Life Sciences Leaflets FREE DOWNLOAD ISSN 2277-4297(Print)0976–1098(Online)

PHYTOCHEMISTRY AND PHARMACOLOGY OF SOME

MEDICINALLY IMPORTANT OF FAMILY

RUBIACEAE

*KUMUD TANWAR1 AND JAYA MATHUR2 Universal Impact 1 Factor 0.9285:2012; DEPARTMENT OF CHEMISTRY, JNIT, JAIPUR , 1.2210:2013 RAJASTHAN (INDIA).

Index Copernicus 2DEPARTMENT OF CHEMISTRY, RAJASTHAN UNIVERSITY, ICV 2011: 5.09 JAIPUR , RAJASTHAN (INDIA). ICV 2012: 6.42 ICV 2013: 15.8 Corresponding author’s e-mail: tanwar_kumud @ yahoo.co.in ICV 2014:89.16

NAAS Rating ABSTRACT: 2012 : 1.3; 2013-2014- The present work is a review of five medicinally important plants of family 2015:2.69 namely- Anthocephalus cadamba, Mitragyna parvifolia,

Received on: tinctoria, Hamelia patens and Ixora coccinea. These plants are credited with th 10 August 2015 innumerable medicinal properties. Herbs are staging a comeback and herbal

Revised on: ‘renaissance’ is happening all over the globe. This article discusses the th 24 November 2015 distribution, morphology, various uses of these plants in traditional systems of

Accepted on: medicines. Also the major phytochemical constituents present in these plants th 10 December 2015 and the different studies conducted on the various pharmacological activities

Published on: exhibited by these plants such as anti-diabetic, anti-oxidant, anti-tumor, anti- st 1 February 2016 inflammatory, anti-microbial, anti-diarrhoeal,etc. have been dealt with in

Volume No. detail. This review indicates the immense medicinal and therapeutic value of Online & Print these plants. 72 (2016)

Page No. KEY WORDS: Anthocephalus cadamba, Mitragyna parvifolia, Morinda 67 to 100 tinctoria, Hamelia patens, Ixora coccinea , Morphology, Phytochemistry, Life Sciences Leaflets Pharmacology, Bio-activity. is an international open access print & e journal, peer reviewed, INTRODUCTION: worldwide abstract Plants are storehouses of various products of industrial, medicinal and listed, published every pharmacological importance. Plants had been used for medicinal purposes long month with ISSN, RNI Free- membership, before the recorded history. The use of medicinal plants figured in the ancient downloads and access.

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Life Sciences Leaflets FREE DOWNLOAD ISSN 2277-4297(Print)0976–1098(Online) manuscripts such as the Bible, the Rig-Vedas, the Iliad, the Odyssesy and the History of Herodotus. Many indigenous cultures used herbs in treatment of diseases and in some traditional medicinal systems (e.g. Ayurveda) the herbal therapies were used systematically. With the advancement in the field of synthetic chemistry, scientists began synthesizing the compounds and their derivatives. This resulted in the transition from raw herbs to synthetic pharmaceuticals. Over time, the use of herbal medicines declined in favour of synthetic pharmaceuticals. But the last two decades have witnessed a tremendous resurgence in the interest and use of medicinal plant products. This has been fuelled by the rising cost of prescription medications, realization of hazardous side effects associated with the use of synthetic drugs, developing interest of people in returning to natural or organic remedies and bio-prospecting of new plant derived drugs. According to World Health Organization about 80% of people worldwide rely on herbal medicines for some aspect of their primary healthcare. Plant derived drugs are considered safer than conventional medications. These are biologically more compatible, harmless and efficacious. Many such drugs are currently in use for treatment of various diseases. The extract of Ginko biloba is useful in Alzheimer’s disease and dementia. Catharanthus roseus yields anti- tumor agents such as vinblastine and vincristine. Hypericum perforatum, also called St. John’s wort, is well known for its antidepressant effects. Valeriana officinalis is a sleep inducing agent. Echinaceae preparations (from Echinaceae purpurea and other Echinaceae species) are used to bolster immunity. Ricinus communis yields the laxative castor oil. Undoubtedly, medicinal plants have become an integral component of research developments in the pharmaceuticals industries. The primary focus of this research is on the isolation and characterization of active medicinal constituents from plants and on the active screening of natural products to yield pharmacologically active compounds. Once the domain of health food and speciality stores, phytomedicines have re-emerged into the mainstream as evidenced by their availability for sale at retail outlets, the extent of their advertisement in media and recent entrance of major pharmaceutical companies into the production of phytomedicinal products. Encouraged by these remarkable achievements in the field of plant chemistry, we present a review of five medicinally important plants of family Rubiaceae. The work mainly reviews the investigations and studies done by various workers on the phytochemistry and pharmacology / bioactivity of these plants. 1. Anthocephalus cadamba

Synonyms: Anthocephalus chinensis, Anthocephalus macrophyllus, Anthocephalus indicus, Neolamarckia cadamba.

Common Names: Kadam, Kadamba-Vriksha.

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Taxonomy:

Kingdom - Plantae

Subkingdom - Tracheobionta

Super division - Spermatophyta

Division - Magnoliophyta

Subclasss - Asteridae

Order - Rubiales

Family - Rubiaceae

Genus - Neolamarckia

Species - Neolamarckia cadamba (Roxb.) F. Bosser

Distribution: This plant grows naturally in Australia, China, India, Indonesia, Malaysia, Papua New Guinea, Philippines, Singapore and Vietnam. It is found widely distributed throughout the greater part of India, especially at low levels in wet places.

Plant morphology: A.cadamba is a upto 37.5 m high and 2.4 m in girth with straight cylindrical bole. The bark is grey, smooth in young , rough and longitudinally fissured in old trees. The of this plant are ovate, elliptical-oblong in shape with their length ranging from 7.5 to 18 cm and breath is about 4.5 to 16 cm. The leaves have entire margin, pulvinus base, mucronate apex, glabrous surface with pinnate venation1. are orange or yellow in colour, in solitary globose head. are flushy, orange, globose, pseudocarp of compressed angular capsules with persistent calyx 2. Seeds are small and muriculate.

Traditional uses: This plant finds wide applications in folk medicines. It is used in the treatment of fever, anaemia, as anti-diuretic and for improvement of semen quality 3. It also finds uses in uterine complaints, blood diseases, eye-inflammation, diarrheoa, leprosy, dysentery and stomatitis 1. Ayurveda indicates use of dried stem bark in disorders of female genital tract and bleeding disorders. The bark of the plant posseses astringent, anti-inflammatory, digestive, carminative, diuretic, expectorant, constipating and antihelmentic properties and is given to treat fever and inflammation of eyes. Leaves of the plant find uses as astringent. The warm aqueous extract of leaves has been used in treatment of pain, swelling and for cleansing and better wound healing. This plant has been found to contain cinchotannic acid which was used to control fever long before the knowledge of quinine to be effective in malaria. In some places the plant is used in the treatment of snake-bite.

Phytochemistry: The following chemical constituents have been reported from different parts of this plant –

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 Heartwood, leaves, flowers and seeds contain typical alkaloid cadambine and its derivatives4.  Major constituents of bark are triterpenoid glycosides, saponins, indole alkaloids, cadambine, 3α- dihydrocadambine, cadamine, isocadambine and isodihydrocadambine and its derivatives 5-10.  Stem bark contains a pentacyclic triterpenic acid called cadambagenic acid along with quinovic acid11.  Leaves of this plant contain alkaloids- 3β-dihydrocadambine and 3β-isodihydrocadambine along with an acid named chlorogenic acid11.  Leaves also contain indole alkaloids called aminocadambine A and aminocadambine B 11, 12.  Two novel triterpenoid saponins named phelasin A and phelasin B have been isolated from bark of this plant13.  Two triterpenoid glycosides namely glycosides A and B have been reported from the bark of the plant and are defined as- 3-O- [α-L-rhamnopyranosyl]-quinovic acid-28-O-[β-D- glucopyranosyl] ester and 3-O-[β-D- glucopyranosyl]-quinovic acid-28- O-[β-D- glucopyranosyl] ester respectively14.  Flowers of Anthocephalus cadamba yield an essential oil having linalool, geraniol, geranyl acetate, linalyl acetate, α-selinene, 2-nonanol, β-phellandrene, α-bergamottin, terpinolene, p-cymol, curcumene, camphene and myrcene as the major constituents11.  Seeds are composed of water-soluble polysaccharides D-xylose, D-mannose and D-glucose in the molar ratio 1: 3 : 5 15.

Cadambine 3α- Dihydrocadambine

Isodihydrocadambine Cadamine

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Cadambagenic acid Quinovic Acid

Chlorogenic acid Aminocadambine A

Aminocadambine B

Pharmacological Studies / Bio-activity: The literature survey revealed that many parts of this plant are used in treatment of various diseases and disorders. The various pharmacological studies conducted on this plant are summarized in the table given below-

S.No. Bio-activity Exhibited by plant part / Experimental study / Reference compound of plant organism used no.

1. Anti-diabetic a. Methanolic extract of Significant 16 bark hypoglycemic effect in alloxan induced diabetic rats. b. Alcoholic and aqueous Significant reduction in extract of roots blood glucose level in 17 normoglycemic and

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alloxan induced diabetic rats.

2. Antidiarrhoeal Dry hydroethanolic extract Decrease in total of flowering tops number of feacal 18 droppings in castor-oil induced diarrhea in swiss albino mice.

3. Analgesic Aqueous and ethanolic Significant reduction in extract of leaves number of writhing 19 induced by acetic acid in swiss albino mice

4. Anti- Methanolic extract of bark Potent activity found in inflammatory studies on carrageenan, dextran and mediators 20 (histamine and serotonin) induced paw edema and cotton-pallet induced granuloma, in swiss albino male mice and male rats.

5. Anti-pyretic Petroleum ether, solvent Study used yeast ether, chloroform, ethanol induced hyperpyrexia extracts of leaves method and was carried 21 out on Wister strain rats weighing 150-200gm. Profound activity was observed (as indicated by reduction of body temperature in test animals).

6. Antioxidant a. Alcoholic and aqueous Study indicated potent extract of whole plant antioxidant activity by inhibition of lipid 22,23 peroxidation and increase in superoxide dismutase and catalase activity in rats.

b. Ethanolic extract of Study showed leaves and fruits significant DPPH (1,1- Diphenyl-2-picryl- 2 hydrazyl) radical scavenging activity of

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extract.

7. Anti-microbial a. Petroleum-ether, Strong activity found chloroform and acetone against strains of 24 extracts of leaves Escherichia coli, Staphylococcus aureus, Aspergillus niger, Candida albicans, Pseudomonas aeruginosa and Salmonella typhi, by 22 agar cup plate diffusion method. b. Alcoholic and aqueous extract of whole plant Potent activity found in study on 7 bacteria and 4 fungi by agar diffusion method. c. Alcoholic and aqueous extract of fruits ( Significant activities ripened and unripened) observed in studies 25 conducted on Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa using disc diffusion method.

8. Hepatoprotective Chlorogenic acid Intraperitoneal (CGA)from plant administration of CGA to mice exhibited good 26 liver protective action in CCl4 administered mice.

9. Diuretic and a. Methanolic extract of Significant increase in Laxative activity bark urinary output (diuresis).

27 b. Chloroform extract of Potent laxative property bark

10. Antihelmentic Aqueous and ethanolic Potent activity against extract of mature barks Earthworms, tapeworms 11 and roundworms.

11. Wound healing Alcoholic and aqueous Appreciable wound extract of whole plant healing activity in rats

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shown from wound 22 contraction and increased tensile strength.

2. Mitragyna parvifolia

Synonyms : Nauclea parvifolia Roxb., Stephegyne parvifolia (Roxb.) Korth.

Common Names : Kaim, Kadamb

Taxonomy :

Kingdom - Plantae

Subkingdom - Tracheobionta

Superdivision - Spermatophyta

Division - Magnoliophyta

Subclass - Asteridae

Order -

Family - Rubiacea

Genus - Mitragyna

Species - Mitragyna parvifolia

Distribution: Mitragyna parvifolia is found widely distributed in Nepal, India, Ceylon, Malaysia, Pakistan, Burma, Sri Lanka and Bangladesh. It grows in tropical regions and subtropical regions of Asia and Africa. It is found widely distributed in India up to an altitude of 1200 metres.

Plant Morphology: Mitragyna parvifolia is a large tree which attains a height of 40 to 50 feet. The stem is erect and branching. Leaves of this plant are dark green in colour, with petioles of about 1to 4 centimetres in length. The leaves are simple, smooth, rounded, opposite, and decussate. Flowers are creamy-white or yellow in colour, fragrant, found in terminal heads, in ball-shaped clusters; the

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peduncle being supported by a pair of bract like oblong leaves. Fruits are capsules arranged in globose heads, 2 to 3 millimeters long, ribbed. Seeds are many, small and 10-ribbed.

Traditional Uses: The plant is credited with innumerable medicinal properties and is widely used by tribal people and other ayurvedic practitioners. In Ayurveda, the bark of this plant is used for treatment of blood-related diseases. The bark and roots are used to treat fever, colic and muscular pain, burning sensation, poisoning, gynaecological disorders, cough, edema and as an aphodisiac28- 29. The juice augments the quantities of breast milk in lactating mothers and also works as lactodepurant. Wounds and ulcers are dressed with its leaves to alleviate pain, swelling and for better healing 30. The plant bark can be used in the preparation of commercially viable phytomedicine31. The plant also finds uses in the expulsion of worms. In Andhra Pradesh (in India) fresh juice of this plant is used to treat jaundice32. In Karnataka (in India) stem bark is used for biliousness33. The Bark paste is applied externally for muscular pains34. Powdered bark is boiled with fruits and inhaled through mouth for treatment of toothache35.

Phytochemistry: M. parvifolia is an important tree having a large number of important phytoconstituents especially alkaloids. Various indolic and oxindolic alkaloids reported from this species are of significant biological importance28-29.The major chemical constituents isolated from this plant are:

 Leaves of this plant contain scopoletin, thermophyllin, daucosterol, quinonic acid, β- sitosterol, indolin and oxindolic alkaloids36 mainly mitraphylline, isomitraphylline, 16,17- dihydro-17β-hydroxyisomitraphylline and 16,17-dihydro-17β-hydroxymitraphylline29 along with pteropodine, isoteropodine, speciophylline and uncarine37.

 Stem bark revealed the presence of alkaloids, flavonoids, glycosides and tannins38.  The Indole alkaloids of this plant are of considerable importance as they are the precursors or the starting materials for the biogenesis of corresponding oxindole alkaloids39.

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H H OCH3 H

N O

N H N O H H H N O O Et H H H3CO

OCH O 3

Speciophylline Mitraphylline

18 O H3C 17 O H N O 10 C OCH3 16 22 23 H 21 12 9 N 6 5 14 15 O 13 8 3 N H N O O 2 7 H O Uncarine Isopteropodine

16,17-dihydro-17β-hydroxyisomitraphylline 16,17-dihydro-17β-hydroxymitraphylline

Pharmacological Studies / Bio-activity: Various parts of this plant are used in treatment of many diseases and disorders. The different pharmacological studies performed on this plant have been summarized in the table given below-

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S.No. Bioactivity Exhibited by Plant Experimental study / Reference part/compound of plant organism used no.

1. Antihelmentic Methanolic extract of Potent activity found in the in 40 stem bark vitro study against adult earthworm Pheretima posthuma (dose level at 100mg/ml).

2. Anticonvulsant Ethanolic extract of leaves Significant activity evaluated 41 for effects in seizures induced by Pentylenetetrazole (PTZ) and maximal electroshock convulsion methods in mice.

3. Anti- Ethanolic extract of dried Significant activity observed in 42,47,48 inflammatory leaves/fruits/ Mitragynine the study using Carrageenan- induced paw edema method in rats at different dose levels.

4. Antinociceptive Ethanolic extract of dried Evaluated using the Tail-flick 42 leaves of plant / method in mice at various dose Mitragynine levels. It has effects on guinea- pigileum.

5. Antiarthritic Methanolic extract of Potent activity found in rodent 43 leaves model of mice.

6. Antipyretic Methanolic extract of Study conducted using 43 leaves Brewer’s yeast induced pyrexia in rats. The extract was found to be potent in reducing fever.

7. Acute toxicity Methanolic / ethylacetate Plant found to be practically 44 extract of leaves non-toxic at the LD50 dose recorded 5g/kg/wt.

8. Anxiolytic Methanolic / Ethyl Potent activity observed in 44 acetate extract of stem study using the elevated plus bark maze and marble burying test in mice.

9. Antimicrobial Ethanolic extract of leaves The extract significantly inhibited S.aureus. 45

10. Analgesic Ethanolic extract of leaves The extract at the dose of 46,47 activity / fruits 500mg/kg showed strong

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activity in mice models using Eddy’s hot plate methods.

11. Antioxidant Ethanolic extract of leaves Extract subjected to in vitro 48,49 antioxidant assays namely the DPPH(2,2-diphenyl-1- picrylhydrazyl) assay. The antioxidant activity in the reducing power assay was found to increase in a concentration dependent manner.

12. Cytotoxicity Acetone extract of bark Exhibited highest cytotoxic 50 effect on He La cells.

13. Anti-diabetic Alkaloid-16,17-Dihydro- In vivo study on neonatal 51 17b-hydroxy Wistar albino rats showed that isomitraphylline (DHIM) DHIM stimulates β-cell proliferation and reduces pancreatic cell apoptosis in diabetic treated rats.

14. Anti-Viral Plant extract in various Study showed 40-62% 52 solvents protection against Bovine Herpes Virus-1

3. Morinda tinctoria Synonyms: Morinda tomentosa Heyne, Morinda pubescens, .

Common names: It is locally known as “Togaru”, Indian mulberry, Aal or Nunaa.

Taxonomy:

Kingdom - Plantae

Subkingdom - Tracheobionta

Super division - Spermatophyta

Division - Magnoliophyta

Subclasss - Asteridae

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Order - Rubiales

Family - Rubiaceae

Genus - Morinda

Species - Morinda tintoria (Roxb.)

Distribution: This plant grows naturally in Thailand, Malaysia, South Asia, India, Burma. It is found widely distributed throughout the southern part of India, especially at the eastern slopes of the ghats in India.

Plant morphology: It is an evergreen or a small tree that attains a height of about 5-10 m. The leaves are 15-25 cm in length, oblong to lanceolate. The flowers are white coloured, scented, tubular, about 2 cm long. The fruit of this plant is a green syncarp which is nearly 2-2.5 cm in diameter.

Traditional uses: The plant finds immerse utility in various traditional systems of medicines such as Ayurveda and Siddha. Literature survey reveals that traditionally the leaf juice is given orally to children before food for easy digestion 53. The leaves are also administered internally as a tonic and febrifuge 54 . The leaves and roots of this plant are used as astringent, deobstrent, emmengogue and to relive pain in the gout55. The plant is reported to have a broad range of therapeutic and nutritional values56. There is a great demand for fruit extract of this plant in treatment for different kinds of illness such as arthritis, cancer, gastric ulcer, viral infection,liver diseases, diabetes and heart diseases57.

Phytochemistry: The major chemical constituents that have been reported from different parts of this plant are –  The main components isolated from the leaves and fruits are ocotanic acid, terpenoids, scopoletin, rutin, flavonesglycosides, linoleic acid, ursolic acid, quercetin, kaempferol-3-O- rutinoside, anthraquinones, morindone, and morindone-6-O-gentiobioside58-60.  The heartwood showed the presence of tinctomorone, anthraquinone ester, morindone, damnacanthal, nordamnanthal61-62.  Stem bark contains alizarin-1-methyl ether, rubiadin and D-mannitol63.

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 The root bark contains morindone, damnacanthal, nordamnanthal, anthragallol-2, 3-di- methyl ether, soranjidiol, ibericin, 6-primeveroside of morindone, soranjidiol, and ibericin64- 65 .  The compounds isolated from the flowers are apigenin-5,7-dimethylether4'galactoside66, 2- methyl-4-hydroxy-5,7-dimethoxyanthraquinone,4-O-β-D-glucopyranosyl-(1-4)-β-L- rhamnopyranoside, acacetine-7-O-β-D-glucopyranoside67.  Phytochemical screening of the leaf extract revealed the presence of compounds such as scopolamine, malvidin 3,5-diglucoside, different alkaloids, saponins, phytosterols, carbohydrates, proteins, amino acids, tannins, glycosides and flavonoids68-70.  The major components isolated from its fruits are β -D-glucopyranose pentaacetate , 2,6- di-O-( β -D-glucopyranosyl)-1-O-octanoyl- β -D-glucopyranose, 6-O-( β -D- glucopyranosyl)-1-O-octanoyl- β -D-glucopyranose, ascorbic acid, asperulosidic acid, asperuloside tetraacetate, caproic acid, caprylic acid, ethyl caprylate, ethyl caproate, hexanoic acid, octanoic acid , quercetin 3-O-α-L-rhamnopyranosyl-(1-6)- β -D- glucopyranoside71-72.

Ursolic Acid Quercetin

Kaempferol-3-O-rutinoside Acacetine-7-O-β-D-glucopyranoside

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Rubiadin Morindone

Tinctomorone Damnacanthal

Nordamnacanthal Scopoletin

Alizarin

Pharmacological Studies / Bio-activity: From the survey of literature, the utility of this plant in treatment of various diseases and disorders becomes evident. The various pharmacological studies conducted on this plant are summarized in the table given below-

S.No. Bio-activity Exhibited by plant part Experimental study / Reference

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/ compound of plant organism used no.

1. Antioxidant Ethyl acetate and Study indicated potent 73 methanolic extract of antioxidant activity under whole plant oxidative stress such as inflammation, aging, mutagenicity and carcinogenicity.

2. Anti microbial a. Methanolic and Strong activity found chloroform extract of against strains of 74 leaves Escherichia coli, Staphylococcus aureus, Aspergillus niger, Candida albicans, Pseudomonas aeruginosa and Salmonella typhi, by agar cup plate diffusion method. b. Ethyl acetate and chloroform extract of Showed potent activity 74,75 leaves against above mentioned organisms. c. Fruit extract in different solvents Exhibited inhibitory effects 76,77,69 against the pathogens such as Salmonella typhi and Klebsiella pneumonia

d. Methanolic leaf extract / root extract These extracts showed 78,79,80 in different solvents / strong whole plant extract activity against almost all in dichloromethane micro-organisms. and methanol

3. Anti- Aqueous and methanolic Potent activity observed in inflammatory extract of leaves study using carrageenin- 76 induced paw edema method in rats.

4. Anticonvulsant Petroleum ether extract Significant activity found of leaves in albino mice by using maximal electroshock and 55 Pentylenetetrazol methods.

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5. Antidiabetic Aqueous extract of fruits Study exhibited significant control in the blood glucose levels, 81 improvement in the plasma insulin, lipid metabolism and prevention in diabetic complications from lipid peroxidation and antioxidant systems in diabetic rats. 6. Hepatoprotective a. Aqueous and Showed hepatoprotective 82 methanolic leaf activity against extract paracetamol induced heptatoxicity in Sprague’ Dawley rats.

b. Ethanolic fruit 83 extract Study evaluated against D- galactosamin induced liver injury in rats

7. Cytotoxicity Methanolic extract of Extract subjected to 84,85 Roots / Iridoid glycoside various bioassays to evaluate its therapeutical potential. The capability of compound to hinder proliferation in case of cancerous cell line was ascertained by its efficacy to induce cytotoxicity.

8. Cytoprotective Ethanolic extract of Significant activity found effect leaves in study on aspirin pyloric 86 ligation-induced gastric ulcer model and cysteamine-induced duodenal ulcer in Wistar rats.

4. Hamelia patens Jacq. Synonyms: Hamelia erecta Jacq., Hamelia coccinea, Hamelia pedicellata Wernh, Hamelia latifolia Reichb. ex DC.

Common names: Scarlet bush, Fire bush, Hummingbird bush.

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Taxonomy:

Kingdom - Plantae

Subkingdom - Tracheobionta

Super division - Spermatophyta

Division - Magnoliophyta

Sub classs - Asteridae

Order - Rubiales

Family - Rubiaceae

Genus - Hamelia Jacq.

Species - Hamelia patens Jacq.

Distribution: The plant is indigenous to most of South America, the West Indies, Mexico,United States, Great Britain, South Africa and even southern Florida. In India, it is found widely distributed in Karnataka, Kerala and Tamil Nadu.

Plant morphology: Hamelia patens Jacq.is a bush or a small tree, about 1.4-3.0 m tall but sometimes attains a height of about 7 m. This plant produces flowers and fruits throughout the year. Leaves are opposite or grouped in threes or fours and are finely hairy to glabrous. The leaves have petioles that are nearly 1 to 3.5 cm long and blades that are mostly ovate-elliptic to obovate-elliptic with an acute or acuminate tip. Flowers are orange to red in colour, tubular, about 12 to 22 mm in length. The fruit of this plant is a berry which is spherical to elliptical in shape, nearly 7 to 10 mm in length and it turns red and then black at maturity. The seeds are orange brown and about 0.6 to 0.9 mm in length. The plant has a tap root and lateral root system with abundant fine roots. Stem bark is gray and smooth and the inner bark is light green.

Traditional uses: This plant is used in folk medicines against a range of ailments such as athlete’s foot, skin lesions and rash, insect bites, nervous shock, headache, asthma and dysentery87-88. It is widely used in the venezuelam disease, malaria, rheumatism, gastritis, ulcers and as antihemorragic89-90. The various parts of the plant are used in treatment of various disorders of the immune system, reproductive system, central nervous system, cardiovascular system, gastric system, urinary system and blood biochemistry91.

Phytochemistry: The following chemical constituents have been reported from different parts of this plant –

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 The extract of the H. patens revealed the presence of alkaloids, carbohydrates, flavonoids, glycosides, phenols, proteins, quinones, saponins, steroids, coumarins, phytosterols and terpenoids87- 88.  The phytochemical examination of its leaves resulted in the isolation of the alkaloids such as isoteropodin, pteropodine, palmirine, rumberine, mitrajavine, cycloartanols, rosmarinic acid92-94 and ephedrine95.  The various flavanoids isolated from its aerial parts are kaempherol-3-O-rutinoside, (-) epicatechine, 5,7,2ꞌ,5ꞌ-tetrahydroxyflavanone-7-O-a-L-rhamnopyranoside, stigmast-4-en-3,6-dione, 5,7,2ꞌ,5ꞌ- tetrahydroxyflavanone-7-D-glucopyranoside, narirutin and rosmarinic acid90,96. Stems and roots contain starch, protein, lipid and phenol97.

Epicatechine Palmirine

Rumberine Mitrajavine

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5,7,2',5'-tetrahydroxyflavanone -7-O-a-L- 5,7,2',5'-tetrahydroxyflavanone -7-D- rhamnopyranoside glucopyranoside

Narirutin Rosamarinic acid

Pharmacological Studies / Bio-activity: The literature survey has revealed the importance of this plant in treatment of various diseases. The various pharmacological studies that have been performed on this plant are summarized in the table given below-

S.No. Bio-activity Exhibited by plant part / Experimental study / Reference compound of plant organism used no.

1. Anti-leishmanial Ethanolic extract of leaves Showed significant / Palmirine. leishmanicidal activity 98 with IC 50=56µM

2. Anti- Methanol,hexane,chlorofor Study indicated anti- inflammatory m extracts of leaves inflammatory action 99 against the croton oil- induced ear oedema in mice.

3. Antihelmentic Ethanolic extract of Potent activity against different parts of plant Earthworm-Pheretima 97 posthuma

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4. Anti-microbial a. Ethanolic extracts of Significant activities 97 different parts of plant observed in studies conducted on Aspergillus flavus, Aspergillus fumigates and Penicillum sp. using disc diffusion method.

b. Hexane extract of The extract inhibited the 100 whole plant growth of Escherichia coli c. Aqueous extracts of leaves,flowers and Study showed antifungal 101 fruits potentials against Aspergillus fumigates, Candida albicans , Fusarium oxysporum and Rhizoctonia solani .

5. Wound healing Ethanolic extract of whole Appreciable wound plant healing activity in rats shown from wound 102 contraction and increased tensile strength.

6. Antioxidant Hydroalcoholic extract of Study showed 103 leaves. significant DPPH (1,1- Diphenyl-2-picryl- hydrazyl) radical scavenging activity of extract. 7. Cytotoxicity Methanolic extract of The extract exhibited 104 leaves, stem bark and cytotoxic activity on He roots. La cells by using the 3- (4,5-dimethylthiazol-2- yl)-2,5-diphenyl tetrazolium bromide (MTT).

8. Contraction of Methanolic leaf extract Study showed the high 105 Myometrium KCl - induced contraction in rat myometrium

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The immense pharmacological importance of this plant indicates that it can be further exploited to discover the bioactive natural products that may serve as leads in the development of new pharmaceuticals106-107.

5. Ixora coccinea Synonyms : Ixora grandiflora Bot., Ixora bandhuca Roxbg.

Common names: Jungle geranium, Flame of wood, Red Ixora, Rugmini . Taxonomy:

Kingdom - Plantae

Subkingdom - Tracheobionta

Super division - Spermatophyta

Division - Magnoliophyta

Subclasss - Asteridae

Order - Rubiales

Family - Rubiaceae

Genus - Ixora L.-Ixora P.

Species - Ixora coccinea L.

Distribution: It is a common flowering shrub native to Southern India and Sri Lanka. It is found widely distributed from Africa to India to Southern Asia.

Plant morphology: It is a dense, multi-branched evergreen shrub. This plant attains a height of about 1.2–2 m, but it can also reach up to 3.6 m. It has a rounded form, with a spread that may exceed its height. The leaves are glossy, leathery, oblong and are about 10 cm long. The leaves have entire margins and are present in opposite pairs or whorled on the stems.This plant has small tubular, scarlet flowers present in dense rounded clusters 5–13 cm across and are produced almost all through the year.

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Traditional uses: The flowers, leaves, roots, and the stem of this plant are used to treat various ailments in the Indian traditional system of medicine, the Ayurveda, and also in various folk medicines. The fruits, when fully ripe, are used as a dietary source108. In Indochina, root decoction is used to treat urinary disorders, poultice of fresh leaves and stems are used to treat sprains, eczema, boils, and contusions109. The flowers are used to cure dysentery, leucorrhoea, dysmenorrhoea, hemoptysis , catarrhal bronchitis, gonorrhea, bronchitis, sores, chronic ulcer, scabies, cholera and dermatitis110. Decoction of leaf is employed as a lotion for eye troubles and also used as a sedative. Roots and flowers are also used in diarrhea, fever and decoction of roots used for nausea, hiccups and anorexia, sores and chronic ulcers and it possess astringent and antiseptic properties. Decoction prepared from the plant is a good blood purifier and beneficial to skin infections like itches, scabies, boils etc. 111-112.

Phytochemistry: The various chemical constituents that have been reported from different parts of this plant are-  Phytochemical studies indicate that the plant contains important phytochemicals such as lupeol, ursolic acid, oleanolic acid, linolic, sitosterol, rutin, lecocyanadin, anthocyanins, proanthocyanidins, glycosides of kaempferol and quercetin108.  Flowers yield cyanidins, flaconboides, leucocyanidin, rutin , quercetin, flavonoids, steroids and tannins113-114 .  Two new cycloartenol esters, lupeol fatty ester, lupeol, ursolic acid, oleanolic acid and sitosterol have been isolated from flowers115.  The floral extracts of Ixora coccinea showed the presence of phenolic compounds, terpenoids, phytosterols, saponins, coumarins, carbohydrates and glycosides116.  Leaves yield flavonols, kaemferol, quercetin, proanthrocyanidines, phenolic acids and ferulic acids117.  Leaves also contain ixoratannin A-2, epicatechin, procyanidin A-2, cinnamotannin B-1 and the flavone-3-olrhamnoside namely kaempferol-7-O-α-1-rhamnoside, kaempferol-3-O-α- 1- rhamnoside,quercetin-3-O-α-1-rhamnopyranoside and kaempferol-3,7-O-α-1-dirhamnoside 118-119.  Roots contain octadecdienoic acid , aromatic acrid oil, tannins, fatty acids and root oil possesses methyl ester of palmatic , oleic, stearic and linolic acid119.  9, 12-Octadecadienoic acid, di-n-octyl phthalate, β-amyrin, kaempferol-7-O-glucoside, kaempferitrin and quercitrin have also been isolated from the roots.120

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 Flowers of this plant yield an essential oil having monoterpenes like geranyl acetate, sesquiterpenes like cyperene, copaene and triterpenes such as linalyl acetate, neryl acetate, terpineol acetate, borneol aceate and ethyl cinnamate as the major constituents121.

H H

H

HO H Kaempferol Lupeol

OH

H O

H

HO H HO

Cycloartenol Oleanolic acid

Pharmacological Studies / Bio-activity: Many parts of this plant are used in treatment of various diseases and disorders. The literature survey of the various pharmacological studies conducted on this plant are summarized in the table given below-

S.No Bio-activity Exhibited by plant part / Experimental study / Referenc . compound of plant organism used e no.

1. Anti-oxidant Methanolic extract of leaves Study showed significant 122 and flowers DPPH (1,1-Diphenyl-2- picryl-hydrazyl) radical scavenging activity of the extract (due to the presence of phenolics, flavonoids) by using Phosphorous molybdenum method.

2. Anti-diarrhoeal Aqueous extract of leaves or Significant inhibitor 123,116 flowers activity against castor oil induced diarrhoea model

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in rats.

3. Analgesic Methanolic extract of Significant reduction in 124 flowers and leaves number of writhing induced by acetic acid in swiss albino mice

4. Anti- Aqueous leaf extract Potent activity observed in 125 inflammatory study conducted on rats by carrageenan –induced paw edema and cotton pellet granuloma tests.

5. Anti-asthmatic Hydro alcoholic extract of Studied in an ovalbumin 126 leaves (OVA)-induced asthmatic rat model. The extract suppressed eosinophilia and significantly inhibited AHR in rat with OVA- induced asthma.

6. Cytotoxicity and Methanolic extract of Activity studied in 127 Anti-tumor flowers comparison to intraperitoneally transplanted Dalton's lymphoma (ascitic and solid tumors) and Ehrlich ascites carcinoma tumors in mice. The active fraction inhibited tritiated thymidine incorporation in cellular DNA.

7. Anti-microbial a. Ethanol, ethyl acetate, Study confirmed broad 128 ether and aqueous spectrum of anti-bacterial extracts of whole plant activity against both Gram positive and Gram negative bacteria.

b. Ethyl acetate extract of Potent activity against leaves drug-resistant pathogenic 109 bacteria by agar well diffusion and broth dilution methods. c. Ethanolic, methanolic and distilled water Exhibited antibacterial extracts of flowers activities studied by well 129 plate method and filter

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paper method.

8. Hepatoprotective Ethanolic extract of whole Studied on albino male plant / Ixorapeptide I and Wistar rats. The two novel Ixorapeptide II derivative peptides- 130, 131 Ixorapeptide I and Ixorapeptide II, exhibited selective potency against Hep3b liver cancer cell line.

9. Antihelmentic Root extract in different Potent activity against solvents Earthworm- Pheretima 132 posthuma.

10. Chemoprotective Methanolic extract of Study showed that the flowers / Triterpenoids and extract prevented a 133,80 ursolic acid. decrease in body weight, hemoglobin levels and leucocyte counts of mice treated with cisplatin.

11. Wound healing a. Alcoholic extract of Studied by using a dead 134 flowers space wound model in rats. Significant increase in granuloma tissue weight, tensile strength, hydroxyproline and glycosaminoglycan content was observed.

b. Ethanolic extract of Exhibited significant roots (P<0.001) wound healing 128 activity.

12. Anti-diabetic Aqueous extract of leaves Study showed significant 135 reduction in blood glucose level in alloxan induced diabetic albino rats.

13. Antinociceptive Aqueous leaf extract Considerable activity 136 observed in study using three models of nociception (tail flick, hot plate and formalin) in male rats at various dose levels.

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14. Anti-ulcer Methanolic extract of leaves Potent anti ulcerogenic 137 properties found in study conducted in pyloric ligation and hypothermic- restraint stress induced gastric ulcer models in albino rats.

15. Cardioprotective Methanolic extract of leaves Effect of extract against 138 doxorubicin-induced cardiac toxicity in albino Wistar rats was studied and cardioprotection of extract (due to its antioxidant properties) was confirmed.

16. Anti-leishmanial Ethylacetate and Evaluated against 139 methanolic extract of leaves Leishmania donovani (strainAG83) promastigotes by in vitro promastigote cell toxicity assay using MTT [3-(4,5- dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide]. Results showed considerable inhibition in growth of organism.

17. Antibiotic Aqueous extract of flowers Activity of extract as 140 antibiotic showed more inhibitory zones than compared to the standard antibiotics.

CONCLUSION

The discussion on these plants reveals their tremendous medicinal utility. Their wide applications in folk medicines and pharmacology are indicative of more possibilities of exploration and research in these plants. Besides their current medicinal uses, they are potential sources of medicinally important compounds and drugs in future. Further evaluation needs to be carried out in order to use these plants in formulations for their practical and clinical applications which will prove useful for the welfare of the mankind.

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ACKNOWLEDGEMENTS: We deeply acknowledge Prof. R.T.Pardasani, Head and Dean, Chemistry department, Central University, Ajmer, Rajasthan, for his guidance and support. We are also thankful to the Departments of Chemistry of JNIT University and Rajasthan University, Jaipur, for providing all the necessary facilities.

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