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Centaurii herba Centaury 2015

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CENTAURII HERBA Centaury

2015

ESCOP Monographs were first published in loose-leaf form progressively from 1996 to 1999 as Fascicules 1-6, each of 10 monographs © ESCOP 1996, 1997, 1999

Second Edition, completely revised and expanded © ESCOP 2003

Second Edition, Supplement 2009 © ESCOP 2009

ONLINE SERIES ISBN 978-1-901964-32-5

Centaurii herba - Centaury

Published by the European Scientific Cooperative on Phytotherapy (ESCOP) Notaries House, Chapel Street, Exeter EX1 1EZ, United Kingdom www.escop.com

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Important Note: Medical knowledge is ever-changing. As new research and clinical experience broaden our knowledge, changes in treatment may be required. In their efforts to provide information on the efficacy and safety of herbal drugs and herbal preparations, presented as a substantial overview together with summaries of relevant data, the authors of the material herein have consulted comprehensive sources believed to be reliable. However, in view of the possibility of human error by the authors or publisher of the work herein, or changes in medical knowledge, neither the authors nor the publisher, nor any other party involved in the preparation of this work, warrants that the information contained herein is in every respect accurate or complete, and they are not responsible for any errors or omissions or for results obtained by the use of such information. Readers are advised to check the product information included in the package of each medicinal preparation they intend to use, to be certain that the information contained in this publication is accurate and that changes have not been made in the recommended dose or in the contraindications for administration.

Edited by Simon Mills and Roberta Hutchins Cover photographs by Prof Salvador Cañigueral Folcara (Centaurium erythraea) and Martin Willoughby Cover and text design by Martin Willoughby Typeset in Optima by Roberta Hutchins

Plant illustrated on the cover: Centaurium erythraea FOREWORD

It is a great pleasure for me to introduce the online era of ESCOP Monographs. Interest in herbal medicinal products continues to stimulate research on herbal substances and the body of knowledge in this field is steadily growing. ESCOP takes account of this by preparing new monographs and - as the only organisation in the field at the moment - particularly through regular revision of our published monographs. In order to provide readers and authorities with balanced compilations of scientific data as rapidly as possible, ESCOP Monographs will be published online from now on. This contemporary way of publishing adds further momentum to ESCOP’s endeavours in the harmonization of European standards for herbal medicinal products.

The Board of ESCOP wishes to express its sincere gratitude to the members of the Scientific Committee, external experts and supervising editors, and to Peter Bradley, the final editor of every monograph published up to March 2011. All have voluntarily contributed their time and scientific expertise to ensure the high standard of the monographs.

Liselotte Krenn Chair of the Board of ESCOP

PREFACE

Over the 15 years since ESCOP published its first monographs, initially as loose-leaf documents then as two hardback books, ESCOP Monographs have achieved a reputation for well-researched, comprehensive yet concise summaries of available scientific data pertaining to the efficacy and safety of herbal medicinal products. The Second Edition, published in 2003 with a Supplement in 2009, covered a total of 107 herbal substances.

The monograph texts are prepared in the demanding format of the Summary of Product Characteristics (SPC), a standard document required in every application to market a medicinal product for human use within the European Union and ultimately providing information for prescribers and users of individual products.

As a change in style, literature references are now denoted by the name of the first author and year of publication instead of reference numbers; consequently, citations at the end of a monograph are now in alphabetical order. This is intended to give the reader a little more information and perspective when reading the text.

Detailed work in studying the pertinent scientific literature and compiling draft monographs relies to a large extent on the knowledge, skills and dedication of individual project leaders within ESCOP Scientific Committee, as well as invited experts. After discussion and provisional acceptance by the Committee, draft monographs are appraised by an eminent Board of Supervising Editors and all comments are taken into account before final editing and approval. In this way a wide degree of consensus is achieved, but it is a time-consuming process.

To accelerate the publication of new and revised monographs ESCOP has therefore decided to publish them as an online series only, commencing in 2011. We trust that rapid online access will prove helpful and convenient to all users of ESCOP Monographs.

As always, ESCOP is indebted to the many contributors involved in the preparation of monographs, as well as to those who provide administrative assistance and hospitality to keep the enterprise running smoothly; our grateful thanks to them all. NOTES FOR THE READER

From 2011 new and revised ESCOP Monographs are published as an online series only. Earlier monographs are available in two books, ESCOP Monographs Second Edition (2003) and the Second Edition Supplement 2009, but are not available online for copyright reasons.

After purchase of a single monograph, the specific items to be downloaded are:

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Members of ESCOP Board of Supervising Editors ESCOP Scientific Committee Board of Directors of ESCOP ABBREVIATIONS used in ESCOP monographs

AA arachidonic acid ABTS 2,2’-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) ACE angiotensin converting enzyme ADP adenosine diphosphate ALAT or ALT alanine aminotransferase (= SGPT or GPT) ALP alkaline phosphatase anti-IgE anti-immunoglobulin E ASA acetylsalicylic acid ASAT or AST aspartate aminotransferase (= SGOT or GOT) ATP adenosine triphosphate AUC area under the concentration-time curve BMI body mass index BPH benign prostatic hyperplasia b.w. body weight cAMP cyclic adenosine monophosphate CI confidence interval

Cmax maximum concentration of a substance in serum CNS central nervous system CoA coenzyme A COX cyclooxygenase CSF colony stimulating factor CVI chronic venous insufficiency CYP cytochrome P450 d day DER drug-to-extract ratio DHT dihydrotestosterone DNA deoxyribonucleic acid DPPH diphenylpicrylhydrazyl DSM Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association) ECG electrocardiogram

ED50 effective dose in 50% of cases EDTA ethylenediamine tetraacetate EEG electroencephalogram EMA European Medicines Agency ENT ear, nose and throat ER oestrogen receptor ERE oestrogen-responsive element FSH follicle-stimulating hormone GABA gamma-aminobutyric acid Gal galactose GFR glomerular filtration rate GGTP gamma-glutamyl transpeptidase GOT glutamate oxalacetate transaminase (= SGOT) GPT glutamate pyruvate transaminase (= SGPT) GSH glutathione (reduced) GSSG glutathione (oxidised) HAMA Hamilton Anxiety Scale 12-HETE 12-hydroxy-5,8,10,14-eicosatetraenoic acid HDL high density lipoprotein HIV human immunodeficiency virus HMPC Committee on Herbal Medicinal Products (of the EMA) HPLC high-performance liquid chromatography 5-HT 5-hydroxytryptamine (= serotonin)

IC50 concentration leading to 50% inhibition ICD-10 International Statistical Classification of Diseases and Related Health Problems, Tenth Revision ICH The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ICSD International Classification of Sleep Disorders IFN interferon IL interleukin i.m. intramuscular iNOS inducible nitric oxide synthase INR International Normalized Ratio, a measure of blood coagulation (clotting) tendency i.p. intraperitoneal IPSS International Prostate Symptom Score i.v. intravenous kD kiloDalton KM Index Kuppermann Menopausal Index kPa kiloPascal LC-MS liquid chromatography-mass spectrometry

LD50 the dose lethal to 50% of animals tested LDH lactate dehydrogenase LDL low density lipoprotein LH luteinizing hormone 5-LOX 5-lipoxygenase LPS lipopolysaccharide

LTB 4 leukotriene B4 M molar (concentration) MAO monoamine oxidase MBC minimum bactericidal concentration MDA malondialdehyde MFC minimum fungicidal concentration MIC minimum inhibitory concentration Mr molecular MRS Menopause Rating Scale MRSA methicillin-resistant Staphylococcus aureus MTD maximum tolerated dose MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MW molecular weight NBT nitro blue tetrazolium NF-kB necrosis factor kappa-B NO nitric oxide NOS nitric oxide synthase n.s. not significant NSAID non-steroidal anti-inflammatory drug ovx ovariectomy or ovariectomized ORAC oxygen radical absorbance capacity PA pyrrolizidine alkaloid PAF platelet activating factor PCR polymerase chain reaction PEG polyethylene glycol PGE prostaglandin E PHA phythaemagglutinin p.o. per os POMS profile of mood states PVPP polyvinylpolypyrrolidone RANKL receptor activator of nuclear factor kappa-B ligand RNA ribonucleic acid RT-PCR reverse transcription polymerase chain reaction s.c. subcutaneous SCI spinal cord injury SERM selective oestrogen receptor modulator SGOT or GOT serum glutamate oxalacetate transaminase (= ASAT or AST) SGPT or GPT serum glutamate pyruvate transaminase (= ALAT or ALT) SHBG sex hormone binding globulin SOD superoxide dismutase SSRI selective serotonin reuptake inhibitor STAI state-trait anxiety inventory t1/2 elimination half-life TBARS thiobarbituric acid reactive substances TGF-b transforming growth factor-beta TNF tumour necrosis factor TPA 12-O-tetradecanoylphorbol-13-acetate URT upper respiratory tract URTI upper respiratory tract infection UTI urinary tract infection VAS visual analogue scale VLDL very low density lipoprotein CENTAURII HERBA 2015 Centaury

DEFINITION

Centaury consists of the whole or cut dried flowering aerial parts of Centaurium erythraea Rafn. s.l. including Centaurium majus Zeltner and Centaurium suffruticosum (Griseb.) Ronniger [syn. Erythraea centaurium Pers., C. umbellatum Gilib., C. minus Garsault].

The material complies with the European Pharmacopoeia [Centaury].

Fresh material may also be used, provided that when dried it complies with the European Pharmacopoeia.

CONSTITUENTS

The characteristic, bitter-tasting constituents are secoiridoid glucosides, principally swertiamarin (2-8%) and smaller amounts (0.1 to 0.5%) of gentiopicroside (gentiopicrin) and sweroside, with bitterness values of about 12,000 [van der Sluis 1985a, 1985b, Schimmer 1994a, Hoffmann-Bohm 2010, Aberham 2011]. Two intensely bitter m-hydroxybenzoyl esters of sweroside, centapicrin and deacetylcentapicrin, with bitterness values of about 4,000,000, are also present [Sakina 1976, van der Sluis 1985b, Schimmer 1994a]. Other iridoids include centauroside (a dimeric secoiridoid), secologanin, 6’-m-hydroxybenzoyl-loganin [Takagi 1982], dihydrocornin (a cyclopentane iridoid), gentioflavoside [Do 1987] and the secoiridoid alkaloid gentianine [Rulko 1972, Bishay 1978].

Various methoxylated xanthones [Nestha 1982, 1983, 1984, van der Sluis 1985a, 1985b, Schimmer 1994a, Valentao 2000, 2002, Hoffmann-Bohm 2010] including eustomin (1-hydroxy-3,5,6,7,8-pentamethoxyxanthone) and 8-demethyleustomin [Schimmer 1996].

Other constituents include phenolic acids, such as p-coumaric, o-hydroxy- phenylacetic, ferulic, protocatechuic, sinapic, vanillic [Hatjimanoli 1977, Dombrowicz 1988, Sharaf 2003], hydroxyterephthalic and 2,5-dihydroxy- terephthalic acids [Hatjimanoli 1988]; flavonoids [Sharaf 2003]; phytosterols (b-sitosterol, stigmasterol, campesterol and others) [Popov 1969, Aquino 1985, Loizzo 2008]; 5-formyl-2,3-dihydroisocoumarin [Valentao 2003a]; amino acids [Petlevski 2002]; small amounts of essential oil (up to 0.02%) [Jovanović 2009, Jerković 2012] and triterpenoids [Bellavita 1974, Loizzo 2008, Jäger 2009].

CLINICAL PARTICULARS

Therapeutic indications Dyspeptic complaints; lack of appetite [Centaurium 1983, Bisset 1994, Leung 1996, Newall 1996, Hoffmann-Bohm 2010].

Posology and method of administration

Dosage

Adults: 1-4 g of the drug as a maceration, infusion or decoction in 150 mL of water, up to 3 times daily [Centaurium 1983, Bisset 1994, Leung 1996, Newall 1996, Hoffmann-Bohm 2010]; 2-4 mL of liquid extract (1:1, ethanol 25 % V/V), up to 3 times daily [Centaurium 1983, Newall 1996, Hoffmann-Bohm 2010]; tincture (1:5, ethanol 70 % V/V), 2-5 g daily [Hoffmann-Bohm 2010].

Children: proportion of adult dose according to age or body weight, in ethanol- free dosage forms.

The dosage may be adjusted according to the bitterness sensitivity of the individual.

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Method of administration In vivo experiments For oral administration in liquid preparations. For lack of appetite, administered half to one hour before meals [Hoffmann-Bohm Anti-inflammatory activity 2010]; for dyspepsia, taken after meals. In the air pouch granuloma test in rats a dry aqueous extract of centaury (3.8:1), applied topically as 5% and 10% creams, Duration of administration exhibited significant transdermal anti-inflammatory activity No restriction. If symptoms persist, medical advice should be compared to placebo (p<0.01). The anti-inflammatory activity of sought. the extract was also demonstrated in Freund’s adjuvant-induced polyarthritis, in rats treated orally with doses of 10-500 mg per Contra-indications day (p<0.01) [Berkan 1991]. As with other drugs containing bitter substances, peptic ulcers are a contra-indication for centaury [Hoffmann-Bohm 2010]. A dry ethanolic extract, administered orally to rats at 100 mg/ kg b.w., inhibited carrageenan-induced paw oedema by 40 % Special warnings and special precautions for use compared to control (p<0.01) [Capasso 1983]. None required. Gastroprotective effects Interaction with other medicaments and other forms of Male Sprague-Dawley rats were treated intragastrically with interaction a 50% ethanolic extract at 100 mg/kg b.w. for 7 days and None reported. additionally on day 7 with 200 mg/kg acetylsalicylic acid (ASA) 4 hours before sacrifice. Controls received saline during the Pregnancy and lactation same period and 200 mg/kg ASA on day 7. The extract led to No data available. In accordance with general medical practice, a 77% inhibition of gastric lesions (p<0.05). The increase in the product should not be used during pregnancy or lactation catalase and malondialdehyde and the decrease in reduced without medical advice. glutathione caused by ASA were improved by the extract. The augmentation of myeloperoxidase activity, as an index of Effects on ability to drive and use machines neutrophil infiltration into gastric mucosal tissue due to ASA, None known. was significantly reduced (p<0.05) as compared to control [Tuluce 2011]. Undesirable effects None reported. Effects on hyperglycaemia and lipid profiles Male C57BL/6J mice received a high fat diet to induce type-2 Overdose diabetes. Simultaneous intragastric treatment with a dry extract No toxic effects reported. (80% ethanol, yield 17.3 %) at a dose of 2 g/kg b.w. daily for 20 weeks resulted in a significant reduction of the mean fasting blood glucose level (p<0.05) from week 14 until week 20 as PHARMACOLOGICAL PROPERTIES compared to untreated animals on the high fat diet. At the end of the experiment, plasma insulin concentrations, insulin resistance Pharmacodynamic properties calculated by the homeostasis model assessment and plasma triglyceride levels were also significantly lower (p<0.05). No In vitro experiments significant differences were observed between the treated group on high fat diet and controls on standard diet [Hamza 2010]. Antioxidant and radical scavenging activities A lyophilized hot water extract of centaury (7.5:1) exhibited In a similar experiment type-2 diabetes was first established by antioxidant activity as shown by scavenging of superoxide radical 17 weeks of high fat diet. After this period treatment was started in the NADH/PMS system (IC50 120.2 µg/mL) as well as xanthine with the extract (80% ethanol, yield 17.3 %) at 2 g/kg b.w. oxidase inhibitory activity (IC50 73.2 µg/mL) [Valentao 2001]. daily for 18 weeks. At the end of the study body weight, mean fasting blood glucose level, plasma insulin concentration and In the hydroxyl radical assay a lyophilized infusion (1:100; insulin resistance were significantly better (p<0.05) as compared yield 13.4%) showed an IC50 of 44.4 µg/mL [Valentao 2003b]. to untreated animals on the high fat diet. Administration of the extract also improved hypertriglyceridaemia and An infusion of powdered centaury (1:110; 100 µL) led to a hypercholesterolaemia (p<0.05) without influencing HDL- 73.3% inhibition of desoxyribose decomposition [Gião 2008]. cholesterol [Hamza 2011].

Methanolic extracts demonstrated moderate to low radical In streptozotocin (STZ)-induced diabetic male Wistar rats, scavenging and antioxidant activities in various assays [Šiler treatment with 200 mg/kg b.w. of a lyophilized aqueous extract 2014, Tusevski 2014]. (1:10; yield 12%) for 30 days resulted in a significant reduction of serum glucose (p<0.001) and increase of serum insulin Antimicrobial activity levels (p<0.01). Elevated triglycerides and total cholesterol In a panel of 17 bacteria gentiopicroside was most active against in the diabetic rats were decreased significantly (p<0.001) Serratia marescens with a MIC of 6.3 µg/mL [Kumarasamy by the extract. Markers of oxidative stress such as pancreatic 2003a]. In a similar study on 14 different bacteria swertiamarin malondialdehyde, protein carbonyl content and GSH as well showed the highest activity against Citrobacter freundii (MIC as the decline in antioxidant enzymes in the pancreas (SOD, 5 µg/mL) [Kumarasamy 2003b]. catalase, GSH peroxidase) due to the induced diabetes were improved significantly (p<0.001 to p<0.01) by the extract. Other effects Histological examination of the pancreas revealed a significant A chloroform extract containing mainly terpenes and fatty acids (p<0.01) increase in number and diameter of islets in the extract moderately inhibited a-amylase and a-glucosidase with IC50 group as compared to the untreated diabetic group [Sefi 2011]. values of 64.9 and 74.9 µg/mL respectively. The effect against angiotensin converting enzyme was weak [Loizzo 2008]. The effects of centaury on blood glucose levels, hepatic glycolytic

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and gluconeogenic enzymes and their substrates, as well as antly inhibiting carbachol-induced contractions of the proximal on the lipid profile, were studied in male Wistar rats. Ten days colon in rats in a dose-dependent manner (p<0.05) after oral after induction of diabetes with STZ the animals were treated administration at 150 mg/kg and 300 mg/kg b.w. [Yamahara 1991]. intragastrically with a methanolic dry extract (yield 23.1%) for 12 days with 125, 250 or 500 mg/kg b.w. per day (short Clinical studies term treatment s.t.t.) or for 45 days with 250 mg/kg b.w. per No published clinical data currently available. day (long term treatment l.t.t.). Glibenclamide (2.5 mg/kg b.w. intragastrically) served as positive control. During s.t.t. blood Pharmacokinetic properties glucose concentrations were significantly (p<0.05) reduced by By anaerobic incubation with a mixture, and with individual all doses as compared to the start of the treatment. In l.t.t. the strains, of human intestinal bacteria, swertiamarin was positive effect on blood glucose regulation was most pronounced converted to three metabolites: erythrocentaurin, 5-hydroxy- up to day 30. The extract and glibenclamide normalised the methylisochroman-1-one and gentianine. This demonstrated diabetes-induced increases in liver glucose concentration, that orally administered swertiamarin can be transformed into glucose-6-phosphatase and fructose-1,6-biphosphatase activity, a nitrogen-containing, biologically active substance by flora of as well as the decreases in liver glycogen content and glycogen the human gastrointestinal tract [El-Sedawy 1989]. phosphorylase activity. Increased triglycerides, LDL, HDL and cholesterol levels in diabetic rats were restored to the levels Preclinical safety data of untreated normal rats by all doses of the extract in s.t.t. [Stefkov 2014]. Acute toxicity A dried aqueous decoction (1:10; yield not specified) admin- Hepatoprotective effects istered orally at doses of 1 to 15 g/kg b.w. to male and female A dried methanolic extract (6.2:1) was tested for its hepato- mice did not cause any signs of toxicity at any dose level. After protective effects in male Wistar rats receiving the extract i.p. administration at doses of 2 to 14 g/kg b.w. adverse effects intragastrically at a dose of 300 mg/kg b.w. for 6 days or at a such as anorexia, piloerection and hypoactivity were observed single dose of 900 mg/kg before challenge with paracetamol. The at higher doses from 8 g upwards; asthenia, diarrhoea and strong increase in SGPT, SGOT and LDH levels induced by the convulsions occurred in both sexes at doses above 12 g/kg b.w. acute administration of paracetamol was markedly attenuated The i.p. LD50 was calculated as 12.13 g/kg [Tahraoui 2010]. by both pretreatments. The extract alone (300 mg/kg b.w. for 6 days; no paracetamol challenge) slightly reduced LDH but Isolated iridoids were shown to be toxic in the brine shrimp did not change SGPT and SGOT as compared to the untreated lethality assay (LC50 values: gentiopicroside 24 µg/mL, swertia- control. Histopathological examination of the livers confirmed marin 8.0 µg/mL, sweroside 34 µg/mL, podophyllotoxin as the hepatoprotective effects of the extract [Mroueh 2004]. control 2.7 µg/mL) [Kumarasamy 2003a,b].

Isolated gentiopicroside significantly inhibited the production Repeated dose and chronic toxicity studies of TNF in carbon tetrachloride-induced and bacillus Calmette- A dried aqueous decoction (1:10; yield not specified) was Guérin/lipopolysaccharide-induced models of hepatic injury administered orally to male and female Wistar albino rats at in mice after i.p. injection at 30 mg/kg (p<0.05) or 60 mg/kg 100, 600 and 1200 mg/kg b.w. daily for 90 days. No lethality b.w. (p<0.01) daily for 5 days [Kondo 1994]. or significant differences in body weight changes or in animal behaviour were noted in any of the groups. Blood cell counts Other effects were unaffected and haematological parameters remained The antipyretic activity of a dry aqueous extract of centaury (3.8:1) within normal limits throughout treatment. The only change was demonstrated in rats after intragastric administration of 50- was a slight but significant decrease in mean red blood cell 100 mg in a yeast-induced fever test (p<0.05) [Berkan 1991]. volume (600 mg/kg: p<0.05 after 30 days and p<0.01 after 60 and 90 days; 1200 mg/kg: p<0.05 after 90 days; compared to A diuretic effect was shown in rats after oral administration of control). In the biochemical profiles plasma creatinine, urea, 8% or 16% aqueous extract of centaury at 10 mL/kg b.w. daily total proteins, total bilirubin, cholesterol, ALAT and ASAT for one week. From the fifth day of treatment urine volume remained unchanged. Blood glucose and triglycerides were was increased significantly (p<0.05) with the lower dose, and significantly reduced (p<0.05) at doses of 600 and 1200 mg/ both doses led to a significant increase of sodium, chloride kg from 60 days until the end of treatment [Tahraoui 2010]. and potassium excretion (p<0.01 – p<0.001). At the end of the treatment a diminution in creatinine clearance was observed Mutagenicity and carcinogenicity (p<0.05 for the lower dose) [Haloui 2000]. Centaury extracts have been evaluated in the Ames mutagenicity test using Salmonella typhimurium strains TA98 and TA100 (with Pretreatment of rats with a 50% ethanolic extract at an intragastric and without activation by S9 mix), with rather conflicting results. dose of 100 mg/kg b.w. for 7 days significantly (p<0.05) improved An inspissated extract showed weak mutagenicity in TA98, but the increases in ALAT, ASAT, creatinine and potassium induced negative results were obtained with a fluid extract and a tincture by administration of 200 mg/kg of ASA on day 7 [Ozkol 2011]. in strains TA98 and TA100 [Schimmer 1994b]. In another study, a fluid extract and a tincture showed weak mutagenicity in strain Larvae of red flour beetles (Tribolium castaneum) on a diet TA100, but not in strain TA98 [Göggelmann 1986]. containing 10% of a methanolic extract gained significantly (p<0.05) less weight over 8 days than untreated control and An ethanolic extract of centaury at 200 µL/plate displayed starved larvae. Larval mortality was 62% after ten days and markedly antimutagenic potency in Salmonella typhimurium emergence of adult insects reduced to 33.7% as compared strains TA98 and TA100, inhibiting mutagenicity induced by to 0% and 100%, respectively, in untreated control. Treated 2-nitrofluorene (2-NF) and 2-aminoanthracene (2-AA) by over larvae had a significantly reduced a-amylase activity (p<0.05). 50 %. Furthermore, isolated eustomin at 50 µg/plate showed Progeny production of F1 adults was completely suppressed strong inhibition, 76 % against 2-NF and 64 % against 2-AA in by the extract [Jbilou 2008]. strain TA100; 8-demethyleustomin was also active, with results of 43 % and 39 % respectively, but no inhibition was detected Isolated swertiamarin showed anticholinergic activity, signific- from secoiridoid or polar fractions of centaury [Schimmer 1996].

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REFERENCES Hatjimanoli M, Debelmas A-M. Étude de Centaurium umbellatum Gil. Identification des acides phénols. Ann Pharm Fr 1977;35:107-11. Aberham A, Pieri V, Croom EM Jr., Ellmerer E, Stuppner H. Analysis of iridoids, secoiridoids and xanthones in Centaurium erythraea, Hatjimanoli M, Favre-Bonvin J, Kaouadji M, Mariotte A-M. Frasera caroliniensis and Gentiana lutea using LC-MS and RP-HPLC. Monohydroxy- and 2,5-dihydroxy terephthalic acids, two unusual J Pharm Biomed Anal 2011;54:517-25. http://dx.doi.org/10.1016/j. phenolics isolated from Centaurium erythraea and identified in other jpba.2010.09.030 Gentianaceae members. J Nat Prod 1988;51:977-80. http://dx.doi. org/10.1021/np50059a030 Aquino R, Behar I, Garzarella P, Dini A, Pizza C. Composizione chimica e proprietà biologiche della Erythraea centaurium Rafn. Boll Soc Ital Hoffmann-Bohm K, Heubl G, Seitz R. Centaurium. In: Reichling J, Biol Sper 1985;61:165-9. Blaschek W, Hilgenfeldt U, Holzgrabe U, Ruth P, Schulz V (editors). HagerROM 2010. Hagers Enzyklopädie der Arzneistoffe und Drogen. Bellavita V, Schiaffella F, Mezzetti T. Triterpenoids of Centaurium Berlin-Heidelberg: Springer-Verlag, 2010. erythraea. Phytochemistry 1974;13:289-90. http://dx.doi.org/10.1016/ S0031-9422(00)91319-0 Jäger S, Trojan H, Kopp T, Laszczyk MN, Scheffler A. Pentacyclic Triterpene Distribution in Various Plants – Rich Sources for a New Berkan T, Üstünes L, Lermioglu F, Özer A. Antiinflammatory, analgesic, Group of Multi-Potent Plant Extracts. Molecules 2009;14:2016-31. and antipyretic effects of an aqueous extract of Erythraea centaurium. http://dx.doi.org/10.3390/molecules14062016 Planta Med 1991;57:34-7. http://dx.doi.org/10.1055/s-2006-960011 Jbilou R, Amri H, Bouayad N, Ghailani N, Ennabili A, Sayah F. Insecticidal Bishay DW, Shelver WH, Wahba Khalil SK. Alkaloids of Erythraea effects of extracts of seven plant species on larval development, centaurium Pers. growing in Egypt. Planta Med 1978:33;422-3. http:// a-amylase activity and offspring production of Tribolium castaneum dx.doi.org/10.1055/s-0028-1097408 (Herbst) (Insecta: Coleoptera: Tenebrionidae). Bioresource Technol 2008;99:959-64. http://dx.doi.org/10.1016/j.biortech.2007.03.017 Bisset NG, editor (translated from Wichtl M, editor. Teedrogen). Centaurii herba - Lesser centaury. In: Herbal Drugs and Phytopharmaceuticals. Jerković I, Gašo-Sokač D, Pavlović H, Marijanović Z, Gugić M, Petrović I, Stuttgart: Medpharm, Boca Raton-London: CRC Press, 1994:134-6. Kovač S. Volatile Organic Compounds from Centaurium erythraea Rafn. (Croatia) and the Antimicrobial Potential of Its Essential Oil. Molecules Capasso F, Mascolo N, Morrica P, Ramundo E. Phytotherapeutic 2012;17:2058-72. http://dx.doi.org/10.3390/molecules17022058 profile of some plants used in folk medicine. Boll Soc Ital Biol Sper 1983;59:1398-404. Jovanović O, Radulović N, Stojanović G, Palić R, Zlatković B, Gudžić B. Chemical Composition of the Essential Oil of Centaurium erythraea Centaurium. In: British Herbal Pharmacopoeia 1983. Bournemouth: Rafn. (Gentianaceae) from Serbia. J Essent Oil Res 21;4:317-22. http:// British Herbal Medicine Association, 1983:55-6. dx.doi.org/10.1080/10412905.2009.9700181

Centaury. Centaurii herba. European Pharmacopoeia, Council of Europe. Kondo Y, Takano F, Hojo H. Suppression of chemically and immunologically induced hepatic injuries by gentiopicroside in mice. Do T, Popov S, Marekov N, Trifonov A. Iridoids from Gentianaceae Planta Med 1994;60:414-6. http://dx.doi.org/10.1055/s-2006-959521 plants growing in Bulgaria. Planta Med 1987;53:580. http://dx.doi. org/10.1055/s-2007-969048 Kumarasamy Y, Nahar L, Sarker SD. Bioactivity of gentiopicroside from the aerial parts of Centaurium erythraea. Fitoterapia 2003a;74:151-4. Dombrowicz E, Swiatek L, Zadernowski R. Phenolic acids in bitter drugs. http://dx.doi.org/10.1016/S0367-326X(02)00319-2 Part III. Examination of Herba Centaurii. Farm Pol 1988;44:657-60. Kumarasamy Y, Nahar L, Cox PJ, Jaspars M, Sarker SD. Bioactivity of El-Sedawy A, Yue-Zhong Shu, Hattori M, Kobashi K, Namba T. Metabolism secoiridoid glycosides from Centaurium erythraea. Phytomedicine of swertiamarin from Swertia japonica by human intestinal bacteria. 2003b;10:344-7. http://dx.doi.org/10.1078/094471103322004857 Planta Med 1989;55:147-50. http://dx.doi.org/10.1055/s-2006-961909 Leung AY, Foster S. Centaury. In: Encyclopedia of Common Natural Gião MS, González-Sanjosé ML, Muñiz P, Rivero-Pérez MD,Kosinska Ingredients, 2nd ed. New York-Chichester: John Wiley, 1996:143-5. M, Pintado ME, Malcata FX. Protection of deoxyribose and DNA from degradation by using aqueous extracts of several wild plants. J Sci Food Loizzo MR, Saab AM, Tundis R, Menichini F, Bonesi M, Piccolo V, Statti Agric 2008;88:633-40. http://dx.doi.org/10.1002/jsfa.3128 GA, de Cindio B, Houghton PJ, Menichini F. In vitro inhibitory activities of plants used in Lebanon traditional medicine against angiotensin Göggelmann W, Schimmer O. Mutagenic activity of phytotherapeutical converting enzyme (ACE) and digestive enzymes related to diabetes. drugs. In: Knudsen I, editor. Genetic toxicology of the diet. New York: J Ethnopharmacol 2008;119:109-16. http://dx.doi.org/10.1016/j. Alan R Liss, 1986:63-72. jep.2008.06.003

Haloui M, Louedec L, Michel J-P, Lyoussi B. Experimental diuretic effects Mroueh M, Saab Y, Rizkallah R. Hepatoprotective activity of Centaurium of Rosmarinus officinalis and Centaurium erythraea. J Ethnopharm erythraea on acetaminophen-induced hepatotoxicity in rats. Phytother 2000;71:465-72. http://dx.doi.org/10.1016/S0378-8741(00)00184-7 Res 2004;18:431-3. http://dx.doi.org/10.1002/ptr.1498

Hamza N, Berke B, Cheze C, Agli AN, Robinson P, Gin H, Moore N. Neshta NM, Glyzin VI, Patudin AV. A new xanthone compound from Prevention of type 2 diabetes induced by high fat diet in the C57BL/6J Centaurium erythraea. IV. Khim Prir Soedin 1984:110 [Russian], mouse by two medicinal plants used in traditional treatment of diabetes translated into English as: Chem Nat Compd 1984:20;108. http://dx.doi. in the east of Algeria. J Ethnopharmacol 2010;128:513-8. http://dx.doi. org/10.1007/BF00574812 org/10.1016/j.jep.2010.01.004 Neshta NM, Glyzin VI, Savina AA, Patudin AV. A new xanthone Hamza N, Berke B, Cheze C, Le Garrec R, Lassalle R, Agli AN, Robinson compound from Centaurium erythraea. III. Khim Prir Soedin 1983:787 P, Gin H, Moore N. Treatment of high fat diet induced type 2 diabetes [Russian], translated into English as: Chem Nat Compd 1983:19;750-1. in C57BL/6J mice by two medicinal plants used in traditional treatment http://dx.doi.org/10.1007/BF00575194 of diabetes in the east of Algeria. J Ethnopharmacol 2011;133:931-3. http://dx.doi.org/10.1016/j.jep.2010.11.019 Neshta NM, Nikolaeva GG, Sheichenko VI, Patudin AV. A new xanthone

4 CENTAURII HERBA

compound from Centaurium erythraea. Khim Prir Soedin 1982:258 Tahraoui A, Israili ZH, Lyoussi B. Acute and sub-chronic toxicity of [Russian], translated into English as: Chem Nat Compd 1982:18;240-1. a lyophilised aqueous extract of Centaurium erythraea in rodents. J http://dx.doi.org/10.1007/BF00577215 Ethnopharmacol 2010;132:48-55. http://dx.doi.org/10.1016/j.jep. 2010.07.038 Newall CA, Anderson LA, Phillipson JD. Centaury. In: Herbal Medicines - A Guide for Health-Care Professionals. London: Pharmaceutical Takagi S, Yamaki M, Yumioka E, Nishimura T, Sakina K. Studies on the Press, 1996:67. constituents of Erythraea centaurium (Linné) Persoon. II. The structure of centauroside, a new bis-secoiridoid glucoside. Yakugaku Zasshi Ozkol H, Tuluce Y, Koyuncu I, Balahoroglu R. A biochemical study 1982;102:313-7. on the protective potential of Centaurium erythraea L. in rats at acute aspirin exposure. Fresenius Environ Bull 2011;20:2699-703. Tuluce Y, Ozkol H, Koyuncu I, Ine H. Gastroprotective effect of small centaury (Centaurium erythraea L) on aspirin-induced gastric Petlevski R, Hadzija M, Slijepcevic M, Juretic D. Amino acids in damage in rats.Toxicol Ind Health 2011;27:760-8. http://dx.doi. lesser centaury (Centaurii herba) and yarrow (Millefolii herba) herbs. org/10.1177/0748233710397421 Farmaceutski Glasnik 2002;58:119-25. Tusevski O, Kostovska A, Iloska A, Trajkovska L, Gadzovska Simic S. Popov S. Sterols of the Gentianaceae family. Compt Rend Acad Bulg Phenolic production and antioxidant properties of some Macedonian Sci 1969;22:293-6. medicinal plants. Cent Eur J Biol 2014;9:888-900. http://dx.doi.org/ 10.2478/s11535-014-0322-1 Rulko F, Witkiewicz K. Gentiana alkaloids. Part VII. Alkaloids of centaury (Erythrea centaurium Pers.). Diss Pharm Pharmacol 1972;24:73-7. Valentao P, Areias F, Amaral J, Andrade P, Seabra R. Tetraoxygenated xanthones from Centaurium erythraea. Nat Prod Lett 2000;14:319-23. Sakina K, Aota K. Studies on the constituents of Erythraea centaurium http://dx.doi.org/10.1080/10575630008043763 (Linné) Persoon. I. The structure of centapicrin, a new bitter secoiridoid glucoside. Yakugaku Zasshi 1976;96:683-8. Valentao P, Fernandes E, Carvalho F, Andrade PB, Seabra RM, Bastos ML. Antioxidant activity of Centaurium erythraea infusion evidenced Schimmer O, Mauthner H. Centaurium erythraea Rafn - Tausend- by its superoxide radical scavenging and xanthine oxidase inhibitory güldenkraut. Z Phytotherapie 1994a;15:299-306. activity. J Agric Food Chem 2001;49:3476-79. http://dx.doi.org/10.1021/ jf001145s Schimmer O, Krüger A, Paulini H, Haefele F. An evaluation of 55 commercial plant extracts in the Ames mutagenicity test. Pharmazie Valentao P, Andrade PB, Silva E, Vicente A, Santos H, Bastos ML, 1994b;49:448-51. Seabra RM. Methoxylated Xanthones in the Quality Control of Small Centaury (Centaurium erythraea) Flowering Tops. J Agric Food Chem Schimmer O, Mauthner H. Polymethoxylated xanthones from the 2002;50:460-3. http://dx.doi.org/10.1021/jf0109571 herb of Centaurium erythraea with strong antimutagenic properties in Salmonella typhimurium. Planta Med 1996;62:561-4. http://dx.doi. Valentao P, Andrade PB, Silva AMS, Moreira MM, Seabra RM. Isolation org/10.1055/s-2006-957973 and Structural Elucidation of 5-Formyl-2,3-Dihydroisocoumarin from Centaurium erythraea Aerial Parts. Nat Prod Res 2003a;17:361-4. http:// Sefi M, Fetoui H, Lachkar N, Tahraoui A, Lyoussi B, Boudawara dx.doi.org/10.1080/1057563031000081938 T, Zeghal N. Centaurium erythrea (Gentianaceae) leaf extract alleviates streptozotocin-induced oxidative stress and b-cell damage Valentao P, Fernandes E, Carvalho F, Andrade PB, Seabra RM, Bastos in rat pancreas. J Ethnopharmacol 2011;135:243-50. http://dx.doi. ML. Hydroxyl radical and hypochlorous acid scavenging activity of org/10.1016/j.jep.2011.02.029 small Centaury (Centaurium erythraea) infusion. A comparative study with green tea (Camellia sinensis). Phytomedicine 2003b;10:517-22. Sharaf M, El-Ansari MA, Weglarz Z, Geszprych A. Phenolic constituents http://dx.doi.org/10.1078/094471103322331485 of centaury. Herba Polonica 2003;49:174-9. van der Sluis WG. Chemotaxonomical investigations of the genera Šiler B, Živković S, Banjanac T, Cvetković J, Nestorović Živković J, Blackstonia and Centaurium (Gentianaceae). Plant Syst Evol 1985b; Ćirić A, Soković M, Mišić D. Centauries as underestimated food addit- 149:253-86. http://dx.doi.org/10.1007/BF00983311 ives: Antioxidant and antimicrobial potential. Food Chem 2014;147: 367-76. http://dx.doi.org/10.1016/j.foodchem.2013.10.007 van der Sluis WG. Secoiridoids and xanthones in the genus Centaurium Hill (Gentianaceae), a pharmacognostical study [Dissertation]. Stefkov G, Miova B, Dinevska-Kjovkarovska S, Petreska Stanoeva J, University of Utrecht, 1985a. Stefova M, Petrusevska G, Kulevanova S. Chemical characterization of Centaurium erythrea L. and its effects on carbohydrate and lipid Yamahara J, Kobayashi M, Matsuda H, Aoki S. Anticholinergic action metabolism in experimental diabetes. J Ethnopharmacol 2014;152:71-7. of Swertia japonica and an active constituent. J Ethnopharmacol http://dx.doi.org/10.1016/j.jep.2013.11.047 1991;33:31-5. http://dx.doi.org/10.1016/0378-8741(91)90157-9

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The second edition of ESCOP Monographs, published as a hardback book in 2003 with a Supplement in 2009, has been widely acclaimed for its authoritative information on the therapeutic uses of herbal medicines. Monographs covering a total of 107 herbal substances include extensive summaries of pharmacological, clinical and toxicological data, and copious references to scientific literature form an important part of each text.

Although publication in the form of books was convenient in the past, ESCOP recognizes that online publication now offers a number of advantages, not least in facilitating rapid publication of individual monographs as soon as all stages of preparation have been completed. Commencing from 2011, therefore, new and revised monographs will be published online only.

The European legislative framework for herbal medicines has advanced considerably over the past decade. Directive 2004/24/EC introduced a simplified registration procedure for traditional herbal medicinal products in EU member states and imposed a 2011 deadline for the registration of certain products on the market. The Committee on Herbal Medicinal Products (HMPC), established in 2004 as part of the European Medicines Agency, has made substantial progress in the preparation of Community Herbal Monographs and associated documentation to provide a more harmonized approach to the scientific assessment of herbal medicinal products throughout the European Community

Whether the evaluation of a herbal medicine is based on evidence of clinical efficacy (well- established use) or on experience and historical use of that product (traditional use) those involved at all levels of the regulatory process need access to detailed, reliable and structured summaries of the available efficacy and safety data. ESCOP monographs meet that requirement and offer an invaluable source of scientific information on herbal medicines to regulators, manufacturers, academics, researchers, health professionals and numerous others.