Menyanthidis trifoliatae foliumBogbean Leaf

MonographsThe Scientific Foundation for Herbal Medicinal Products

2013

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The Scientific Foundation for Herbal Medicinal Products

MENYANTHIDIS TRIFOLIATAE FOLIUMBogbean Leaf

2013

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 SERIESISBN 978-1-901964-12-7

Menyanthidis trifoliatae folium - Bogbean Leaf

© ESCOP 2013

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

www.escop.com

All rights reservedExcept for the purposes of private study, research, criticism or review no part of this text

may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, without the written permission of the publisher.

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 HutchinsCover photograph by Prof. Salvador Cañigueral (Menyanthes trifoliata)

Cover and text design by Martin WilloughbyTypeset in Optima by Roberta Hutchins

Plant illustrated on the cover: Menyanthes trifoliata

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 KrennChair 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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ABBREVIATIONS used in ESCOP monographs

AA arachidonic acidABTS 2,2’-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)ACE angiotensin converting enzymeADP adenosine diphosphateALAT or ALT alanine aminotransferase (= SGPT or GPT)ALP alkaline phosphataseanti-IgE anti-immunoglobulin EASA acetylsalicylic acidASAT or AST aspartate aminotransferase (= SGOT or GOT)ATP adenosine triphosphateAUC area under the concentration-time curveBMI body mass indexBPH benign prostatic hyperplasiab.w. body weightcAMP cyclic adenosine monophosphateCI confidence intervalCmax maximum concentration of a substance in serumCNS central nervous systemCoA coenzyme ACOX cyclooxygenaseCSF colony stimulating factorCVI chronic venous insufficiencyCYP cytochrome P450d dayDER drug-to-extract ratioDHT dihydrotestosteroneDNA deoxyribonucleic acidDPPH diphenylpicrylhydrazylDSM Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association)ECG electrocardiogramED50 effective dose in 50% of casesEDTA ethylenediamine tetraacetateEEG electroencephalogramEMA European Medicines AgencyENT ear, nose and throatER oestrogen receptorERE oestrogen-responsive elementFSH follicle-stimulating hormoneGABA gamma-aminobutyric acidGal galactoseGFR glomerular filtration rateGGTP gamma-glutamyl transpeptidaseGOT glutamate oxalacetate transaminase (= SGOT)GPT glutamate pyruvate transaminase (= SGPT)GSH glutathione (reduced)GSSG glutathione (oxidised)HAMA Hamilton Anxiety Scale12-HETE 12-hydroxy-5,8,10,14-eicosatetraenoic acidHDL high density lipoproteinHIV human immunodeficiency virusHMPC Committee on Herbal Medicinal Products (of the EMA)HPLC high-performance liquid chromatography 5-HT 5-hydroxytryptamine (= serotonin)IC50 concentration leading to 50% inhibitionICD-10 International Statistical Classification of Diseases and Related Health Problems, Tenth RevisionICH The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human UseICSD International Classification of Sleep DisordersIFN interferonIL interleukini.m. intramusculariNOS inducible nitric oxide synthaseINR International Normalized Ratio, a measure of blood coagulation (clotting) tendency

i.p. intraperitonealIPSS International Prostate Symptom Scorei.v. intravenouskD kiloDaltonKM Index Kuppermann Menopausal IndexkPa kiloPascalLC-MS liquid chromatography-mass spectrometryLD50 the dose lethal to 50% of animals tested LDH lactate dehydrogenaseLDL low density lipoproteinLH luteinizing hormone5-LOX 5-lipoxygenaseLPS lipopolysaccharideLTB4 leukotriene B4M molar (concentration)MAO monoamine oxidaseMBC minimum bactericidal concentrationMDA malondialdehydeMFC minimum fungicidal concentrationMIC minimum inhibitory concentrationMr molecularMRS Menopause Rating ScaleMRSA methicillin-resistant Staphylococcus aureusMTD maximum tolerated doseMTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromideMW molecular weightNBT nitro blue tetrazoliumNF-kB necrosis factor kappa-BNO nitric oxide NOS nitric oxide synthasen.s. not significantNSAID non-steroidal anti-inflammatory drugovx ovariectomy or ovariectomizedORAC oxygen radical absorbance capacityPA pyrrolizidine alkaloidPAF platelet activating factorPCR polymerase chain reactionPEG polyethylene glycolPGE prostaglandin EPHA phythaemagglutininp.o. per osPOMS profile of mood statesPVPP polyvinylpolypyrrolidoneRANKL receptor activator of nuclear factor kappa-B ligandRNA ribonucleic acidRT-PCR reverse transcription polymerase chain reactions.c. subcutaneousSCI spinal cord injury SERM selective oestrogen receptor modulatorSGOT or GOT serum glutamate oxalacetate transaminase (= ASAT or AST)SGPT or GPT serum glutamate pyruvate transaminase (= ALAT or ALT)SHBG sex hormone binding globulinSOD superoxide dismutaseSSRI selective serotonin reuptake inhibitorSTAI state-trait anxiety inventoryt1/2 elimination half-lifeTBARS thiobarbituric acid reactive substancesTGF-b transforming growth factor-betaTNF tumour necrosis factorTPA 12-O-tetradecanoylphorbol-13-acetateURT upper respiratory tractURTI upper respiratory tract infectionUTI urinary tract infectionVAS visual analogue scaleVLDL very low density lipoprotein

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MENYANTHIDIS TRIFOLIATAE FOLIUM 2013

Bogbean Leaf

DEFINITION

Bogbean leaf consists of the dried, entire or fragmented leaves of Menyanthes trifoliata L. The material complies with the monograph of the European Pharmacopoeia [Bogbean Leaf].

CONSTITUENTS

The main characteristic constituents are iridoid glycosides - approx. 1% of bitter substances including the iridoid loganin and the seco-iridoids foliamenthin, dihydrofoliamenthin, menthiafolin and sweroside. Maximum concentrations of bitter substances were recorded during flower-bud initiation [Hänsel 1966; Battersby 1968; Gessner 1974; Maksimova 1980; Steinegger 1988; Junior 1989; Wagner 1996; Martz 2009]. Flavonol glycosides such as isoquercitrin, hyperoside and rutin [Krebs 1957; Lebreton 1973; Mel’chakova 1976; Bohm 1986; Wagner 1996], as well as trifolin [Krebs 1958]. Chlorogenic acid and other phenolic acids such as caffeic, ferulic, sinapic, vanillic and protocatechuic acids [Herrmann 1959; Ciaceri 1972; Swiatek 1986]. Coumarins - scopoletin (6-methoxy-7-hydroxycoumarin), scoparone (6,7-dimethoxycoumarin) and braylin [Ciaceri 1972; Adamczyk 1990].

Other constituents include ascorbic acid, tannins [Pamakstyte-Jukneviciene 1971; Maksimova 1980], polysaccharides [Kuduk-Jaworska 2004], polypeptides [Lindholm 2002] and phytosterols [Popov 1969]. The alkaloid gentianine has been reported [Steinegger 1951; Rulko 1969] but may be an artefact [Cordell 1981].

CLINICAL PARTICULARS

Therapeutic indications

As a bitter [BHP 1996; Bruneton 1999] in loss of appetite, peptic discomfort and atonic dyspepsia [Schilcher 2007], as well as for gall bladder and biliary tract disorders [Sweetman 2007].

Posology and method of administration

Dosage

Dried powdered leaf0.5-2.0 g two to three times daily [BHP 1976; Steinegger 1988; Blaschek 2007].

Cut drug 0.5-1 g as an infusion in 150 mL boiling water taken half-an-hour before meals [Steinegger 1988; Bisset 1994; Blaschek 2007; Wichtl 2009]. Liquid extract (1:1; 25% ethanol)1-2 mL; two to three times daily [BHP 1976; Steinegger 1988].

Tincture (1:5; 45% ethanol)1-3 mL; three times daily [BHP 1976; Steinegger 1988; Blaschek 2007].

Method of administrationFor oral administration. Duration of administrationNo restriction. If symptoms persist or worsen, medical advice should be sought.

ContraindicationsNone known. Not recommended in cases of diarrhoea, dysentery or colitis [BHP 1976; Steinegger 1988; Blaschek 2007].

Special warnings and special precautions for useNone required.

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Interaction with other medicaments and other forms of interactionNone reported. Due to their structure and low content the coumarins are presumed not to interact with anticoagulants [Williamson 2009].

Pregnancy and lactationIn accordance with general medical practice, the product should not be used during pregnancy or lactation without medical advice.

Effects on ability to drive and use machines None known.

Undesirable effectsCan irritate the stomach and induce vomiting in sensitive individuals [Steinegger 1988; Blaschek 2007]. OverdoseMay lead to nausea, vomiting and diarrhoea [Blaschek 2007].

PHARMACOLOGICAL PROPERTIES

Pharmacodynamic propertiesBogbean leaf is required to have a minimum bitterness value of 3000.

In vitro experiments

Antibacterial activityA 70%-ethanolic extract (1:5) [Moskalenko 1986] and an aqueous extract [Brantner 1994] of bogbean leaf showed activity against various microorganisms including strains of Staphylococcus aureus, Bacillus subtilis and Escherichia coli. Using the microdilution broth method MIC values (mg/mL, calculated as the dry residue) were 25.7, 29.4 and 25.7 respectively [Brantner 1994].

Anti-inflammatory activityAqueous extracts (0.2 mg/mL) from bogbean leaf produced a low percentage inhibition of prostaglandin biosynthesis (22%) in comparison with 1 μg/mL of indomethacin (88%) and 76 μg/mL of quercetin (96%). In the PAF-exocytosis assay the aqueous extracts (0.25 mg/mL) also produced a low inhibition (35%) when compared to 100 μM of the PAF-inhibitor BN 52021 [Tunón 1995].

Enzymatic activation of iridoid glycosides with b-glucosidase yield an active hydrolysed-iridoid product (H-iridoid). H-loganin prepared from loganin (1mM) preincubated with enzyme (0.5 mM) (iridoid:enzyme =1.0:0.5 V/V) showed significant inhibition of thromboxane B2 formation in intact HEL cells at 10, 50 and 100 μM (p<0.05) compared to vehicle only. Significant inhibitory activities were recorded on COX-1 (IC50 value of 3.55 μM; p<0.05) compared to aspirin (7.23 μM), against PGE2 at 50 and 100 μM (p<0.05) and suppression of TNFa (IC50 value of 154.6 μ M; p<0.05) compared to vehicle (DMSO) [Park 2010].

Immunomodulatory activityTests using human blood-derived lymphocytes and granulocytes showed that some polysaccharide fractions isolated from bogbean leaf were strongly immunostimulatory, while other fractions were potent immunosuppressive and anti-inflammatory agents [Kuduk-Jaworska 2004].

Maturation of human dendritic cells (DCs) in the presence of a lyophilised aqueous extract of Menyanthes trifoliata (50 μg/mL) did not affect expression of the surface molecules but

reduced the ratio of secreted IL-12p40/IL-10, compared with cells matured in the absence of extracts. Allogeneic CD4+ T cells co-cultured with DCs matured in the presence of an aqueous extract secreted less IFN-g, IL-10 and IL-17 than CD4+ T cells co-cultured with DCs matured without an extract (p<0.05) [Jonsdottir 2011].

In vivo experiments

Anti-inflammatory activityWhen applied topically, some of the phenolic acids present in bogbean leaf have shown anti-inflammatory activity against tetradecanoylphorbol acetate (TPA)-induced mouse ear oedema (protocatechuic acid, 71.6% inhibition, p<0.001; ferulic acid, 71.0% inhibition, p<0.001) [Fernandez 1998]. Loganin applied topically (in acetone or 80% aqueous ethanol) at 1 mg/ear inhibited TPA-induced mouse ear oedema by 76.8%. The effect of oral administration at 100 mg/kg b.w. was minimal and short-lived, with maximum activity at 3 hours (n = 6) [Recio 1994].

Oral administration of loganin to type 2 diabetic db/db mice (n=6 or 10) at a dose of 100 mg/kg b.w. daily for 8 weeks significantly reduced liver weight (p<0.01), hepatic glucose (p<0.05), triglycerides (p<0.01) and total cholesterol levels (p<0.01) compared to control mice receiving vehicle only; 20 mg/kg had no significant effect. Levels of biomarkers (TBARS and ROS) associated with oxidative stress in the liver and kidney were also evaluated. Both 20 and 100 mg/kg loganin significantly reduced TBARS and ROS (p<0.01) in liver, while in the kidneys both dose levels reduced ROS (p<0.01) but only the higher dose reduced TBARS (p<0.05) [[Yamabe 2010].

In a continuation of the experiment the effects on diabetic db/db mice receiving loganin (20 or 100 mg/kg b.w./day p.o.) were compared with vehicle-treated db/db and non-diabetic m/m mice. Administration of loganin at both dose levels led to a reduced food intake (g/day) by db/db mice compared to vehicle-only controls (p<0.05). With 100 mg/kg b.w. a lowering in serum glucose (p<0.01) and an elevation of leptin (p<0.05) were observed. Diabetic oxidative stress was significantly up-regulated in the liver of db/db mice and loganin (100 mg/kg) administration decreased expressions of hepatic proteins Nox-4 (p<0.01) and p22phox (p<0.05). Hepatic levels of ROS and TBARS were higher in db/db mice in comparison to m/m mice. Loganin administration at both dose-levels down-regulated hepatic protein expression of NF-kB, COX-2 and iNOS. At a dose of 100 mg/kg loganin led to a significantly reduced expression (p<0.05) of the anti-inflammatory factor Nrf-2 [Park 2011].

Pharmacokinetic properties No data available for bogbean leaf.

A study using rats (n = 5) examined the tissue distribution of loganin. After a single oral dose of 20 mg/kg b.w. the highest level was found in kidney tissue, followed by stomach, lung and small intestine. Peak levels in most tissues were attained at 90 minutes. No long-term accumulation of loganin was found in rat tissues. The results indicated that the kidney was the major distribution tissue of loganin in rats [Li 2006] and can have a nephroprotective effect [Jiang 2011].

Preclinical safety data

MutagenicityExtracts from bogbean leaf have been evaluated in the Ames mutagenicity test using Salmonella typhimurium strains TA98 and TA100 (with and without activation by S9 mix). Tinctures

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(1:5, ethanol 60% and 70%) and a fluid extract (1:1, ethanol 25%) gave negative results with TA100 and also with TA98 (without activation), but showed weak mutagenicity with TA98 activated by S9 mix. An undefined dry extract showed weak mutagenicity with TA98, both without and with activation [Schimmer 1994].

Clinical safety data No data available.

REFERENCES

Adamczyk U, Brown SA, Lewars EG, Swiatek L. Lactones of Menyanthes trifoliata. Plantes Méd Phytothér 1990;24:73-8.

Battersby AR, Burnett AR, Knowles GD, Parsons PG. Seco-cyclopentane glucosides from Menyanthes trifoliata: foliamenthin, dihydrofoliamenthin and menthiafolin. Chem Comm 1968;1277-80.

Bisset NG (translated from Wichtl M, ed. Teedrogen). Menyanthidis folium. In: Herbal Drugs and Phytopharmaceuticals. Stuttgart: Medpharm, Boca Raton: CRC Press 1994:339-341.

Blaschek W, Ebel S, Hackenthal E, Holzgrabe U, Keller K, Reichling J, Schulz V (editors). In: Hagers Enzyklopädie der Arzneistoffe und Drogen (10 Lyc - Mos), Folgeband 6. Wissenschaftliche Verlagsgesellschaft, Stuttgart 2007:528-41.

Bogbean Leaf - Menyanthidis trifoliatae folium. European Pharmacopoeia, Council of Europe.

Bogbean. In: British Herbal Pharmacopoeia 1996. Bournemouth: British Herbal Medicine Association 1996:42-3.

Bohm BA, Nicholls KW, Ornduff R. Flavonoids of the Menyanthaceae: intra- and inter-familial relationships. Am J Bot 1986;73:204-13.

Brantner A, Grein E. Antibacterial activity of plant extracts used externally in traditional medicine. J Ethnopharmacol 1994;44:35-40.

Bruneton J. Buckbean. In: Pharmacognosy: Phytochemistry; Medicinal Plants, 2nd ed. Lavoisier Paris 1999:607.

Ciaceri G. Chromatographic identification of coumarin derivatives in Menyanthes trifoliata L. Fitoterapia 1972;43:134-8.

Cordell GA. Chapter 1. In: Introduction to alkaloids, Wiley Interscience 1981:13-14.

Fernandez MA, Saenz MT, Garcia MD. Anti-inflammatory activity in rats and mice of phenolic acids isolated from Scrophularia frutescens. J Pharm Pharmacol 1998;50:1183-6.

Gessner O, Orzechowski G. Chapter V - N-freie Bitterstoffe als Hauptwirkstoffe. In: Gift- und Arzneipflanzen von Mitteleuropa, 3rd ed. Heidelberg: Carl Winter, Universitäts Verlag 1974:335-6.

Hänsel R. Glycosidische bitterstoffe der monoterpenreihe. Planta Med 1966;1:S61-77.

Herrmann K. Über das Vorkommen von Gerbstoffen, Oxyzimtsäuren und Oxykumarinen in den Blattdrogen des DAB 6. Arch Pharm 1959;292:325-9.

Jiang W-L, Zhang S-P, Hou J, Zhu H-B. Effect of loganin on experimental diabetic nephropathy. Phytomedicine 2012;19(3-40 :217-22. http://dx.doi.org/10.1016/j.phymed.2011.08.064

Jonsdottir G, Omarsdottir S, Vikingsson A, Hardardottir I, Freysdottir J. Aqueous extracts from Menyanthes trifoliata and Achillea millefolium affect maturation of human dendritic cells and their activation of

allogeneic CD4+ cells in vitro. J Ethnopharmacol 2011;136:88-93. http://dx.doi.org/10.1016/j.jep.2011.04.006

Junior P. Weitere Untersuchungen zur Verteilung und Struktur der Bitterstoffe von Menyanthes trifoliata. Planta Med 1989;55:81-6.

Krebs KG, Matern J. Flavonglykoside in Menyanthes trifoliata L. (Bitterklee). Naturwiss 1957;44:422-3.

Krebs KG, Matern J. Constituents of Menyanthis trifoliata III. Identification of trifolioside and trifolin. Arch Pharm Ber Dtsch Pharm Ges 1958;63:163-5.

Kuduk-Jaworska J, Szpunar J, Gasiorowski K, Brokos B. Immunomodulating polysaccharide fractions of Menyanthes trifoliata L. Z Naturforsch C 2004;59:485-93.

Lebreton P, Dangy-Caye MP. Contribution biochimique à l’étude taxinomique des Gentianacées. Plantes Méd Phytothér 1973;7:87-94.

Li X, Wang Q, Zhang L, Xu L, Yin W. HPLC study of tissue distribution of loganin in rats. Biomed Chromatogr 2006;20:1087-92. http://dx.doi.org/10.1002/bmc.646

Lindholm P, Gullbo J, Claeson P, Göransson U, Johansson S, Backlund A et al. Selective cytotoxicity evaluation in anticancer drug screening of fractionated plant extracts. J Biomol Screen 2002;7:333-40.

Maksimova TA, Baronova II, Yudina VF. Seasonal development of Menyanthes trifoliata L. and the dynamics of the content of bitter glycosides, ascorbic acid and tannins in the leaves. Rastit Resur 1980;16:559-66 (Russian), through Chem Abstr 94:44169.

Martz F, Turunen M, Julkunen-Tiitto R, Lakkala K, Sutinen M-L. Effect of the temperature and the exclusion of UVB radiation on the phenolics and iridoids in Menyanthes trifoliata L. leaves in the subarctic. Environmental Pollution 2009;157:3471-78. http://dx.doi.org/10.1016/j.envpol.2009.06.022

Mel’chakova TN, Kharitonova NP. Rutin and hyperoside levels in Menyanthes trifoliata. Khim Prir Soedin 1976;1:106 (Russian), through Chem Abstr 85:43688.

Menyanthes. In: British Herbal Pharmacopoeia Part 1. Cowling: British Herbal Medicine Association 1976:143.

Moskalenko SA. Preliminary screening of far-eastern ethnomedicinal plants for antibacterial activity. J Ethnopharmacol 1986;15:231-59.

Pamakstyte-Jukneviciene G. Chemical composition of sweet flag (Acorus calamus) and buckbean (Menyanthes trifoliata). Bot Sady Pribaltiki Ozolins (Riga) 1971:445-50, through Chem Abstr 76:138157.

Park CH, Tanaka T, Kim JH, Cho EJ, Park JC, Shibahara N, Yokozawa T. Hepatoprotective effects of locanin, iridoid glycoside from Corni Fructus, against hyperglycemia-activated signalling pathway in liver of type 2 diabetic db/db mice. Toxicology 2011;290:14-21. http://dx.doi.org/10.1016/j.tox.2011.08.004

Park SK, Kim BH, Chang I-M. Inhibitory potencies of several iridoids on cyclooxygenase-1, cyclooxygenase-2 enzyme activities, tumour necrosis factor-a and nitric oxide production in vitro. eCAM 2010;7:41-45. http://dx.doi.org/10.1093/ecam/nem129

Popov S. Sterols of the Gentianaceae family. Compt Rend Acad Bulg Sci 1969;22:293-6.

Recio MC, Giner RM, Manez S, Rios JL. Structural considerations on the iridoids as anti-inflammatory agents. Planta Med 1994; 60:232-234

Rulko F. Alkaloids of Gentianaceae V. Alkaloids of Menyanthes trifoliata L. Rocz Chem 1969;43:1831-6.

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MENYANTHIDIS TRIFOLIATAE FOLIUM

Schilcher H, Kammerer S, Wegener T. Bitterkleeblätter (Menyanthidis folium). In: Leitfaden Phytotherapie, 3. Auflage. Elsevier Urban & Fischer, München, Jena 2007;60-61.

Schimmer O, Krüger A, Paulini H, Haefele F. An evaluation of 55 commercial plant extracts in the Ames mutagenicity test. Pharmazie 1994;49:448-51. Steinegger E, Weibel T. Untersuchungen über den Alkaloidgehalt offizineller Gentianaceen. Pharm Acta Helv 1951;26:259-70.

Steinegger E, Hansel R. Bitterklee. In: Lehrbuch der Pharmakognosie und Phytopharmazie, 4th ed. Berlin: Springer-Verlag 1988:599-601.

Sweetman S. (editor). Martindale, The Complete Drug Reference, 35th ed. Pharmaceutical Press, London 2007.

Swiatek L, Adamczyk U, Zadernowski R. Content of phenolic acids in leaves of Menyanthes trifoliata. Planta Med 1986;52:530.

Tunón H, Olavsdotter C, Bohlin L. Evaluation of anti-inflammatory

activity of some Swedish medicinal plants. Inhibition of prostaglandin synthesis and PAF-induced exocytosis. J Ethnopharmacol 1995;48:61-76.

Wagner H, Bladt S. Chapter 3 - Bitter Drugs. In: Plant Drug Analysis - A Thin Layer Chromatography Atlas, 2nd ed. Heidelberg: Springer-Verlag, 1996:84-7.

Wichtl M. Menyanthidis trifoliatae folium. In: Wichtl M (editor). Teedrogen und Phytopharmaka. 5th ed. Stuttgart : Wissenschaftliche Verlagsgesellschaft mbH, 2009:446-448.

Williamson E, Driver S and Baxter K, editors. Bogbean. In: Stockley’s Herbal Medicines Interactions - A guide to the interactions of herbal medicines, dietary supplements and nutraceuticals with conventional medicines. Pharmaceutical Press, London-Chicago 2009:77.

Yamabe N, Noh JS, Park CH, Kang KS, Shibahara N, Tanaka T, Yokozawa T. Evaluation of loganin, iridoid glycoside from Corni Fructus, on hepatic and renal glucolipipotoxicity and inflammation in type 2 diabetic db/db mice. European Journal of Pharmacology 2010;648:179-187. http://dx.doi.org/10.1016/j.ejphar.2010.08.044

MOST RECENT VERSIONS

Title Common name Publication

ABSINTHII HERBA Wormwood Second Edition, 2003AGNI CASTI FRUCTUS Agnus Castus Second Edition, 2003AGRIMONIAE HERBA Agrimony Supplement 2009ALCHEMILLAE HERBA Lady's Mantle Online Series, 2013ALLII SATIVI BULBUS Garlic Second Edition, 2003ALOE BARBADENSIS Barbados Aloes Supplement 2009ALOE CAPENSIS Cape Aloes Second Edition, 2003ALTHAEAE RADIX Marshmallow Root Second Edition, 2003ANGELICAE RADIX Angelica Root Supplement 2009ANISI FRUCTUS Aniseed Second Edition, 2003ARNICAE FLOS Arnica Flower Second Edition, 2003BALLOTAE NIGRAE HERBA Black Horehound Supplement 2009BETULAE FOLIUM Birch Leaf Second Edition, 2003BOLDI FOLIUM Boldo Leaf Second Edition, 2003CALENDULAE FLOS Calendula Flower Second Edition, 2003CAPSICI FRUCTUS Capsicum Supplement 2009CARVI FRUCTUS Caraway Fruit Second Edition, 2003CARYOPHYLLI AETHEROLEUM Clove Oil Online Series, 2014CENTAURII HERBA Centaury Second Edition, 2003CENTELLAE ASIATICAE HERBA Centella Supplement 2009CHELIDONII HERBA Greater Celandine Second Edition, 2003CIMICIFUGAE RHIZOMA Black Cohosh Online Series, 2011CINNAMOMI CORTEX Cinnamon Second Edition, 2003CRATAEGI FOLIUM CUM FLORE Hawthorn Leaf and Flower Second Edition, 2003CRATAEGI FRUCTUS Hawthorn Berries Supplement 2009CUCURBITAE SEMEN Pumpkin Seed Supplement 2009CURCUMAE LONGAE RHIZOMA Turmeric Second Edition, 2003CURCUMAE XANTHORRHIZAE RHIZOMA Javanese Turmeric Supplement 2009CYNARAE FOLIUM Artichoke Leaf Supplement 2009ECHINACEAE ANGUSTIFOLIAE RADIX Narrow-leaved Coneflower Root Supplement 2009ECHINACEAE PALLIDAE RADIX Pale Coneflower Root Supplement 2009ECHINACEAE PURPUREAE HERBA Purple Coneflower Herb Supplement 2009ECHINACEAE PURPUREAE RADIX Purple Coneflower Root Supplement 2009ELEUTHEROCOCCI RADIX Eleutherococcus Supplement 2009EUCALYPTI AETHEROLEUM Eucalyptus Oil Second Edition, 2003FILIPENDULAE ULMARIAE HERBA Meadowsweet Second Edition, 2003FOENICULI FRUCTUS Fennel Second Edition, 2003FRANGULAE CORTEX Frangula Bark Second Edition, 2003FUMARIAE HERBA Fumitory Supplement 2009GENTIANAE RADIX Gentian Root Online Series, 2014GINKGO FOLIUM Ginkgo Leaf Second Edition, 2003GINSENG RADIX Ginseng Second Edition, 2003GRAMINIS RHIZOMA Couch Grass Rhizome Supplement 2009GRINDELIAE HERBA Grindelia Supplement 2009HAMAMELIDIS AQUA Hamamelis Water Online Series, 2012HAMAMELIDIS CORTEX Hamamelis Bark Online Series, 2012HAMAMELIDIS FOLIUM Hamamelis Leaf Online Series, 2012HARPAGOPHYTI RADIX Devil’s Claw Root Supplement 2009HEDERAE HELICIS FOLIUM Ivy Leaf Second Edition, 2003HIPPOCASTANI SEMEN Horse-chestnut Seed Second Edition, 2003HYDRASTIS RHIZOMA Goldenseal rhizome Online Series, 2013HYPERICI HERBA St. John’s Wort Second Edition, 2003JUNIPERI PSEUDO-FRUCTUS Juniper Second Edition, 2003LAVANDULAE FLOS/AETHEROLEUM Lavender Flower/Oil Supplement 2009LICHEN ISLANDICUS Iceland Moss Second Edition, 2003LINI SEMEN Linseed Second Edition, 2003LIQUIRITIAE RADIX Liquorice Root Second Edition, 2003

LUPULI FLOS Hop Strobile Second Edition, 2003MALVAE FLOS Mallow Flower Supplement 2009MARRUBII HERBA White horehound Online Series, 2013MATRICARIAE FLOS Matricaria Flower Second Edition, 2003MELALEUCAE AETHEROLEUM Tea Tree Oil Supplement 2009MELILOTI HERBA Melilot Second Edition, 2003MELISSAE FOLIUM Melissa Leaf Online Series, 2013MENTHAE PIPERITAE AETHEROLEUM Peppermint Oil Second Edition, 2003MENTHAE PIPERITAE FOLIUM Peppermint Leaf Second Edition, 2003MENYANTHIDIS TRIFOLIATAE FOLIUM Bogbean Leaf Online Series, 2013MILLEFOLII HERBA Yarrow Supplement 2009MYRRHA Myrrh Online Series, 2014MYRTILLI FRUCTUS Bilberry Fruit Online Series, 2014OLIBANUM INDICUM Indian Frankincense Supplement 2009ONONIDIS RADIX Restharrow Root Second Edition, 2003ORTHOSIPHONIS FOLIUM Java Tea Online Series, 2014PASSIFLORAE HERBA Passion Flower Second Edition, 2003PAULLINIAE SEMEN Guarana Seed Supplement 2009PIPERIS METHYSTICI RHIZOMA Kava-Kava Second Edition, 2003PLANTAGINIS LANCEOLATAE FOLIUM/HERBA Ribwort Plantain Leaf/Herb Online Series, 2013PLANTAGINIS OVATAE SEMEN Ispaghula Seed Second Edition, 2003PLANTAGINIS OVATAE TESTA Ispaghula Husk Second Edition, 2003POLYGALAE RADIX Senega Root Second Edition, 2003PRIMULAE RADIX Primula Root Second Edition, 2003PRUNI AFRICANAE CORTEX Pygeum Bark Supplement 2009PSYLLII SEMEN Psyllium Seed Second Edition, 2003RATANHIAE RADIX Rhatany Root Supplement 2009RHAMNI PURSHIANI CORTEX Cascara Second Edition, 2003RHEI RADIX Rhubarb Second Edition, 2003RIBIS NIGRI FOLIUM Blackcurrant Leaf Second Edition, 2003ROSAE PSEUDO-FRUCTUS Dog Rose Hip Supplement 2009ROSMARINI FOLIUM Rosemary Leaf Second Edition, 2003RUSCI RHIZOMA Butcher’s Broom Second Edition, 2003SALICIS CORTEX Willow Bark Second Edition, 2003SAMBUCI FLOS Elder flower Online Series, 2013SALVIAE OFFICINALIS FOLIUM Sage Leaf Second Edition, 2003SALVIA TRILOBAE FOLIUM Sage Leaf, Three-lobed Online Series, 2014SENNAE FOLIUM Senna Leaf Second Edition, 2003SENNAE FRUCTUS ACUTIFOLIAE Alexandrian Senna Pods Second Edition, 2003SENNAE FRUCTUS ANGUSTIFOLIAE Tinnevelly Senna Pods Second Edition, 2003SERENOAE REPENTIS FRUCTUS (SABAL FRUCTUS) Saw Palmetto Fruit Second Edition, 2003SERPYLLI HERBA Wild Thyme Online Series, 2014SOLIDAGINIS VIRGAUREAE HERBA European Golden Rod Second Edition, 2003SILYBI MARIANI FRUCTUS Milk Thistle Fruit Supplement 2009SYMPHYTI RADIX Comfrey Root Online Series, 2012TANACETI PARTHENII HERBA Feverfew Online Series, 2014TARAXACI FOLIUM Dandelion Leaf Second Edition, 2003TARAXACI RADIX Dandelion Root Second Edition, 2003THYMI HERBA Thyme Second Edition, 2003TORMENTILLAE RHIZOMA Tormentil Online Series, 2013TRIGONELLAE FOENUGRAECI SEMEN Fenugreek Second Edition, 2003URTICAE FOLIUM/HERBA Nettle Leaf/Herb Second Edition, 2003URTICAE RADIX Nettle Root Second Edition, 2003UVAE URSI FOLIUM Bearberry Leaf Online Series, 2012VACCINII MACROCARPI FRUCTUS Cranberry Supplement 2009VALERIANAE RADIX Valerian Root Supplement 2009VIOLAE HERBA CUM FLORE Wild Pansy Supplement 2009VITIS VINIFERAE FOLIUM Red Vine Leaf Supplement 2009ZINGIBERIS RHIZOMA Ginger Supplement 2009

7

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.

MonographsThe Scientific Foundation for Herbal Medicinal Products

www.escop.com ISBN 978-1-901964-12-7

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