovirus II, vaccinia mice at a dose of 10 g/kg, was inactive vs virusZO257, and LPPI virusZO274. Hot water ex- stress-induced (restraint) ulcersZO237. Water tract of the dried rhizome, in cell culture at extract of the dried rhizome, administered a concentration of 500 Pg/mL, was inactive intraperitoneally to rats at a dose of 1 mg/g, on herpes simplex I virus. A dose of 300 mg/ was active vs Shay ulcers. The results were kg, administered intragastrically to female significant at p < 0.001 levelZO328. Ethanol mice, was active on herpes simplex I (95%) extract of the dried rhizome, admin- virusZO138. Hexane extract of the dried rhi- istered by gastric intubation to rats at a dose zome, in cell culture, was active on rhinovi- of 500 mg/kg, significantly lowered ulcer in- rus type 1-B virusZO131. Hot water extract of dex of necrotizing agents (80% ethanol, the dried rhizome, in cell culture at a con- 0.6% HCl, 0.2 M NaOH, and 25% NaCl), centration of 0.5 mg/mL, was inactive on and was active vs aspirin-, indomethacin-, herpes simplex I virus, measles virus, and ZO339 and cold stress-induced ulcers. The extract poliovirus I . was inactive vs reserpine- and Shay-induced Anti-yeast activity. The essential oil, on ulcersZO184. Water extract of the dried agar plate, was inactive on Saccharomyces ZO127 rhizome in a preparation containing Atracty- cervisiae . Ethanol (95%) extract of the lodes macrocephala, Amomum species, Magno- dried rhizome, in broth culture at a concen- tration of 10%, was inactive on Candida lia officinalis, Citrus aurantium ssp. nobilis, albicans, Candida glabrata, and Candida Pachyma hoelen, Elettaria cardamomum, Panax tropicalisZO340. Ethanol (90%) extract of the ginseng, Saussurea lappa, Glycyrrhiza species, dried rhizome, on agar plate at a concentra- and Zizyphus vulgaris, administered tion of 500 mg/disc, was inactive on Can- intraduodenally to rats at a dose of 1 g/kg, dida albicansZO318. was active vs aspirin-, histamine-, stress- Arachidonate metabolism inhibition. De- (water immersion), and pylorus ligation-in- coction of the dried rhizome, at a concen- ZO338 duced ulcers . tration of 0.3 mg/plate, was active on sheep Antivertigo effect. Powdered rhizome, ad- vesicular gland microsomal fractionZO315. ministered orally to human adults at a dose Decoction of the dried rhizome, adminis- ZO284 of 1 g/person, was active vs seasickness . tered intraperitoneally to rats at a dose of Rhizome, administered orally to adults of 0.74 g/animal, was inactive. Serum from rats both sexes at a dose of 1 g/person, was inac- fed the decoction was added to sheep vesi- tive. The treatment was administered 2 cular gland microsomal fraction. Arachi- hours before the subjects were rotated in a donic acid metabolism in gland enzyme chair making head movement until a symp- mixture was measured. The system was not tom short of vomiting was reachedZO183. affected by rat serum lipidsZO315. Hot water Antiviral activity. Aqueous low-speed su- extract of the dried rhizome in a mixture pernatant of the rhizome, at a concentration containing 7 g Bupleurum falcatum, 5 g of 1% and the rhizome juice, produced Pinellia ternata, 3 g Scutellaria baicalensis, 3 g strong activity on virus-top necrosisZO172. Panax ginseng, 4 g Zingiber officinale, 3 g Decoction of the rhizome together with c at Zizyphus vulgaris, and 2 g Glycyrrhiza glabra a concentration of 250 Pg/mL, was active in 700 mL water, administered intragastri- on HIV-1 and Rauscher murine leukemia cally to mice on days 1–3, was activeZO341. A viruses. Reverse transcriptase activity was mixture of Zingiber officinale (Rh), Bupleu- inhibitedZO209. Water extract of the rhizome, rum falcatum (Rt), Scutellaria baicalensis in cell culture at a concentration of 10%, (Rt), Pinellia ternata (Tu), Zizyphus jujuba was inactive on herpes virus type 2, A2- (Fr), Panax ginseng (Rt), and Glycyrrhiza ZINGIBER OFFICINALE 529 glabra (Rh), in cell culture, was active on subcutaneously to mice at a dose of 10.0 g/ macrophagesZO123. kg, had no effectZO237. Aspartate transaminase effect. Decoction Carcinogenesis inhibition. Decoction of of the dried rhizome, taken orally by 80 the dried rhizome, in the ration of rats at a adults of both sexes with hepatitis B anti- concentration of 20% of the diet, was gen-positive chronic hepatitis at a dose of equivocal vs azoxymethane-induced aber- 7.5 g/day for 6 months, was activeZO123. The rant crypt fociZO343. treatment consisted of Zingiber officinale Cardiac depressant activity. Hot water ex- (Rh), Bupleurum falcatum (Rt), Scutellaria tract of the dried rhizome, at a concentra- baicalensis (Rt), Pinellia ternata (Tu), tion of 3 mg/mL, was active on the guinea Zizyphus jujuba (Fr), Panax ginseng (Rt), and pigZO336. ZO123 Glycyrrhiza glabra (Rh) . Cardiotonic activity. Gingerol, a constitu- Bacterial stimulant activity. Powdered rhi- ent of ginger, tested in the guinea pig iso- zome, in broth culture at a concentration of lated atrial cells at a concentration of 3 u 2 g/L, was active on Lactobacillus planta- 10–6 M, produced an increase in the degree ZO285 rum . and the rate of longitudinal contractions. In Barbiturate potentiation. Ethanol (95%) the guinea pig left atria, gingerol produced and methanol (75%) extracts of the rhi- little influence on the action potential, al- zome, administered intraperitoneally to though it increased the contractile force of male mice at a dose of 500 mg/kg, were the atria. The whole-cell patch-clamp ex- inactiveZO221. Methanol extract of the rhi- periments showed that the slow inward zome, administered intraperitoneally to current was little affected by gingerol in the mice at a dose of 500 mg/kg on days 1–3, voltage-clamped guinea pig cardiac myo- was inactiveZO265. Water extract of the dried cytes. The measurement of extravesicular rhizome, administered by gastric intubation 2+ to mice at a dose of 4 g/kg, was active. A Ca uptake of fragmented sarcoplasmic mixture of Zingiber officinale, Glycyrrhiza reticulum prepared from canine cardiac glabra, Panax ginseng, Scutellaria baicalensis, muscle in a concentration-dependent man- ZO049 Zizyphus jujuba, Pinellia ternata, Bupleurum ner . Gingerol, isolated from the rhizome, 2+ falcatum, Cinnamomum cassia, and Paeonia stimulated the Ca -pumping activity of albiflora was usedZO250. Hot water extract of fragmented sarcoplasmic reticulum prepared the dried rhizome, administered by gastric from the rabbit skeletal and dog cardiac intubation to male mice at a dose of 1 g/kg, muscles. The extravesicular Ca2+ concentra- was inactive. A mixture of Pinellia ternata tions of the heavy fraction of the frag- (Tu), Magnolia obovata (Bk), Perilla frutes- mented sarcoplasmic reticulum were cens (Aer), Zibngiber officinale (Rh), and measured directly with a Ca2+ electrode to Poria cocos (Fr) (6, 3, 2, 1, and 5 g, respec- examine the effect. Gingerol, at a concen- tively) was used. A dose of 2 g/kg was tration of 3–30 PM, accelerated the Ca2+- activeZO342. Hot water extract of the dried pumping rate of skeletal and cardiac rhizome, administered by gastric intubation to sarcoplasmic reticulum in a concentration- male mice at a dose of 4 g/kg, was inac- dependent manner. Gingerol also activated tiveZO342. Methanol (50%) extract of the Ca2+-adenosine triphosphatase (ATPase) dried rhizome, administered subcutaneously activities of skeletal and cardiac sarcoplas- to mice at a dose of 10 g/kg, was active and a mic reticulum (EC50, 4 PM). The activation dose of 3 g/kg was inactiveZO237. of the Ca2+-ATPase activity was completely Capillary permeability. Methanol (50%) reversed by 100-fold dilution with the fresh extract of the dried rhizome, administered saline solution. Kinetic analysis of the acti- 530 MEDICINAL PLANTS OF THE WORLD vating effects of gingerol suggests that the duced by hexamethonium but was not en- activation of sarcoplasmic reticulum Ca2+- tirely eliminated by phentolamine. The ATPase is uncompetitive and competitive pressure response disappeared with spinal regarding Mg. Adenosine triphosphate destruction at the sacral cord level. The sec- (ATP) at concentrations of 0.2–0.5 mM ond response that occurred when the sys- and above 1 mM, respectively. Kinetic temic blood pressure regained its original analysis also suggested that the activation by pressure was not affected by hexametho- gingerol in mixed-type with respect to free nium, phentolamine, or spinal destruction. Ca2+ and this enzyme is activated probably Pressor response induced by the injection of resulting from the acceleration of enzyme- [6]-shogaol (10 Pg) into the perfusion cir- substrate complex breakdown. Gingerol had cuit was not affected by phentolamine and no significant effect on sarcolemma Ca2+- spinal destructionZO056. Ethanol (95%) ex- ATPase, myosin Ca2+-ATPase, actin-acti- tract of the rhizome, administered by iv in- vated myosin ATPase and cyclic adenosine fusion to dogs at a dose of 5 mL/animal at a monophosphate (cAMP)-phosphodieste- rate of 1 mL/minute, increased the heart rase activitiesZO051. rateZO314. Cardiovascular effect. [6]-shogaol, ad- Cell proliferation inhibition. The rhizome, ministered intravenously to rats at a dose in cell culture at a concentration of 3.75%, of 0.5 mg/kg, produced a rapid fall in blood was active on human fibroblastZO096. Decoc- pressure, bradycardia, and apnea. There was tion of the dried rhizome, at a concentra- a marked pressure pressor response in blood tion of 50 Pg/mL, produced weak activity on pressure that occurred after the rapid fall. A the mouse mesangial cellsZO139. dose of 3.6 PM produced inotropic and Chemopreventitive effect. The antitumor chronotropic actions on isolated atria in promotional activity of [6]-gingerol, a ma- rats. The effect disappeared by repeated in- jor pungent principle of the rhizome, was in- jections or pretreatment of 100 mg/kg ad- vestigated using a two-stage mouse skin ministered subcutaneouslyZO054. Intravenous carcinogenesis model. Topical application doses of 0.1 to 0.5 Pg produced a pressor re- of the extract onto shaven backs of female sponse in a dose dependent manner. The mice before each topical dose of 12-O- response was markedly reduced by spinal tetradecanoylphorbol-13-acetate signifi- destruction at the sacral cord level. Norepi- cantly inhibited 7,12-dimethylbenz[a] nephrine (10 Pg/kg, intravenously) induced -anthracene-induced skin papilloma gen- pressor response that was not affected by spi- esis. The extract also suppressed TPA-in- nal destruction. In rats in which the spinal duced epidermal ornithine decarboxylase cord was destroyed at the thoracic cord activity and inflammationZO024. level, [6]-shogaol-induced pressor response Cholagogic effect. The effect of ginger on was reduced by hexamethonium (10 mg/kg, bile secretion was examined to clarify the intravenously) and phentolamine (10 mg/ stomachic action of ginger and to investi- kg, intravenously). When the spinal cord gate its active constituents. The results in- was destroyed at the sacral level, the pressor dicated that the acetone extracts, which response was not affected by these block- contain the essential oils and pungent prin- ades. In the hindquarters of rats that were ciples, produced an increase in the bile se- perfused with rat’s blood, [6]-shogaol pro- cretion. Further analyses for the active duced two pressor responses on the perfu- constituents of the acetone extracts through sion pressure. The first was accompanied by column chromatography indicated that [6]- a rise in systemic blood pressure, was re- gingerol and [10]-gingerol, which are the ZINGIBER OFFICINALE 531 pungent principles, are mainly responsible at a dose of 4 g/kg, produced no change in for the cholagogic effectZO059. the electroencephalogram (EEG), behavior, Choleretic activity. Acetone extract of the or active and resting cycles. A mixture of dried rhizome, administered intraduoden- Zingiber officinale, Glycyrrhiza glabra, Panax ally to rats at a dose of 500 mg/kg, was ac- ginseng, Scutellaria baicalensis, Zizyphus tive. The water extract was inactive, and jujuba, Pinellia ternata, Bupleurum falcatum, the chromatographic fraction, at a dose of Cinnamomum cassia, and Paeonia albiflora 150 mg/kg, was activeZO344. was usedZO250. Ethanol (95%) extract of the Cholesterol absorption inhibition. Oleo- rhizome, administered intraperitoneally to resin, administered orally to rats, was active male mice at a dose of 500 mg/kg, did not ZO217 on cholesterol-primed animals . produce any depressant activityZO221. Ethanol Cholesterol ester formation. Decoction of (95%) extract of the rhizome, administered the dried rhizome, administered intragastri- intravenously to rabbits at a dose of 1.5 mL/ cally to mice at a dose of 1.2 g/kg, produced animal, produced a stimulating activityZO314. no effect. The study was conducted with a Coagulation effect. The decoction, ether mixture of Zingiber officinale (Rh), Bupleu- extraction and suspension liquid of roasted rum falcatum (Rt), Scutellaria baicalensis ginger and charcoal of ginger, had markedly (Rt), Pinellia ternata (Tu), Zizyphus jujuba shortened the blood coagulation time in (Fr), Panax ginseng (Rt), and Glycyrrhiza mice. The decoction, ether extraction of glabra (Rh)ZO111. fresh ginger and dried ginger, did not have Choline acetyltransferase induction. Wa- any effect. The decoction of ginger charcoal ter extract of the rhizome, in cell culture at has stronger effect than roasted ginger in a concentration of 200 Pg/mL and a dose of shortening the blood coagulation time in 500 mg/kg administered intragastrically to mice. The effect of the decoction of ginger male rats, were active on astroglial cells. The extract was used in combination with charcoal on blood coagulation time in- ZO035 dried Pinellia ternata, Citrus aurantium, Po- creases when the dosage is increased . ria cocos, Citrus unshiu, Glycyrrhiza glabra, Corticosterone induction. Hot water ex- Polygala tenuifolia, Scrophularia ningpoensis, tract of the rhizome, administered by gastric Panax ginseng, Rhemannia glutinosa, and intubation to rats at a dose of 1.1 g/kg, was Zizyphus jujubaZO106. active. The dose also increased the plasma Circulation stimulation. Hot water extract level of prednisolone. A mixture of 8 g of the dried rhizome, administered intrave- Bupleurum species, 3 g Glycyrrhiza glabra, 3 nously to rabbits at a dose of 4.5 mg/kg, was g Zizyphus jujuba, 1 g Zingiber officinale, 3 g equivocalZO345. Panax ginseng, 8 g Pinellia ternata, and 3 g Clastogenic effect. Crude aqueous extract Scutellaria baicalensis was used. Results were of the rhizome, administered by gavage at significant at p < 0.01 levelZO259. Hot water doses of 0.5, 1, 2, 5, and 10 g/kg body weight extract of a mixture of 7 g Bupleurum and ginger oil, administered intraperito- falcatum, 2 g Glycyrrhiza glabra, 3 g Zizyphus neally at doses of 1.25 and 2.50 mL/kg body inermis, 4 g Zingiber officinale, 3 g Panax gin- weight, were evaluated in mice. Attention seng, 5 g Pinellia ternata, and 3 g Scutellaria was drawn to the weakness of the clasto- baicalensis, administered intraperitoneally genic activity expressed by ginger extract. to rats at a dose of 200 mg/kg, produced an In comparison, ginger oil produced a higher increase in serum adrenal corticosterone vs frequency of chromosomal aberrationsZO013. carrageenan-induced pedal edema. The CNS effects. Water extract of the rhizome, mixture, at a concentration of 0.1 mg/mL, administered to mice by gastric intubation was inactive on the adrenal gland vs basal 532 MEDICINAL PLANTS OF THE WORLD and ACTH-induced corticosterone release calensis, Zizyphus vulgaris, Panax ginseng, from rat adrenal gland slicesZO283. Magnolia obovata, Glycyrrhiza glabra, and cAMP stimulation. A mixture of 7 g Bu- Perilla frutescens was usedZO259. pleurum falcatum, 2 g Glycyrrhiza glabra, Desmutagenic activity. Aqueous high- 3 g Zizyphus inermis, 4 g Zingiber officinale, speed supernatant of the fresh fruit juice, on 3 g Panax ginseng, 5 g Pinellia ternata, and 3 g agar plate at a concentration of 0.5 mL/ Scutellaria baicalensis, administered intra- plate, was active on Salmonella typhimurium peritoneally to rats at a dose of 200 mg/kg, TA98 vs mutagenicity of l-tryptophane py- increased cAMP levels in pituitary and rolysis products. The assay was done in the adrenal gland but not in the hypothalamus. presence of S9 mixZO275. Fresh fruit juice, at a The increases were inhibited by dexame- concentration of 0.5 mL/plate, was active thasoneZO283. on Salmonella typhimurium TA98ZO276. Cyclo-oxygenase-2 inhibition. Seventeen Digestive effect. The fresh rhizome, ad- pungent oleoresins of ginger and synthetic ministered orally to rats at a dose of 50 mg%, analogs were evaluated for inhibition on significantly enhanced intestinal lipase ac- cyclooxygenase-2 enzyme activity in the tivity and also the disaccharidases sucrase intact cell. The compounds exhibited a and maltaseZO027. concentration and structure dependent in- Diuretic activity. Ethanol (50%) extract of hibition of the enzyme, with IC50 values in the dried aerial parts, administered intrap- the range of 1–25 PM. Ginger constitu- eritoneally to rats at a dose of 45 mg/kg, was ents, 8-paradol and 8-shogaol, as well as two activeZO262. Methanol (50%) extract of the synthetic analogs, 3-hydroxy-1-(4-hydroxy- dried rhizome, administered subcutaneously 3-methoxyphenyl)decane and 5-hydroxy-1- to mice at a dose of 10 g/kg, was inactiveZO237. (4-hydroxy-3-methoxyphenyl)dodecane, DNA polymerase inhibition. Decoction of showed strong inhibitory effects on cyclo- the rhizome, at a concentration of 500 Pg/ oxygenase enzyme activity. The SAR analy- mL, was active on D and E inhibition and sis of these compounds revealed that the inactive on gamma inhibition. This study features that affect cyclooxygenase inhibi- was conducted with a mixture of Bupleurum tion are lipophilicity of the alkyl side chain, falcatum (Rt), Scutellaria baicalensis (Rt), substitution pattern of hydroxy and carbo- Pinellia ternata (Tu), Zizyphus jujuba (Fr), nyl groups on the side chain, and substitu- Panax ginseng (Rt), and Glycyrrhiza glabra tion pattern of hydroxy and methoxy groups (Rh)ZO203. Water extract of the mixture, at a on the aromatic moietyZO006. concentration of 500 Pg/mL, was active on Cytotoxic activity. Water extract of the D, E, and J inhibition when reverse tran- rhizome, in cell culture at a concentration scriptase activity from HIV was assayedZO203. of 10% was inactive on HeLa cellsZO257. Etha- Enzymatic activity. A reductive metabo- nol (95%), petroleum ether, and methyl lism of S-(+)-[6]-gingerol [1-(4'-hydroxy-3'- chloride extracts of the dried rhizome, at a methoxyphenyl)-5-hydroxydecan-3-one], concentration of 320 Pg/mL, were inactive was investigated in vitro with phenobar- on Raji cellsZO319. bital-induced rat liver 10,000g supernatant Degranulation inhibition. Hot water ex- containing the NADPH-generating system. tract of the rhizome, in cell culture at a con- The ethyl acetate-extractable products were centration of 0.1 mg/mL, was active vs isolated and two metabolites were identified compound 48/40-induced degranulation of as disatereomers of [6]-gingerdiol by gas mast cells. A mixture of Bupleurum falcatum, chromatography/mass spectrometry. The ra- Pinellia ternata, Poria cocos, Scutellaria bai- tio of the two isomers formed was about 1:5, ZINGIBER OFFICINALE 533 suggesting the stereospecific reduction of S- used as the treatment of paralytic ileus, was (+)-[6]-gingerol by carbonyl reductase investigated in vitro. A dose of 30–300 Pg/ activity present in the postmitochondrial mL produced a significant inhibition on car- supernatant fraction of rat liverZO031. Ginger bachol-induced contraction in a concentra- oil, administered orally to Swiss albino mice tion dependent manner of the rat distal at a dose of 10 PL/day for 14 days, signifi- colon. The treatment contained 20% Zan- cantly elevated aryl hydrocarbon hydroxy- thoxylum fruit, 30% ginseng root, and 50% lase and glutathione S-transferase activities. ginger rhizome. Although each of them had There was no significant effect on cyto- no effect on carbachol-induced contraction, chrome P450 and acid soluble sulfhydryl the combination of three ingredients pro- glutathione S-transferaseZO033. duced significant inhibitionZO007. Acetone Epstein–Barr virus early antigen activa- extract of the rhizome, administered intra- tion. Ether extract and the decoction, in gastrically to mice at a dose of 75 mg/kg, in- cell culture at a concentration of 5 Pg/mL, creased gastric motilityZO192. Acetone extract inhibited antigen activationZO346. of ginger, administered orally to mice at a Fibrinolytic activity. The administration dose of 75 mg/kg, [6]-shogaol at 2.5 mg/kg, of 50 g of fat to 30 healthy adult volunteers or a [6]-, [8]- or [10]-gingerol at 5 mg/kg en- decreased fibrinolytic activity from a mean hanced the transport of charcoal meal. The of 64.20 to 52.10 units (p < 0.001). Supple- effects of these substances were similar to or mentation of 5 g of ginger powder with the slightly weaker than metoclopramide and fatty meal not only prevented the fall in fi- donperidoneZO044. Dried rhizome, taken brinolytic activity but actually increased it orally by adults at a dose of 1 g/person, did significantly (p < 0.001)ZO004. not reduce gastric motilityZO115. Dai-Kenchu- Gastric exfoliation effect. DNA content To and each ingredient were investigated of gastric aspirates was determined after on upper gastrointestinal motility and intragastric infusions of 2, 4, and 6 g of gin- mechanism of action. Five dogs were ger daily. The mean changes of DNA-p/ equipped with four-strain gauge-force trans- minute in the gastric aspirates after the 2- ducers on the gastric body, antrum, duode- and 4-g doses were 1.37 r 2.3 and 6.74 r num, and jejunum to measure contractile 3.06, respectively. Doses of 0.6 g or more activity of the circular muscle. Dai-Kenchu- produced a significant increase in exfolia- To (1.5 g) or the separate ingredients Zan- tion of gastric surface epithelial cells in hu- thoxylum fruit, ginseng root, or dried ginger man subjectsZO043. rhizome (1 g each) was administered by Gastric secretory inhibition. Water ex- bolus into the gastric lumen. Zanthoxylum tract of the entire plant, administered by fruit elicited phasic contractions mainly in gastric intubation to rabbits at a dose of 169 the duodenum and jejunum, whereas dried mg/kg, was active. The methanol extract at ginger rhizome induced phasic contractions a concentration of 114 mg/kg was also in the antrum. Ginseng root had no effect. activeZO187. Phasic contractions induced by intragastric Gastrointestinal effect. Ginger root, in Dai-Kenchu-To were inhibited by atropine combination with ginseng, Zanthoxylum and hexamethonium at all sites, although fruit, and malt sugar, administered orally to ondansetron inhibited these contractions in guinea pigs at a concentration of 10–300 the antrum and duodenumZO021. Ginger rhi- mg/kg, significantly improved carbachol-ac- zome extract (2 u 100 mg) was investigated celerated small intestinal transit in a dose- in fasting and postprandial gastroduodenal dependent mannerZO001. Dai-Kenchu-To, motility with stationary manometry in 12 534 MEDICINAL PLANTS OF THE WORLD healthy volunteers. The interdigestive an- increase in serum glutamate pyruvate tran- tral motility was significantly increased by saminase (GPT) resulting from D-galac- ginger during phase III of the migrating mo- tosamine-induced liver injuryZO282. tor complex. The volunteers also had a sig- GPT inhibition. Hot water extract of the nificantly increased motor response to a test rhizome, administered by gastric intuba- meal in the corpus; a trend to an increased tion to rats at dosages of 100 and 400 mg/ motor response during ginger treatment was kg, was active vs CCl4-induced hepatotox- seen in all other regions of interest. The icity. Methionine (100 mg/kg) was added to treatment improved gastroduodenal motil- the 100 mg/kg dose. The results were sig- ity in the fasting state and after the standard nificant at p < 0.01 level. The treatment test mealZO022. Methanol (50%) extract of also contained Bupleurum falcatum (Rt), the dried rhizome, administered subcutane- Scutellaria baicalensis (Rt), Pinellia tern- ously to mice at a dose of 10 g/kg, inhibited ataPinellia ternata (Tu), Zizyphus jujuba (Fr), gastric secretion. The extract had no effect Panax ginseng (Rt), and Glycyrrhiza glabra on gastric motilityZO237. (Rh)ZO267. Hot water extract of the rhi- Glucose metabolism stimulation. Ethanol zome, administered intragastrically to mice

(95%) extract of the rhizome, adminis- for a period of 1 month, was active vs CCl4- tered in the drinking water of mice at a con- and galactosamine-induced toxicity. The centration of 5%, was active. The extract, extract was used in combination with 7 g in combination with Hordeum vulgare, Bupleurum falcatum, 5 g Pinellia ternata, 3 g Rhizoma zingiberis, Ligusticum chuanxiong, Scutellaria baicalensis, 2 g Glycyrrhiza gla- Lilium brownii, Nephelium longa, and Poly- bra, 1 g Zingiber officinale, 3 g Panax gin- gonum multiflorum, increased glucose oxida- seng, and 3 g Zizyphus jujuba in 700 mL tion in epididymal fat pads of obese C57BL/ waterZO185. 6J miceZO137. Hair-stimulant effect. Decoction of the Glucosidase inhibition. Ethanol extract of rhizome, applied topically to human adults, the dried rhizome produced 26% inhibition was active. A mixture of Polygonum multi- of D-glucosidase on the rat intestineZO100. florum, Allium sativum, Zingiber officinale, Glutamate oxaloacetate transaminase Panax ginseng, Carthamus tinctorius, Platy- inhibition. Hot water extract of the rhi- codon grandiflorum, Biota orientalis, Ligusti- zome, administered by gastric intubation to cum wallichii, Salvia miltiorrhiza, Angelica rats at dosages of 100 and 400 mg/kg, was sinensis, and Tetrapanax papyrifera. The bio- ZO112 active vs CCl4-induced hepatotoxicity. Me- logical activity has been patented . thionine (100 mg/kg) was added to the 100 Hepatic oxygenase activity. Ginger, mg/kg dose. The results were significant at p administered orally to rats, significantly sti- < 0.01 level. The treatment also consisted mulated liver microsomal cytochrome of Bupleurum falcatum (Rt), Scutellaria P450-dependent aryl hydroxylase and cyto- baicalensis(Rt), Pinellia ternata (Tu), Zizy- chrome b5ZO045. phus jujuba (Fr), Panax ginseng (Rt), and Hepatitis antigen expression. Decoction Glycyrrhiza glabra (Rh)ZO267. Hot water of mixture of Zingiber officinale (Rt), Bupleu- extract of a mixture of 7 g Bupleurum rum falcatum (Rt), Scutellaria baicalensis falcatum, 2 g Glycyrrhiza glabra, 3 g Zizyphus (Rt), Pinellia ternata (Tu), Zizyphus jujuba inermis, 4 g Zingiber officinale, 3 g Panax gin- (Fr), Panax ginseng (Rt), and Glycyrrhiza seng, 5 g Pinellia ternata, and 3 g Scutellaria glabra (Rh), taken orally by 80 patients with baicalensis, administered intraperitoneally hepatitis B antigen-positive chronic hepati- to rats at a dose of 200 mg/kg, suppressed tis at a dose of 7.5 g/day for 6 months, pro- ZINGIBER OFFICINALE 535 duced seroconversion to antihepatitis B tered by gastric intubation to male rats at a antibody in eight patients, 15 became se- dose of 4 g/kg, was inactiveZO342. ronegative, and 11 had a decrease of hepati- Immunomodulatoy activity. Water ex- tis B antigen levels of more than 50%ZO123. tract of a mixture of Glycyrrhiza glabra (Rt), Histamine-release inhibition. Hot water Panax ginseng (Rt), Bupleurum falcatum (Rt), extract of the rhizome, in cell culture at a Scutellaria baicalensis (Rt), Zingiber officinale concentration of 0.1 mg/mL, was active vs (Rh), Angelica acutiloba (Rt), Atractylodes compound 48/40-induced histamine release. japonica (Rh), Astragalus membranaceus A mixture of Bupleurum falcatum, Pinellia (Rt), Citrus unshiu (Pericarp), and Cimifuga ternata, Poria cocos, Scutellaria baicalensis, simplex (Rh), administered to mice in the Zizyphus vulgaris, Panax ginseng, Magnolia diet at a dose of 115.6 mg/kg, elevated the obovata, Glycyrrhiza glabra, and Perilla mitogenic activity of concavalin A (Con frutescens was usedZO205. A), lipopolysaccharide, phorbol myristate Hydrogen peroxide inhibition. The vola- acetate, and phytohemagglutinin. Water tile oil, taken as a scavenger, inhibited the extract of Glycyrrhiza glabra (Rt), Panax gin- production of hydrogen peroxide in seng (Rt), Bupleurum falcatum (Rt), Scutel- chondrocytes induced by fulvic acid from laria baicalensis (Rt), Zingiber officinale (Rh), Kashin-Beck disease areaZO014. Pinellia ternata (Tu), and Zizyphus vulgaris Hypertensive activity. Ethanol (95%) ex- (Fr), in the diet of mice at a dose of 178 mg/ tract of the rhizome, administered intrave- kg, suppressed the mitogenic activity of phy- nously to dogs at a dose of 5 mL/animal and tohemagglutinin and phorbol myristate ac- a rate of 1 mL per minute, was activeZO314. etate. Water extract of Bupleurum falcatum Hyperthermic effect. Water extract of the (Rt), Scutellaria baicalensis (Rt), Zingiber rhizome, administered by gastric intubation officinale (Rh), Paeonia albiflora (Rt), Pinellia to mice at a dose of 4 g/kg, was inactive. The ternata (Tu), Zizyphus vulgaris (Fr), Rheum extract was used in combination with tanguticum (Rh), and Citrus aurantium (Fr), Glycyrrhiza glabra, Panax ginseng, Scutellaria in the diet of mice at a dose of 192.6 mg/kg, baicalensis, Zizyphus jujuba, Pinellia ternata, suppressed the mitogenic activity of phyto- Bupleurum fatcatum, Cinnamomum cassia, hemagglutinin and phorbol myristate acet- and Paeonia albifloraZO250. ateZO347. Hypoglycemic activity. Ethanol (50%) Immunostimulant activity. Hot water ex- extract of the aerial parts, administered by tract of the rhizome, administered intraperi- gastric intubation to rats at a dose of 45 mg/ toneally to mice at a dose of 2 mg/kg, was kg, was activeZO262. Ethanol (80%) extract of active. The extract was used in combination the rhizome, administered intragastrically to with Astragalus membranaceus, Atractylodes rabbits at a dose of 100 mg/kg, was act- lancea, Panax ginseng, Angelica acutiloba, iveZO292. Glycyrrhiza glabra, Bupleurum falcatum, Hypotensive activity. Methanol (50%) ex- Zizyphus vulgaris, Citrus unshiu, and Cimici- tract of the dried rhizome, administered fuga simplexZO196. Ethanol (80%) extract of the intravenously to rats at doses of 0.25 and 0.5 dried rhizome, administered intragastrically g/kg (dry weight of plant), was activeZO237. to male rats at a dose of 800 mg/kg, was active Hypothermic activity. Hot water extract vs sheep erythrocyte-induced hemaggluti- of a mixture of Pinellia ternata (Tu), Magno- nation and inactive vs sheep erythrocyte- lia obovata (Bk), Perilla frutescens (Aer), induced B- and T-cell proliferationZO105. Zingiber officinale (Rh), and Poria cocos (Fr) Insect growth inhibition. 6-Dehydro- (6, 3, 2, 1, and 5 g, respectively), adminis- shogaol isolated by steam distillation from 536 MEDICINAL PLANTS OF THE WORLD fresh rhizome exhibited moderate insect Lipid peroxide formation inhibition. Me- growth regulatory and antifeedant activity thylene chloride extract of the rhizome, at a against Spilosoma obliquaZO005. concentration of 0.02%, was activeZO130. Interferon-induction stimulation. Hot Lipolytic effect. Ethanol (95%) extract of water extract of the rhizome, at a concen- the rhizome, in the drinking water of obese tration of 6 Pg/mL, was active. A dose of 2 mice at a concentration of 5%, was active. g/kg, administered intragastrically to mouse, The extract was used in combination with was active, and 100 mg/kg, administered Hordeum vulgare, Rhizoma zingiberis, Ligusti- intraperitoneally to mice, was active vs cum chuanxiong, Lilium brownii, Nephelium polymyxin-B induced interferon secretion longa, and Polygonum multiflorumZO137. inhibition. The extract used was in com- Lymphocyte blastogenesis stimulant. bination with Bupleurum chinense, Pinellia Water extract of the heartwood, adminis- ternata, Scutellaria baicalensis, Zizyphus juju- tered intraperitoneally to mice at a dose of ba, Panax ginseng, and Glycyrrhiza glabraZO197. 250 mg/kg, induced an accumulation of B Decoction of Zingiber officinale (Rh), Bu- lymphocytes in the peritoneal cavity and pleurum falcatum (Rt), Scutellaria baicalensis spleen, and functional maturation of B cells (Rt), Pinellia ternata (Tu), Zizyphus jujuba was observed as indicated by antibody (Fr), Panax ginseng (Rt), and Glycyrrhiza responsesZO349. glabra (Rh), in cell culture at a concentra- Macrophage cytotoxicity enhancement. tion of 100 Pg/mL, was active. Peripheral Hot water extract of the rhizome, adminis- lymphocytes from eight patients with tered by gastric intubation to mice at a dose chronic active hepatitis, four with HbeAg of 600 mg/kg, was inactive on LEUK-L1210. and four with anti-Hbe were cultured. The preparation used also contained RHbeAg or HbeAg both stimulated inter- Bupleurum falcatum, Pinellia ternata, feron (IFN)-J production, which was Scutellaria baicalensis, Zizyphus jujuba, Panax enhancedZO108. ginseng, and Glycyrrhiza glabraZO268. Interleukin-1-D release inhibition. Hot Memory retention impairment. Acetone/ water extract of the rhizome, administered water extract of the rhizome, administered intragastrically to female mice at a dose of intragastrically to male rats at a dose of 1 mg/ 20 mg/mL, was active vs influenza virus in- kg, was inactive vs inhibitory avoidance fected animals. Results significant at p < conditioning and water maze perform- 0.001 levelZO099. anceZO094. Intestinal absorption inhibition. Metha- Memory retention improvement. Decoc- nol extract of the dried rhizome at a con- tion of the rhizome, administered intra- centration of 1% and water extract at a gastrically to male mice at a dose of 1 g/kg, concentration of 0.01%, administered by produced amelioration of memory registra- perfusion on the rat, were active vs absorp- tion impairment induced by ethanol in step tion of sulfaguanidineZO348. through and step down tests. The decoction Larvicidal activity. Water and acetone ex- was used in combination with Glycyrrhiza tracts of the rhizome were inactive on Aedes glabra (Rt), Saussurea lappa (Rt), Zizyphus aegyptiZO303. jujuba (Fr), Zizyphus jujuba (Sd), and Eupho- Leukocyte migration inhibition. Ethanol ria longana (Aril)ZO202. The powdered rhi- (80%) extract of the dried rhizome, admin- zome, administered intragastrically to rats, istered intragastrically to rats at a dose of increased passive avoidance test latency in 800 mg/kg, was active vs sheep erythrocyte- aged animals. The rhizome was used in com- induced leucocyte migrationZO105. bination with Pinellia ternata, Phyllostachys ZINGIBER OFFICINALE 537 nigra, Citrus aurantium, Poria cocos, Citrus mannerZO052. Water extract of the rhizome, unshiu, Glycyrrhiza glabra, Polygala tenui- on agar plate at a concentration of 100 mg/ folia, Scrophularia ningpoensis, Panax ginseng, mL, was inactive on Bacillus subtilis H- Rhemannia glutinosa, and Zizyphus jujubaZO350. 17(Rec+) and produced weak activity on Metabolism. Zingerone, 4-(4-hydroxy-3- Salmonella typhimurium TA100ZO244. The hot methoxyphenyl) butan-2-one, a pungent water extract, at a concentration of 12.5 mg principle of ginger, has been investigated in of dried rhizome/disc, was active on Salmo- rats. Oral or intraperitoneal dosage of 100 nella typhimurium TA100. A concentration mg/kg resulted in urinary excretion of most of 50 mg/disc was inactive on Salmonella metabolites within 24 hours, mainly as glu- typhimurium TA98. Histidine was removed curonide and/or sulphate conjugates. Al- from the extract before testing and meta- though zingerone itself accounted for bolic activation had no effect on the roughly 50–55% of the dose, reduction to resultsZO238. Methanol extract of the rhizome, the corresponding carbinol (11–13%) also on agar plate at a concentration of 100 mg/ occurred. Side chain oxidation took place mL, was inactive on Bacillus subtilis H- at all three available sites and oxidation at 17(Rec+)ZO244. Ethanol (70%) extract of the the three-position, giving rise to C6-C2 me- rhizome, on agar plate at a concentration of tabolites, predominated. Appreciable biliary 4 mg/mL, was inactive on Escherichia coli excretion occurred (40% in 12 hours). Bil- PQ37 when assayed by SOS Chromotest, iary studies and studies in vitro using cecal and inactive on Salmonella typhimurium microorganisms indicated that several O- TA1535 when assayed by SOS UMU demethylated metabolites found in the testZO207. Ethanol (95%) extract of the rhi- urine are of bacterial originZO062. zome, on agar plate at a concentration of Mitogenic activity. Alcohol insoluble frac- 100 Pg/plate, was active on Salmonella tion and the water extract of rhizome, at a typhimurium TA100 and TA1535, and inac- concentration of 200 Pg/mL, were inactive tive on TA98 and TA1538ZO278. Ethanol on the mouse thymus. The alcohol soluble (95%) extract of the dried rhizome, on agar fraction, at a concentration of 100 Pg/mL, plate at a concentration of 10 mg/plate, pro- was activeZO166. duced strong activity on Salmonella typhimu- Molluscicidal activity. Methanol extract rium TA102ZO327. Ethanol (70%), and water of the dried rhizome, at a concentration of and chloroform extracts of the ethanol ex- 100 ppm, produced 20% mortality on tract of the dried rhizome, on agar plate at a Bulinus globosusZO351. concentration of 50 mg/mL, were inactive Mutagenic activity. Ginger extract and the on Escherichia coli PQ 37. Metabolic activa- constituents gingerol, shogaol, and zingerone tion had no effect on the resultsZO352. Hot were tested in Salmonella typhimurium strains water extract of the dried rhizome, on agar TA100, TA98, TA1535, and TA1538 in the plate at a concentration of 50 mg/disc, was presence of S9 mix. Gingerol and shogaol inactive on Salmonella typhimurium TA100 were mutagenic in metabolic activation in and TA98ZO326. strains TA100 and TA1535. Zingerone was Natural-killer cell enhancement. Polysac- nonmutagenic in all of the four strains with charide fraction of the rhizome, adminis- or without S9 mix. When the mutagenicity tered intragastrically to female mice at a of gingerol and shogaol was tested in the dose of 1 g/kg, produced weak activity vs presence of different concentrations of mononuclear cell incubated with YAC-1 zingerone, it was observed that zingerone cellsZO092. suppressed the mutagenic activity in both Nausea inhibitory effect. Women with of the compounds in a dose-dependent nausea and vomiting during pregnancy were 538 MEDICINAL PLANTS OF THE WORLD treated within a randomized double-masked intybus, Mentha arvensis, Commiphora design to receive either 1 g of ginger per day mukul, and Sesamum indicum given in di- or an identical placebo for 4 days. During vided doses of 4.6 g in 24 hours. Six g of a the 5-month period, 70 women partici- decoction of Lavandula stoechas was also pated. They were graded by the severity of given in some cases. Seventy-six percent of their nausea using visual analog scales and the patients were cured, 16% showed a par- recording the number of vomiting episodes tial response, and 8% did not show any in the previous 24 hours before treatment improvementZO263. and again during 4 consecutive days while Pancreatic effect. Ginger (50 mg%), ad- taking the treatment. The visual analog ministered orally to rats, significantly scores of posttherapy minus baseline nausea enhanced pancreatic lipase activity and sig- decreased significantly in the ginger group nificantly stimulated trypsin and chymot- (2.1 compared with 0.9, p = 0.14). The rypsin. The stimulatory influence was not number of vomiting episodes also decreased observed when the treatment was restricted ZO018 significantly in the ginger group (1.4) com- to a single dose . pared with the placebo group (0.3, p < Passive cutaneous anaphylaxis inhibi- 0.001). Likert scales showed that 28 of 32 in tion. Acetone extract of the dried rhizome, the ginger group had improvement in nau- administered intragastrically to rats at a dose of 200 mg/kg, was active vs IgE-sensitized sea symptoms compared with 10 of 35 in the animalsZO353. placebo group (p < 0.001). No adverse ef- Pepsin inhibition. Water extract of the rhi- fect of ginger on pregnancy outcome was zome, administered by gastric intubation to detectedZO008. rabbits at a dose of 125 mg/kg, was active. Decoction of the Nematocidal activity. Results significant at p < 0.05 level. The rhizome, at a concentration of 10 mg/mL, ZO200 extract also contained Pinellia ternata (Rh), was inactive on Toxocara canis . Water Atractylis species (Rh), Citrus aurantium extract of the rhizome, in cell culture at a (Pl), Pachyma hoelen fruit body, Panax gin- concentration of 10 mg/mL was inactive on seng (Rt), Glycyrrhiza glabra (Rt), Zingiber Toxacara canis. The methanol extract at a officinale (Rh), and Zizyphus jujuba (Fr)ZO258. ZO157 concentration of 1 mg/mL was active . Phagocytosis activity. Ethanol (80%) ex- Nerve growth factor stimulation. Pow- tract of the rhizome, in cell culture at a con- dered rhizome, administered intragastrically centration of 500 Pg/mL, did not decrease to rats, was active on the brain. A Kampo the rate of activity on mouse spleen lympho- medicine “Kami-Untan-To,” with Pinellia cytes (DBA/2)ZO292. ternata, Phykllostachys nigra, Citrus aurantium, Pharmacokinetics. [6]-Gingerol, the pun- Poria cocos, Citrus unshiu, Glycyrrhiza glabra, gent constituent of ginger, was studied after Polygala tenuifolia, Scrophularia ningpoensis, bolus intravenous injection at a dose of 3 Panax ginseng, Rhemannia glutinosa, Zizyphus mg/kg to rats. Quantitative analysis with jujuba, and Zingiber officinale was usedZO350. high reproducibility was achieved over the Neuromuscular blocking activity. Decoc- concentration range of 0.2–40 Pg/mL. A tion of the dried rhizome, taken orally by two-compartment open model described the human adults of both sexes at a dose of 4.6 plasma concentration-time curve. [6]- g/person, was active on 25 patients with Gingerol was rapidly cleared from plasma spastic facial paralysis. The patients were with a terminal half-life of 7.23 minutes and treated with a mixture of Piper longum, a total body clearance of 16.8 mL/minutes/ Zingiber officinale, Piper cubeba, Curcuma kg. Serum protein binding of [6]-gingerol zedoaria, Juniperus communis, Cichorium was 92.4%ZO038. ZINGIBER OFFICINALE 539

Phosphodiesterase inhibition. Hot water inhibited platelet aggregation induced by extract of the rhizome, at a concentration several aggregation agents, including ara- of 1 mg/mL, was inactiveZO163. chidonate, in a dose-dependent manner. It Plaque formation suppressant. Water inhibited the platelet cyclooxygenase prod- extract of the rhizome was inactive on Strep- ucts, and this effect correlated well with its tococcus mutans. The methanol and metha- inhibitory effects on platelet aggregation nol/water extracts were active; IC50 were induced by the agents. The effects were greater than 1000, 60, and 230 Pg/mL, dose-dependent. Although it inhibited the respectivelyZO272. biosynthesis of 6-keto-F1-D in rat aortic Platelet aggregation inhibition. Gingerol rings from labeled arachidonate, it did not was evaluated for its ability to inhibit hu- reduce prostacyclin production from endo- man platelet activation, as compared to genous arachidonate pool in aortic rings. aspirin, by measuring the effect on arachi- The extract was further extracted into three donic acid-induced platelet serotonin organic solvents in order of increasing release and aggregation in vitro. The IC50 for polarity (N-hexane, chloroform, and ethyl arachidonic acid-induced (at EC50 was 0.75 acetate). An analysis of the N-hexane ex- mM) serotonin release by aspirin was 23.4 tract revealed at least three clearly separated PM. Gingerol inhibited the arachidonic TLC bands containing constituents that acid-induced platelet reaction in a similar inhibited platelet thromboxane generation dose range as aspirin, with IC50 values be- simultaneously increasing lipoxygenase tween 45.3 and 82.6 PM. The analogues productsZO061. Chloroform, N-hexane, and (G1-G7), were also effective inhibitors of ethyl acetate extracts of the rhizome re- arachidonic acid-induced platelet aggrega- duced platelet thromboxane formation from tion. Maximum inhibitory values of 10.5 exogenous arachidonate and inhibited and 10.4 PM for G3 and G4, respectively, platelet aggregation induced by arachi- were approximately twofold greater than as- donate, epinephrine, ADP, and collagen. pirin (ICmax 6 PM). The other analogues The aqueous extract reduced the formation maximally inhibited arachidonic acid-in- of thromboxane from arachidonate-labeled duced platelet aggregation at approx 20–25 platelets without showing effects on plate- PMZO002. Aqueous extract of ginger was let phospholipase activity. Thromboxane found to inhibit aggregation induced by formation in labeled platelets on activation ADP, epinephrine, collagen, and arachi- with calcium ionophore A23187 was re- donate in a dose-dependent manner in duced by ginger components isolated from 2 vitro. A correlation was found between the TLC bands, in a dose-dependent manner. amounts of ginger extract needed to inhibit At the higher dose, lipoxygenase products platelet aggregation and those to inhibit were also reduced. The incorporation of platelet thromboxane synthesis. The extract arachidonate into platelet phospholipids reduced platelet prostaglandin-endoperox- increased in platelets treated with aqueous ides. A dose-related inhibition of platelet ginger extractZO053. [6]-Shogaol, extracted thromboxane and prostaglandin (PGF2-D, from semidried ginger inhibited carrag-

PGE2 and PGD2) synthesis was affected by eenan-induced swelling of the hind paw in ginger extract. The extract inhibited bio- rats and arachidonic acid-induced platelet synthesis of prostacyclin in rat aorta from aggregation in rabbits; it prevented PGI 2 labeled arachidonate. It mildly inhibited the release from the aorta of rats when tested as synthesis of prostacyclin from endogenous an inhibitor of platelet aggregation. The re- pool of AA in the rat aortaZO060. The extract sults indicated that shogaol might have an 540 MEDICINAL PLANTS OF THE WORLD inhibitory action on cyclo-oxygenase in duced weak activity on the rabbit micro- both platelets and aorta. Investigation of somesZO251. Decoction of the dried rhizome, the effects of shogaol on cyclo-oxygenases administered intraperitoneally to rats at a in rabbit platelets and microsome fractions dose of 0.74 g/animal, was inactive. Serum of rat aorta indicated that shogaol inhibited from rats fed the decoction was added to cyclo-oxygenase activities of both tissues in sheep vesicular gland microsomal fraction a concentration-dependent manner. The and the proportion of PGH2 in arachidonic effect of shogaol on 5-lipoxygenase from acid metabolites measured. The system was RBL-1 cells indicated that shogaol produced not affected by rat serum lipidsZO315. an inhibitory action on 5-lipoxygenase Proteolytic activity. Hot water extract of activityZO055. Dried ginger was investigated in the rhizome, at a concentration of 1 mg/mL, eight healthy male volunteers in a random- was inactiveZO235. ized double-blind study of the effects of 2 g Prothrombin time decrease. Hot water dried ginger or placebo capsules. Bleeding extract of the rhizome, administered time, platelet count, thromboelastography, intragastrically to mice for 1 month, was and whole blood platelet aggregometry were active. The extract was used in combination performed 3 hours and 24 hours after the with 7 g Bupleurum falcatum, 5 g Pinellia treatment. There were no differences be- ternata, 3 g Scutellaria baicalensis, 2 g Gly- tween ginger and placebo in any of the vari- cyrrhiza glabra, 1 g Zingiber officinale, 3 g ables measured. The effect of ginger on Panax ginseng, and 3 g Zizyphus jujuba in 700 thromboxane synthetase activity is dose de- mL waterZO185. pendent, or only occurs with fresh ginger, Renal function improvement. Decoction and that up to 2 g of dried ginger is unlikely of the dried rhizome, taken orally by 15 pa- to cause platelet dysfunction when used tients with chronic renal failure resulting therapeuticallyZO032. Dried ginger, adminis- from chronic glomerulonephritis, polycystic tered orally in two doses of 2.5 g each to disease, tuberculosis, or diabetes, at variable male volunteers who consumed 100 g of but- dosage levels, was active. The patients were ter in 7 days, significantly (p < 0.001) in- dosed three times daily for 3 months with a hibited the platelet aggregation induced by combination of Zingiber officinale and Panax ADP and epinephrine. Serum lipids, how- ginseng. Improvements were seen in blood ever, remained unchanged in both ginger urea nitrogen, edema, fatigue, nausea, and treated and control groupsZO034. Powdered constipation without effect on hematocrit rhizome, administered orally to human or albumin. The effect decreased after 6 adults at a dose of 5 g/person, was active vs monthsZO316. ADP- and epinephrine-induced aggrega- Respiratory stimulant effects. Ethanol tionsZO162. The rhizome, taken orally by hu- (95%) extract of the rhizome, administered man adults at a dose of 2 g/person, was intravenously to dogs at a dose of 3 mL/ani- inactiveZO032. Water extract of the dried rhi- mal, was activeZO314. zome, at a concentration of 5 mg/mL, was Reverse transcriptase activity. Water ex- active vs arachidonic acid-, collagen-, and tract of Zingiber officinale (Rh), Bupleurum ADP-induced aggregationZO322. falcatum, Scutellaria baicalensis (Rt), Pinellia PG inhibition. Ethanol (80%) extract of ternata (Tu), Zizyphus jujuba (Fr), Panax gin- the rhizome, in cell culture at a concentra- seng (Rt), and Glycyrrhiza glabra (Rh), at a tion of 100 Pg/mL, was active on concentration of 200 Pg/mL, was active on leukocytesZO292. Hot water extract of the rhi- Moloney murine leukemia virus and zome, at a concentration of 750 Pg/mL, pro- HIVZO203. ZINGIBER OFFICINALE 541

Reverse transcriptase inhibition. Decoc- apparent dissociation constants of 0.1 and tion of the rhizome, in cell culture, was ac- 0.68 PM, 3 and 35 PM, and 1 and 15 mM, tive on Rauscher murine leukemia virus. respectively. After seven 30-second applica- The study was conducted with a prescrip- tions of 1 PM capsaicin or 100 PM piperine tion consisted of Bupleurum falcatum (Rt), (in a buffer with 2 mM Ca2+), each inter- Scutellaria baicalensis (Rt), Pinellia ternata spersed with 2-minute 50-second washes, (Tu), Zizyphus jujuba (Fr), Panax ginseng the peak currents were inhibited by approx (Rt), and Glycyrrhiza glabra (Rh)ZO203. 60 and 40%, respectively. In contrast, 30 Serotonin antagonist activity. Acetone mM zingerone failed to evoke a current extract of the rhizome, at a concentra- after six applications. After complete tac- tion of 25 Pg/mL, was active on the guinea hyphylaxis produced by 30 mM zingerone, pig ileum vs serotonin-induced contract- 1 PM capsaicin failed to evoke a current, ionsZO186. suggesting that these two compounds cross- Smooth muscle relaxant activity. The es- desensitize. The physiological responses sential oil was active on the guinea pig tra- produced by these compounds can be ratio- chea and ileum, ED50 171 and 36 mg/L, nalized, in part, by their different activation respectivelyZO270. and sensitization kinetics, and perhaps by Superoxide dismutase stimulation. Etha- the existence of different subtypes of vanil- nol (95%) extract of the fresh aerial parts, loid receptorsZO026. administered intraperitoneally to mice at a Taste-modifying effect. Water extract of dose of 0.5 g/kg, was inactiveZO164. the dried rhizome, administered intragastri- Tachyphylactic activity. Zingerone, a cally to male rats at a dose of 50 mg/mL, in- natural pungent-tasting compound in gin- creased activity of vagal gastric nerve. The ger, was evaluated by whole cell patch- extract also blocked the suppression of vagal clamp studies performed on rat trigeminal gastric nerve activity induced by Pinellia ganglion. The inward currents activated by ternataZO317. zingerone (30 mM) had peak times of Teratogenic effect. A patented extract of approx 2 seconds, and all currents exhibited garlic, administered by gavage to 22 preg- marked desensitization. Capsaicin (1 PM) nant rats at concentrations of 100, 333, and activated a variety of inward currents hav- 1000 mg/kg from days 6 to 15 of gestation, ing peak times ranging from 2 to 46 seconds produced no maternal or developmental that desensitized to various extents rang- toxicity. The rats were sacrificed on day 21 ing from 0 to 100%. The inward currents of gestation and examined for standard activated by piperine (100 PM) had peak parameters of reproductive performance. times of approx 25 seconds, and all exhib- The fetuses were examined for signs of ited a small desensitization. Piperine- and teratogenic and toxic effects. No deaths or zingerone-induced currents were found only treatment related adverse effects were in cells that could be activated by capsaicin. observedZO009. Ginger tea, administered to Capsazepine (10 PM), an established an- Sprague–Dawley rats from gestation day 6– tagonist of capsaicin-induced currents, in- 15 at a dose of 20 or 50 g/L and then sacri- hibited the current evoked by piperine and ficed at day 20, produced no maternal zingerone, suggesting that all three com- toxicity. However, embryonic loss in the pounds activate vanilloid receptors. Dose- treatment groups was two times that of con- response relationships for capsaicin, trols (p < 0.05). No gross morphological piperine, and zingerone obtained at a hold- malformations were seen in the treated ing potential of 60 mV had threshold and fetuses. Fetuses exposed to the ginger tea 542 MEDICINAL PLANTS OF THE WORLD were significantly heavier than controls, an patients had made good improvement in the effect that was greater in female fetuses and arms but very little in the legs. Four of the was not correlated with increased placental patients were unable to stand or walkZO320. size. Treated fetuses also had more advanced Toxicity assessment. Ethanol (50%) ex- skeletal development as determined by mea- tract of the aerial parts, administered intra- surement or sternal and metacarpal ossifica- peritoneally to mice, produced LD50 178 mg/ tion centersZO011. kgZO262. Thermogenic activity. Chloroform extract Toxicity assessment. Ethanol (90%) ex- of the dried rhizome, at concentrations of 5 tract of the dried rhizome, administered and 50 Pg/mL administered by perfusion to intraperitoneally to mice, produced LD50 of the hind limb of rats, stimulated oxygen 1 g/kgZO318. uptakeZO128. Toxicological evaluation. The effect of Thromboxane A2 inhibition. Rhizome, a patented standardized ginger extract, taken orally by human adults at a dose of EV.EXT 33, was studied in rats. The extract 70 g/person for 7 days, was activeZO188. had no significant effect on blood glucose Thromboxane effect. The effect of raw gin- levels at the doses used. It also had no sig- ger, taken orally by women at a dose of 5 g nificant effects on coagulation parameters daily for 7 days, was investigated. Throm- or on warfarin-induced changes in blood boxane determination was made in serum coagulation, indicating that it did not in- obtained after blood clotting. The values teract with warfarin. It did not decrease sys- obtained were 782 r 482 pmol/mL serum tolic blood pressure or increase heart rate in before ginger consumption and after con- the ratZO012. sumption 498 r 164 pmol/mLZO048. Tryptophan pyrrolase stimulation. Hot Thromboxane synthetase inhibition. Gin- water extract of 7 g Bupleurum falcatum, 5 g ger has been found to act as a potent inhibi- Pinellai ternata, 3 g Scutellaria baicalensis, 4 g tor of thromboxane synthetase, raising Zingiber officinale, 3 g Panax ginseng, 3 g Zizyphus levels of prostacyclin, without a concomi- inermis, and 2 g Glycyrrhiza glabra, adminis- tant rise in PGE2 or PGF2-DZO057. tered intraperitoneally to rats at a dose of Toxic effect. Decoctions of dried and 200 mg/kg, suppressed decrease in hepatic roasted ginger were investigated on four ex- tryptophan pyrrolase resulting from D-galac- perimental gastric ulcer models. The acute tosamine-induced liver injuryZO282. toxicity test has shown that the LD50 of the Tumor necrosis factor inhibition. Ethanol roasted ginger decoction administered orally (95%) extract of the rhizome, in cell cul- was 170.6 r 1.1 g/kg and the LD50 of the ture at a concentration of 100 Pg/mL, was dried ginger decoction was over 250 g/ inactive on macrophage cell line RAW kgZO042. Ethanol (80%) extract of the rhi- 264.7 vs LPS induction of TNF-DZO171. zome, administered intragastrically to mice Tumor promotion inhibition. Ethyl ac- at a dose of 3 g/kg, was activeZO292. Ether ex- etate and methanol extracts of the dried rhi- tract of the rhizome adulterated with phe- zome, in cell culture at a concentration of nol ester-triorthocresyl phosphate produced 50 Pg/mL, produced weak activity on C3H/ paralysis in human adults who ingested 1– 10T1/2 cells vs tetradecanoyl phorbol ac- 20 ounces of the extract. The symptoms etate-induced acetate phospholipid synthe- appeared 4–35 days after the ingestion. Four sis. The hexane extract was inactiveZO095. to 6 years after the onset of the paralysis, Ethanol (95%) and petroleum ether ex- only three of the patients had recovered tracts of the dried rhizome, in cell culture at enough to walk without support. Most of the a concentration of 160 and 80 Pg/mL, re- ZINGIBER OFFICINALE 543 spectively, produced weak activity on Raji on norepinephrine and PGF2-D-induced cells vs 12-O-tetradecanoylphorbol-13- contraction using mouse mesenteric veins. acetate-induced EBV-EA activation. The Both constituents inhibited the contractile methyl chloride extract, at a concentration responses to norepinephrine. The crude of 40 Pg/mL, was activeZO319. extract and S-(+)-[6]-gingerol potentiated Tumor promotion inhibition. Methanol the PGF2-D-induced contraction, whereas extract of the fresh aerial parts, in cell cul- processed ginger extract and [6]-shogaol ture at a concentration of 200 Pg, was active inhibited the contractionZO047. on EBV vs 12-O-hexadecanoylphorbol-13- WBC stimulant. Decoction of Zingiber acetate-induced virus activationZO286. officinale (Rh), Bupleurum falcatum, Scutel- Turgal stimulant activity. Hot water ex- laria baicalensis (Rt), Pinellia ternata (Tu), tract of 7 g Bupleurum falcatum, 5 g Pinellai Zizyphus jujuba (Fr), Panax ginseng (Rt), and ternata, 3 g Scutellaria baicalensis, 4 g Zingiber Glycyrrhiza glabra (Rh), in cell culture at a officinale, 3 g Panax ginseng, 3 g Zizyphus concentration of 20 Pg/mL, produced an inermis, and 2 g Glycyrrhiza glabra, adminis- average enhanced response of 40%. Re- tered intraperitoneally to rats at a dose of sponse was enhanced 34% when pokeweed 200 mg/kg, decreased the volume of exudate mitogen-induced peripheral mononuclear in carrageenan-induced pleurisyZO282. cell proliferation was assayed. The treat- Urease inhibition. Water extract of the ment was inactive vs enhancement of rhizome, at a concentration of 0.3 mg/mL, phytohemagglutinin-induced peripheral was inactiveZO167. mononuclear cell proliferation, enhance- Vasoconstrictive effect. Gingerols were ment of Con A-induced peripheral mono- evaluated on the isolated mouse and rat nuclear cell proliferation, leukocytes obtained blood vessels. Leukotrienes C4 and D4, a from patients with AIDS, Con A-induced thromboxane A2, PGF2-D, PGI2-Na, proliferation in leukocytes obtained from PGE2, the stable PGI2 derivative TRK-100, patients with AIDS, phytohemagglutinin- and PGD2, induced contraction in longitu- induced proliferation in leukocytes obtained dinal segments of mouse mesenteric veins in from patients with AIDS, and 23% in- that order of potency. Exogenous arachi- creased vs pokeweed mitogen-induced pro- donic acid did not cause contraction. The liferation in leukocytes obtained from mesenteric veins also contracted in response patients with AIDSZO320. to norepinephrine and phenylephrine but Weight-gain inhibition. Ethanol (95%) not to clonidine. The gingerols alone re- extract of the rhizome, in the drinking wa- laxed the muscle transiently and then aug- ter of obese (C57BL/6J) mice, was active. mented response to prostaglandin F2-D, The extract was used in combination with prostaglandin E2, prostaglandin I2-Na, and Hordeum vulgare, Zingiberis rhizoma, Ligisti- TRK-100, but suppressed the response to cum chuanxiong, Lilium brownii, Nephelium ZO137 prostaglandin D2. [6]-gingerols also poten- longa, and Polygonum multiflorum . tiated the PGF2-D-induced contraction in REFERENCES longitudinal segments of the rat mesenteric ZO001 Satoh, K., Y. Kase, T. Hayakawa, P. vein and vena cava, but inhibited it in cir- Murata, A. Ishige, and H. Sasaki. Dai- cular segments of rat aorta and longitudinal kenchu-to enhances accelerated small segments of the mouse mesenteric intestinal movement. Biol Pharm Bull 2001; 24(10): 1122–1126. ZO046 arteries . Crude and processed ginger ex- ZO002 Koo, K. L., A. J. Ammit, V. H. 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ZO255 Sircar, N. N. Pharmaco-therapeutics of ZO267 Kim, J. S., G. H. Kim, and I. H. Kim. Dasemani drugs. Ancient Sci Life Studies on the concurrent administra- 1984; 3(3): 132–135. tions of sosiho-tang extract and me- ZO256 Jain, S. P., and H. S. Puri. Ethnomedical thionine. Effects on the liver lesion plants of Jaunsar-Bawar Hills, Uttar induced by carbon tetrachloride in Pradesh, India. J Ethnopharmacol rats. Korean J Pharmacog 1986; 17(2): 1984; 12(2): 213–222. 148–152. ZO257 May, G., and G. Willuhn. Antiviral ZO268 Ito, H., and K. Shimura. Effects of a activity of aqueous extracts from me- blended Chinese medicine, xiao-chai- dicinal plants in tissue cultures. Arz- hu-tang, on Lewis lung carcinoma neim-Forsch 1978; 28(1): 1–7. growth and inhibition of lung metasta- ZO258 Chang, I. K., and S. I. L. Park. Effects sis, with special reference to macro- of Yukgunja-tang on secretion of gas- phage activation. Jap J Pharmacol tric juice and movements of isolated 1986; 41: 307–314. stomach. Korean J Pharmacog 1984; ZO269 Chen, C. C., R. T. Rosen, and C. T. 15(3): 128–133. Ho. Chromatographic analyses of iso- ZO259 Shimizu, K., S. Amagaya, and Y. meric shogaol compounds derived from Ogihara. Combination effects of isolated gingerol compounds of ginger shosaikoto (Chinese traditional medi- (Zingiber officinale Roscoe). J Chroma- cine) and prednisolone on the anti-in- togr 1986; 360: 175–184. flammatory action. J Pharmacobio ZO270 Reiter, M., and W. Brandt. Relaxant Dyn 1984; 9(1): 105–127. effects on tracheal and ileal smooth ZO260 Hedberg, I., O. Hedbrg, P. J. Madati, muscles of the guinea pig. Arzneim- K. E. Mshigeni, E. N. Mshiu, and G. Forsch 1985; 35(1): 408–414. Samuelsson. Inventory of plants used ZO271 Chen. C. C., R. T. Rosen, and C. T. in traditional medicine in Tanzania. II. Ho. Chromatographic analyses of Plants of the families Dilleniaceae- gingerol compounds in ginger (Zingiber Opiliaceae. J Ethnopharmacol 1983; officinale Roscoe). J Chromatogr 1986; 9(1): 105–127. 360: 163–173. ZO261 Velazco, E. A. Herbal and traditional ZO272 Namba, T., M. Tsunezuka, D. M. R. B. practices related to maternal and child Dissanayake, et al. Studies on dental health care. Rural Reconstruction caries prevention by traditional medi- Review 1980; 35–39. cines (part VII) screening of ayurvedic ZO262 Aswal, B. S., D. S. Bhakuni, A. K. Goel, medicines for anti-plaque action. K. Kar, B. N. Mehrotra, and K. C. Shoyakugaku Zasshi 1985; 39(2): Mukherjee. Screening of Indian plants 146–153. for biological activity, part X. Indian J ZO273 Kada, T., K. Morita, and T. Inoue. Exp Biol 1984; 22(6): 312–332. Anti-mutagenic action of vegetable ZO263 Siddiqui, N. A., and M. Z. Hasan. factor(s) on the mutagenic principle of Therapeutic response of Arab medi- tryptophan pyrolysate. Mutat Res cines in cases of Laquwa. Bull Islamic 1978; 53: 351–353. Med 1981; 1: 366–374. ZO274 Dean, M. A., A. S. Dhaliwal, and W. ZO264 Woo, W. S., E. B. Lee, K. H. Shin, S. R. Jones. Effects of Zingiberaceae rhi- S. Kang, and H. J. Chi. A review of re- zome extract of the infectivity of search on plants for fertility regulation cyanophage LPP-1. Trans Ill State in Korea. Korean J Pharmacog 1981; Acad Sci Suppl 1987; 80: Abstr 83. 12(3): 153–170. ZO275 Morita, K., M. Hara, and T. Kada. ZO265 Shin, K. H., and W. S. Woo. A survey Studies on natural desmutagens: of the response of medicinal plants on screening for vegetable and fruits fac- drug metabolism. Korean J Pharmacog tors active in inactivation of mu- 1980; 11: 109–122. tagenic pyrolysis products from amino ZO266 Singh, Y. N. Traditional medicine in acids. Agr Biol Chem 1978; 42(6): Fiji: Some herbal folk cures used by Fiji 1235–1238. Indians. J Ethnopharmacol 1986; ZO276 Yamaguchi, T., Y. Yamashita, and T. 15(1): 57–88. Abe. Desmutagenic activity of peroxi- ZINGIBER OFFICINALE 557

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Glossary

Abdominal. Pertaining to the part of trunk ing together in suspension of antigen-bear- that lies between the thorax and the pelvis. ing cells, microorganisms, or particles in Abortifacient. An agent that induces the the presence of specific antibodies (aggluti- premature expulsion of a fetus. nins). Abortion. Giving birth to an embryo or Agrobacterium tumefaciens. A species of fetus prior to the stage of viability. bacteria of the family Rhizobiaceae. It is a Abscess. A circumscribed collection of pus; small, Gram-negative, aerobic, flagellated a cavity formed by liquefaction necrosis rod that is found in the soil or in the roots within the solid tissue. or stems of plants. Most species produce hy- Aconitine. A poisonous drug from the dried pertrophies (galls) in plant stems. tuberous root of Aconitum napellus. It was Ailment. Any disease or affection of the once given internally as a febrifuge and gas- body; usually refers to slight or mild disorder. tric anesthetic. Aleurone. The outermost layer of the en- Ad libitum. At pleasure. dosperm. Adenocarcinoma. Carcinoma derived D-Tocopherol. Vitamin E. from glandular tissue or in which the tumor Alkaloid. A large, varied group of complex cells form recognizable glandular structures; nitrogen-containing compounds, usually may be classified according to the predomi- alkaline, that reacts with acids to form nant pattern of cell arrangement, as papil- soluble salts, many of which have physi- lary, alveolar, etc., or according to a ological effect on humans, e.g., nicotine particular products of the cells, as mucinous and, caffeine, etc. adenocarcinoma. Allergen. A compound that produces an Adenoma. A benign epithelial tumor in allergic reaction. which the cells form recognizable glandular Allergy. A state of hypersensitivity induced structures or in which the cells are clearly by exposure to a particular antigen (aller- derived from glandular epithelium. gen) resulting in harmful immunological Adrenalectomize. To excise one or both reactions on subsequent exposures. adrenal glands. Alopecia. Baldness; absence of the hair Agglutination. Clumping; the process of from skin in areas where it normally is union in the healing of a wound; the clump- present.

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 561 562 MEDICINAL PLANTS OF THE WORLD

Amastigote. Any of the bodies represent- Anthelmintic. Vermifuge; an agent that ing the morphologic (leishmanial) stage in destroys and expels worms from the intes- the life cycle of all trypanosomatic protozoa tine. resembling the typical adult form of mem- Anti-acne. Preventing the inflammatory bers of the genus Leishmania. disease of the pilosebaceous unit. Amenorrhea. Absence or abnormal stop- Anti-amoebic. Destroying or suppressing page of menstruation. the growth of amoebae. Analgesic. An agent that relieves pain Anti-ancylostomiasis. Preventing the in- without causing loss of consciousness. fection with hookworms of the genus Anaphrodisiac Antiaphrodisiac; an agent Ancyclostoma. suppressing sexual desire. Anti-atherogenic. Preventing the forma- Anaphylactic. Related to anaphylaxis; tion of atheromatous lesions in the arterial manifesting extremely great sensitivity to intima. foreign protein or other material. Anti-atherosclerotic. Preventing the for- Ancylostomiasis. Infection with hook- mation of plaques containing cholesterol, worms of the genus Ancyclostoma. lipoid material, and lipophages within the Androgenetic alopecia. A progressive, intima and inner media of large- and me- diffuse, symmetric loss of scalp hair in dium-sized arteries. the 20s and early 30s with hair loss from the Antibacterial. Destroys or stops the growth vertex and frontoparietal regions. In females of bacteria. beginning somewhat later, with less severe Antibody. Sensitize; substance evoked in hair loss in the frontocentral area of the humans or animals by an antigen, and char- scalp. acterized by reacting specifically with the Anemia. A reduction below normal in the antigen in some demonstrable way. number of erythrocytes per cu mm, in the Anticarcinogen. An agent to counteract quantity of hemoglobin, or in the volume of cancer. the packed red cells per 100 mL of blood, Anticathartic. An agent that prevents which occurs when equilibrium between evacuation of the bowels. blood loss and blood production is dis- Anticholesterolemic. Promoting a reduc- turbed. tion in cholesterol levels in the blood. Anesthetic. An agent that is used to abol- Anticlastogenic. Preventing disruption or ish the sensation of pain. breakage, as of chromosomes. Angina. Spasmodic, choking, or suffocative Anticonvulsant. An agent that prevents or pain. relieves convulsions or cramps. Angioedema. A vascular reaction involv- Anticrustacean. Antiparasitical; an agent ing the deep dermis, subcutaneous, or sub- that prevents parasite infections or diseases mucosal tissues, representing localized caused by parasites. edema caused by dilatation and increased Antidiabetic. An agent that prevents or permeability of the capillaries, and charac- alleviates diabetes. terized by development of giant wheals. Antidiarrheal. An agent to relieve diar- Angiotensin. Any of a family of polypeptide rhea. vasopressor hormones formed by the cata- Antidysrrhythmic. Preventing arrhythmia. lytic action of rennin on rennin substrate. Anti-emetic. Prevents or alleviates nausea Anodyne. A medicine that relieves pain and vomiting. through reducing nerve excitability, milder Anti-epileptic. An agent that combats the than analgesic. convulsions or seizures of epilepsy. GLOSSARY 563

Antifebrile. Antipyretic. Antimycobacterial. An agent that is effec- Antifungal. An agent that inhibits the tive against Mycobacteria; a genus of bacte- growth or multiplication of fungi, or kills ria occurring as Gram-positive, aerobic, them outright. mostly slow-growing, slightly curved or Antigalactogogue. Prevents or decreases straight rods, sometimes branching and fila- secretion of milk. mentous, and distinguished by acid-fast Antigen. Any substance that, under appro- staining. It contains many species, includ- priate conditions, induces a specific immune ing the highly pathogenic that cause tuber- response and reacts with the products of culosis or leprosy. that response. Anti-nematodal. An agent that is effective Antiglaucomic. Preventing the eye diseases against nematode (roundworm); a class of characterized by an increase in intraocular tapered cylindrical helminthes, many spe- pressure, which causes pathological changes cies of which are parasites. in the optic disk and typical defects in the Anti-nociceptive. Having an analgesic ef- field of vision (glaucoma). fect; reducing sensitivity to painful stimuli. Antihalitosis. An agent that prevents of- Antioxidant. An agent that prevents or de- fensive breath. lays deterioration by the action of oxygen. Antihemolytic. Preventing hemolysis. Antioxytocic. An agent that prevents uter- Antihistaminic. Neutralizing the effect or ine contractions during childbirth. inhibiting production of histamine. Antiparasitical. Destructive to parasites. Antihypercholesterolemic. Effective in Antiphlogistic. An agent that counteracts decreasing or preventing an excessively inflammation and fever. high level of cholesterol in the blood. Antiprogesterone. An agent that reduces Antihyperglycemic. An agent that coun- the progesterone level. teracts high levels of glucose in the blood. Antiproteinemic. An agent that reduces an Antihyperlipemic. An agent that prevents excess of protein in the blood. an elevated concentration of triglycerides in Antiprotozoan. Antiprotozoal; destroying the blood; reduces arterial plaques. protozoa, or checking their growth or repro- Antihypertensive. An agent that reduces duction. abnormally high blood pressure. Antipyretic. An agent to reduce fever; feb- Anti-implantation. Preventing the attach- rifuge. ment of the blastocyst to the epithelial lin- Antiradiation. An agent capable of coun- ing of the uterus, its penetration through the teracting the effects of radiation; effective epithelium, and in humans, its embedding in against radiation injury. the compact layer of the endometrium, be- Antirheumatic. An agent that relieves or ginning 6 or 7 days after fertilization. cures rheumatism. Anti-inflammatory. An agent that reduces Antischistosomal. Effective against a genus or neutralizes inflammation. of trematode parasites or flukes (schisto- Antimicrobial. An agent that inhibits the somes). growth or multiplication of micro-organ- Antisecretory. Inhibiting or diminishing isms, or kills them. gastric secretion. Antimitogenic. An agent that prevents mi- Antiseptic. Preventing sepsis, decay, and tosis (indirect division of a cell) or cell putrefaction; also an agent that kills germs, transformation. microbes. Antimutagenic. A substance that antago- Antispasmodic. An agent that relieves nizes the mutagenic effects of other sub- spasms, usually of smooth muscle, as in ar- stances. teries, bronchi, intestine, bile duct, ureters, 564 MEDICINAL PLANTS OF THE WORLD or sphincters, but also of voluntary muscle; Ascaris. Roundworm (maw-worm; eel- spasmolytic. worm) found in the small intestine, causing Antithrombotic. Preventing or interfering colicky pains and diarrhea, especially in with the formation of thrombi (an aggrega- children. tion of blood factors). Ascites. Excessive accumulation of seri- Antithyroid. Counteracting the function- ous fluid in the peritoneal (abdominal) ing of the thyroid, especially in its synthesis cavity. of thyroid hormone. Asthenia. Lack or loss of strength, usually Antitumor. Preventing or effective against involving muscular system. tumors or cancer formation. Anticar- Asthma. A condition marked by recurrent cinogen. attacks of paroxysmal dyspnea, with wheez- Antitussive. Preventing or relieving cough. ing resulting from spasmodic contraction of Antiulcerative. Preventing or promoting the bronchi. Some cases of asthma are the healing of ulcers. allergic manifestations in sensitized persons. Antiulcerogenic. Preventing the produc- Astringent. An agent that causes tissue to tion of ulcers. contract. Antivertigo. Counteracting an illusory Astrocyte. One of the large neuroglia cells sense that either the environment or the of nervous tissue. body is revolving; it may result from disease Atopic. Allergic; related to atopy (a genetic of the inner ear or may be due to distur- predisposition toward the development of bances of the vestibular centers or pathways immediate hypersensitivity reactions against in the central nervous system. common environmental allergens. Antiviral. An agent that inhibits growth or Atractyloside. A highly poisonous steroid multiplication of viruses, or kills them. from Atractylis gummifera with a strychnine- Anti-yeast. An agent that inhibits the like action, producing convulsion of a hy- growth or , multiplication of or kills yeasts. poglycemic nature. Atractyloside interferes Aphrodisiac. Any drug that arouses the with oxidative reactions, the citric acid sexual instinct; increasing or exciting the cycle, and nerve conduction. sexual desire. Atrium. The upper chamber of each half of Apoliprotein. Any of the protein constitu- the heart; the portion of nasal cavity; in the ents of lipoproteins, grouped by function in lung, a subdivision of the alveolar duct from four classes A, B, C, and E (the former which alveolar sacs open. apolipoprotein [apo] D is now apo A-III). Aural. Within the ear (auris). Apoptosis. Fragmentation of a cell into Baldness. Alopecia; absence of hair from membrane-bound particles that are elimi- the scalp. nated by phagocytosis. Programmed cell Benign prostatic hyperplasia. Age-associ- death. ated enlargement of the prostate, resulting Arrhythmia. Any variation from the nor- from proliferation of both glandular and mal rhythm of the heartbeat; it may be an stromal elements, beginning generally in abnormality of either the rate, regularity, or the fifth decade of life. It may cause urethral site of impulse origin or the sequence of ac- compression and obstruction. tivation. Biliary. Pertaining to the bile, to the bile Arterial thrombosis. The formation of an ducts, or to the gallbladder. aggregate of blood factors (thrombus), pri- Biliousness. An imprecisely delineated marily platelets and fibrin, with entrapment congestive disturbance with anorexia, coated of cellular elements in the arteries. tongue, constipation, headache, dizziness, Arthritis. Inflammation of a joint. pasty complexion, and rarely, slight jaun- GLOSSARY 565 dice; assumed to result from hepatic dys- Cataleptic. Pertaining to, characterized by, function. or inducing the condition of maintaining Blennorrhagia. Discharge from mucus sur- whatever body posture one is placed in faces. (catalepsy). Blistering. The formation of a blister; vesi- Cataract. A loss of transparency of the cation. crystalline lens of eye, or of its capsule. Bradycardia. Brachycardia; bradyrhythmia; Cecolectomy. Excision of a segment or all oligocardia; slowness of the heartbeat under of cecum. 60 beats per minute. Cercaria. The free-swimming trematode Bradypnea. Abnormal slowness of breathing. larva that emerges from its host snail, in Bronchoconstrictor. Constricting or nar- humans it penetrates the skin directly. rowing the lumina of the air passages of the Cerebral ischemia. Infarction; an ischemic lungs. condition of the brain, producing a persis- Bronchodilator. An agent that causes ex- tent focal neurological deficit in the area of pansion of the lumina of the air passages of distribution of one of the cerebral arteries. the lung. Chalazion. An eyelid mass that results from Cachexia. A general lack of nutrition and chronic inflammation of a meibomian wasting occurring in the course of a chronic gland and shows a granulomatous reaction disease or emotional disturbance. to liberated fat when subjected to histo- Calculi. Abnormal concretion occurring pathological examination. within the animal boy and usually composed Charcoal. Carbon prepared by charring of mineral salts. wood or other organic material. Calefacient. An agent causing a sense of Chemiluminescence. Luminescence pro- warmth in the part to which it is applied. duced by the direct transformation of Carcinogen. A substance that predisposes chemical energy into light energy. cancer development. Chilblain. A recurrent localized erythema Carcinogenesis. The production of carci- and doughy subcutaneous swelling caused noma. by exposure to cold associated with damp- Carcinoma. A malignant new growth made ness, and accompanied by pruritus and a up of epithelial cells tending to infiltrate the burning sensation, usually involving the surrounding tissues and give rise to meta- hands, feet, ears, and face in children; the stases. legs and toes in women; and the hands and Cardiac. Pertaining to the heart. fingers in men. Cardiovascular. Pertaining to the heart Cholagogue. An agent that stimulates the and blood vessels. bile flow to the intestines. Cardiotonic. An agent that has a tonic ef- Cholecystectomy. Surgical removal of the fect on the heart. gallbladder. Carminative. An agent that relieves the Cholelithiasis. The presence or formation presence of an excessive amount of gas in of gallstones. the stomach and intestine; preventing the Cholestatic. Pertaining to or characterized formation or causing the expulsion of flatus. by suppression or stopping of the flow of bile Carrageenan. Carrageenin; a polysaccharide (cholestasis), having intrahepatic or extra- obtained from Irish moss; a galactosan sul- hepatic causes. fate resembling agar in molecular structure. Cholesterogenesis. Synthesis of cholesterol. Catalase. An enzyme (EC 1.11.1.6; a he- Cholinergic. Relating to nerve fibers that moprotein), catalyzing the decomposition cause effects similar to those induced by ace- of hydrogen peroxide to water and oxygen. tylcholine. 566 MEDICINAL PLANTS OF THE WORLD

Chronotropic. Affecting the time or rate, of the carbon monoxide derivative) for a as the rate of contraction of the heart. cytochrome occurring in most tissues and Clara cells. Unciliated cells occurring at containing a protoheme IX prosthetic the boundary where alveolar ducts branch group. It serves as the oxygenating catalyst from the bronchioles. in a wide variety of reactions catalyzed by Clastogenic. Giving rise to or inducing dis- monooxygenases. Cytochrome P450 acti- ruption or breakages, as of chromosomes. vates molecular oxygen for an attack on the Clofibrate. An antihyperlipidemic agent substrate. used to reduce elevated serum lipids when Cytophatic. Pertaining to, or characterized administered orally. by, pathological changes in cells. CNS. Central nervous system. Cytotoxic. An agent that is toxic to certain Colic. Pertaining to the colon; acute ab- organs, tissues, or cells. dominal pain; characteristically, intermittent Decoction. A preparation made by boiling visceral pain with fluctuations corresponding a plant part in water; a boiled extract. to smooth muscle peristalsis. Dental enamel. A hard, thin, transcluent Conjunctivitis. Inflammation of the deli- layer of calcified substance that envelops cate membrane that lines the eyelids and and protects the dentin of the crown of the covers the exposed surface of the sclera tooth. It is the hardest substance in the body (conjunctiva), generally consisting of con- and is almost entirely composed of calcium junctival hyperemia associated with a dis- salts. charge. Denture stomatitis. Generalized inflam- Constipation. Infrequent or difficult evacu- mation of the oral mucosa observed some- ation of feces. times in patient with new dentures or with Contraceptive. An agent that diminishes old, ill-fitting ones, caused by Candida the likelihood of or prevents conception. albicans, characterized by redness, swelling, Corpus luteum. A yellow glandular mass in and painfulness of the mucosa coming in the ovary formed by an ovarian follicle that contact with the denture. has matured and discharged its ovum. If the Dermatitis. Inflammation of the skin. ovum has been impregnated, the corpus lu- Diabetes mellitus. A chronic syndrome of teum increases in size and persist for several impaired carbohydrate, protein, and fat me- months. tabolism owing to insufficient secretion of Corticosterone. A natural corticoid with insulin or to target tissue insulin resistance. moderate glucocorticoid activity and some Diabetes. A general term referring to disor- mineralocorticoid activity, possessing life- ders characterized by excessive urine excre- maintaining properties in adrenalectomized tion (polyuria), as in diabetes mellitus and animals and several other activities peculiar diabetes insipidus. to the adrenal cortex. Its actions closely re- Diuretic. An agent promoting urination. semble those of cortisol, except that it is not DMBA. 7,12-dimethylbenz[a]anthracene; a anti-inflammatory. humorigenic agent. Counter-irritant. An agent that produces Dopaminergic. Pertaining to neurons that inflammation or irritation when applied release dopamine and to the effects exerted locally to affect another, usually irritated, thereby; activated or transmitted by dopa- surface to stimulate circulation, e.g., lini- mine. ment. Dopamine. A catecholamine formed in the Cytochrome P450. Trivial name (P for pig- body by the decarboxylation of dopa; an ment, 450 nm for the absorption maximum intermediate product in the synthesis of GLOSSARY 567 norepinephrine; acts as a neurotransmitter Emmenagogue. A substance that promotes in the central nervous system. It is also pro- or assists the flow of menstrual fluid. duced peripherally and acts on peripheral Emollient. An agent that smoothes and receptors, e.g., in blood vessels. protects the skin when applied locally. Down syndrome. A chromosome disorder Emphysema. A pathological accumulation characterized by a small, antheropos- of air in tissues or organs; applied especially teriorly flattened skull; short, flat-bridge to such a condition of the lungs. nose; epicanthal fold; short phalanges; wid- Endometrium. The inner mucous mem- ened spaces between the first and second brane of the uterus, the thickness and struc- digits of hands and feet; and moderate to ture of which vary with the phase of the severe mental retardation. menstrual cycle. Dromotropic. Affecting the conductivity Endothelium. The layer of epithelial cells of a nerve fiber. that lines the cavities of the heart and of Dysentery. Any of various disorders the blood and lymph vessels and the serous marked by inflammation of the intestines, cavities of the body, originating from the especially of the colon, and attended by pain mesoderm. in the abdomen, tenesmus, and frequent Endotoxin. A heat-stable bacterial toxin stools containing blood and mucus. not freely liberated into the surrounding Dysmenorrhea. Painful menstruation. medium. Endotoxins are released only when Dyspnea. Sense of difficulty in breathing, the integrity of the cell wall is disturbed, are often associated with lung or heart disease. less potent than most exotoxins, are less Dysuria. Painful or difficult urination. specific, and do not form toxoids. When Eccentric hypertophy. Hypertrophy of a injected in large quantities, endotoxins pro- hollow organ, with dilatation of this cavity. duce hemorrhagic shock and severe diar- Eczema. A pruritic papulovesicular der- rhea. Smaller amounts cause fever, altered matitis occurring as a reaction to many resistance to bacterial infections, leukope- exogenous and endogenous agents, charac- nia followed by leukocytosis, and numerous terized in a acute stage by erythema, edema other biological effects. associated with a serious exudates between Endovenous. Intravenous. the cells of the epidermis and an inflamma- Enema. A liquid injected or to be injected tory infiltrate in the dermis, oozing and ve- into the rectum. siculation, and crusting and scaling. In the Enteropathy. An intestinal disease. chronic stage by the lichenification or Enterotoxin. A toxin specifically affecting thickening or both, signs of excoriations, cells of the intestinal mucosa, causing vom- and hyperpigmentation or hypopigment- iting and diarrhea, e.g., those elaborated by ation or both. species of Bacillus, Clostridium, Escherichia, Edema. The presence of abnormally large Staphylococcus, and Vibrio. amounts of fluid in the intercellular tissue Epididymal. Pertaining to the epididymis; of the body; usually applied to demonstrable the elongated cord-like structure along the accumulation of excessive fluid in the sub- posterior border of the testis, whose elon- cutaneous tissues. gated coiled duct provides for the storage, Embryopathy. A morbid condition of the transit, and maturation of spermatozoa, and embryo or a disorder resulting from abnor- is continuous with the ductus deferens. mal embryonic development. Epstein–Barr virus. A herpes-like virus Emesis. Vomiting. found in cell cultures of Burkitt lymphoma; Emetic. An agent that induces vomiting. also, antibodies reactive with Epstein–Barr 568 MEDICINAL PLANTS OF THE WORLD

B virus have been reported in cases of infec- cornavirus, affecting wild and domestic ani- tious mononucleosis. mals, chiefly cattle, pigs, sheep, goats, and Erysipelas. A specific, acute, inflammatory other ruminants, and very rarely humans. It disease caused by a hemolytic Streptococcus. is marked by an eruption of vesicles on the The eruption, limited to the skin and lips, buccal cavity, pharynx, legs, and feet; sharply defined, is usually accompanied by sometimes the skin of the udder or teats is severe constitutional symptoms. involved. Erythema. Redness of the skin, inflam- FSH. Follicle-stimulating hormone. mation. Furuncle. A painful nodule formed in the Estrogens. A substance that induces female skin by circumscribed inflammation of the hormonal activity. corium and subcutaneous tissue, enclosing Expectorant. An agent that induces the a central slough or “core.” It is caused by sta- removal (coughing up) of mucous secretion phylococci. from the lungs. Galactogogue. An agent that promotes se- Fatty acids. Hydrolysis products of fats. cretion of milk. Febrifuge. That which reduces fever; anti- Gallbladder (cholecyst; vesica biliaris; pyretic. vesica fellea). The pear-shaped reservoir Fibrinolysis. The hydrolysis of an elastic, for the bile in the postinferior surface of he filamentous protein (fibrin) derived from fi- liver, between the right and quadrate lobe; brinogen by the action of thrombin, which the cystic duct projects to join the common releases fibrinopeptides A and B (co-fibrins bile duct. A and B) from fibrinogen in co-agulation of Gallstone. A concretion, usually of choles- the blood. terol, formed in the gallbladder or bile duct. Filariasis. The presence of parasites filariae Gargle. A solution used for rinsing in medi- in the blood and tissues of the body. May be cating the mouth and throat. asymptomatic, and living worms cause mini- Gastroenteritis. Inflammation of the stom- mal tissue reaction. Death of the adult ach and intestinal tract. worms causes marked inflammation and Gastroesophageal reflux. Reflux of the lymphatic obstruction. stomach and duodenal contents into the Flatulent colic. Tympanites; distention of esophagus, which may sometimes occur the abdomen, resulting from the presence of normally, particularly in the distended gas or air in the intestine or in the perito- stomach postprandially, or as a chronic neal cavity, as in peritonitis and typhoid pathological condition. fever. Gastroesophageal. Pertaining to the Flavonoids. A class of tricyclic molecules, stomach and esophagus, as the gastroeso- usually occurring in glycosidic form and phageal junction. widely distributed in plants, often as a pig- Genotoxic. Damaging to DNA, causing ment. mutations or cancer. Foam cells. Cells with a peculiar vacu- GI. Gastrointestinal. olated appearance owing to the presence of Glomerular. Pertaining to, or of the nature complex lipoids; such cells are seen notably of tuft or cluster (glomerulus), composed of in xanthoma. blood vessels or nerve fibers, especially a re- Follicular. Pertaining to the lymph nodule. nal glomerulus. Follicular cells. Cells located in the epithe- Glutathione. A tripeptide, widely distrib- lium of follicles. uted in animal and plant tissues. It exists in Foot-and-mouth disease. An acute, ex- reduced (GSH) and oxidized (GSSH) tremely contagious disease caused by pi- forms, and it functions in various redox re- GLOSSARY 569 actions, in the formation and maintenance Hepatitis. Inflammation of the liver, usu- of disulfide bonds in proteins and in trans- ally from the viral infection, sometimes port of amino acids across cell membranes. from toxic agents. In erythrocytes, these reactions prevent Hepatoblastoma. A malignant intra- oxidative damage by reduction of methemo- hepatic tumor occurring in infants and globin, and peroxides. young children and consisting chiefly of Glycosides. Sugar esters. embryonic hepatic tissue. Goitrogenic. Producing an enlargement of Herpes. Any inflammatory skin disease the thyroid gland, causing a swelling in the caused by a herpesvirus and characterized by front part of the neck. the formation of clusters of small vesicles. Gonorrhea. A contagious catarrhal inflam- When used alone, the term may refer to her- mation of the genital mucous membrane, pes simplex or Herpes zoster. transmitted chiefly by coitus, and resulting HMG-CoA reductase. 3-Hydroxy-3-me- from Neisseria gonorrhoeae. thylglutaryl coenzyme A-reductase. Gout. An inherited metabolic disorder oc- Hoarseness. A rough or noisy quality of curring especially in men, characterized by voice. a raised but variable blood uric acid level, Homocysteine. A sulfur-containing amino recurrent acute arthritis of sudden onset, acid, a homologue of cysteine, produced by deposition of crystalline sodium urate in the demethylation of methionine, and an connective tissues and articular cartilage, intermediate in the biosynthesis from me- and progressive chronic arthritis. thionine via cystathionine. Gum. Water swellable carbohydrate deriva- Husk. The shell; the outer covering of some tives. fruits as of corn and many other cereals. HDL cholesterol. High-density lipoprotein An agent that per- cholesterol. Hypercholesterolemic. tains to, is characterized by, or tends to pro- Hematopoiesis. The formation and devel- opment of blood cells. duce an excess of cholesterol in the blood. Hemolysis. Disruption of the integrity of Hyperemesis gravidorum. Pernicious the red cell membrane causing release of vomiting of pregnancy. hemoglobin. Hyperemia. An excess of blood in a part; Hemorrhage. Bleeding; a flow of blood, engorgement. especially if it is very profuse. Hyperglycemic. Pertaining to, character- Hemorrhoid. A varicose dilatation of a ized by, or causing an increase in the level vein of the superior or inferior hemorrhoidal of glucose in the blood. plexus, resulting from a persistent increase Hyperkeratosis. Hypertrophy of the cor- in venous pressure. neous layer of the skin, or any disease char- Hemostat. An agent that checks hemorrhage acterized by it. when properly applied to a bleeding point. Hyperlipemic. Pertaining to, characterized Hemostatic. A compound that retards by, or causing an elevated concentration of bleeding. any or all of the lipids in the plasma. Hemotoxic. Poisonous to the blood and Hypertension. High arterial pressure. Vari- hematopoietic system (system pertaining ous criteria for its threshold have been to or effecting the formation of blood cells). suggested, from 140 mmHg systolic and 90 Hepatectomy. Removal of a part of the mmHg diastolic, to 200 mmHg systolic and liver. 110 mmHg diastolic. Hypertension may Hepatic. An agent that promotes the well- have no known cause (idiopathic or idio- being of the liver and increases the secre- pathic) or may be associated with other pri- tion of bile. mary diseases (secondary). 570 MEDICINAL PLANTS OF THE WORLD

Hypertensive. Causing or marking a rise in Immunoglobulin. Immunoprotein; glyco- blood pressure. protein of animal origin with known anti- Hyperthermia. Abnormally high body body activity, or protein related by chemical temperature, especially that induced for structure, which may or may not have anti- therapeutic purposes. body activity. Divided into five classes: IgM, Hypertriglyceridemic. Pertaining to, char- IgG, IgA, IgD, and IgE on the basis of struc- acterized by, or causing an increase in the ture and biological activity. level of triglyceride in the blood. Immunostimulant. Stimulating various Hyperventilation. Increased pulmonary functions or activities of the immune system. ventilation beyond that needed to maintain Immunosuppressant. An agent capable of the blood gases within the normal ranges. suppressing immune responses. Hypnotic. A drug that acts to induce sleep. Inebriation. The condition of being drunk. Hypocholesterolemic. Pertaining to, char- Infestation. Parasitic attack or subsistence acterized by, or producing an abnormally on the skin and its appendages, as by insects, diminished amount of cholesterol in the mites, or ticks. blood. Infusion. A preparation made by soaking a Hypofertile. Having diminished reproduc- plant part in hot or cold water, e.g., tea. tive capacity. Inotropic. Affecting the force or energy of Hypogammaglobulinemia. A condition muscular contractions. Negatively inotro- characterized by abnormally low levels of all pic—weakening the force of muscular con- classes of immunoglobulins. tractions. Positively inotropic—increasing Hypoglycemic. Causing a deficiency of the strength of muscular contractions. blood glucose. Insecticidal. An agent selectively poison- Hypotensive. Causing or marking a lower- ous to insects. ing of blood pressure. Interferon. Any of a family of glycoproteins Hypouricemia. Deficiency of uric acid in that exert virus-nonspecific but host-spe- the blood, along with xanthinuria, resulting cific antiviral activity by inducing the tran- from deficiency of xanthineoxidase, the scription of cellular genes coding for enzyme required for conversion of hypoxan- antiviral proteins that selectively inhibit thine to xanthine and of xanthine to uric the synthesis of viral RNA and proteins. acid. Interferons have immunoregulatory func- Hypoxia. Reduction of oxygen supply to tions and can inhibit the growth of nonviral tissue below physiological levels despite intracellular parasites. adequate perfusion of the tissue by blood. Interleukin. A generic term for a group of Hypoventilation. Underventilation; re- multifunctional cytokines that are produced duced alveolar ventilation in relation to the by a variety of lymphoid and nonlymphoid oxygen consumption. cells and whose effects occur at least partly Hysteria. A diagnostic term, referrable to a within the lymphopoietic system. wide variety of psychogenic symptoms that Intragastric. Situated or occurring within may be mental, sensory, motor, or visceral. the stomach. Idiopathy. A morbid state of spontaneous Intraperitoneal. Within the peritoneal origin; one neither sympathetic nor trau- cavity. matic. Ischemia. Deficiency of blood in a part, Immunogenicity. The property that usually results from functional constriction endows a substance with the capacity to pro- or actual obstruction of a blood vessel. voke an immune response, or the degree to Isotype. An immunoglobulin heavy- or which a substance possesses this property. light-chain class or subclass characterized GLOSSARY 571 by antigenic determinants in the constant Libido. Conscious or unconscious sexual region. desire; creative energy. Any passionate form Jaundice. A syndrome characterized by of life force. hyperbilirubinemia (excessive concentra- Lipogenetic. Lipogenic; forming, producing tions of bilirubin in the blood) and deposi- or caused by fat. tion of bile pigment in the skin, mucous Lipolytic. Pertaining to, characterized by, membranes, and sclera with resulting yellow or causing the decomposition or splitting up appearance of the patient. of fat (lipolysis). Karyotype. The chromosome characteris- Lithiasis. A condition characterized by the tics of an individual or of a cell line, usually formation of calculi and concretions. presented as a systematized array of meta- Lobar pneumonia. An acute febrile disease phase chromosomes from a photomicro- produced by Streptococcus pneumoniae, and graph of a single cell nucleus arranged in marked by inflammation of one or more pairs in descending order of size and accord- lobes of the lung, together with consolida- ing to the position of centromere. tion. It is attended with chill, followed by Labor. The function of the female organ- sudden elevation of temperature, dyspnea, ism by which the product of conception is rapid breathing, pain in the side, and cough, expelled from the uterus through the vagina with blood-stained expectoration. The to the outside world. symptoms abate after 1 week. Larvicidal. Destructive to insect larvae. Luteal. Pertaining to or having the proper- Laxative. An agent that promotes evacua- ties of the corpus luteum or its active prin- tion of the bowels. A mild purgative. ciple. LDL cholesterol. Low-density lipoprotein Lymphoblast. A morphologically immature cholesterol. lymphocyte; an activated lymphocyte that Leprosy. A slowly progressive, chronic in- has been transformed in response to anti- fectious disease caused by Mycobacterium genic stimulation. leprae and characterized by the development Lymphohistiocytic. Involving lymphocytes of granulomatous or neurotropic lesions in and histiocytes. the skin, mucous membranes, nerves, bones, Lymphopoietic. Pertaining to, character- and viscera. ized by, or causing the development of lym- Lesion. Any pathological or traumatic dis- phatic tissue (lymphopoiesis). continuity of tissue or loss of function of a Malaria. An infectious disease endemic in part. parts of Africa, Asia, Turkey, the West Leucorrhea. A whitish, viscid discharge Indies, Central and South America, and from the vagina and uterine cavity. Oceania, caused by protozoa of the genus Leukocyte. White blood cells. Plasmodium, and usually transmitted by the Leukocytosis. A transient increase in the bites of infected anopheline mosquitoes. It number of leukocytes in the blood, result- is characterized by prostration associated ing from hemorrhage, fever, infection, in- with paroxysms of high fever, shaking chills, flammation, etc. sweating, anemia, and splenomegaly, which Leukotriene. Biologically active compound may lead to death. functions as regulators of allergic and in- Malignancy. The property or condition of flammatory reactions. They are identified by being resistant to treatment (malignant). the letters A, B, C, D, and E, with subscripts Mastocytoma. A nodular cutaneous mast indicating the number of double bonds in cell infiltrate, which is usually present at the molecule. birth or soon after as a solitary nodule, al- LH. Luteinizing hormone. though three to four lesions may occur. Le- 572 MEDICINAL PLANTS OF THE WORLD sions typical of urticaria pigmentosa may It would cause cessation of, multiplication occur later. of normal cells. Measles. A highly contagious infectious Nephritis. Inflammation of the kidney. disease caused by paramyxovirus, common Nephropathy. Disease of the kidneys. among children and seen in the unimmune Nephrotoxic. Toxic or destructive to kid- of any age. Characteristically, coryza, cervi- ney cells. cal lymphadentitis, Koplik’s spotspalpebral Neuralgia. Pain extending along the course conjunctivitis, photophobia, malagia, mal- of one or more nerves. Many varieties of aise, and a harassing cough with steadily neuralgia are distinguished according to the mounting fever precede the skin eruption. part affected, as brachial, facial, occipital, or Melanoid. Resembling melanin. supraorbital, or to the case, as anemic, dia- Menorrhagia. Hypermenorrhea; excessive betic, gouty, malarial, or syphilitic. uterine bleeding occurring at regular inter- Neurasthenia. A syndrome of chronic vals, the period of blood being of usual du- mental and physical weakness and fatigue, ration. which was supposed to be caused by exhaus- Methemoglobinemia. The presence of tion of the nervous system. methemoglobin in the blood, resulting in Neutrophil. A granular leukocyte, having cyanosis and headache, dizziness, fatigue, a nucleus with three to five lobes connected ataxia, dyspnea, tachycardia, nausea, vom- by slender threads of chromatin, and cyto- iting, drowsiness, stupor, coma, and some- plasm containing fine inconspicuous gran- times death. ules. Neutrophils have the properties of Miscarriage. Loss of products of conception chemotaxis: adherence to immune com- from the uterus before the fetus is viable; plexes, and phagocytosis. spontaneous abortion. Nigrostratial. Projecting from the substan- Mitogenic. An agent that affects cell divi- tia nigra to the corpus striatum; said of a sion. bundle of nerve fibers. Molluscacidal. Destructive to snails and Non-Hodgkin’s lymphoma. A heterog- other mollusks. enous group of a malignant lymphomas, the Monocytic. Pertaining to or, characterized only common feature being an absence of by a mononuclear phagocytic leukocytes, the giant Reed-Sternberg cells characteris- formed in bone marrow and transported to tic of Hodgkin’s disease. They arise from the tissues, as of the lung and liver, where they lymphoid components of the immune sys- develop into macrophages. tem, and present a clinical picture broadly Morbidity. A disease condition or state, the similar to that of Hodgkin’s disease, except incidence or prevalence of a disease or of all the disease is initially more widespread, with diseases in a population. the most common manifestation being Mutagenic. Causing change or inducing ge- painless enlargement of one or more periph- netic mutation. eral lymph nodes. Myocardial infarction. An area of coagu- Occlusion. The act of closure or state of lation necrosis in a tissue resulting from lo- being closed; an obstruction or a closing off. cal ischemia in the heart. Oleoresins. Natural mixtures of resins and Nausea. Sickness at the stomach; an incli- volatile oils. nation to vomit. Ophthalmic. Healing for disorders and dis- Nematocidal. Destroying nematode worms. eases of the eye. Neoplasia. The formation of a new tissue, Osteoarthritis. Noninflammatory degen- with uncontrolled and progressive growth. erative joint disease occurring chiefly in older persons, characterized by degeneration GLOSSARY 573 of the articular cartilage, hypertophy of Pepsin. A general name for several names bone at the margins, and changes in the syn- of the gastric juice that catalyze the hydroly- ovial membrane, accompanied by pain and sis of the protein to form polypeptides. stiffness. Per rectum. By the way of rectum. Osteoclast. A large multinuclear cell asso- Periodontosis. Juvenile periodontitis; a ciated with the absorption and removal of rare form that has an onset at puberty, is bone, osteoclasts become highly active in more common in females, and is manifested the presence of parathyroid hormone, caus- by deep periodontal pockets, usually involv- ing increased bone resorption and release of ing the first molars and incisors. bone salts (phosphorus, and especially cal- Pessary. An instrument placed in the va- cium) into the extracellular fluid. gina to support the uterus or rectum or as a Ovalbumin. An albumin obtainable from contraceptive device; a medicated vaginal the whites of eggs. suppository. Oviposition. The act of laying or deposit- Phagocytosis. Ingestion and digestion of ing eggs. bacteria and particles by phagocytes. PAC. Premature atrial complex; a single Pheromone. A substance secreted to the ectopic atrial beat arising prematurely, outside of the body by an individual and per- manifests electrocardiographically as an ceived (as by smell) by a second individual, abnormally shaped premature P wave, usu- releasing a specific reaction of behavior in ally with a slightly increased PR interval. It the percipient. occurs in normal hearts, sometimes associ- Phospholipidemia. The presence of phos- ated with the use of stimulants, but may be pholipids in the blood. associated with structural heart disease. Phytotoxic. Pertaining to phytotoxin, or Pancreatic. Pertaining to the pancreas; a plant poison; inhibiting the growth of plants. large, elongated, racemose gland situated Phytotoxin. An exotoxin produced by cer- transversely behind the stomach, between tain species of higher plants; they are resis- the spleen and duodenum, producing insu- tant to proteolytic digestion, and are lin, glucagons, somatostatin, polypeptide effective when taken by mouth. (the endocrine part), and a pancreatic juice Platelet aggregation. Clumping together that contains enzymes essential to protein of platelets as part of a sequential mecha- digestion (the exocrine part). nism leading to the initiation and formation Papilloma. A benign epithelial neoplasm of a thrombus or hemostatic plug. producing finger-like or verrucous projec- Platelet. Disc-like structure, 2–4 mm in di- tions from the epithelial surface. ameter, found in the blood of all mammals Parakeratosis. Persistence of the nuclei of and chiefly known for its role in blood co- the keratinocytes into the stratum corneum agulation. (horny layer) of the skin. Parakeratosis is Pleural empyema. Accumulation of a liq- normal in the epithelium of true mucous uid inflammation product made up of leu- membrane of the mouth and vagina. kocytes (pus) in a cavity of the lungs. Parkinson’s disease. Neurological disorder Pleurisy. Inflammation of the pleura, with characterized by hypokinesia, tremor, and exudation into its cavity and on its surface. muscular rigidity. Pneumonia. Inflammation of the lungs Pectoral. Pertaining to the thorax or chest; with consolidation. relieving disorders of the respiratory tract, Pneumonitis. Inflammation of the lungs. as an expectorant. Pneumothrax. An accumulation of air or Pediculicide. An agent that destroys para- gas in the pleural space, which may occur sitic insects (lice). spontaneously or as a result of trauma or a 574 MEDICINAL PLANTS OF THE WORLD pathological process, or be introduced de- Purgative. An agent that causes cleansing liberately. or watery evacuation of the bowels, usually Poliovirus. A virus of the genus Enterovirus with griping (painful cramps). that is the etiological agent of poliomyeli- Pus. A liquid inflammation product com- tis, separable on the basis of specificity of posed made up of cells (leukocytes) and a neutralizing antibody into three serotypes, thin protein-rich fluid called liquor puris. designated types 1, 2, and 3. PVC. Pulmonary venous congestion; prema- Pollinosis. Allergic reaction in the body to ture ventricular contraction. the airborne pollen of plants, resulting in Pyretic. Pertaining to or of the nature of the seasonal type of hay fever or rose cold. fever. Polymorphonuclear cells. Cells having a Rabies. An acute infectious disease of the nucleus deeply lobed or so divided that it central nervous system affecting most mam- appears to be multiple. mals including humans, caused by rhabdovi- Poultice. A moist, usually warm or hot mass rus. Typical symptoms include paresthesia of plant material applied to the skin, or with and a burning sensation or pain at the site cloth between the skin and plant material, of inoculation, periods of hyperexcitability, to effect a medicinal action. agitation, delirium, hallucinations, and bi- zarre behavior, between which the person is Prolactin. A hormone secreted by special often cooperative and lucid. cells of the anterior pituitary gland that A state of violent anger; a total dis- stimulates and sustains lactation in postpar- Rage. charge of the sympathetic portion of the tum mammals, the mammary glands having autonomic system. been prepared by other hormones, includ- RBBB. Right bundle branch block. ing estrogens, progesterone, growth hor- Reflux. A backward or return flow. mone, corticosteroids, and insulin. Gastroesophageal reflux. Reflux of the Promastigote. Any of the bodies represent- stomach and duodenal contents into the ing the morphological stage in the life cycle esophagus, which may sometimes occur nor- of certain tryptanosomatid protozoa resem- mally, particularly in the distended stomach bling the typical adult form of members of postprandially, or as a chronic pathological the genus Leptomonas. condition. Prostaglandin (PG). Components derived Renal. Pertaining to the kidney. from unsaturated 20-carbon fatty acids, pri- Resins. Water-insoluble mixtures of resins, marily arachidonic acid, via the cyclo- their acids, and alcohols. oxygenase pathway. They are extremely Reticulocyte. A young red blood cell show- potent mediators of a diverse group of physi- ing a basophilic reticulum under vital ological processes. staining. Proteinemia. An excess of proteins in the Rhinitis. Inflammation of nasal mucosa. blood. Salivary. Pertaining to the clear, alkaline, Proteolytic. Pertaining to, characterized somewhat viscid secretion from the parotid, by, or promoting the splitting of proteins submaxillary, sublingual, and smaller mu- by hydrolysis of the peptide bonds with cous glands of the mouth. formation of smaller polypeptides (pro- Saponin. A glycoside compound in plants, teolysis). which, when shaken with water, has a foam- Psoriatic. Pertaining to, affected with, or of ing or “soapy” action. the nature of a common chronic, squa- Sarcolemma. The delicate plasma mem- mous dermatosis with polygenic inheritance brane thatwhich invests every striated and a fluctuating course (psoriasis). muscle fiber. GLOSSARY 575

Sarcoma. Any of the group of tumors Spermicidal. Destructive to spermatozoa. usually arising from the connective tissue, Suppository. A medicated mass adapted for although the term now includes some of introduction into the rectal, vaginal, or ure- epithelial origin; most are malignant. Many thral orifice of the body. types have prefixes denoting the type of Sphincter. A ring-like band of muscle fi- tissue or structure involved, e.g., fibrosar- bers that constricts a passage or closes a coma. natural orifice. Schistosomiasis. The state of being in- Splenomegaly. Enlargement of a large, fected with flukes of the genus Schistosoma. gland-like, ductless organ situated in the Scorbutic. Concerning or affected with upper part of the abdominal cavity on the scurvy. left side and lateral to the cardiac end of the Scrofula. Tuberculosis involving the lymph stomach (spleen). nodes of the neck, usually occurs in early SRBC. Sheep red blood cells. life, now rarely seen. Steroidogenic. Producing steroids. Scabies. A contagious dermatitis of humans Sterols. Molecules related to cholesterol and various animals, caused by the itch and some hormones. mite, Sarcoptes scabiei, and characterized by Stimulant. An agent to increase body me- a popular eruption over tiny, raised sinu- tabolism. A compound that excites ous burrows produced by digging into the Stimulant, CNS. mental function. upper layer of the epidermis by the egg- Sting. An injury caused by the venom of laying female mite, which is accompanied a plant or animal (biotoxin) introduced by intense pruritus and sometimes associ- into the individual or with which he or she ated with eczema and secondary bacterial has come in contact, together with the infection. mechanical trauma caused by the organ Seasonal rhinoconjunctivitis (SRC). In- responsible for its introduction. flammation of the mucus membranes of the Stomachic. A preparation that gives nose and eyes. strength and tone to the stomach. Also used Sedative. An agent that allays excitement. to stimulate the appetite. Semliki Forest virus. A species of viruses Stupor. A lowered level of consciousness of the genus Alphavirus, originally isolated manifested by the subject’s responding only from Aedes mosquitoes in Western Uganda; to vigorous stimulation. it is widespread in Africa, where it appears Subcutaneous. Beneath the skin. to be nonpathogenic, although infections of Submandibular. Below the bone of the laboratory workers have occurred. lower jaw (mandible). Sp. Abbreviation for species (singular). Sudorific. Diaphoretic; a compound that Spp. Abbreviation for species (plural). increases perspiration. Spasmogenic. Relating to the production Suspension. A preparation of a finely of, or causing spasms. divided drug intended to be incorporated in Spasmolytic. An agent to lessen muscle some suitable liquid vehicle before it is used, spasms or cramps; antispasmodic. or already incorporated in such a vehicle. Speech. The utterance of vocal sounds con- Sympathomimetic. Mimicking the effects veying ideas. of impulses conveyed by adrenergic post- Spermatogonium. An undifferentiated ganglionic fibers of the sympathetic nervous germ cell of a male, originating in a semi- system. niferous tubule and dividing into two pri- Synovial fluid. A transparent alkaline vis- mary spermatocytes. cid fluid, resembling the white of an egg, se- 576 MEDICINAL PLANTS OF THE WORLD creted by the synovial membrane, and con- Tincture. An alcoholic or hydroalcoholic tained in joint cavities, bursae, and tendon solution prepared from biological substances sheaths. or from chemical substances. Tachycardia. A raised heart beat rate. Tocopherol. Any of a series of structurally Tachyphylaxis. Rapid immunization similar compounds, methyl-substituted against the effect of toxic doses of an extract tocols. of serum by previous injection of small Tonic. An ambiguous term referring to a doses; rapidly decreasing response to a drug substance thought to have overall positive or physiologically active agent after admin- medicinal effect of an unspecified nature. istration of a few doses. Tonsil. A small, rounded mass of tissue, es- Tannin. Bitter principle of plant contain- pecially of lymphoid tissue. ing plant polyphenols. Tourette’s syndrome. A syndrome of facial Tapeworm. A parasitic intestinal cestode and vocal tics with onset in childhood, pro- worm having a flattened, band-like form. gressing to generalized jerking movements The eggs of tapeworms are ingested by the in any part of the body, with echolalia and intermediate host, they produce the larval coprolalia. stage in tissues. When the flesh of interme- Toxic. Pertaining to, resulting from, or of diate host is eaten, the larvae develop the nature of a poison or toxin. Manifesting within the alimentary canal of the defini- the symptoms of severe infections. tive host into adult tapeworms. Trabecula. A general term for a supporting T-cells. T-lymphocytes; thymus-dependent or anchoring strand of a connective tissue, lymphocytes; the cells primarily responsible such as a strand extending from a capsule for cell-mediated immunity. into the substance of the enclosed organ. Tenifuge. Taeniafuge; an agent that expels Tranquilizer. An agent that reduces psy- tapeworms. chotic behavior. Teratogen. A substance that can cause the Triacylglycerol. Triglyceride; a compound deformity of a fetus. consisting of three molecules of fatty acids Terpenes. Hydrocarbon volatile oils, often esterified to glycerol. It is a neutral fat syn- with a strong smell. thesized from carbohydrates for storage in Tetanus. An acute, often fatal, infectious animal adipose cells. On enzymatic hydroly- disease caused by anaerobic, spore-forming sis, it releases free fatty acids in the blood. bacillus Clostridium tetani. The clinical Tuberculosis. Any of the infectious dis- manifestations are the result of tetanospas- eases of man and animals caused by species min, a potent neurotoxin elaborated by the Mycobacterium and characterized by the for- germinating spores. mation of tubercles and caseous necrosis in Thermogenic. Producing heat. the tissues. Thrombocytosis. Increased numbers of Ulcerative gingivitis (acute necrotizing platelets in the peripheral blood. ulcerative gingivitis; ANUG). A progres- Thyroid gland. One of the endocrine sive painful infection, also occurring in glands, normally situated in the lower part subacute and recurrent forms, marked by of the front of the neck and consisting two crateriform lesions of the interdental papil- lobes, one on either side of the trachea and lae that are covered by pseudomembra- joined in front by a narrow isthmus. It ex- nous slough and circumscribed by linear cretes, stores, and liberates the thyroid hor- erythema; fetid breath, increased salivation, mones, which play major endocrine roles in and spontaneous gingival hemorrhage are regulating the metabolic rate. additional features. GLOSSARY 577

Ulcerogenic. Leading to the production Vaginitis. Inflammation of the vagina of ulcers. marked by pain and by a purulent discharge. Urease. An enzyme of the hydrolase class Vasoconstrictor. An agent that causes blood that catalyzes the hydrolysis of urea to CO2 vessels to constrict, or narrow the caliber. and ammonia. It is nickel protein found in Vasodilator. An agent that causes blood micro-organisms and plant that is frequently vessels to relax and dilate. used in clinical assays of plasma urea con- Vermicidal. Having worm-killing properties. centrations. Vermifuge. Anthelmintic; an agent that Urticaria. A vascular reactions, usually kills worms. transient, involving the upper dermis, VLDL cholesterol. Very low-density lipo- representing localized edema, caused by di- protein cholesterol. latation and increased permeability of cap- Vulnerary. An agent used for healing illaries, and marked by the development of wounds, fresh cuts, etc., usually used as a wheals. poultice. Vaccine. A suspension of attenuated or Waxes. Esters of fatty acids with high-mo- killed micro-organisms or of antigenic pro- lecular-weight alcohols. teins derived from them. WBC. White blood cells. CROSS REFERENCE 579

Cross Reference

Common Names Country Latin bionomial ’O:yz Laos Saccharum officinarum A´-li Colombia Nicotiana tabacum Aale India Zingiber officinale Aankha India Saccharum officinarum Acchellu India Sesamum indicum Aceituna Spain Olea europaea Aco Wales Nicotiana tabacum Ada India Zingiber officinale Adarak India Zingiber officinale Adhu India Zingiber officinale Adi India Zingiber officinale Adraka Pakistan Zingiber officinale Adruka India Zingiber officinale Aduva Nepal Zingiber officinale Afifindi Ecuador Zingiber officinale Afu Africa Zingiber officinale Agnimanth Nepal Zingiber officinale Aisiksikimi United States Camellia sinensis Aisskssiinainikimm United States Oryza sativa Ajenjibre Cuba Zingiber officinale Ajenjibre Mexico Zingiber officinale Ajijilla Ecuador Zingiber officinale Ajilla Ecuador Zingiber officinale Ajinibre Mexico Zingiber officinale Ajirinrin Ecuador Zingiber officinale Ajonjoli Spain Sesamum indicum Ak Pakistan Saccharum officinarum Akakur China Zingiber officinale Akeita France Coffea arabica Aleysi Suriname Oryza sativa Alha India Zingiber officinale Aliah Indonesia Zingiber officinale

From: Medicinal Plants of the World, vol. 3: Chemical Constituents, Traditional and Modern Medicinal Uses By: I. A. Ross © Humana Press Inc., Totowa, NJ 579 580 MEDICINAL PLANTS OF THE WORLD

Alla India Zingiber officinale Allam India Zingiber officinale Almindelig hamp Denmark Cannabis sativa Almindelig Denmark Hordeum vulgare Aloruz Arabic countries Oryza sativa Alyvos Lithuania Olea europaea American dwarf palm tree United States Serenoa repens Ampeu Cambodia Saccharum officinarum Anaargeel Iran Cocos nucifera Anjadana Pakistan Ferula assafoetida Araabia kohvipuu Estonia Coffea arabica Araisa Samoa Oryza sativa Ardak India Zingiber officinale Ardakam India Zingiber officinale Arisi India Oryza sativa Arlysen Cornwall Hordeum vulgare Aros Netherlands Antilles Oryza sativa Aroz France Oryza sativa Arpa Hungary Hordeum vulgare Arpa Turkey Hordeum vulgare Arpa Turkmenistan Hordeum vulgare Arre kokosi Albania Cocos nucifera Arros Spain Oryza sativa Arroz colorado Argentina Oryza sativa Arroz macho Argentina Oryza sativa Arroz preto Brazil Oryza sativa Arroz rojo Bolivia Oryza sativa Arroz rojo Colombia Oryza sativa Arroz rojo Costa Rica Oryza sativa Arroz rojo Cuba Oryza sativa Arroz rojo Ecuador Oryza sativa Arroz rojo Honduras Oryza sativa Arroz rojo Mexico Oryza sativa Arroz rojo Nicaragua Oryza sativa Arroz rojo Panama Oryza sativa Arroz rojo Paraguay Oryza sativa Arroz rojo Peru Oryza sativa Arroz rojo Puerto Rico Oryza sativa Arroz rojo Venezuela Oryza sativa Arroz vermelho Brazil Oryza sativa Arroz Portugal Oryza sativa Arroz Spain Oryza sativa Arstniecibas ingvers Latvia Zingiber officinale Aruz Ecuador Oryza sativa Asa Japan Cannabis sativa Asafetida England Ferula assafoetida Asafetida Croatia Ferula assafoetida Asafetida Finland Ferula assafoetida Asafetida Germany Ferula assafoetida Asafetida Guyana Ferula assafoetida Asafetida Iceland Ferula assafoetida Asafetida Lithuania Ferula assafoetida CROSS REFERENCE 581

Asafetida Netherlands Ferula assafoetida Asafetida Poland Ferula assafoetida Asafetida Russia Ferula assafoetida Asafetida Spain Ferula assafoetida Asafetida Sweden Ferula assafoetida Asafetida United States Ferula assafoetida Asafetide France Ferula assafoetida Asafootida Estonia Ferula assafoetida Asafotida Germany Ferula assafoetida Asant Germany Ferula assafoetida Aseituna Netherlands Antilles Olea europaea Asgumetakui Africa Zingiber officinale Ashadital India Sesamum indicum Ashwagolam India Plantago ovata Assa Foetida France Ferula assafoetida Assafetida Italy Ferula assafoetida Asunglasemtong India Zingiber officinale Atuja Malaysia Zingiber officinale A-wei China Ferula assafoetida Aza Greece Ferula assafoetida Azeitona Portugal Olea europaea Azucar, cane de Canary Islands Saccharum officinarum Azucar, cane de Guatemala Saccharum officinarum Babka Poland Plantago ovata Baco Wales Nicotiana tabacum Bagasse China Saccharum officinarum Bahia coconut palm Brazil Cocos nucifera Bang Egypt Cannabis sativa Baojiang China Zingiber officinale Barhanj Arabic countries Plantago ovata Bariis Somalia Oryza sativa Bariktil India Sesamum indicum Barley Guyana Hordeum vulgare Barley United Kingdom Hordeum vulgare Barley United States Hordeum vulgare Barlysyn Wales Hordeum vulgare Beras Malaysia Oryza sativa Beuing Indonesia Zingiber officinale Bhaang India Cannabis sativa Bhaango Nepal Cannabis sativa Bidr qtn Arabic countries Plantago ovata Bijan Malaysia Sesamum indicum Birhni India Oryza sativa Black bush United States Larrea tridentata Blond psyllium Arabic countries Plantago ovata Boko Philippines Cocos nucifera Boktel Malaysia Daucus carota Bokti Indonesia Daucus carota Bortol Sudan Daucus carota Bugas Philippines Oryza sativa Buko Philippines Cocos nucifera Bunna Ethiopia Coffea arabica 582 MEDICINAL PLANTS OF THE WORLD

Buzar qatona Arabic countries Plantago ovata Byg Denmark Hordeum vulgare Bygg Faeroe Islands Hordeum vulgare Bygg Iceland Hordeum vulgare Bygg Norway Hordeum vulgare Cabbage palm United States Serenoa repens Ca-fae Thailand Coffea arabica Café Africa Coffea arabica Café Argentina Coffea arabica Café Bolivia Coffea arabica Café Brazil Coffea arabica Café Catalonia Coffea arabica Café Chile Coffea arabica Café Ecuador Coffea arabica Café France Coffea arabica Café Peru Coffea arabica Café Portugal Coffea arabica Café Spain Coffea arabica Café Vietnam Coffea arabica Cafea Romania Coffea arabica Caffe Finland Coffea arabica Caffe Italy Coffea arabica Caife Ireland Coffea arabica Cairead Ireland Daucus carota Caj Albania Camellia sinensis Caj Croatia Camellia sinensis Caj Czech Republic Camellia sinensis Caj Hawaii Camellia sinensis Caj Serbia Camellia sinensis Cana comun Spain Saccharum officinarum Cana de assucar Portugal Saccharum officinarum Cana de azucar Canary Islands Saccharum officinarum Cana de azucar Guatemala Saccharum officinarum Cana de azucar Mexico Saccharum officinarum Cana de azucar Spain Saccharum officinarum Cana dulce Canary Islands Saccharum officinarum Cana dulce Spain Saccharum officinarum Canaduz Spain Saccharum officinarum Canamiel Spain Saccharum officinarum Canamo indico Spain Cannabis sativa Canapa indica Italy Cannabis sativa Cane, sugar India Saccharum officinarum Canhamo Portugal Cannabis sativa Canna da zucchero Italy Saccharum officinarum Canna mele Italy Saccharum officinarum Canne de sucre France Saccharum officinarum Cares Nepal Cannabis sativa Caretysen Cornwall Daucus carota Carot Cambodia Daucus carota Carot Vietnam Daucus carota Carota Italy Daucus carota Carota salvatica Italy Daucus carota CROSS REFERENCE 583

Carota Italy Daucus carota Carote Italy Daucus carota Carotola Germany Daucus carota Carotte sauvage Mauritius Daucus carota Carotte France Daucus carota Carradje The Isle of Man (Manx) Daucus carota Carrot sauvage Belgium Daucus carota Carrot sauvage Canada Daucus carota Carrot sauvage France Daucus carota Carrot sauvage Tunisia Daucus carota Carrot Guyana Daucus carota Carrot United Kingdom Daucus carota Carrot United States Daucus carota Cay gung Vietnam Zingiber officinale Cay mia Vietnam Saccharum officinarum Cay Turkey Camellia sinensis Ceai Romania Camellia sinensis Cebada Spain Hordeum vulgare Cenoura brava Portugal Daucus carota Cenoura selvagem Brazil Daucus carota Cenoura Portugal Daucus carota Cevada Portugal Hordeum vulgare Cha Brazil Camellia sinensis Cha China Camellia sinensis Cha Hawaii Camellia sinensis Cha Pacific Islands Camellia sinensis Cha Portugal Camellia sinensis Cha’ncat Mexico Saccharum officinarum Chaam-kkae Korea Sesamum indicum Chai Bulgaria Camellia sinensis Chai Georgia Coffea arabica Chai Mozambique Camellia sinensis Chai Russia Camellia sinensis Chai Tanzania Camellia sinensis Chai Ukraine Camellia sinensis Chai Zaire Camellia sinensis Chaj Macedonia Camellia sinensis Chanvre cultive France Cannabis sativa Chanvre de l’Inde France Cannabis sativa Chanvre France Cannabis sativa Chanvrier sauvage France Cannabis sativa Chaparral England Larrea tridentata Chaparral United States Larrea tridentata Chapepnomen ba Ecuador Zingiber officinale Charas India Cannabis sativa Chayna roslina Ukraine Camellia sinensis Ch-chientzu China Plantago ovata Chiang China Zingiber officinale Chichambara Nicaragua Zingiber officinale Chinesischer tea Germany Camellia sinensis Chitta Africa Zingiber officinale Chnay Cambodia Zingiber officinale 584 MEDICINAL PLANTS OF THE WORLD

Chou palmiste France Serenoa repens Churras India Cannabis sativa Cno coco England Cocos nucifera Cno coco Ireland Cocos nucifera Cocco Italy Cocos nucifera Coco da Bahia Brazil Cocos nucifera Coco da India Portugal Cocos nucifera Coco fruto Spain Cocos nucifera Coco Portugal Cocos nucifera Coco Spain Cocos nucifera Coconut Guyana Cocos nucifera Cocotera Spain Cocos nucifera Cocotier France Cocos nucifera Cocotier Romania Cocos nucifera Coffee Guyana Coffea arabica Coffee United Kingdom Coffea arabica Coffee United States Coffea arabica Com cay lua Vietnam Oryza sativa Common plantain Arabic countries Plantago ovata Coqueiro da Bahia Brazil Cocos nucifera Coqueiro Portugal Cocos nucifera Corifa del Malabar Italy Serenoa repens Creosote bush Guyana Larrea tridentata Creosote bush England Larrea tridentata Creosote bush United States Larrea tridentata Creosotum United States Larrea tridentata Cro bainney The Isle of Man Cocos nucifera Cukornad Hungary Saccharum officinarum Cukrova trtina Czech Republic Saccharum officinarum Culoare masline Romania Olea europaea Cunuc yacu Ecuador Camellia sinensis Curral Scotland Daucus carota Curran Scotland Daucus carota Cycam Bulgaria Sesamum indicum Da ma cao China Cannabis sativa Da ma ren China Cannabis sativa Da ma China Cannabis sativa Daab India Cocos nucifera Dafu Kenya Cocos nucifera Dafu Mozambique Cocos nucifera Dafu Tanzania Cocos nucifera Dafu Zaire Cocos nucifera Dagga South Africa Cannabis sativa Dansk pot Denmark Cannabis sativa Dauco marino Italy Daucus carota Daucus carotte France Daucus carota Dee la Thailand Sesamum indicum Dege e ullirit Albania Olea europaea Dé-oo-wé Colombia Nicotiana tabacum Devil’s dung United States Ferula assafoetida Djae Indonesia Zingiber officinale Djahe Netherlands Zingiber officinale CROSS REFERENCE 585

Djoflatao Iceland Ferula assafoetida Dohány Hungary Nicotiana tabacum Driveldrikis Latvia Ferula assafoetida Dua Vietnam Cocos nucifera Duhan Albania Nicotiana tabacum Duhan Croatia Nicotiana tabacum Duivelsdrek Netherlands Ferula assafoetida Dulce, cana Canary Islands Saccharum officinarum Dumber Croatia Zingiber officinale Dumbier lekarstvy Slovakia Zingiber officinale Duvan Serbia Nicotiana tabacum Duvn Serbia Nicotiana tabacum Dwarf Evergreen Oak United States Larrea tridentata Dybaco Wales Nicotiana tabacum Dyvelsdrak Denmark Ferula assafoetida Dyvelsdrekk Norway Ferula assafoetida Dyvelstrack Sweden Ferula assafoetida Dzhindzhifil Bulgaria Zingiber officinale E´-li Colombia Nicotiana tabacum Eaj Czech Republic Camellia sinensis Eajovnik Czech Republic Camellia sinensis Echemik Bulgaria Hordeum vulgare Echter hanf Germany Cannabis sativa Echter tabak Germany Nicotiana tabacum Elb Albania Hordeum vulgare Elia Greece Olea europaea Ellu India Sesamum indicum Engifer Iceland Zingiber officinale Eorna Scotland Hordeum vulgare Erus Malaysia Oryza sativa Esrar Turkey Cannabis sativa Euroopa olipuu Estonia Olea europaea Eylbert Israel Olea europaea Faco Wales Nicotiana tabacum Ferule persique France Ferula assafoetida Fyglys Wales Nicotiana tabacum Ga feh China Coffea arabica Gaajara India Daucus carota Gaanjaa Nepal Cannabis sativa Gafae Thailand Coffea arabica Gahzar India Daucus carota Gaiweruam Germany Daucus carota Gajar India Daucus carota Gajiimaa Nepal Cannabis sativa Gajjarakkilangu India Daucus carota Gajor India Daucus carota Gamug Tibet Zingiber officinale Gan jinang China Zingiber officinale Gan zhe China Saccharum officinarum Ganiesi Nicaragua Saccharum officinarum Ganja Guyana Cannabis sativa Ganja India Cannabis sativa 586 MEDICINAL PLANTS OF THE WORLD

Ganna Nepal Saccharum officinarum Ganna Pakistan Saccharum officinarum Gannaa India Saccharum officinarum Gannaa Pakistan Saccharum officinarum Garase South Africa Hordeum vulgare Gawz el Hindi Arabic countries Cocos nucifera Gazar baladi India Daucus carota Gazar India Daucus carota Gazur India Daucus carota Gelbe Rube Germany Daucus carota Gele peen Netherlands Daucus carota Gele Wortel Netherlands Daucus carota Gember Indonesia Zingiber officinale Gember Netherlands Zingiber officinale Gendari Pakistan Saccharum officinarum Gengibre Brazil Zingiber officinale Gengibre Portugal Zingiber officinale Gengibre Spain Zingiber officinale Gengibre Venezuela Zingiber officinale Gergelim Brazil Sesamum indicum Gerst Netherlands Hordeum vulgare Gerste Germany Hordeum vulgare Gewone gerst Netherlands Hordeum vulgare Ghah’veh Iran Coffea arabica Ghimbir Romania Zingiber officinale Gin Myanmar Zingiber officinale Gingebre Mauritius Zingiber officinale Gingebre Spain Zingiber officinale Gingebre Vietnam Zingiber officinale Gingelly United Kingdom Sesamum indicum Gingembre France Zingiber officinale Ginger Brazil Zingiber officinale Ginger China Zingiber officinale Ginger Greece Zingiber officinale Ginger Guyana Zingiber officinale Ginger India Zingiber officinale Ginger Jamaica Zingiber officinale Ginger Japan Zingiber officinale Ginger Nepal Zingiber officinale Ginger Nicaragua Zingiber officinale Ginger Philippines Zingiber officinale Ginger Sri Lanka Zingiber officinale Ginger Taiwan Zingiber officinale Ginger Tanzania Zingiber officinale Ginger United States Zingiber officinale Ginger Venezuela Zingiber officinale Gobernadora England Larrea tridentata Gobernadora Spain Larrea tridentata Gobernadora United States Larrea tridentata Godenvoedsel Netherlands Ferula assafoetida Gojabghbegh Armenia Zingiber officinale Goma Japan Sesamum indicum CROSS REFERENCE 587

Grand tabac France Nicotiana tabacum Grease bush United States Larrea tridentata Greasewood United States Larrea tridentata Grifa Spain Cannabis sativa Grote waaier palm Netherlands Serenoa repens Guamis Spain Larrea tridentata Gujjur India Daucus carota Gujjur-jo-beej India Daucus carota Gularot Faeroe Islands Daucus carota Gulerod Denmark Daucus carota Gullerodder Denmark Daucus carota Gulrot Norway Daucus carota Gung Vietnam Zingiber officinale Guo zhe China Saccharum officinarum Gyin sein Myanmar Zingiber officinale Gyin Myanmar Zingiber officinale Gyomber Hungary Zingiber officinale Hab zargah Arabic countries Plantago ovata Hachis Spain Cannabis sativa Haidd Wales Hordeum vulgare Hajupihka Finland Ferula assafoetida Halia bara Malaysia Zingiber officinale Halia Malaysia Zingiber officinale Haliya merah Malaysia Zingiber officinale Haliya Indonesia Zingiber officinale Hamp Denmark Cannabis sativa Hamp Norway Cannabis sativa Hampa Sweden Cannabis sativa Hampjurt Iceland Cannabis sativa Hamppu Finland Cannabis sativa Hanf Germany Cannabis sativa Harilik ingver Estonia Zingiber officinale Harilik kanep Slovenia Cannabis sativa Harilik seesam Estonia Sesamum indicum Harilik suhkruroog Estonia Saccharum officinarum Haschischpflanze Germany Cannabis sativa Hash United Kingdom Cannabis sativa Hashas Turkey Cannabis sativa Hashish Morocco Cannabis sativa Have-gulerod Denmark Daucus carota Havijk Iran Daucus carota Havuc Turkey Daucus carota Havupunkit Finland Saccharum officinarum Hediondilla Spain Larrea tridentata Hei chih ma China Sesamum indicum Hemp United Kingdom Cannabis sativa Hengu India Ferula assafoetida Hennep Netherlands Cannabis sativa Hentgagan engouz Armenia Cocos nucifera Herbata Poland Camellia sinensis Hind kinnabi Turkey Cannabis sativa Hindistancevizi Turkey Cocos nucifera 588 MEDICINAL PLANTS OF THE WORLD

Hing Bangladesh Ferula assafoetida Hing India Ferula assafoetida Hingu India Ferula assafoetida Hli Papua-New Guinea Zingiber officinale Hogesoppu India Nicotiana tabacum Hong cai tou China Daucus carota Hong da gen China Daucus carota Hong gan zhe China Saccharum officinarum Hong lu fai China Daucus carota Hong luo bo China Daucus carota Hu lu fai China Daucus carota Hu luo bo China Daucus carota Huang luo bo China Daucus carota Hu-lo-po-tze China Daucus carota Huo ma cao China Cannabis sativa Huo ma China Cannabis sativa I kokosit Albania Cocos nucifera Icayi Rwanda Camellia sinensis Iikh India Saccharum officinarum Ikherothi Africa Daucus carota Ikhhu Pakistan Saccharum officinarum Ikhofi Africa Coffea arabica Ikofu South Africa Coffea arabica Ilayisi Africa Oryza sativa Ilikherothi Africa Daucus carota Ilitye Africa Camellia sinensis Imberias Lithuania Zingiber officinale Imbir Poland Zingiber officinale Imbir Russia Zingiber officinale Imbyr Ukraine Zingiber officinale Inber Israel Zingiber officinale Inbwer Germany Zingiber officinale Inchi India Zingiber officinale Indian hemp United Kingdom Cannabis sativa Indische hennep Netherlands Cannabis sativa Indischer hanf Germany Cannabis sativa Indisk hamp Sweden Cannabis sativa Ingee India Zingiber officinale Ingefara Sweden Zingiber officinale Ingefer Denmark Zingiber officinale Ingefer Norway Zingiber officinale Ingu India Ferula assafoetida Inguru Japan Zingiber officinale Inguru Sri Lanka Zingiber officinale Inguva India Ferula assafoetida Ingver Croatia Zingiber officinale Ingver Slovenia Zingiber officinale Ingverijuur Estonia Zingiber officinale Ingwer Germany Zingiber officinale Ingwer Tanzania Zingiber officinale Inkivaari Finland Zingiber officinale Isiot Bulgaria Zingiber officinale CROSS REFERENCE 589

Isphghol India Plantago ovata Itiye Africa Camellia sinensis Jae Indonesia Zingiber officinale Jahe Indonesia Zingiber officinale Jahi Malaysia Zingiber officinale Jaitun India Olea europaea Jamaica ginger United States Zingiber officinale Jamveel Iran Zingiber officinale Janzabeil Sudan Zingiber officinale Jarilla Spain Larrea tridentata Jazar barri Iraq Daucus carota Jecam Croatia Hordeum vulgare Jecam Serbia Hordeum vulgare Jeczmien Poland Hordeum vulgare Jeemen Czech Republic Hordeum vulgare Jenegibre Venezuela Zingiber officinale Jengibre Cuba Zingiber officinale Jengibre Spain Zingiber officinale Jenibre Guatemala Zingiber officinale Jenjibre Ecuador Zingiber officinale Jenjibre Nicaragua Zingiber officinale Jeung China Zingiber officinale Jiang China Zingiber officinale Jinjaa Japan Zingiber officinale Jitabdoogh Armenia Olea europaea Jiteni Armenia Olea europaea Ju zhong lu China Serenoa repens Julipe India Olea europaea Ka’fe Israel Coffea arabica Kaafi India Coffea arabica Kaapi Central America Coffea arabica Kaapi Mexico Coffea arabica Kaapiopalmu Finland Serenoa repens Kaareti New Zealand Daucus carota Kaawa Uganda Coffea arabica Kafa Serbia Coffea arabica Kafa Turkey Cocos nucifera Kafe Albania Coffea arabica Kafe Bulgaria Coffea arabica Kafe Czech Republic Coffea arabica Kafe Gambia Coffea arabica Kafe Greece Coffea arabica Kafe Latin America Coffea arabica Kafe Senegal Coffea arabica Ka-fei China Coffea arabica Kaffe Denmark Coffea arabica Kaffe Norway Coffea arabica Kaffe Sweden Coffea arabica Kaffee Germany Coffea arabica Kaffeeplante Norway Coffea arabica Kaffeestrauch Germany Coffea arabica Kaffi Iceland Coffea arabica 590 MEDICINAL PLANTS OF THE WORLD

Kafija Latvia Coffea arabica Kahawa Africa Coffea arabica Kahioa Arabic countries Coffea arabica Kahva Bosnia Coffea arabica Kahve Turkey Coffea arabica Kahvi Finland Coffea arabica Kai China Zingiber officinale Kallamu India Zingiber officinale Kama I anguza Afghanistan Ferula assafoetida Kama I anguza Pakistan Ferula assafoetida Kan chiang Vietnam Zingiber officinale Kaneh Israel Saccharum officinarum Kanga Papua-New Guinea Zingiber officinale Kannabis Finland Cannabis sativa Kannabisu Japan Cannabis sativa Kansha Japan Saccharum officinarum Kanvoc Greece Nicotiana tabacum Kape Philippines Coffea arabica Kapva Greece Nicotiana tabacum Karga India Oryza sativa Karida Greece Cocos nucifera Karlikova palma Ukraine Serenoa repens Karlikovaya palma Russia Serenoa repens Karot Australia Daucus carota Karot Cambodia Daucus carota Karot Netherlands Antilles Daucus carota Karot Philippines Daucus carota Karote Albania Daucus carota Karote Hawaii Daucus carota Karoti Samoa Daucus carota Karoto Greece Daucus carota Karotte Germany Daucus carota Karotten Germany Daucus carota Karotter Denmark Daucus carota Karuthellu India Sesamum indicum Karuvathu kelengu India Daucus carota Karyda Greece Cocos nucifera Kava Croatia Coffea arabica Kava Czech Republic Coffea arabica Kava Lithuania Coffea arabica Kava Slovakia Coffea arabica Kava Slovenia Coffea arabica Kava Ukraine Coffea arabica Kave Hungary Coffea arabica Kave Israel Coffea arabica Kawa Poland Coffea arabica Kayam India Ferula assafoetida Kdyuir Turkmenistan Daucus carota Ke ke ye zi Taiwan Cocos nucifera Kelapa Indonesia Cocos nucifera Kelapa Malaysia Cocos nucifera Keong China Zingiber officinale CROSS REFERENCE 591

Kerati Papua-New Guinea Zingiber officinale Kerp Albania Cannabis sativa Khaerot Thailand Daucus carota Khand Pakistan Saccharum officinarum Khasa India Sesamum indicum Kherm´-ba Ecuador Nicotiana tabacum Khing Laos Zingiber officinale Khing Thailand Zingiber officinale Khing-daen Thailand Zingiber officinale Khnehey Cambodia Zingiber officinale Khnhei phlung Cambodia Zingiber officinale Khokhonate South Africa Cocos nucifera Khuong Vietnam Zingiber officinale Khyen-seing Myanmar Zingiber officinale Kinkh Thailand Zingiber officinale Kinnab Turkey Cannabis sativa Kintoki Japan Zingiber officinale Kion Peru Zingiber officinale Kis legyezopalma Hungary Serenoa repens Kkae Korea Sesamum indicum Klao Thailand Oryza sativa Klapper Netherlands Cocos nucifera Klapperboom Netherlands Cocos nucifera Ko Hawaii Saccharum officinarum Koarn Netherlands Hordeum vulgare Koba Japan Sesamum indicum Kobari India Cocos nucifera Kobbai India Cocos nucifera Kobbai Sri Lanka Cocos nucifera Kobbera India Cocos nucifera Kobbera Sri Lanka Cocos nucifera Kofe Russia Coffea arabica Koffee India Coffea arabica Koffi United Kingdom Coffea arabica Koffie Netherlands Coffea arabica Koffie South Africa Coffea arabica Koffieboom Netherlands Coffea arabica Kofi Botswana Coffea arabica Kofi South Africa Coffea arabica Kofii India Coffea arabica Kofje Netherlands Coffea arabica Kohv Estonia Coffea arabica Kok mak phao Laos Cocos nucifera Kokas Ethiopia Cocos nucifera Kokkofoinika Greece Cocos nucifera Koko yashi Japan Cocos nucifera Koko Spain Cocos nucifera Kokonet Ethiopia Cocos nucifera Kokos orekonosnyi Russia Cocos nucifera Kokos Bulgaria Cocos nucifera Kokos Croatia Cocos nucifera Kokos Czech Republic Cocos nucifera 592 MEDICINAL PLANTS OF THE WORLD

Kokos Germany Cocos nucifera Kokos Netherlands Cocos nucifera Kokos Russia Cocos nucifera Kokos Sweden Cocos nucifera Kokos Ukraine Cocos nucifera Kokosa Slovenia Cocos nucifera Kokoshneta Iceland Cocos nucifera Kokosnoed Denmark Cocos nucifera Kokosnoot Netherlands Cocos nucifera Kokosnot Sweden Cocos nucifera Kokosnus Israel Cocos nucifera Kokosnuss Germany Cocos nucifera Kokosnut Netherlands Cocos nucifera Kokosnut Spain Cocos nucifera Kokosov orah Croatia Cocos nucifera Kokosov orah Serbia Cocos nucifera Kokosov orech Bulgaria Cocos nucifera Kokosov Bulgaria Cocos nucifera Kokosova palma Slovenia Cocos nucifera Kokosovaia pal’ma Russia Cocos nucifera Kokosovy orech Czech Republic Cocos nucifera Kokosovy orech Slovakia Cocos nucifera Kokosovyj orech Ukraine Cocos nucifera Kokosovyj orjekh Russia Cocos nucifera Kokospalm Netherlands Cocos nucifera Kokospalm Sweden Cocos nucifera Kokospalme Denmark Cocos nucifera Kokospalme Germany Cocos nucifera Kokronoto Suriname Cocos nucifera Kokus Israel Cocos nucifera Kokusnod Faeroe Islands Cocos nucifera Kokuszdio Hungary Cocos nucifera Konga Papua-New Guinea Zingiber officinale Konjed Iran Sesamum indicum Konopie siewne Poland Cannabis sativa Konopie Poland Cannabis sativa Konoplja Slovenia Cannabis sativa Koohii Japan Coffea arabica Kookospahkina Finland Cocos nucifera Kookospalm Estonia Cocos nucifera Kookospalmu Finland Cocos nucifera Kope Hawaii Coffea arabica Kopi Indonesia Coffea arabica Kopi Malaysia Coffea arabica Ko-pi Sri Lanka Coffea arabica Ko-pyi Korea Coffea arabica Korn Sweden Hordeum vulgare Kreosotestrauch Germany Larrea tridentata Kronto Suriname Cocos nucifera Kultur hanf Germany Cannabis sativa Kunyit terus Malaysia Zingiber officinale Kunzhut Russia Sesamum indicum CROSS REFERENCE 593

Kunzuut Estonia Sesamum indicum Kushiar Pakistan Saccharum officinarum Lag Guyana Cocos nucifera Lahja Indonesia Zingiber officinale Lao jiang China Zingiber officinale Lee-cah fee United States Coffea arabica Lei Admiralty Islands Zingiber officinale Lia Indonesia Zingiber officinale Linga Philippines Sesamum indicum Lisn al kalb Arabic countries Plantago ovata Lobak merah Malaysia Daucus carota Loso Congo Oryza sativa Luama Vietnam Oryza sativa Lukux-ri Colombia Nicotiana tabacum Luya Philippines Zingiber officinale Ma ha hing Laos Ferula assafoetida Ma phra on Thailand Cocos nucifera Maak muu Thailand Cocos nucifera Mach’ca Ecuador Hordeum vulgare Maco Wales Nicotiana tabacum Maconha Portugal Cannabis sativa Mahora Romania Nicotiana tabacum Mak un on Myanmar Cocos nucifera Man nga Laos Sesamum indicum Maphrao Thailand Cocos nucifera Mar India Cocos nucifera Marchew Poland Daucus carota Marihana Netherlands Cannabis sativa Marihouava Greece Cannabis sativa Marihuana Bulgaria Cannabis sativa Marihuana Croatia Cannabis sativa Marihuana Czech Republic Cannabis sativa Marihuana Denmark Cannabis sativa Marihuana France Cannabis sativa Marihuana Germany Cannabis sativa Marihuana Hungary Cannabis sativa Marihuana Mexico Cannabis sativa Marihuana Poland Cannabis sativa Marihuana Russia Cannabis sativa Marihuana Serbia Cannabis sativa Marihuana Spain Cannabis sativa Marihuana Ukraine Cannabis sativa Marihuana United States Cannabis sativa Marijuana France Cannabis sativa Marijuana Italy Cannabis sativa Marijuana Mexico Cannabis sativa Marijuana Portugal Cannabis sativa Marijuana Sweden Cannabis sativa Mashinin Japan Cannabis sativa Maslin Romania Olea europaea Maslina Bulgaria Olea europaea Maslina Croatia Olea europaea 594 MEDICINAL PLANTS OF THE WORLD

Maslina Serbia Olea europaea Maslina Ukraine Olea europaea Masline Israel Olea europaea Masliniu Romania Olea europaea Maslinov Croatia Olea europaea Maslinov Serbia Olea europaea Mchele Mozambique Oryza sativa Mchele Tanzania Oryza sativa Mchele Zaire Oryza sativa Meacan dearg Ireland Daucus carota Mehrzeilige Gerste Germany Hordeum vulgare Merde du diable France Ferula assafoetida Mia Vietnam Saccharum officinarum Mitmerealine oder Estonia Hordeum vulgare Mittho-tel India Sesamum indicum Mnazi Mozambique Cocos nucifera Mnazi Southeastern Africa Cocos nucifera Mnazi Tanzania Cocos nucifera Mnazi Zaire Cocos nucifera Moa China Sesamum indicum Moba Tanzania Saccharum officinarum Mohlware South Africa Olea europaea Mohre Germany Daucus carota Mohrrube Germany Daucus carota Monitahoohra Finland Hordeum vulgare Morkov Bulgaria Daucus carota Morkov Macedonia Daucus carota Morkov Romania Daucus carota Morkov Russia Daucus carota Morkva Ukraine Daucus carota Moronen Wales Daucus carota Morot Sweden Daucus carota Mpunga Africa Oryza sativa Mrkva Yugoslavia Daucus carota Mtangwizi Tanzania Zingiber officinale Mua chi China Sesamum indicum Mu-lu´ Colombia Nicotiana tabacum Mupunga Botswana Oryza sativa Mupunga Zambia Oryza sativa Mupunga Zimbabwe Oryza sativa Mvuje Mozambique Ferula assafoetida Mvuje Tanzania Ferula assafoetida Mvuje Zaire Ferula assafoetida Myglys Wales Nicotiana tabacum Myoga Japan Zingiber officinale Naarakel India Cocos nucifera Naariyal kaa per India Cocos nucifera Naariyal kaa per Pakistan Cocos nucifera Naariyal India Cocos nucifera Naariyal Pakistan Cocos nucifera Nadiya India Cocos nucifera Nagara India Zingiber officinale CROSS REFERENCE 595

Naishekar Iran Saccharum officinarum Nalikeran Malaysia Cocos nucifera Nanivaara India Cocos nucifera Naral India Cocos nucifera Nargil Arabic countries Cocos nucifera Nargil Iran Cocos nucifera Narial India Cocos nucifera Narikela India Cocos nucifera Narikol India Cocos nucifera Narival Nepal Cocos nucifera Nariyal India Cocos nucifera Narkel India Cocos nucifera Nasi Indonesia Oryza sativa Natsume yashi Japan Cocos nucifera Navadna konoplja Slovenia Cannabis sativa Navadni tobak Slovenia Nicotiana tabacum Nazi Mozambique Cocos nucifera Nazi Tanzania Cocos nucifera Nazi Zaire Cocos nucifera Nga Laos Sesamum indicum Ngaa Thailand Sesamum indicum Ngesnges Papua-New Guinea Zingiber officinale Ngjyre ulliri Albania Olea europaea Nhybaco Wales Nicotiana tabacum Nicotiane France Nicotiana tabacum Niistsikapa’s United States Daucus carota Niska palma Bulgaria Serenoa repens Niyog Philippines Cocos nucifera Niyok Hawaii Cocos nucifera Niyok Pacific Islands Cocos nucifera Nkrabo Africa Zingiber officinale Nkrama Africa Zingiber officinale Nkrawusa Africa Zingiber officinale No China Oryza sativa Noble cane United States Saccharum officinarum Noce di cocco Italy Cocos nucifera Noix de coco France Cocos nucifera Nora-ninjij Japan Daucus carota Noz de coco Portugal Cocos nucifera Nuca de cocos Romania Cocos nucifera Nuez de coco Spain Cocos nucifera Nuvvulu India Sesamum indicum Nyior Malaysia Cocos nucifera Oarn The Isle of Man (Manx) Hordeum vulgare Oastre Spain Olea europaea Obeko Japan Plantago ovata Ohra Finland Hordeum vulgare Oi daeng Thailand Saccharum officinarum Oi Thailand Saccharum officinarum Olajbogyo Hungary Olea europaea Olajfa Hungary Olea europaea Olbaum Germany Olea europaea 596 MEDICINAL PLANTS OF THE WORLD

Oleifi Netherlands Antilles Olea europaea Olewydden England Olea europaea Oliba Spain Olea europaea Olifa Iceland Olea europaea Oliif Spain Olea europaea Oliivi Finland Olea europaea Olijf Netherlands Olea europaea Oliondo Spain Olea europaea Olipuus Estonia Olea europaea Oliv Sweden Olea europaea Oliva europska Slovakia Olea europaea Oliva Czech Republic Olea europaea Oliva Ethiopia Olea europaea Oliva Hungary Olea europaea Oliva Italy Olea europaea Oliva Portugal Olea europaea Oliva Romania Olea europaea Oliva Russia Olea europaea Oliva Spain Olea europaea Oliva Ukraine Olea europaea Olivas Latvia Olea europaea Olive England Olea europaea Olive France Olea europaea Olive Germany Olea europaea Olive Guyana Olea europaea Olive The Isle of Man (Manx) Olea europaea Olive United States Olea europaea Oliveira Portugal Olea europaea Oliven Denmark Olea europaea Oliven Norway Olea europaea Olivenbaum Germany Olea europaea Olivera Spain Olea europaea Olivgront Sweden Olea europaea Olivo Spain Olea europaea Olivove drevo Czech Republic Olea europaea Olivovnik europsky Slovakia Olea europaea Olivovnik Czech Republic Olea europaea Olivy Czech Republic Olea europaea Oliwka Poland Olea europaea Oljka Slovenia Olea europaea Oljypuu Finland Olea europaea Olyf Cornwall Olea europaea Olyva Ukraine Olea europaea Ordoggyoker Hungary Ferula assafoetida Orez Romania Oryza sativa Orge France Hordeum vulgare Oriz Albania Oryza sativa Oriz Bulgaria Oryza sativa Oriz Macedonia Oryza sativa Orizen Bulgaria Oryza sativa Orizov Bulgaria Oryza sativa Orz Romania Hordeum vulgare CROSS REFERENCE 597

Orzo Italy Hordeum vulgare Oshoga Japan Zingiber officinale Oti United States Camellia sinensis Oulivie France Olea europaea Padi ketek Indonesia Oryza sativa Pagári-mulé Colombia Nicotiana tabacum Pahari gajar India Daucus carota Palana Papua-New Guinea Zingiber officinale Palma de coco Spain Cocos nucifera Palma del cocco Italy Cocos nucifera Palma enana Americana Spain Serenoa repens Palma kokosowa Poland Cocos nucifera Palma nana Italy Serenoa repens Palma sabal Spain Serenoa repens Palmeen The Isle of Man (Manx) Serenoa repens Palmera de coco Spain Cocos nucifera Palmet Netherlands Serenoa repens Palmetta Della Florida Italy Serenoa repens Palmetto de la sierra Spain Serenoa repens Palmetto fan palm United States Serenoa repens Palmetto, dark United States Serenoa repens Palmier nain France Serenoa repens Palmier pitic Romania Serenoa repens Palmito Portugal Serenoa repens Palmito Spain Serenoa repens Paloondo Spain Larrea tridentata Paparean Indonesia Oryza sativa Pastanaga Spain Daucus carota Pastenade France Daucus carota Pastenaga France Daucus carota Pastinaca selvatica Italy Daucus carota Peen Netherlands Daucus carota Perungayam India Ferula assafoetida Perunkaya India Ferula assafoetida Perunkayan Sri Lanka Ferula assafoetida Petun Brazil Nicotiana tabacum Phakchi-daeng Thailand Daucus carota Pia di udi Ecuador Zingiber officinale Pia nuni Ecuador Zingiber officinale Piperoriza Greece Zingiber officinale Pirinac Croatia Oryza sativa Pirinac Serbia Oryza sativa Pirinac Turkey Oryza sativa Pirinac Yugoslavia Oryza sativa Pirinc Turkey Oryza sativa Pirunpaska Finland Ferula assafoetida Pirunpihka Finland Ferula assafoetida Pitta gajur India Daucus carota Pogaku India Nicotiana tabacum Pokala India Nicotiana tabacum Polgaha Sri Lanka Cocos nucifera Porkanchaa Thailand Cannabis sativa 598 MEDICINAL PLANTS OF THE WORLD

Porkkana Finland Daucus carota Pot Denmark Cannabis sativa Psillo indiano Germany Plantago ovata Pugaiyilai India Nicotiana tabacum Pugas Hawaii Oryza sativa Pugas Pacific Islands Oryza sativa Qahve Azerbaijan Coffea arabica Qahve Yemen Coffea arabica Qahwah Arabic countries Coffea arabica Qasab al sukkar Arabic countries Saccharum officinarum Qasab es sukkar Arabic countries Saccharum officinarum Qinnib Arabic countries Cannabis sativa Qolli Boliwia Olea europaea Qolli Peru Olea europaea Qoqus Israel Cocos nucifera Queen Anne’s lace Canada Daucus carota Quing jiang China Zingiber officinale Qurayta Arabic countries Plantago ovata Raamathan India Ferula assafoetida Rabell Spain Olea europaea Raihi New Zealand Oryza sativa Rasi India Sesamum indicum Rebla Arabic countries Plantago ovata Rechina fena Iran Ferula assafoetida Reesa India Oryza sativa Reis England Oryza sativa Reis Germany Oryza sativa Reise The Isle of Man (Manx) Oryza sativa Reisi South Africa Oryza sativa Rhizoma, zingiberis Japan Zingiber officinale Rice Guyana Oryza sativa Rice India Oryza sativa Rice United Kingdom Oryza sativa Rice United States Oryza sativa Riesen hanf Germany Cannabis sativa Riisi Finland Oryza sativa Rijst Netherlands Oryza sativa Ris Denmark Oryza sativa Ris Faroe Islands Oryza sativa Ris France Oryza sativa Ris Norway Oryza sativa Ris Russia Oryza sativa Ris Sweden Oryza sativa Ris Switzerland Oryza sativa Ris Ukraine Oryza sativa Risch melna Switzerland Daucus carota Risgryn Sweden Oryza sativa Riso Italy Oryza sativa Riz France Oryza sativa Riz Rwanda Oryza sativa Rizs Hungary Oryza sativa Ruokaporkana Finland Daucus carota CROSS REFERENCE 599

Ruzi Greece Oryza sativa Rys Netherlands Oryza sativa Rys South Africa Oryza sativa Ryz Poland Oryza sativa Ryze Czech Republic Oryza sativa Saat-Gerste Germany Hordeum vulgare Sabal du Mexique France Serenoa repens Sabal du Texas France Serenoa repens Sabal United States Serenoa repens Saccar Nepal Saccharum officinarum Saeng gang Korea Zingiber officinale Sagapeen Netherlands Ferula assafoetida Sagepalme Germany Serenoa repens Sagepalmefruchte Germany Serenoa repens Sagpalmetto Sweden Serenoa repens Sahacar Nepal Saccharum officinarum Sahachar Nepal Saccharum officinarum Saidun India Olea europaea Saidun Sri Lanka Olea europaea Sakhara India Saccharum officinarum Sakharnyi trostnik kul’turnyi Russia Saccharum officinarum Sakharnyi trostnik lekarstvennyi Russia Saccharum officinarum Salebyeo Korea Oryza sativa San geung China Zingiber officinale Sang keong China Zingiber officinale Sargarepa Croatia Daucus carota Sargarepa Hungary Daucus carota Sargarepa Serbia Daucus carota Sasim Arabic countries Sesamum indicum Satou kibi Japan Saccharum officinarum Saw palmetto Guyana Serenoa repens Saw palmetto United Kingdom Serenoa repens Saw palmetto United States Serenoa repens Sechszeilige Gerste Germany Hordeum vulgare Seesami Finland Sesamum indicum Segwere South Africa Daucus carota Semsem United Kingdom Sesamum indicum Serenoa palmu Finland Serenoa repens Seruma erva Portugal Cannabis sativa Sesam Denmark Sesamum indicum Sesam Germany Sesamum indicum Sesam Spain Sesamum indicum Sesam Sweden Sesamum indicum Sesame France Sesamum indicum Sesame United Kingdom Sesamum indicum Sesame United States Sesamum indicum Sesamfre Iceland Sesamum indicum Sesami Greece Sesamum indicum Sesamkruid Netherlands Sesamum indicum Sesamo Italy Sesamum indicum Sesamo Portugal Sesamum indicum Sesamo Spain Sesamum indicum 600 MEDICINAL PLANTS OF THE WORLD

Sesamzaad Netherlands Sesamum indicum Setan bokosu Turkey Ferula assafoetida Seytan tersi Turkey Ferula assafoetida Sezam indicky Slovakia Sesamum indicum Sezam Croatia Sesamum indicum Sezam Czech Republic Sesamum indicum Sezam Poland Sesamum indicum Sezam Russia Sesamum indicum Sezam Ukraine Sesamum indicum Sezama seklas Latvia Sesamum indicum Sezama Slovenia Sesamum indicum Sezamas Lithuania Sesamum indicum Sezamo Spain Sesamum indicum Sga smug Tibet Zingiber officinale Shecerna trska Croatia Saccharum officinarum Shecerna trska Serbia Saccharum officinarum Sheingho Myanmar Ferula assafoetida Shen jiang China Zingiber officinale Shengijang China Zingiber officinale Shing-kun Tibet Ferula assafoetida Shohkyoh Japan Zingiber officinale Shokyo Japan Zingiber officinale Shokyo Taiwan Zingiber officinale Shooshma Armenia Sesamum indicum Shooshmayi good Armenia Sesamum indicum Shouga Japan Zingiber officinale Shoukyo Japan Zingiber officinale Shoukyo Taiwan Zingiber officinale Shringaveran India Zingiber officinale Shukku India Zingiber officinale Shumshum Israel Sesamum indicum Shuntya India Zingiber officinale Sibada Hawaii Hordeum vulgare Sibada Pacific Islands Hordeum vulgare Sim-sim Arabic countries Sesamum indicum Sim-sim Netherlands Sesamum indicum Sinh khuong Vietnam Zingiber officinale Sinziminli Africa Zingiber officinale Skenjabil Morocco Zingiber officinale Skenjbir Morocco Zingiber officinale Sladkornitrs Slovenia Saccharum officinarum Sman-sga Tibet Zingiber officinale Sockerror Sweden Saccharum officinarum Sokeriruoko Finland Saccharum officinarum Solfjaderspalm Sweden Serenoa repens Sonth India Zingiber officinale Sourdj Armenia Coffea arabica Spangur India Plantago ovata Speisemohre Germany Daucus carota Speisemohren Germany Daucus carota Spisegulerod Denmark Daucus carota Spogel Iran Plantago ovata CROSS REFERENCE 601

Sragne Cambodia Oryza sativa Sringaaran India Zingiber officinale Stinkasant Germany Ferula assafoetida Stinking gum United States Ferula assafoetida Sugar cane Barbados Saccharum officinarum Sugar cane Guyana Saccharum officinarum Sugar cane India Saccharum officinarum Sugar cane Indonesia Saccharum officinarum Sugar cane Iran Saccharum officinarum Sugar cane Jamaica Saccharum officinarum Sugar cane Tanzania Saccharum officinarum Sugar cane Trinidad Saccharum officinarum Sugarcane Hawaii Saccharum officinarum Sugarcane, blue ribbon United States Saccharum officinarum Suikerriet Netherlands Saccharum officinarum Sukkerroer Denmark Saccharum officinarum Sukkerror Norway Saccharum officinarum Sunth India Zingiber officinale Sunthi India Zingiber officinale Suom Finland Sesamum indicum Susam Albania Sesamum indicum Susam Bulgaria Sesamum indicum Susam Turkey Sesamum indicum Susan Romania Sesamum indicum Sutho Nepal Zingiber officinale Sven Sweden Sesamum indicum Szezam Hungary Sesamum indicum Szezammag Hungary Sesamum indicum Szezammag Israel Sesamum indicum T’ha’ari Tahiti Cocos nucifera Taa Germany Camellia sinensis Tabac France Nicotiana tabacum Tabac Spain Nicotiana tabacum Tabacco Virginia Italy Nicotiana tabacum Tabacni izdelki Slovenia Nicotiana tabacum Tabaco Brazil Nicotiana tabacum Tabaco Mexico Nicotiana tabacum Tabaco Portugal Nicotiana tabacum Tabaco Spain Nicotiana tabacum Tabaco Venezuela Nicotiana tabacum Tabák Czech Republic Nicotiana tabacum Tabak Germany Nicotiana tabacum Tabak Netherlands Nicotiana tabacum Tabak South Africa Nicotiana tabacum Tabak Russia Nicotiana tabacum Tabaka Suriname Nicotiana tabacum Tabako France Nicotiana tabacum Tabako Netherlands Antilles Nicotiana tabacum Tabako Philippines Nicotiana tabacum Tabako Spain Nicotiana tabacum Tabaku Netherlands Antilles Nicotiana tabacum Tabat France Nicotiana tabacum 602 MEDICINAL PLANTS OF THE WORLD

Tae Ireland Camellia sinensis Taima Japan Cannabis sativa Tal India Sesamum indicum Tamaku India Nicotiana tabacum Tambaku India Nicotiana tabacum Tamrakatu India Nicotiana tabacum Tangauzi Tanzania Zingiber officinale Tangawizi Tanzania Zingiber officinale Tao China Oryza sativa Te Scotland Camellia sinensis Te Denmark Camellia sinensis Te Faeroe Islands Camellia sinensis Te France Camellia sinensis Te Italy Camellia sinensis Te Norway Camellia sinensis Te Spain Camellia sinensis Te Suriname Camellia sinensis Te Switzerland Camellia sinensis Te Wales Camellia sinensis Tea plant England Camellia sinensis Tea Australia Camellia sinensis Tea England Camellia sinensis Tea Guyana Camellia sinensis Tea Hungary Camellia sinensis Tea United States Camellia sinensis Teboe Indonesia Saccharum officinarum Tebu telur Malaysia Saccharum officinarum Tebu Indonesia Saccharum officinarum Tebu Malaysia Saccharum officinarum Tebusk Denmark Camellia sinensis Tebuske Sweden Camellia sinensis Tee Finland Camellia sinensis Tee Germany Camellia sinensis Tee Netherlands Camellia sinensis Tee South Africa Camellia sinensis Teel France Sesamum indicum Teepensas Finland Camellia sinensis Tembakau Indonesia Nicotiana tabacum Tembakau Malaysia Nicotiana tabacum Temmdki Turkmenistan Nicotiana tabacum Tenkaya India Cocos nucifera Tenkaya Sri Lanka Cocos nucifera Tennai marama India Cocos nucifera Tennai marama Sri Lanka Cocos nucifera Tertuyagas Ecuador Zingiber officinale Teufelsdreck Germany Ferula assafoetida Tey The Isle of Man (Manx) Camellia sinensis Teye South Africa Camellia sinensis The France Camellia sinensis The Indonesia Camellia sinensis The Malaysia Camellia sinensis Thee Netherlands Camellia sinensis CROSS REFERENCE 603

Theesoort Netherlands Camellia sinensis Theestrauch Germany Camellia sinensis Theestruik Netherlands Camellia sinensis Theler France Camellia sinensis Thenga India Cocos nucifera Thenga Malaysia Cocos nucifera Thenga Sri Lanka Cocos nucifera Thenginkai India Cocos nucifera Thengu India Cocos nucifera Thengu Sri Lanka Cocos nucifera Thenkaii India Cocos nucifera Thenkaii Sri Lanka Cocos nucifera Thybaco Wales Nicotiana tabacum Ti Congo Camellia sinensis Ti Samoa Camellia sinensis Ti Scotland Camellia sinensis Tii Greenland Camellia sinensis Tii New Zealand Camellia sinensis Tii Northwest Territories, Canada Camellia sinensis Til Arabic countries Cannabis sativa Til India Sesamum indicum Til Pakistan Sesamum indicum Tila India Sesamum indicum Till France Sesamum indicum Tisi India Sesamum indicum Tiwu Sudan Saccharum officinarum To pi’avare Rarotonga Saccharum officinarum Tobac Ireland Nicotiana tabacum Tobacco Australia Nicotiana tabacum Tobacco Guyana Nicotiana tabacum Tobacco Iceland Nicotiana tabacum Tobacco Italy Nicotiana tabacum Tobacco Kenya Nicotiana tabacum Tobacco New Zealand Nicotiana tabacum Tobacco United Kingdom Nicotiana tabacum Tobacco United States Nicotiana tabacum Tobacco West Indies Nicotiana tabacum Tobak Denmark Nicotiana tabacum Tobak Sweden Nicotiana tabacum Tobaken Sweden Nicotiana tabacum Tobakk Norway Nicotiana tabacum Tobakken Denmark Nicotiana tabacum Tombaca Scotland Nicotiana tabacum Tombagey The Isle of Man (Manx) Nicotiana tabacum Ton oi Thailand Saccharum officinarum Too moo China Hordeum vulgare Toombak Sudan Nicotiana tabacum Tra Vietnam Camellia sinensis Tsa Philippines Camellia sinensis Tsinstsimin China Zingiber officinale Tsintsimir China Zingiber officinale Tubbak Faeroe Islands Nicotiana tabacum 604 MEDICINAL PLANTS OF THE WORLD

Tubo Philippines Saccharum officinarum Tue Papua-New Guinea Saccharum officinarum Tumbako Mozambique Nicotiana tabacum Tumbako Tanzania Nicotiana tabacum Tumbako Zaire Nicotiana tabacum Tupakka Finland Nicotiana tabacum Tutun Romania Nicotiana tabacum Tütün Turkey Nicotiana tabacum Twak South Africa Nicotiana tabacum Tybaco Wales Nicotiana tabacum Tyton szlachetny Poland Nicotiana tabacum Tyutyun Bulgaria Nicotiana tabacum Tyutyun Ukraine Nicotiana tabacum Ufuta Mozambique Sesamum indicum Ufuta Tanzania Sesamum indicum Ugwayi Botswana Nicotiana tabacum Ugwayi South Africa Nicotiana tabacum Ugwayi South Africa Nicotiana tabacum Ukha India Saccharum officinarum Ukhu Nepal Saccharum officinarum Uliva Switzerland Olea europaea Ullastre Spain Olea europaea Ulli Albania Olea europaea Ullir Albania Olea europaea Umupunga Africa Oryza sativa Ungbin Myanmar Cocos nucifera Usa India Saccharum officinarum Usurp China Hordeum vulgare Uuka India Saccharum officinarum Vaaristubukas Estonia Nicotiana tabacum Vanglo Germany Sesamum indicum Vary Madagascar Oryza sativa Velna suds Latvia Ferula assafoetida Vild gulerod Benin Daucus carota Vild gulerod Denmark Daucus carota Viljelty porkkana Finland Daucus carota Vill gulrot Norway Daucus carota Virginiantupakka Finland Nicotiana tabacum Virginiatobak Sweden Nicotiana tabacum Virginiatobakk Norway Nicotiana tabacum Virginischer tabak Germany Nicotiana tabacum Virginsk tobak Denmark Nicotiana tabacum Vrai chanvre France Cannabis sativa Vung Vietnam Sesamum indicum Wai Papua-New Guinea Zingiber officinale Warak sabun masasah Arabic countries Plantago ovata Weed Guyana Cannabis sativa Wijen Indonesia Sesamum indicum Wild carrot Canada Daucus carota Wild carrot England Daucus carota Wild carrot New Zealand Daucus carota Wild gulerod Denmark Daucus carota CROSS REFERENCE 605

Wild rice Australia Oryza sativa Wilde mohre Germany Daucus carota Wilde peen Belgium Daucus carota Wilde peen Netherlands Daucus carota Wilde wortel Belgium Daucus carota Wildmorot Sweden Daucus carota Wortel Indonesia Daucus carota Wortel Netherlands Daucus carota Wortel South Africa Daucus carota Xian ma China Cannabis sativa Yachmen Russia Hordeum vulgare Yachmin Ukraine Hordeum vulgare Yaku-q’oniwan Ecuador Camellia sinensis Yallu India Sesamum indicum Yang hua luo bo China Daucus carota Ye hu luo bo China Daucus carota Ye ma China Cannabis sativa Ye shu China Cocos nucifera Ye zi China Cocos nucifera Ye´-ma Brazil Nicotiana tabacum Zaitun Indonesia Olea europaea Zanahoria Silvestre Dominican Republic Daucus carota Zanahoria silvestre Chile Daucus carota Zanahoria silvestre Peru Daucus carota Zanahoria silvestre Spain Daucus carota Zanahoria silvestre Venezuela Daucus carota Zanahoria Puerto Rico Daucus carota Zanahoria Spain Daucus carota Zangbil Israel Zingiber officinale Zangvil Israel Zingiber officinale Zanjabeel India Zingiber officinale Zanjabeel Saudi Arabia Zingiber officinale Zanjabil Arabic countries Zingiber officinale Zanjabil Iran Zingiber officinale Zapaliczka cuchnaca Poland Ferula assafoetida Zaya Turkmenistan Camellia sinensis Zayit Israel Olea europaea Zaytun Arabic countries Olea europaea Zaz Iran Ferula assafoetida Zazvor Czech Republic Zingiber officinale Zazvor Slovakia Zingiber officinale Zebbug Malta Olea europaea Zeituni Mozambique Olea europaea Zeituni Tanzania Olea europaea Zeituni Zaire Olea europaea Zelzlane Arabic countries Sesamum indicum Zencebil Turkey Zingiber officinale Zencefil Turkey Zingiber officinale Zenzero Italy Zingiber officinale Zenzevero Italy Zingiber officinale Zetis Georgia Olea europaea Zetiskhili Georgia Olea europaea 606 MEDICINAL PLANTS OF THE WORLD

Zeyatin Turkmenistan Olea europaea Zeytin Turkey Olea europaea Zeytoon Armenia Olea europaea Zi jiang China Zingiber officinale Zi ma zi China Sesamum indicum Zingiber Spain Zingiber officinale Zingibil Oman Zingiber officinale Zinjabil Yemen Zingiber officinale Zinjibil Ethiopia Zingiber officinale Zinzam Mauritius Zingiber officinale Zuckerrohr Germany Saccharum officinarum INDEX 607

Index

A Alcohol interactions Cannabis sativa, 40 Abortifacient activity Aldosterone Cannabis sativa, 39 Nicotiana tabacum inhibition of synthesis, 285 Coffea arabica, 162 Alkaline phosphatase Daucus carota, 202–203 Cannabis sativa stimulation, 40 Nicotiana tabacum, 284 Larrea tridentate stimulation, 265 Plantago ovata, 421 Allergenic effect Saccharum officinarum, 440 Cannabis sativa, 40 Sesamum indicum, 491 Cocos nucifera, 121–122 Acetylacetyl CoA ligase Coffea arabica, 162 Olea europaea stimulation, 379 Coffea arabica, 177 Acetylacetyl CoA thiolase Ferula assafoetida, 226 Olea europaea stimulation, 379 Hordeum vulgare, 239–240 Acetylcholine inhibition. See Antiallergenic activity Saccharum officinarum effects on release, 440 Nicotiana tabacum, 285–286, 314–315 Acetylcholine receptor Olea europaea, 379–381 Nicotiana tabacum studies, 323 Plantago ovata, 421 Acetylglucoseaminidase Saccharum officinarum, 440–441 Olea europaea inhibition, 379 Sesamum indicum, 49 Acetylhydrolase activity Zingiber officinale, 517 Nicotiana tabacum, 284–285 Alveolart macrophage Acne Nicotiana tabacum effects, 286 Oryza sativa antiacne activity, 405 Ameliatory effect Acquired immunodeficiency syndrome. See Human immu- Hordeum vulgare, 240 nodeficiency virus Aminopeptidase Acyl-CoA cholesterol acyl transferase inhibition Cocos nucifera effects, 122, 123 Sesamum indicum, 491 Aminopyrene-N-demethylase Zingiber officinale, 517 Cannabis sativa induction, 40 Adrenocorticotropic hormone Amnesia Zingiber officinale induction, 517 Cannabis sativa risks, 40–41, 92–93 α-Adrenoreceptor blocking Amphetamines Serenoa repens, 463 cannabis interactions, 52–53 Agglutinin activity α-Amylase Daucus carota, 203 Coffea arabica inhibition, 162 Airspace permeability Amyotrophic lateral sclerosis Nicotiana tabacum effects, 285 Cannabis sativa studies, 41 Alanine aminotransferase Analgesia effect Coffea arabica induction, 162 Cannabis sativa, 41–43 Zingiber officinale inhibition, 517 Cocos nucifera, 123

607 608 MEDICINAL PLANTS OF THE WORLD

Nicotiana tabacum, 286 Olea europaea, 381 Olea europaea, 381 Oryza sativa, 405 Saccharum officinarum, 441 Plantago ovata, 421 Zingiber officinale, 517–518 Saccharum officinarum, 441 Anaphrodisiac effect Sesamum indicum, 492 Cannabis sativa, 43 Zingiber officinale, 518–519 Anaphylactic activity Anticancer activity Sesamum indicum, 491–492 Camellia sinensis, 9 Oryza sativa, 405 Cocos nucifera prevention, 141–142 Plantago ovata, 421 Anticarcinogenic activity inhibitors. See Antianaphylactic activity Camellia sinensis, 9–11 Androgenic effect Cocos nucifera, 123 Serenoa repens, 463–464 Coffea arabica, 164, 167–169 Androgen receptor binding Ferula assafoetida, 226, 228 Serenoa repens, 464 Olea europaea, 384 Anemia Oryza sativa, 408 Coffea arabica induction, 163 Plantago ovata, 424 Anesthetic activity Zingiber officinale, 529 Nicotiana tabacum, 286–287 Anticataract activity Zingiber officinale, 518 Camellia sinensis, 11 Anticathartic effect Angiogenesis Zingiber officinale, 519 Nicotiana tabacum inhibition, 287 Anticlastogenic activity Angiotensin-II inhibition Coffea arabica, 164 Zingiber officinale, 518 Daucus carota, 204 Angiotensin-converting enzyme Olea europaea, 381–382 Cannabis sativa inhibition, 43 Anticoagulation activity Ankylosing spondylitis Ferula assafoetida, 226 Cannabis sativa studies, 43 Hordeum vulgare, 240 Anti-aging activity Anticonvulsant activity Coffea arabica, 163 Cocos nucifera, 123 Anti-allergenic activity Nicotiana tabacum, 287 Daucus carota, 203 Olea europaea, 382 Hordeum vulgare, 240 Zingiber officinale, 520 Zingiber officinale, 518 Anticrustacean activity Anti-amoebic activity Olea europaea, 382 Daucus carota, 203 Serenoa repens, 464 Hordeum vulgare, 240 Sesamum indicum, 492 Larrea tridentate, 265 Zingiber officinale, 521 Zingiber officinale, 518 Anticytotoxic activity Anti-anaphylactic activity Daucus carota, 204 Cannabis sativa, 43 Antidiabetic activity Zingiber officinale, 538 Hordeum vulgare, 240 Oryza sativa, 409 Larrea tridentate, 265–266 Anti-androgenic effect Plantago ovata, 421–422 Cannabis sativa, 43 Antidiarrheal activity Serenoa repens, 464 Camellia sinensis, 11 Anti-arrhythmic activity Cocos nucifera, 123 Olea europaea, 381–382 Hordeum vulgare, 240 Anti-arthritic effect Oryza sativa, 405 Cannabis sativa, 43 Plantago ovata, 422 Antibacterial activity Zingiber officinale, 521 Nicotiana tabacum, 287 Antidiuretic activity Larrea tridentate, 265 Cannabis sativa, 45 Camellia sinensis, 9 Anti-edema activity Cannabis sativa, 43–44 Daucus carota, 204 Cocos nucifera, 123 Serenoa repens, 464 Coffea arabica, 163–164 Zingiber officinale, 521 Hordeum vulgare, 240 Anti-emetic activity Daucus carota, 203–204 Cannabis sativa, 44 Ferula assafoetida, 226 Zingiber officinale, 521–522, 524–525, 537–538 INDEX 609

Anti-estrogenic effect Antihyperuricemic activity Cannabis sativa, 44 Olea europaea, 383 Daucus carota, 204 Antihypothermic effect Nicotiana tabacum, 287 Zingiber officinale, 523 Serenoa repens, 464–465 Anti-implantation effect Antifertility effect Saccharum officinarum, 443 Cannabis sativa, 44 Sesamum indicum, 492 Coffea arabica, 164 Anti-inflammatory activity Daucus carota, 204 Camellia sinensis, 12 Ferula assafoetida, 227 Cannabis sativa, 45 Larrea tridentate, 266 Cocos nucifera, 124 Antifungal activity Coffea arabica, 164 Oryza sativa, 405–406 Ferula assafoetida, 227 Sesamum indicum, 492 Hordeum vulgare, 242 Camellia sinensis, 11 Olea europaea, 383 Hordeum vulgare, 240–241 Oryza sativa, 406–407 Cannabis sativa, 44–45 Saccharum officinarum, 443 Cocos nucifera, 123–124 Serenoa repens, 465 Daucus carota, 204 Sesamum indicum, 492, 495 Ferula assafoetida, 227 Zingiber officinale, 523–524 Larrea tridentate, 266 Antilipidemic activity Zingiber officinale, 522 Cocos nucifera, 124 Nicotiana tabacum, 287 Antimitogenic activity Antihelminthic activity Coffea arabica, 164 Larrea tridentate, 265 Antimutagenic activity Zingiber officinale, 518 Camellia sinensis, 12–14 Antihemolytic activity Coffea arabica, 164–165 Coffea arabica, 164 Ferula assafoetida, 227–228 Sesamum indicum, 492 Oryza sativa, 407 Antihistamine activity Sesamum indicum, 493 Oryza sativa, 406 Zingiber officinale, 524 Antihypercholesterolemic activity Antimycobacterial activity Camellia sinensis, 11–12 Cannabis sativa, 45 Oryza sativa, 406 Olea europaea, 383 Cocos nucifera, 124 Anti-nematodal activity Ferula assafoetida, 226–227 Cannabis sativa, 45 Hordeum vulgare, 241 Daucus carota, 205, 209 Olea europaea, 382 Plantago ovata, 423 Plantago ovata, 422–423, 428 Sesamum indicum, 497 Saccharum officinarum, 441–442 Zingiber officinale, 525, 538 Sesamum indicum, 492 Anti-nociceptive activity Zingiber officinale, 519–520, 523 Cocos nucifera, 124 Antihyperglycemic activity Anti-neoplastic effect Oryza sativa, 406 Camellia sinensis, 14 Ferula assafoetida, 227 Antioxidant activity Hordeum vulgare, 241–242 Serenoa repens, 465 Olea europaea, 382 Oryza sativa, 407 Plantago ovata, 423 Daucus carota, 205 Saccharum officinarum, 442–443 Cannabis sativa, 45 Zingiber officinale, 523 Cocos nucifera, 124–125, 139 Antihyperlipidemic activity Coffea arabica, 165–166 Oryza sativa, 406 Ferula assafoetida, 228 Plantago ovata, 423 Nicotiana tabacum, 287–288 Antihypertensive activity Olea europaea, 387 Ferula assafoetida, 227 Sesamum indicum, 493 Olea europaea, 382–383 Zingiber officinale, 525–526 Sesamum indicum, 492 Antioxidative effect Antihypertriglyceridemic activity Camellia sinensis, 14 Larrea tridentate, 266 Antiparasitic activity Plantago ovata, 423 Cocos nucifera, 125 610 MEDICINAL PLANTS OF THE WORLD

Ferula assafoetida, 228 Sesamum indicum, 493 Hordeum vulgare, 242 Zingiber officinale, 528 Antiphlogistic activity Anti-yeast activity Serenoa repens, 465 Camellia sinensis, 15 Antiproliferative activity Cocos nucifera, 125 Camellia sinensis, 15 Coffea arabica, 166 Antiproteinemic effect Daucus carota, 206 Cocos nucifera, 125 Hordeum vulgare, 244 Antiprotozoan activity Larrea tridentate, 266 Camellia sinensis, 15 Nicotiana tabacum, 289 Antipyretic activity Olea europaea, 384 Olea europaea, 383 Oryza sativa, 407 Zingiber officinale, 526 Plantago ovata, 423 Antirheumatic effect Saccharum officinarum, 443 Zingiber officinale, 526 Sesamum indicum, 493 Antischistosomal activity Zingiber officinale, 528 Zingiber officinale, 526 Anxiolytic activity Antispasmodic activity Cannabis sativa, 46 Camellia sinensis, 15 Aphrodisiac activity Cannabis sativa, 45 Cannabis sativa, 46, 86–87 Coffea arabica, 166 Apolipoproteins Daucus carota, 205 Cocos nucifera effects on synthesis, 125, 133–134 Ferula assafoetida, 228 Apoptosis Oryza sativa, 407 Ferula assafoetida effects, 228 Zingiber officinale, 526–527 Nicotiana tabacum induction, 289 Antispermatogenic effect Olea europaea induction, 384 Cannabis sativa, 45 Oryza sativa induction, 407 Antistress activity Serenoa repens induction, 465–466 Cannabis sativa, 45–46 Sesamum indicum induction, 493 Nicotiana tabacum, 288–289 Appetite Anti-thrombotic activity Cannabis sativa effects, 63 Olea europaea, 383 Cocos nucifera effects, 131 Saccharum officinarum, 443 Plantago ovata suppression, 423, 426 Anti-tumor activity Arachidonic acid Cannabis sativa, 46 Olea europaea effects on metabolism, 384 Coffea arabica, 166 Zingiber officinale effects on metabolism, 528–529 Daucus carota, 205–206 Arginine arylamidase Ferula assafoetida, 228 Olea europaea inhibition, 384 Hordeum vulgare, 242–243 Aromatase Larrea tridentate, 266 Nicotiana tabacum inhibition, 289 Oryza sativa, 407 Serenoa repens, 466 Sesamum indicum, 493 Arrhythmogenic effect Zingiber officinale, 527 Cocos nucifera, 125 Anti-ulcer activity Coffea arabica, 166 Cannabis sativa, 46 Nicotiana tabacum, 290 Ferula assafoetida, 228 Arteritis Hordeum vulgare, 243–244 cannabis induction, 53–54, 70 Olea europaea, 383 Aryl hydrocarbon hydroxylase Oryza sativa, 407 Nicotiana tabacum induction, 290, 318 Zingiber officinale, 527–528 Ascorbic acid Antiviral activity Nicotiana tabacum effects on metabolism, 317–318, 339 Camellia sinensis, 15 Aspartate aminotransferase Cannabis sativa, 46 Hordeum vulgare inhibition, 247 Cocos nucifera, 125 Saccharum officinarum effects, 447 Coffea arabica, 166 Sesamum indicum inhibition, 495 Hordeum vulgare, 244 Zingiber officinale effects, 529, 534 Larrea tridentate, 266 Atherosclerosis Nicotiana tabacum, 289 Cocos nucifera studies, 125–126 Olea europaea, 383–384 Coffea arabica studies, 166 Oryza sativa, 407 Hordeum vulgare studies, 240 INDEX 611

Nicotiana tabacum and atherogenesis, 290 Bronchodilator activity Olea europaea studies, 381 Cannabis sativa, 51 Plantago ovata protection, 421 Bupivacaine Saccharum officinarum protection, 443–444 Nicotiana tabacum effects on kinetics, 292 Zingiber officinale protection, 518 Butyryl cholinesterase Atopic dermatitis Cocos nucifera effects on activity, 126 Oryza sativa therapy, 407 Atrial fibrillation C Cannabis sativa use risks, 77 Calcium release Attention deficit hyperactivity disorder Serenoa repens inhibition, 466 Cannabis sativa studies, 46–47 Camellia sinensis, 1–19 Auditory function botanical description, 2 Cannabis sativa studies, 47 chemical constituents, 2–9 common names, 1–2 B origin and distribution, 2 Barbiturate potentiation pharmacological activities and clinical trials, 9–19 Cannabis sativa, 47 traditional medical uses, 2 Zingiber officinale, 529 Cannabinoid receptor Behavioral effects antagonists in reversal addiction, 85 Cannabis sativa, 47 Cannabis sativa effects Nicotiana tabacum, 290–291 brain, 50–51 Benign prostatic hypertrophy placenta, 55 Serenoa repens studies, 466–468, 472–474 Cannabis sativa, 29–94 Benzo(a) pyrene hydroxylase botanical description, 30 Nicotiana tabacum induction, 291 chemical constituents, 32–39 Benzphetamine demethylase common names, 29–30 Nicotiana tabacum induction, 291 origin and distribution, 30 Bile acids pharmacological activities and clinical trials, 39–94 Olea europaea stimulation of secretion, 384 traditional medical uses, 30–32 Plantago ovata stimulation, 423–424, 426 Capgras syndrome Binocular depth inversion reduction Cannabis sativa association, 54 Cannabis sativa, 48 Capillary permeability Birth defects Zingiber officinale effects, 529 Coffea arabica, 176 Carbamazepine Birth-weight Plantago ovata effects on absorption, 421 Cannabis sativa studies, 48 Carboxyhemoglobin effect Coffea arabica studies, 166 Nicotiana tabacum, 292 Nicotiana tabacum effects, 291 Carcinogenic activity Bladder dysfunction Cannabis sativa, 54 Cannabis sativa studies, 48–49 Cocos nucifera, 126–127 Blood flow Coffea arabica, 168 Coffea arabica effects, 166 Nicotiana tabacum, 292–297 Blood pressure effect. See also Antihypertensive activity; Plantago ovata, 424–425 Hypertensive activity Saccharum officinarum, 444 Cocos nucifera, 126 Sesamum indicum, 493 Coffea arabica, 162–163 Cardiotonic activity Nicotiana tabacum, 291 Daucus carota, 206 Saccharum officinarum, 443 Zingiber officinale, 529–530 stress reactivity prevention and Cannabis sativa, 49 Cardiovascular effects Bone mineral density Cannabis sativa, 55 Coffea arabica studies, 166–167 Cocos nucifera, 127–128 Bone resorption Coffea arabica, 168–169 Saccharum officinarum inhibition, 444 Ferula assafoetida, 228 Brain Hordeum vulgare, 244 metabolic response to caffeine, 167 Nicotiana tabacum, 297 Bronchitis Zingiber officinale, 530 Nicotiana tabacum risks, 299 Cardiovascular fatality Bronchoconstrictor activity Cannabis sativa, 39, 73, 88 Cannabis sativa, 51 Carotid artery thickening Nicotiana tabacum, 292 Saccharum officinarum, 444–445 612 MEDICINAL PLANTS OF THE WORLD

Catalase Chylomicron Daucus carota inhibition, 206 Nicotiana tabacum effects on metabolism, 299 Cataleptic effect Cimetidine Cannabis sativa, 55 Nicotiana tabacum effects on kinetics, 299–300 Cataract Citrate lyase Nicotiana tabacum risks, 297 Hordeum vulgare inhibition, 244 Cell proliferation Clastogenic activity Nicotiana tabacum effects, 297–298 Nicotiana tabacum, 300 Oryza sativa inhibition, 408 Zingiber officinale, 531 Serenoa repens effects, 466–467 Clinical endocannabinoid deficiency Zingiber officinale inhibition, 530 diseases, 56 Central nervous system effects Coagglutination activity Cannabis sativa, 55–56 Cocos nucifera, 129 Coffea arabica, 170 Coagulative effect Daucus carota, 206 Saccharum officinarum, 445–446 Ferula assafoetida, 228 Serenoa repens, 467 Nicotiana tabacum, 300 Zingiber officinale, 531 Zingiber officinale, 531 Cocos nucifera, 117–143 Cerebral blood flow botanical description, 118–119 Coffea arabica effects, 169 chemical constituents, 120–121 Cerebral ischemia common names, 117–118 Saccharum officinarum studies, 445 origin and distribution, 119 Cervical cancer pharmacological activities and clinical trials, 121–143 Nicotiana tabacum risks, 298 traditional medical uses, 119–120 Cervical dilation Coffea arabica, 155–184 Plantago ovata, 424 botanical description, 156 C-fos chemical constituents, 157–162 Nicotiana tabacum effects on expression, 298 common names, 155–156 Chemiluminescence origin and distribution, 156 Nicotiana tabacum studies, 298 pharmacological activities and clinical trials, 162–184 Chemoprevention traditional medical uses, 156–157 Zingiber officinale, 530 Cognition Cholagogic effect Cannabis sativa effects Zingiber officinale, 530–531 adolescents and adults, 56–58 Cholelithiasis aging declines, 50 Larrea tridentate prophylaxis, 267–268 memory effects, 70–71 Choleretic activity spatial working memory, 88 Zingiber officinale, 531 visuospatial memory, 93 Cholestatic liver disease Coffea arabica effects, 170 Cocos nucifera effects, 128 Zingiber officinale effects on memory, 536–537 Cholesterol Collagenase Cocos nucifera effects on metabolism, 128–129 Nicotiana tabacum effects, 300 Hordeum vulgare effects on metabolism, 244 Colon cancer Plantago ovata effects on metabolism, 430 Coffea arabica risks, 170 Plantago ovata inhibition of absorption, 424 Plantago ovata studies, 425 Saccharum officinarum effects on metabolism, 445, 452 Coma Sesamum indicum effects on metabolism, 493–494 cannabis induction, 53 Zingiber officinale effects on metabolism, 531 Complement Cholesteryl ester transfer protein Olea europaea inhibition, 384 Coffea arabica effects, 170–171 Constipation Choline acetyltransferase Plantago ovata studies, 424 Zingiber officinale induction, 531 Coronary heart disease Chromosome aberration Camellia sinensis prevention, 15 Nicotiana tabacum induction, 298–299 Coffea arabica risks, 170–171 Chronic obstructive pulmonary disease Corticosteroid activity Nicotiana tabacum risks, 299 Sesamum indicum, 494 Chronotropic effects Corticosterone induction Olea europaea, 384 Zingiber officinale, 531–532 Saccharum officinarum, 444 Cyclin D Sesamum indicum, 494 Nicotiana tabacum effects on expression, 301 INDEX 613

Cyclo-oxygenase Diabetic ketoacidosis Cannabis sativa inhibition, 59 Cannabis sativa risks, 60 Hordeum vulgare inhibition, 244 Diabetogenic effect Nicotiana tabacum induction, 301 Saccharum officinarum, 446 Olea europaea inhibition, 384 Digestibility Serenoa repens, 467 Plantago ovata studies, 426–427 Zingiber officinale inhibition, 532 Zingiber officinale studies, 532 Cytochrome b5 Digestive enzyme inhibition Nicotiana tabacum induction, 301 Ferula assafoetida, 228–229 Cytochrome C oxidase Digital necrosis Nicotiana tabacum inhibition, 301 Cannabis sativa, 60 Cytochrome P450 expression Diltiazem Camellia sinensis, 15–16 Nicotiana tabacum effects on kinetics, 303 Cannabis sativa, 59 Discriminative stimulus effect Coffea arabica and drug interactions, 178–179 Cannabis sativa, 60 Nicotiana tabacum, 301–302 Diuretic activity Serenoa repens effects, 467 Cocos nucifera, 130 Cytotoxic activity Daucus carota, 206 Cannabis sativa, 59, 89 Hordeum vulgare, 245 Cocos nucifera, 129–130 inhibition. See Antidiuretic activity Coffea arabica, 171 Nicotiana tabacum, 303 Daucus carota, 206 Olea europaea, 385 Ferula assafoetida, 228 Saccharum officinarum, 446 Hordeum vulgare, 244–245 Serenoa repens, 467 Larrea tridentate, 266 DNA adduct Nicotiana tabacum, 302 Nicotiana tabacum induction, 303–305 Olea europaea, 384–385 Zingiber officinale, 532 Oryza sativa, 408 DNA oxidation Saccharum officinarum, 446 Nicotiana tabacum, 284 Serenoa repens, 467 DNA repair Sesamum indicum, 494 Camellia sinensis effects, 16 Zingiber officinale, 532 DNA synthesis Cannabis sativa inhibition, 60 D Ferula assafoetida inhibition, 229 Nicotiana tabacum effects, 305 Daucus carota, 197–210 Sesamum indicum inhibition, 494 botanical description, 198 Zingiber officinale inhibition, 532 chemical constituents, 200–202 Dopamine common names, 197–198 Cannabis sativa effects on metabolism and release, 60–61 origin and distribution, 198–199 Nicotiana tabacum effects, 305–306 pharmacological activities and clinical trials, 202–210 Down’s syndrome traditional medical uses, 199–200 Coffea arabica impact, 171 Degranulation inhibition Dromotropic effect Zingiber officinale, 532 Olea europaea, 385 Dental caries Dyskinetic activity Saccharum officinarum effects, 446 Cannabis sativa, 61–62 Denture stomatitis Dystonic activity Cocos nucifera studies, 130 Cannabis sativa, 62 Depression Cannabis sativa induction, 59–60 E Dermatitis E-cadherin Coffea arabica induction, 171 Nicotiana tabacum effects on expression, 306 Daucus carota induction, 206 Electron transport Olea europaea induction, 385 Nicotiana tabacum inhibition, 306 Oryza sativa induction, 408 Embryotoxic effect Sesamum indicum studies, 494 Cannabis sativa, 62 Desensitization Coffea arabica, 171 Cocos nucifera studies, 130 Daucus carota, 206–207 Detoxification activity Nicotiana tabacum, 306, 321, 328 Larrea tridentate, 266–267 Sesamum indicum, 494 614 MEDICINAL PLANTS OF THE WORLD

Emphysema Fibrinolytic activity Nicotiana tabacum risks, 306–307 Ferula assafoetida, 229 Endocrine effect Zingiber officinale, 533 Cannabis sativa, 62, 73–74 Fish poison activity β-Endorphin interaction Nicotiana tabacum, 308–309 Cannabis sativa, 47–48 Flashback Endothelial dysfunction cannabis induction, 54 Nicotiana tabacum, 307–308 Fluoride retention Epileptic effect Camellia sinensis, 16 Cannabis sativa, 62–63 Foam cell formation Epstein–Barr virus Saccharum officinarum effects, 447 Cocos nucifera activation, 130 Follicle-stimulating hormone Nicotiana tabacum effects, 308 Cannabis sativa inhibition of release, 64 Zingiber officinale activation, 533 Serenoa repens inhibition of release, 469 Erythrocytic effect Foot-and-mouth disease Cocos nucifera, 130 Nicotiana tabacum studies, 309 Esophageal motility Fos Saccharum officinarum effects, 446–447 Cannabis sativa induction, 52 Estrogenic effect Fungal activity Cannabis sativa, 62 Coffea arabica, 172 Cocos nucifera, 131 Oryza sativa stimulant, 408 Coffea arabica, 171 Daucus carota, 207 G Hordeum vulgare, 245 Gallbladder disease Nicotiana tabacum, 308 Coffea arabica risks, 172 Olea europaea, 385 Coffea arabica risks, 182–183 Oryza sativa, 408 Plantago ovata prevention of gallstones, 426–427 Serenoa repens, 468 Gallbladder function. See also Bile acids Sesamum indicum, 494 Olea europaea effects, 385 Estrus cycle disruption Gastric emptying Cannabis sativa, 63 Oryza sativa effects, 409 Daucus carota, 207 Plantago ovata effects, 427 Ethanol intake Gastric exfoliation effect Saccharum officinarum effects, 453 Zingiber officinale, 533 Ethinylestradiol Gastric mucosal exfoliant activity Plantago ovata effects on kinetics, 426 Ferula assafoetida, 229 Nicotiana tabacum, 309 F Gastric secretory effects Familial Mediterranean fever Cannabis sativa inhibition, 64 Cannabis sativa studies, 63–64 Nicotiana tabacum stimulation, 309 Fatty acids Zingiber officinale inhibition, 533 Cocos nucifera effects on composition and metabolism, Gastric ulcer. See also Antiulcer activity 130–131, 139–140 Nicotiana tabacum studies, 309, 338 Hordeum vulgare effects on metabolism, 248 Gastrin Sesamum indicum effects, 494, 496 Cocos nucifera inhibition, 131 Fatty acid synthase Gastroesophageal reflux Hordeum vulgare inhibition, 245 Coffea arabica risks, 172 Fertilization inhibition Gastrointestinal effect Coffea arabica, 172 Camellia sinensis, 16–17 Serenoa repens, 468–469 Cocos nucifera, 131 Ferula assafoetida, 223–230 Coffea arabica, 172–173 botanical description, 224 Hordeum vulgare, 245–246 chemical constituents, 225–226 Saccharum officinarum, 447 common names, 223 Zingiber officinale, 533–534 origin and distribution, 224 Genotoxicity pharmacological activities and clinical trials, 226–230 Cocos nucifera, 131–132 traditional medical uses, 224 Coffea arabica inhibition, 173 Fibrinogen Nicotiana tabacum, 310–311 Coffea arabica induction, 172 Glaucoma Olea europaea inhibition, 385 Cannabis sativa studies, 45, 65 INDEX 615

Nicotiana tabacum inhibition, 287 Daucus carota, 208 Glioma Hematopoiesis Cannabis sativa studies, 65 Nicotiana tabacum inhibition, 312 Glucose Heme oxygenase Cocos nucifera effects on metabolism, 132 Nicotiana tabacum induction, 312 Zingiber officinale effects on metabolism, 534 Hemoglobin effect Glucose tolerance effect Saccharum officinarum, 448 Hordeum vulgare, 246 Hemostatic effect Plantago ovata, 427 Cocos nucifera, 133 Glucose-6-phosphate dehydrogenase Hemotoxicity Cocos nucifera inhibition, 133 Cocos nucifera, 133 Hordeum vulgare inhibition, 246 Sesamum indicum, 495 Glucosidase Hepatic activity Cannabis sativa inhibition, 65 Cocos nucifera, 133 Sesamum indicum inhibition, 494 Hepatic encephalopathy Zingiber officinale inhibition, 534 Plantago ovata studies, 428 Glutamate–pyruvate–transaminase Hepatitis B Hordeum vulgare inhibition, 247 Zingiber officinale and antigen expression, 534–535 Oryza sativa inhibition, 408 Hepatitis C Saccharum officinarum effects, 447 Cannabis sativa use risks, 65–66 Sesamum indicum inhibition, 495 Hepatotoxicity γ-Glutamyltransferase Cannabis sativa, 66 Coffea arabica inhibition, 172 Daucus carota protection, 204 Glutathione peroxidase Ferula assafoetida protection, 227 Daucus carota inhibition, 207 Hordeum vulgare protection, 241 Nicotiana tabacum inhibition, 312 Larrea tridentate, 267 Glutathione reductase Saccharum officinarum and protection, 441, 448 Daucus carota stimulation, 207 Serenoa repens, 469 Glutathione S-transferase Sesamum indicum protection, 493 Coffea arabica induction, 173 Zingiber officinale protection, 522–623 Daucus carota inhibition, 207–208 Histamine release Nicotiana tabacum effects, 312 Cannabis sativa, 66 Glycemic index inhibition. See Antihistamine activity Cocos nucifera, 133 Zingiber officinale inhibition, 535 Oryza sativa, 408 Homocysteine Plantago ovata effects, 427–428 Coffea arabica effects on levels, 173 Glycotoxins Hordeum vulgare, 235–250 Nicotiana tabacum induction, 312 botanical description, 235–236 Goitrogenic activity chemical constituents, 237–240 Daucus carota, 208 common names, 235 Growth inhibition origin and distribution, 236 Hordeum vulgare, 247 pharmacological activities and clinical trials, 240–250 Serenoa repens, 469 traditional medical uses, 236–237 Growth promotion Human immunodeficiency virus Saccharum officinarum, 447–448 Cannabis sativa use risks, 66 Gynecomastia Cocos nucifera activity in acquired immunodeficiency Cannabis sativa induction, 65 syndrome, 121 Daucus carota therapy in acquired immunodeficiency H syndrome, 203 Hordeum vulgare therapy in acquired immunodefi- Hair ciency syndrome, 239 Cocos nucifera and damage prevention, 133 Hordeum vulgare effects on growth, 247 Hyaluronidase Oryza sativa effects on growth, 408 Coffea arabica inhibition, 173 Serenoa repens effects on growth, 469 Hydrogen peroxide Sesamum indicum effects on growth, 495 Cocos nucifera release inhibition, 133 Zingiber officinale stimulation, 534 Coffea arabica stimulation, 178, 183–184 Halitosis Olea europaea inhibition, 386 Daucus carota treatment, 204 Zingiber officinale inhibition, 535 Hemagglutinin activity 3-Hydroxy-3-methylglutaryl CoA reductase Cannabis sativa, 65 Hordeum vulgare inhibition, 247 616 MEDICINAL PLANTS OF THE WORLD

Olea europaea inhibition, 385–386 Sesamum indicum, 495 Plantago ovata inhibition, 428 Hypotensive activity Saccharum officinarum effects, 448 Cannabis sativa, 67 Hydroxysteroid dehydrogenase inhibition Cocos nucifera, 136 Serenoa repens, 469 Daucus carota, 208 Hypercholesterolemic activity Ferula assafoetida, 229 Camellia sinensis, 17 Olea europaea, 386 Cocos nucifera, 134 Oryza sativa, 409 Coffea arabica, 173–175 Saccharum officinarum, 448 Nicotiana tabacum, 313 Sesamum indicum, 495 Sesamum indicum, 495 Hypothermic activity Hyperemesis Cocos nucifera, 136 cannabinoid induction, 51–52 Olea europaea, 387 Hyperglycemic activity Zingiber officinale, 535 Cannabis sativa, 67 Hypotriglycideremic activity Daucus carota prevention, 204 Hordeum vulgare, 248 Sesamum indicum, 495 Hypouricemic activity Hyperlipidemic activity Olea europaea, 387 Cocos nucifera, 134 Hypoxia Sesamum indicum, 495 Nicotiana tabacum studies, 314 Hyperplasia induction Nicotiana tabacum, 313–314 I Hypertensive activity Immunomodulation Cannabis sativa, 67 Camellia sinensis, 17 inhibition. See Antihypertensive activity Cannabis sativa, 67–68 Nicotiana tabacum, 314 Cocos nucifera, 136 Zingiber officinale, 535 Coffea arabica, 175 Hyperthermic effect Daucus carota, 208 Cocos nucifera, 134 Nicotiana tabacum, 315 Olea europaea, 386 Saccharum officinarum, 448–449 Zingiber officinale, 535 Serenoa repens, 469 Hypertriglyceridemic effect Sesamum indicum, 495 Cocos nucifera, 134–135 Zingiber officinale, 535 Coffea arabica, 175 Immunosuppression Hypocholesterolemic activity Nicotiana tabacum, 315–316 Cocos nucifera, 135 Olea europaea, 387 Daucus carota, 208 Saccharum officinarum prevention, 449 Ferula assafoetida, 229 Infant mortality Hordeum vulgare, 247 Cannabis sativa, 68, 88–89 Olea europaea, 386 Oryza sativa, 408–409 Inflammatory effect Plantago ovata, 428–429 Cannabis sativa, 68–69 Saccharum officinarum, 448 inhibition. See Anti-inflammatory activity Sesamum indicum, 495 Nicotiana tabacum, 316 Hypoglycemic activity Information processing Cannabis sativa, 67, 135 Cannabis sativa effects, 69 Coffea arabica, 175 Inotropic effects Ferula assafoetida, 229 Daucus carota, 209 Hordeum vulgare, 247 Olea europaea, 387 Olea europaea, 386 Sesamum indicum, 495 Oryza sativa, 409 Insect growth inhibition Plantago ovata, 429 Zingiber officinale, 535–536 Saccharum officinarum, 448 Insect repellent Zingiber officinale, 535 Cocos nucifera, 140 Hypolipidemic activity Insecticide activity Cocos nucifera, 135 Cannabis sativa, 69 Ferula assafoetida, 229 Coffea arabica, 175 Hordeum vulgare, 247–248 Larrea tridentate, 267 Plantago ovata, 429 Nicotiana tabacum, 316 Saccharum officinarum, 448 Sesamum indicum, 495 INDEX 617

Insulin traditional medical uses, 264 Camellia sinensis effects, 17 Larvicide activity Olea europaea effects, 387 Sesamum indicum, 496 Plantago ovata effects, 429 Zingiber officinale, 536 Saccharum officinarum antagonism, 449 Laxative effect Insulin-like growth factor-I Hordeum vulgare, 248 Serenoa repens signaling suppression, 469–470 Plantago ovata, 429–430 Intercellular adhesion molecule-1 Leukemia Olea europaea inhibition, 387 Plantago ovata antileukemic activity, 423 Interferon Leukocyte migration Daucus carota induction, 208 Zingiber officinale inhibition, 536 Nicotiana tabacum induction, 316–317 Leukocytosis activity Zingiber officinale induction, 536 Coffea arabica, 175 Interleukin-1 Leukotriene B4 Nicotiana tabacum stimulation, 317 Serenoa repens inhibition, 470 Oryza sativa induction, 409 Lipid peroxidation Sesamum indicum induction, 495–496 Camellia sinensis protection, 18 Zingiber officinale inhibition, 536 Cocos nucifera induction, 133, 137 Interleukin-4 Daucus carota inhibition, 208–209 Daucus carota inhibition, 208 Nicotiana tabacum induction, 313 Interleukin-12 Olea europaea stimulation, 387 Nicotiana tabacum stimulation, 317 Sesamum indicum inhibition, 496 Intestinal motility activity Zingiber officinale inhibition, 536 Cannabis sativa, 69 Lipogenetic effect Intestine Cocos nucifera, 137–138 Cocos nucifera effects, 136 Lipolytic effect Intraocular pressure reduction Hordeum vulgare, 248 Cannabis sativa, 69 Zingiber officinale, 536 Nicotiana tabacum, 317 Lipoprotein lipase Intravenous fluid therapy Cocos nucifera effects, 138 Cocos nucifera, 136–137 Lipoproteins IQ Cocos nucifera effects, 138 Cannabis sativa studies, 69 Coffea arabica effects, 175, 181 Iron absorption effects Nicotiana tabacum effects, 318, 327–328 Camellia sinensis, 17–18 Olea europaea effects, 387–388 Cocos nucifera, 137 Plantago ovata effects, 430 Saccharum officinarum effects, 449–450 J Lipoxygenase inhibition Hordeum vulgare, 248 Juvenile hormone activity Serenoa repens, 470 Cocos nucifera, 137 Liver function K Coffea arabica, 175–176 Daucus carota and regeneration, 209 Kidney damage Low urinary tract symptoms Nicotiana tabacum, 332 Serenoa repens studies, 470 Koro Lung function Cannabis sativa, 39 Cannabis sativa studies, 70 K-ras Luteinizing hormone Coffea arabica and mutagenesis, 175 Cannabis sativa inhibition of release, 69–70 Lymphocyte stimulation L Oryza sativa, 409 Lymphohistiocytic adenoma activity Lactate Serenoa repens, 470–471 Cannabis sativa and inhibition, 69 Larrea tridentate, 263–268 botanical description, 263 M chemical constituents, 264–265 Malaria common names, 263 Cannabis sativa antimalarial activity, 45 origin and distribution, 263–264 Mast cell pharmacological activities and clinical trials, 265–268 Serenoa repens effects, 471 618 MEDICINAL PLANTS OF THE WORLD

Mastocytoma Nicotiana tabacum studies, 323 Nicotiana tabacum induction, 318–319 Olea europaea studies, 387 Memory. See Amnesia; Cognition Zingiber officinale enhancement, 537 Metaplasia Nausea. See Antiemetic activity Nicotiana tabacum induction, 319 Nematocidal activity. See Antinematodal activity Migraine Neonatal abstinence syndrome, 73 Saccharum officinarum studies, 450–451 Nephrotoxicity Mineral utilization Cocos nucifera, 138 Hordeum vulgare effects, 248–249 Nerve growth factor Mitochondrial ATPase Zingiber officinale stimulation, 538 Nicotiana tabacum inhibition, 319 Nervous system development Mitochondrial function Cannabis sativa studies, 71 Nicotiana tabacum studies, 323 Cocos nucifera studies, 133 Neurogenic effects Mitogenic activity Cannabis sativa, 74 Coffea arabica, 176 Coffea arabica, 177 Nicotiana tabacum, 319–320 Neuromuscular blocking Zingiber officinale, 537 Sesamum indicum, 497 Molluscicidal activity Zingiber officinale, 538 Cannabis sativa, 71–72 Neuropathic pain relief Coffea arabica, 176 Cannabis sativa, 74, 83 Nicotiana tabacum, 320 Neuroprotection Olea europaea, 387 Cannabis sativa, 74–75 Sesamum indicum, 496 Nicotiana tabacum, 323–324 Zingiber officinale, 537 Neuropsychological effect Monoamine oxidase Cannabis sativa, 75 Nicotiana tabacum inhibition, 318 Neurotoxicity Sesamum indicum effects, 496 Camellia sinensis protection, 18–19 Monocyte differentiation Zingiber officinale protection, 525 Hordeum vulgare effects, 249 Neurotransmission Mood Cannabis sativa inhibition, 75 Coffea arabica effects, 176 Motion sickness Neutrophil function Zingiber officinale studies, 524 Cocos nucifera studies, 138–139 Motor function Nicorandil Cannabis sativa effects, 72 Nicotiana tabacum effects on kinetics, 324 Multiple sclerosis Nicotiana tabacum, 271–339 Cannabis sativa studies, 72–73 botanical description, 272 Mutagenic activity chemical constituents, 273–284 Cannabis sativa, 73 common names, 271–272 Coffea arabica, 177–177 origin and distribution, 272 Daucus carota, 209 pharmacological activities and clinical trials, 284–339 Ferula assafoetida, 229 traditional medical uses, 272–273 Hordeum vulgare, 249 Nicotine Nicotiana tabacum, 321–323 cannabis interactions, 75 Olea europaea, 387 Nicotinic receptor Oryza sativa, 409 Nicotiana tabacum and desensitization, 303 Serenoa repens, 471 Night vision Sesamum indicum, 496 Cannabis sativa studies, 75 Zingiber officinale, 537 Nitric oxide synthase Myocardial infarction Nicotiana tabacum induction, 324 Cannabis sativa, 73, 88 Cocos nucifera studies, 138 Nitrosamines Coffea arabica, 177 tobacco induction, 307 Myocardial necrosis Nocturnal sleep effect Saccharum officinarum inhibition, 451 Cannabis sativa, 75–76 Myoclonus Non-Hodgkin’s lymphoma Cannabis sativa induction, 82 Nicotiana tabacum risks, 325 Norepinephrine N Cannabis sativa effects, 78 κ Natural-killer cell function Nuclear factor- B Cannabis sativa studies, 73 Nicotiana tabacum inhibition, 325 INDEX 619

O Parkinson’s disease Olea europaea, 373–388 Coffea arabica effects, 178 botanical description, 374 Oryza sativa studies, 409 chemical constituents, 376–379 Pepsin common names, 373–374 Hordeum vulgare inhibition, 249 origin and distribution, 374–375 Zingiber officinale inhibition, 538 pharmacological activities and clinical trials, 379–388 Periodontitis traditional medical uses, 375–376 Hordeum vulgare induction, 249 Olfactory status effects Nicotiana tabacum risks, 327 Ferula assafoetida, 229 Peripheral artery disease Ophthalmic surgical swab Cannabis sativa, 70 Saccharum officinarum uses, 451 P-glycoprotein Oral cancer Camellia sinensis inhibition, 18 Cannabis sativa use risks, 76 Phagocytosis Oral submucosal fibrosis Serenoa repens effects, 471 Camellia sinensis studies, 18 Zingiber officinale effects, 538 Ornithine decarboxylase Pheromone activity Cocos nucifera effects on activity, 139 Cocos nucifera, 139 Nicotiana tabacum effects, 321, 326 Coffea arabica, 179 Oryza sativa, 401–410 Daucus carota, 209 botanical description, 402 Phosphodiesterase chemical constituents, 403–405 Zingiber officinale inhibition, 539 common names, 401–402 Phosphogluconate dehydrogenase origin and distribution, 402 Hordeum vulgare inhibition, 249 pharmacological activities and clinical trials, 405–410 Phospholipase A2 traditional medical uses, 402–403 Serenoa repens inhibition, 471 Osteoarthritis Photoprotection Zingiber officinale protection, 525 Camellia sinensis, 18–19 Ovarian cancer Phytotoxicity Coffea arabica risks, 177–178 Sesamum indicum, 497 Ovarian toxicity Place conditioning effect, 77–78 Nicotiana tabacum, 326 Plant germination effect Oviposition Cannabis sativa, 78 Daucus carota stimulation, 209 Plant growth Ovulation inhibition Larrea tridentate inhibition, 268 Plantago ovata, 419–431 Cannabis sativa, 77 botanical description, 419–420 Coffea arabica, 178 chemical constituents, 420–421 Oxidative stress common names, 419 Nicotiana tabacum, 326–327 origin and distribution, 420 Oxytocin pharmacological activities and clinical trials, 421–431 Daucus carota inhibition, 205 traditional medical uses, 420 Zingiber officinale inhibition, 526 Plaque formation suppression Oxytocinase Zingiber officinale, 539 Cocos nucifera inhibition, 139 Plasmapheresis donors P illicit drug use, 67 Platelet aggregation p53 mutations Cocos nucifera effects, 140 Nicotiana tabacum risks, 327 Olea europaea inhibition, 387–388 Pancreatic cancer Saccharum officinarum effects, 451 Coffea arabica risks, 178 Zingiber officinale inhibition, 539–540 Pancreatic digestive enzymes Pneumomediastinum Cocos nucifera effects, 130 Cannabis sativa risks, 88 Ferula assafoetida effects, 229 Pneumonic effect Plantago ovata effects, 427 Cannabis sativa, 78 Zingiber officinale effects, 538 Postprandial glycemic response reduction Pancreatic toxicity Saccharum officinarum, 451 Cannabis sativa, 77 Postural syncope Nicotiana tabacum, 327 Cannabis sativa, 78 Panic disorder Potassium channel blocking Cannabis sativa, 77 Serenoa repens, 471 620 MEDICINAL PLANTS OF THE WORLD

Prenatal exposure Radioprotection Cannabis sativa studies, 78–82 Oryza sativa, 410 Progesterone 5-α Reductase Daucus carota inhibition, 205, 209 Oryza sativa inhibition, 405 Nicotiana tabacum inhibition, 328–329 Serenoa repens inhibition, 475, 477–478 Prolactin Renal function improvement Cannabis sativa inhibition, 82 Zingiber officinale, 540 Serenoa repens and signaling, 471 Renin–angiotensin–aldosterone system Prostaglandins Coffea arabica effects, 179–180 Nicotiana tabacum induction, 329 Reproduction Olea europaea induction, 388 Cannabis sativa effects, 83–84 Serenoa repens inhibition, 471 Resistance training Sesamum indicum induction, 497 Serenoa repens effects on adaptation, 463 Zingiber officinale inhibition, 540 Respiratory effects Prostaglandin synthetase Cannabis sativa, 54–55, 85 Cannabis sativa inhibition, 82 Cocos nucifera, 141 Coffea arabica inhibition, 179 Coffea arabica, 180 Prostate cancer Hordeum vulgare, 249–250 Nicotiana tabacum, 291–292, 329–333 Nicotiana tabacum risks, 329 Serenoa repens, 475 Serenoa repens studies, 471–472 Zingiber officinale, 540 Prostate hypertrophy. See Benign prostatic hypertrophy Reverse transcriptase Prostate-specific antigen Zingiber officinale effects, 540–541 Serenoa repens suppression, 474–475 Rheumatoid arthritis Prostatitis.chronic pelvic pain syndrome Coffea arabica risks, 180 Serenoa repens studies, 466 RNA polymerase Protease inhibition Coffea arabica inhibition, 180–181 Camellia sinensis, 19 Olea europaea, 388 S Protein kinase C Serenoa repens inhibition, 474 Saccharum officinarum, 437–453 Protein synthesis botanical description, 438 Cannabis sativa inhibition, 82 chemical constituents, 439–440 Daucus carota inhibition, 209 common names, 437–438 Hordeum vulgare inhibition, 249 origin and distribution, 438 Serenoa repens stimulation, 474 pharmacological activities and clinical trials, 440–453 Prothrombin time traditional medical uses, 438–439 Larrea tridentate effects, 268 Salivary secretion Zingiber officinale effects, 540 Oryza sativa effects, 410 Psychosocial morbidity Schizophrenic effect Cannabis sativa, 82–83 Cannabis sativa, 85–86 Psychotic effect Semen Cocos nucifera for coagulation and cryopreservation, 141 Cannabis sativa, 83 Serenoa repens, 461–479 Pyretic activity botanical description, 461–462 Cocos nucifera, 140 chemical constituents, 462 Pyruvate kinase common names, 461 Sesamum indicum inhibition, 497 origin and distribution, 462 pharmacological activities and clinical trials, 463–478 Q traditional medical uses, 462 Serotonin Quil-A saponin toxicity Hordeum vulgare and uptake inhibition, 239 Sesamum indicum, 497 Nicotiana tabacum effects on uptake, 331 Quinone reductase Zingiber officinale inhibition, 518, 541 Daucus carota induction, 209 Sesamum indicum, 487–498 botanical description, 488 R chemical constituents, 490–491 Radiation-induced pneumonitis common names, 487–488 Nicotiana tabacum suppression, 317 origin and distribution, 488 Radical scavenging pharmacological activities and clinical trials, 491–498 Camellia sinensis, 19 traditional medical uses, 488–490 Oryza sativa, 409–410 Sex hormone-binding globulin Sesamum indicum, 497 Coffea arabica induction, 181 INDEX 621

Sexual headache Olea europaea inhibition of production, 388 Cannabis sativa association, 86 Superoxide dismutase Sexually transmitted disease Nicotiana tabacum inhibition, 301, 310 Cannabis sativa use risks, 49, 66 Zingiber officinale stimulation, 541 Sister chromatid exchange Surfactant Coffea arabica stimulation, 181 Nicotiana tabacum effects, 331 Daucus carota inhibition, 209 Sympathatomimetic activity Ferula assafoetida stimulation, 229 Nicotiana tabacum, 333–334 Nicotiana tabacum inhibition, 331–332 Skeletal muscle T Daucus carota effects, 209 Skin cancer Tachycardia Larrea tridentate chemoprevention, 268 Cocos nucifera induction, 141 Nicotiana tabacum studies, 302–303, 332 Nicotiana tabacum induction, 334 Skin depigmentation Tachyphylactic activity Coffea arabica, 181 Zingiber officinale, 541 Smooth muscle Taste modification Cannabis sativa effects, 87 Zingiber officinale, 541 Coffea arabica effects, 181–182 Taurocholic acid adsorption Daucus carota effects, 209 Plantago ovata, 430 Ferula assafoetida effects, 230 T-cell Serenoa repens effects, 476 Nicotiana tabacum effects, 334 Zingiber officinale effects, 541 Teratogenic activity Spasmogenic activity Cannabis sativa, 89–90 Cocos nucifera, 141 Nicotiana tabacum, 334–336 Daucus carota, 209 Sesamum indicum, 498 inhibition. See Antispasmodic activity Zingiber officinale, 541–542 Olea europaea, 388 Testosterone Sesamum indicum, 497–498 Nicotiana tabacum inhibition, 336 Spasmolytic activity Serenoa repens effects, 475–477 Daucus carota, 209–210 Thermogenic activity Olea europaea, 388 Zingiber officinale, 542 Serenoa repens, 476–477 Thromboxane A2 Spasticity Serenoa repens effects, 477 Cannabis sativa studies, 87–88 Zingiber officinale inhibition, 542 Spermatogenesis Thromboxane B2 Nicotiana tabacum effects, 333 Olea europaea induction, 388 Spermicidal activity Thymidylate synthetase Cannabis sativa, 88 Coffea arabica inhibition, 183 Cocos nucifera, 141 Thyroid function Sperm motility Coffea arabica effects, 183 Serenoa repens effects, 477 Daucus carota antithyroid activity, 205, 208 Spinal cord ischemia Nicotiana tabacum studies, 336 Saccharum officinarum studies, 452 Olea europaea effects, 388 Stress Oryza sativa effects, 407 Cannabis sativa studies, 62 Tocopherols Coffea arabica relief, 182 Sesamum indicum effects on levels, 491, 498 Stroke Tourette syndrome Cannabis sativa use risks, 76 Cannabis sativa studies, 90–91 Substance-related disorder with dysthymia Toxicity Cannabis sativa, 58 Camellia sinensis, 19 Sudden infant death syndrome Cannabis sativa, 91 Cannabis sativa, 68, 88–89 Coffea arabica effects, 183 Nicotiana tabacum, 333 Ferula assafoetida, 230 Suicide Hordeum vulgare, 250 Cannabis sativa risks, 89 Nicotiana tabacum, 336–337 Coffea arabica risks, 182 Olea europaea, 388 Sunscreen activity Plantago ovata, 430 Coffea arabica, 182 Saccharum officinarum, 442–453 Superoxide Serenoa repens, 477 Cocos nucifera inhibition of production, 141 Sesamum indicum, 498 622 MEDICINAL PLANTS OF THE WORLD

Zingiber officinale, 542 Serenoa repens, 478 Toxicity assessment Zingiber officinale, 543 Camellia sinensis, 19 Vasodilator activity Cannabis sativa, 91 Daucus carota, 210 Cocos nucifera, 141 Ferula assafoetida, 230 Hordeum vulgare, 250 Olea europaea, 388 Oryza sativa, 410 Ventricular septal defect Sesamum indicum, 498 Cannabis sativa risks, 93 Zingiber officinale, 542 Vertigo Transglutaminase Zingiber officinale studies, 528 Nicotiana tabacum inhibition, 337 Viral stimulation Tryptophan pyrrolase Nicotiana tabacum, 339 Zingiber officinale stimulation, 542 Vitamin A Tumor necrosis factor-a coconut oil solubilization, 140 Nicotiana tabacum stimulation, 337–338 Nicotiana tabacum effects, 339 Zingiber officinale inhibition, 542 Tumor promotion W Cocos nucifera, 142 Daucus carota inhibition, 210 Weight gain Ferula assafoetida, 230 Coffea arabica inhibition, 184 Nicotiana tabacum, 325–326 Hordeum vulgare inhibition, 250 Olea europaea, 388 Nicotiana tabacum inhibition, 339 Sesamum indicum inhibition, 498 Olea europaea effects, 388 Zingiber officinale inhibition, 542–543 Plantago ovata effects, 430 Turgal stimulant activity Saccharum officinarum effects, 453 Zingiber officinale, 543 Serenoa repens effects, 478 Tyrosinase Sesamum indicum effects, 498 Cannabis sativa inhibition, 93 White blood cells Hordeum vulgare inhibition, 250 Coffea arabica effects, 184 Nicotiana tabacum inhibition, 338 Daucus carota effects, 210 Olea europaea inhibition, 388 Nicotiana tabacum effects, 318, 328 Sesamum indicum inhibition, 498 Oryza sativa effects, 410 Sesamum indicum effects, 498 U Zingiber officinale effects, 536, 543 UDP-glucuronyltransferase Wilson’s disease Nicotiana tabacum effects, 338 Cannabis sativa studies, 93 Ulcerative colitis Winiwarter-Buerger disease Plantago ovata studies, 430 Cannabis sativa studies, 93–94 Ulcerogenic activity Withdrawal Oryza sativa, 410 Cannabis sativa, 52 Uncoupling protein caffeine, 167 Cocos nucifera effects, 142–143 Wound healing Urease Plantago ovata studies, 430–431 Hordeum vulgare inhibition, 250 Zingiber officinale inhibition, 543 Y Urodynamic effect Serenoa repens, 468 Yeast. See Antifungal activity; Anti-yeast activity Uterus Daucus carota effects, 210 Z Ferula assafoetida effects, 230 Zingiber officinale, 507–543 botanical description, 509 V chemical constituents, 512–517 Vascular permeability common names, 507–509 Cocos nucifera effects, 143 origin and distribution, 509 Vasoconstrictor activity pharmacological activities and clinical trials, 517–543 Nicotiana tabacum, 338–339 traditional medical uses, 509–512 About the Author

A native of Guyana, Ivan A. Ross is a biologist at the United States Food and Drug Administration. At the age of seventeen he was awarded a scholarship by the United States Agency for International Development to study agriculture at Tuskegee University. After completing his studies he returned to Guyana and was appointed to the Guyana Min- istry of Agriculture. During this tour of duty, most of his time was spent in the isolated communities of the Aboriginal populations, incorporating modern agriculture and health care methods with the traditional system. Dr. Ross' interest in traditional medicine originated at this time. He later entered the University of Maryland, College Park, where he studied animal science and biochemistry. In 1987 he joined the United States Department of Health and Human Ser- vices, Food and Drug Administration, as a biologist in the Division of Toxicological Research. He is an active investigator and has published several research articles, primarily dealing with food safety. Other areas of his wide-ranging experi- ence include Lecturer of Agricultural and Rural Development at Gambia College, Gambia, West Africa, and seminars throughout Gambia on food safety, health awareness, and agricul- tural techniques. When not in the laboratory, Dr. Ross is either farming or writing.

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