Frangulae cortexFrangula Bark

MonographsThe Scientific Foundation for Herbal Medicinal Products

2017

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The Scientific Foundation for Herbal Medicinal Products

FRANGULAE CORTEXFrangula Bark

2017

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 978-1-901964-46-2

Frangulae cortex - Frangula Bark

© ESCOP 2017

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 photographs by Sten Porse [CC BY-SA 3.0] via Wikimedia Commons (Frangula alnus)

and Martin WilloughbyCover and text design by Martin Willoughby

Typeset in Optima by Roberta Hutchins

Plant illustrated on the cover: Frangula alnus

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.

Tankred WegenerChair 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:

Front cover Title page Verso Foreword and Preface Notes for the Reader Abbreviations The monograph text Back cover

Information on the member organizations and people involved in ESCOP’s activities can be found on the website (www.escop.com): Members of ESCOP Board of Supervising Editors ESCOP Scientific Committee Board of Directors of ESCOP

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 intervalCCl4 carbon tetrachlorideCmax 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 dihydrotestosteroneDMSO dimethyl sulfoxideDNA 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 synthase

INR International Normalized Ratio, a measure of blood coagulation (clotting) tendencyi.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 EPgp P-glycoproteinPHA 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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Frangula Bark

DEFINITION

Frangula bark consists of the dried, whole or fragmented bark of the stems and branches of Rhamnus frangula L. (Frangula alnus Miller). It contains not less than 7.0 per cent of glucofrangulins, expressed as glucofrangulin A (C27H30O14; Mr 578.5) and calculated with reference to the dried drug.

The material complies with the monograph of the European Pharmacopoeia [Frangulae cortex].

CONSTITUENTS

The main active constituents of the dried bark are glucofrangulins A and B (emodin-6-O-a-L-rhamnosyl-8-O-b-D-glucoside and emodin-6-O-b-D-apiosyl-8-O-b-D-glucoside respectively), frangulins A, B and C (emodin-6-O-b-L-rhamnoside, emodin-6-O-b-D-apioside and emodin-6-O-b-D-xyloside), and emodin-8-O-b-D-glucoside, together with small amounts of other anthraquinone glycosides, dianthrones and aglycones [Wagner 1969; Labadie 1970; Hörhammer 1972; Wagner 1974; Lemli 1978; Hänsel 1994; Hänsel 1999].

CLINICAL PARTICULARS

Therapeutic indicationsFor short term treatment of occasional constipation [Preston 1986; Sonnenberg 1989].

Posology and method of administration

DosageThe correct individual dose is the smallest required to produce a comfortable soft-formed motion.

Adults and children over 12 years: preparations equivalent to 20-30 mg of glucofrangulins daily, calculated as glucofrangulin A [Hänsel 1994].Elderly: dose as for adults.

Not recommended for use in children under 12 years of age.The pharmaceutical form must allow lower dosages.

Method of administrationFor oral administration.

Duration of administrationUse for more than 1 – 2 weeks requires medical supervision. If the symptoms persist during the use of the medicinal product, a doctor or a pharmacist should be consulted.

ContraindicationsNot to be used in cases of: intestinal obstruction and stenosis, atony, inflammatory bowel diseases (e.g. Crohn’s disease, ulcerative colitis), appendicitis; abdominal pain of unknown origin; severe dehydration states with water and electrolyte depletion.Not to be used in pregnancy or in children under 12 years of age [Hänsel 1994; Sweetman 2002].

Special warnings and precautions for useAs for all laxatives, frangula bark should not be given when any undiagnosed acute or persistent abdominal symptoms are present.

If laxatives are needed every day the cause of the constipation should be investigated. Long term use of laxatives should be avoided. Use for more than 2 weeks requires medical supervision. Chronic use may cause pigmentation of the colon (pseudomelanosis coli) which is harmless and reversible after drug

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discontinuation. Abuse with diarrhoea and consequent fluid and electrolyte losses may cause: dependence with possible need for increased dosages; disturbance of the water and electrolyte (mainly hypokalaemia) balance; an atonic colon with impaired function. Intake of anthranoid-containing laxatives for more than a short period of time may result in aggravation of constipation. Hypokalaemia can result in cardiac and neuromuscular dysfunction, especially if cardiac glycosides, diuretics or corticosteroids are taken. Chronic use may result in albuminuria and haematuria.

In chronic constipation stimulant laxatives are not an acceptable alternative to a changed diet [Preston 1986; Müller-Lissner 1988; Sonnenberg 1989; Bingham 1989; Coenen 1990; Klauser 1990a, Klauser 1990b; Bingham 1991; Klauser 1992; Hänsel 1994; Sweetman 2002].

Note: A detailed text with advice concerning changes in dietary habits, physical activities and training for normal bowel evacuation should be included on the package leaflet. An example is given in the booklet “Médicaments à base de plantes” published by the French health authority (Paris: Agence du Médicament).

Interaction with other medicinal products and other forms of interactionHypokalaemia (resulting from long term laxative abuse) potentiates the action of cardiac glycosides and interacts with antiarrhythmic drugs or with drugs which induce reversion to sinus rhythm (e.g. quinidine). Concomitant use with other drugs inducing hypokalaemia (e.g. thiazide diuretics, adrenocorticosteroids and liquorice root) may aggravate electrolyte imbalance [Hänsel 1994].

Pregnancy and lactation

PregnancyNot recommended during pregnancy.

There are no reports of undesirable or damaging effects during pregnancy or on the foetus when used in accordance with the recommended dosage schedule. However, experimental data concerning a genotoxic risk from several anthranoids (e.g. emodin and physcion) and frangula bark extract are not counterbalanced by sufficient studies to eliminate a possible risk [Schmidt 1955; Brown 1976; Liberman 1980; Tikkanen 1983; Bruggeman 1984; Westendorf 1990; Westendorf 1993].

LactationBreastfeeding is not recommended as there are insufficient data on the excretion of metabolites in breast milk.

Excretion of active principles in breast milk has not been investigated. However, small amounts of active metabolites (e.g. rhein) from other anthranoids are known to be excreted in breast milk. A laxative effect in breast-fed babies has not been reported [Faber 1988; Sweetman 2002].

Effects on ability to drive and use machinesNone known. Undesirable effectsAbdominal spasms and pain, in particular in patients with irritable colon; yellow or red-brown (pH dependent) discolouration of urine by metabolites, which is not clinically significant [Cooke 1977; Tedesco 1985; Ewe 1986; Hänsel 1994; Sweetman 2002].

OverdoseThe major symptoms are griping and severe diarrhoea with

consequent losses of fluid and electrolyte, which should be replaced.

Treatment should be supportive with generous amounts of fluid. Electrolytes, particularly potassium, should be monitored; this is especially important in the elderly and the young [Hänsel 1994].

PHARMACOLOGICAL PROPERTIES

Pharmacodynamic properties

1,8-dihydroxyanthracene derivatives possess a laxative effect. For the greater part the glycosides (frangulins and glucofrangulins) are not absorbed in the upper gut; they are converted by the bacteria of the large intestine into the active metabolite (emodin-anthrone). There are two different mechanisms of action:

(i) an influence on the motility of the large intestine (stimulation of peristaltic contractions and inhibition of local contractions) resulting in accelerated colonic transit, thus reducing fluid absorption,

(ii) an influence on secretion processes (stimulation of mucus and active chloride secretion) resulting in enhanced fluid secretion [Casparis 1925; Schultz 1952;Ferguson 1956; Cresseri 1966; Fairbairn 1970; van Os 1976; Fairbairn 1976; Lemmens 1976; Longo 1980; de Witte 1993].

Defecation takes place after a delay of 8-12 hours due to the time taken for transport to the colon and metabolization into the active compound.

In vitro experimentsEmodin inhibited the aggregation of rabbit platelets induced by arachidonic acid and collagen, without affecting that induced by ADP or PAF. Frangulin B selectively and dose-dependently inhibited collagen-induced aggregation and ATP release in rabbit platelets, without affecting those induced by arachidonic acid, ADP, PAF and thrombin. Frangulin B also inhibited the platelet aggregation induced by trimucytin, a collagen receptor agonist [Teng 1993].

Frangulin B showed potent inhibitory activity against tumour necrosis factor-a (TNF-a) formation in lipopolysaccharide/g-interferon-stimulated murine microglial cell line N9 (IC50: 42.6 µM, p<0.01) [Wei 2001].

Anti-proliferative propertiesEmodin displays antiproliferative properties which seem to be related to its role in the regulation of redox status, inhibition of kinases, through activation of microsomal enzymes, activation of repair mechanisms in various cellular systems generating ROS (reactive oxygen species) and increasing the susceptibility of tumour cells to standard cytotoxic therapeutic agents [Shieh 2004, Srinivas 2007].

Other effectsA methanolic extract (undefined) of frangula bark containing anthraquinones and flavonoids was active against various fungi in vitro [e.g. Trichoderma viride, Doratomyces stemonitis, Aspergillus niger, Penicillium verrucosum, Alternaria alternate, Aueobasidium pullulans and Mucor mucedo], and was in most cases superior to isolated emodin [Manjlovic 2005].

Clinical studiesIn a randomized, controlled clinical trial, 45 post-colostomy surgery patients received either a standardized postsurgical laxative protocol (n = 19; intervention group) or laxative

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treatments as preferred by the surgical team (n = 26; comparison group). The standardized protocol consisted of first line treatment with either a combination of sterculia and frangula bark or liquid paraffin, and second line treatment with an iso-osmotic polyethylene glycol. The effects of the treatments on constipation were compared, as measured by faecal loading on plain abdominal film, stomal therapy nurse activity, patient comfort and length of hospital stay. The presence of faecal loading (constipation) was lower (p=0.05) in the intervention group (1 episode) compared to the comparison group (7 episodes). Stomal therapy nurse activity, in terms of the number of empty bag changes, was significantly higher in the comparison group (p=0.03). No statistically significant difference was found regarding the other 2 parameters. The findings of the study support the benefits of this standardized laxative protocol for prevention of constipation for post-colostomy surgery patients [Stott 2012].

Pharmacokinetic propertiesIt is generally assumed (by analogy with sennosides from senna) that the glycosides (frangulins and glucofrangulins) are largely not split by human digestive enzymes in the upper gut and therefore not absorbed to a large extent. They are converted by the bacteria of the large intestine into the active metabolite (emodin-anthrone). Mainly anthraquinone aglycones are absorbed and transformed into their corresponding glucuronide and sulphate derivatives. After oral administration of frangula bark extract, rhein, emodin and traces of chrysophanol are found in human urine [Longo 1980; de Witte 1993].

Oral administration of emodin to rabbits at 10 mg/kg b.w. resulted in a very low serum concentration (approximately 2.5 µg/ml). Emodin was found to be highly bound (99.6%) to serum protein [Liang 1995].

Preclinical safety dataNo studies are available on single dose toxicity, repeated dose toxicity, reproductive toxicity or on in vivo carcinogenicity of frangula bark or frangula bark preparations.

Embryonic / Developmental toxicityMouse embryos at the blastocyst stage administered in vitro with 25-75µM emodin exhibited significantly increased apoptosis and a corresponding decrease in total cell number. The implantation success rate of blastocysts pretreated with emodin was lower than that of control. Moreover, in vitro treatment was associated with increased resorption of post-implantation embryos and decreased fetal weight. In an in vivo mouse model, the application of emodin in drinking water led to apoptosis and decreased cell proliferation, and inhibited early embryonic development to the blastocyst stage [Chang 2012a].

In an in vivo mouse model, application of drinking water con-taining 20-40µM emodin led to decreased oocyte maturation and in vitro fertilization. Pretreatment with a caspase-3-specific inhibitor prevented these effects, suggesting that the impairment of embryo development occurs via a caspase-dependent apoptotic process [Chang 2012b].

The effects of emodin on embryo/fetal growth, viability and morphological development were studied in rats and mice. Ingested dose was 0, 31, 57 and 80-144 mg emodin/kg/day in rats and 0, 94, 391 and 1005 mg emodin/kg/day in mice. The rat maternal lowest observed adverse effect level (LOAEL) was 1700 ppm; the no adverse effect level (NOAEL) was 850 ppm. The rat developmental toxicity NOAEL was ≤ 1700 ppm; LOAEL not established. In mice, maternal toxicity NOAEL was 2500 ppm (LOAEL: 6000 ppm). The developmental toxicity LOAEL was 6000 ppm and the NOAEL was 2500 ppm [Jahnke 2004].

Genotoxicity/CancerogenicityVarious frangula bark extracts have been shown to be genotoxic in several in vitro bacterial mutation tests. Emodin, the main laxative principle of frangula bark, was mutagenic in the Ames test but gave inconsistent results in gene mutation assays (V79 HGPRT), positive results in the UDS test with primary rat hepatocytes but negative results in the SCE assay. Other anthraquinone constituents also gave positive results in limited experiments [Brown 1976; Liberman 1980; Tikkanen 1983; Bruggeman 1984; Westendorf 1990; Müller 1996].

In a 2-year study, male and female F344/N rats were exposed to 280, 830 or 2500 ppm of emodin in the diet, corresponding to an average daily dose of emodin of 110, 320 or 1000 mg/kg b.w. in male rats and 120, 370 or 1100 mg/kg b.w. in female rats. No evidence of carcinogenic activity of emodin was observed in male rats. A marginal increase in the incidence of Zymbal’s gland carcinoma occurred in female rats treated with the high dosage but was interpreted as questionable.

In a further 2-year study, on B6C3F1 mice, males were exposed to 160, 312 or 625 ppm of emodin (corresponding to an average daily dose of 15, 35 or 70 mg/kg b.w.) and females to 312, 625 or 1250 ppm of emodin (corresponding to an average daily dose of 30, 60 or 120 mg/kg b.w.). There was no evidence of carcinogenic activity in female mice. A low incidence of renal tubule neoplasms in exposed males was not considered relevant [NTP Technical Report 1999].

Clinical safety dataDespite a lack of formal preclinical data on frangula bark, epidemiological studies suggest that there is no carcinogenic risk in humans from the use of anthranoid laxatives [Loew 1994; Loew 1997; van Gorkom 1999].

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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 Online Series, 2014ALOE CAPENSIS Cape Aloes Online Series, 2014ALTHAEAE RADIX Marshmallow Root Second Edition, 2003ANGELICAE RADIX Angelica Root Supplement 2009ANISI FRUCTUS Aniseed Online Series, 2014ARNICAE FLOS Arnica Flower Second Edition, 2003ARCTII RADIX Burdock Root Online Series, 2016BALLOTAE NIGRAE HERBA Black Horehound Online Series, 2015BETULAE FOLIUM Birch Leaf Online Series, 2015BOLDI 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 Online Series, 2015CENTELLAE ASIATICAE HERBA Centella Supplement 2009CHELIDONII HERBA Greater Celandine Second Edition, 2003CIMICIFUGAE RHIZOMA Black Cohosh Online Series, 2011CINNAMOMI CORTEX Cinnamon Second Edition, 2003COLAE SEMEN Cola Online Series, 2014CRATAEGI 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 Online Series, 2015FOENICULI FRUCTUS Fennel Second Edition, 2003FRANGULAE CORTEX Frangula Bark Online Series, 2017FUMARIAE 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 Online Series, 2016GRINDELIAE HERBA Grindelia Online Series, 2015HAMAMELIDIS 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, 2003

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LINI SEMEN Linseed Online Series, 2017LIQUIRITIAE RADIX Liquorice Root Second Edition, 2003LUPULI FLOS Hop Strobile Second Edition, 2003MALVAE FLOS Mallow Flower Online Series, 2016MARRUBII 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 Online Series, 2015ORTHOSIPHONIS FOLIUM Java Tea Online Series, 2014PASSIFLORAE HERBA Passion Flower Second Edition, 2003PAULLINIAE SEMEN Guarana Seed Supplement 2009PELARGONII RADIX Pelargonium Root Online Series, 2015PIPERIS 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 Online Series, 2016POLYGALAE RADIX Senega Root Second Edition, 2003PRIMULAE RADIX Primula Root Second Edition, 2003PRUNI AFRICANAE CORTEX Pygeum Bark Supplement 2009PSYLLII SEMEN Psyllium Seed Online Series, 2017RATANHIAE RADIX Rhatany Root Online Series, 2017RHAMNI PURSHIANI CORTEX Cascara Online Series, 2015RHEI RADIX Rhubarb Second Edition, 2003RIBIS NIGRI FOLIUM Blackcurrant Leaf Online Series, 2017ROSAE PSEUDO-FRUCTUS Dog Rose Hip Supplement 2009ROSMARINI FOLIUM Rosemary Leaf Second Edition, 2003RUSCI RHIZOMA Butcher’s Broom Online Series, 2017SALICIS CORTEX Willow Bark Online Series, 2017SAMBUCI 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 Online Series, 2015UVAE URSI FOLIUM Bearberry Leaf Online Series, 2012VACCINII MACROCARPI FRUCTUS Cranberry Supplement 2009VALERIANAE RADIX Valerian Root Supplement 2009VERBASCI FLOS Mullein Flower Online Series, 2014VIOLAE HERBA CUM FLORE Wild Pansy Online Series, 2015VITIS VINIFERAE FOLIUM Red Vine Leaf Supplement 2009ZINGIBERIS RHIZOMA Ginger Supplement 2009

8

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 978-1-901964-46-2

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