Serpylli herbaWild Thyme

MonographsThe Scientific Foundation for Herbal Medicinal Products

2014

www.escop.com

onlineseries

The Scientific Foundation for Herbal Medicinal Products

SERPYLLI HERBAWild Thyme

2014

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 978-1-901964-16-5

Serpylli herba - Wild Thyme

© ESCOP 2014

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 Professor Salvador Cañigueral Folcara (Thymus serpyllum)

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

Plant illustrated on the cover: Thymus serpyllum

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:

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 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

1

SERPYLLI HERBA 2014

Wild Thyme

DEFINITION

Serpylli herba consists of the whole or cut, dried, flowering aerial parts of Thymusserpyllum L.s.l. It contains not less than 3.0 mL/kg of essential oil (dried drug).

The material complies with the European Pharmacopoeia [Wild thyme].

CONSTITUENTS

Essential oil: 0.1 to 0.6% with carvacrol as major compound and variable amounts of thymol, linalool, linalyl acetate, borneol, 1,8-cineole, germacrene D, p-cymene, g-terpinene, myrcene, b-caryophyllene [Loziene 1998; Mockute 2004; Raal 2004; Sefidkon 2004; Stahl-Biskup 2007; Paaver 2008; Cavar 2009, Schilcher 2010, Nedorostova 2011, Hussain 2013]. The composition depends largely on the species, genotype, ontogenic development, origin and growth conditions [Rasooli 2002].

Triterpenoids such as ursolic acid (0.9 to 1.4%) and oleanolic acid (0.37 to 0.48%), and low amounts of 3b-hydroxyolean-12-en-28-oic acid and dihydroursolic acid [Janicsak 2006; Aziz 2008; Stahl-Biskup 2009].

Hydroxycinnamic acids (1.3 to 6.8%) with rosmarinic acid (0.76 to 2.44%) and lithospermic acid (0.31 to 4.28%) as main components [Ziakova 2003; Kulisic 2007; Stahl-Biskup 2007; Fecka 2008, Boros 2010].

Flavonoids (0.95 to 2.99%) such as luteolin-7-O-glucuronide, luteolin-7-O-glucoside, luteolin-7-O-rutinoside, eriocitrin or scutellarin-7-O-b-D-gluco-pyranosyl(1→4)-O-a-L-rhamnopyranoside [Washington 1986; Kulisic 2007; Fecka 2008, Miron 2011].

Tannins (3.4 to 7.4 %) [Stahl-Biskup 2009, Komes 2011]; amino acids [Mazulin 2002].

CLINICAL PARTICULARS

Therapeutic indications

Internal use:Catarrh of the upper respiratory tract [Jänicke 2003; Schilcher 2010; Stahl-Biskup 2007; Stahl-Biskup 2009].

External use:As a bath additive in the supportive treatment of acute or chronic diseases of the respiratory tract [Jänicke 2003; Stahl-Biskup 2007].

Efficacy in these indications is plausible on the basis of human experience and long-standing use.

Posology and method of administration

Dosage

Internal use: Adult daily dose: 4-6 g of the drug [Jänicke 2003; Schilcher 2010; Stahl-Biskup 2007; Stahl-Biskup 2009]. As an infusion, 2 g (1 - 2 teaspoons) in 150 mL of water, 1 cup before meals 2 to 3 times daily [Jänicke 2003; Stahl-Biskup 2007; Stahl-Biskup 2009].

External use:Decoction: 1 g of the drug per litre of water [Jänicke 2003].

Method of administrationFor oral administration and local application.

2

SERPYLLI HERBA

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

ContraindicationsNone known.

Special warnings and special precautions for useNone required.

Interaction with other medicaments and other forms of interactionNone reported.

Pregnancy and lactationNo data available. In accordance with general medical practice, the product should not be used during pregnancy and lactation without medical advice.

Effects on ability to drive and use machinesNone known.

Undesirable effectsNone reported.

OverdoseNo case of overdose reported.

PHARMACOLOGICAL PROPERTIES

Pharmacodynamic properties

In vitro experiments

Antioxidant activityAn extract (80% methanol; 5:1) exhibited antioxidant activity in the ferrylmyoglobin/ABTS•+ assay with a Trolox equivalent antioxidant capacity of 14.7 mM/g dry weight. The effect correlated with the content of total phenolics [Alzoreky 2001].

A ferric reducing/antioxidant power (FRAP) of 10.9 mmol/L was determined for an infusion (3 g/200 mL); this correlated with the total phenol content; a phenol antioxidant coefficient (FRAP/total phenolics) of 3.7 was found [Katalinic 2006].

In a broad screening for antioxidant activity, an infusion (15 g/150 mL dried and residue redissolved to 60 g/L) had an IC50 of 0.45 g/L in the diphenylpicrylhydrazyl (DPPH) assay and an antioxidant activity index of 1.90 in the Rancimat assay. The activity in the carotene bleaching assay was low and the infusion remained without effect in the TBARS assay [Kulisic 2006].

An infusion (2 g/200 mL) showed antioxidant activity in the ABTS assay (equivalent to 2.44 mM Trolox after 5 min extraction). After 15 min extraction the activity was equivalent to approximately 3.6 mM Trolox and after hydrolysis of the extract to approximately 4.8 mM Trolox. In the FRAP assay the capacity was equivalent to 7.48 mM Fe(II) after 5 min extraction, 6.49 mM Fe(II) after 15 min extraction and approximately 16 mM Fe(II) after hydrolysis [Komes 2011].

In the carotene/linoleic acid assay extracts from wild thyme inhibited lipid peroxidation with IC50 values of 261 µg/mL (water extract), 41.2 µg/mL (ethanolic extract) and 96.9 µg/mL (essential oil), whereas the IC50 of butylated hydroxytoluene (BHT) as positive control was 12 µg/mL. The IC50 values in the DPPH assay were 31.6 µg/mL for the water extract, 13.2 µg/mL for the ethanolic extract and 15.7 µg/mL for BHT [Mata 2007].

Copper-induced LDL oxidation was inhibited by an infusion as well as by the essential oil of wild thyme at concentrations of 0.02 g/L [Kulisic2007].

The relative inhibition of copper-catalyzed oxidation of human LDL by the essential oil was 45.5% [Teissedre 2000].

In the DPPH assay the essential oil showed a radical scavenging activity equivalent to 87% of the activity of BHT [Topal 2008].

Antimicrobial activity

In a disc diffusion assay the essential oil showed strong bacteri-cidal activity against Staphylococcus aureus and Bacillus subtilis [Rasooli 2002].

S. aureus, Yersinia enterocolitica and two strains of E. coli were inhibited by the essential oil as shown in a disc diffusion assay and by serial dilution method [Sagdic 2003].

Wild thyme essential oil was in the group with the highest inhibitory activity against infectious vaginal microorganisms such as Candida albicans, Streptococcus agalactiae and Enterococcus faecalis [Arnal-Schnebelen 2004].

In an agar dilution test the essential oil was found to have MICs of <0.05 to <0.2% and maximal tolerated concentrations of <0.006 to <0.05% (v/v) against E. coli, Salmonella typhimurium, S. aureus and Listeria monocytogenes [Oussalah 2007].

The antibacterial activity of the essential oil against different strains of S. aureus was also tested in the vapour phase. MICs for two methicillin-sensitive strains were 33 µL/L, for MRSA 260 µL/L and for several clinical isolates of S. aureus between 66 and 130 µL/L [Nedorostova 2012].

In another study using the agar diffusion method, the essential oil of wild thyme was the most active against E. coli, S. aureus, Klebsiella pneumoniae and Staphylococcus epidermidis as compared to 18 other essential oils [Bulut 2009].

Spore germination and mycelial growth of different Aspergillus species were inhibited by the essential oil in a dose-dependent manner. The inhibition of sporulation was less pronounced [Rahman 2003].

In a box vapour assay for antifungal activity the essential oil was tested and showed high potency against Trichophyton mentagrophytes. The activity was attributed to the content of carvacrol. The results correlated with those of an agar diffusion assay [Inouye 2006]. Acetylcholinesterase inhibitory activityThe essential oil of wild thyme showed the strongest inhibition of acetylcholinesterase (IC50 190 µg/mL) as compared to an ethanolic (IC50 252 µg/mL) and an aqueous extract (IC50 348 µg/mL) of the same plant material [Mata 2007].

Antiproliferative effectsA methanolic dry extract (not further specified) showed cytotoxic activity against MCF-7 and MDA-MB-231 breast cancer cells with IC50 values of 509 and 276 µg/mL. The extract induced apoptosis as shown via analysis of DNA fragmentation and caspase 3/7 activity. The activities of DNA methyltransferase and histonedeacetylase were significantly reduced by 250 and 500 µg/mL of the extract (p<0.05) [Bozkurt 2012].

The essential oil exhibited an antiproliferative activity in MCF-7 cells (IC50 95.8 µg/mL), LN-CaP prostate cancer cells (IC50

3

SERPYLLI HERBA

105.0 µg/mL) and NIH-3T3 fibroblasts (IC50 105.0 µg/mL) [Hussain 2013].

In vivo experimentsAdministration of a freeze dried aqueous extract of wild thyme to euthyroid rats (2.5 mg/100 g b.w. i.v.) decreased serum thyroid stimulating hormone (TSH) concentration by about 50% within 3 hours compared to the control group. The pituitary TSH concentration was significantly reduced to approximately 40% of control (p<0.005-0.001). The concentrations of thyroxine (T4) remained unchanged while triiodothyronine (T3) was slightly decreased. After a high dose of 40 mg/100 g b.w. the serum TSH level and thyroidal secretions decreased rapidly and remained suppressed during the 12 hours observation period. There was also a significant reduction (p<0.005-0.001) in the T4 and T3 levels at 3 and 6 hours post-injection. Serum prolactin levels were significantly increased after the low dose (2.5mg/100g; p<0.05); but significantly decreased after the high dose (40mg/100g; p<0.005-0.001), this effect vanished between 6 and 12 hours after injection. In goitrous rats, a 70% ethanolic extract (5 mg/kg b.w. i.v.) led to a significant decrease (p<0.05-0.01) in the serum TSH concentration. However, the pituitary TSH concentration was increased significantly (p<0.05) only by an ethanolic extract oxidized with KMnO4 [Sourgens 1982].

Clinical studiesNo data available.

Pharmacokinetic properties No data available.

Preclinical safety data No data available.

Clinical safety dataNo data available.

REFERENCES

Alzoreky NS, Nakahara K. Antioxidant activity of some edible Yemeni plants evaluated by ferrylmyoglobin/ABTS•+ assay. Food Sci Technol Res 2001;7:141-4. http://dx.doi.org/10.3136/fstr.7.141

Arnal-Schnebelen B, Hadji-Minaglou F, Peroteau J-F, Ribeyre F, de Billerbeck VG. Essential oils in infectious gynaecological disease: a statistical study of 658 cases. Int J Aromather 2004;14:192-7. http://dx.doi.org/10.1016/j.ijat.2004.09.003

Aziz S, Habib-Ur-Rehman. Studies on the chemical constituents of Thymus serpyllum. Turk J Chem 2008;32:605-14.

Boros B, Jakabová S, Dörnyei Á, Horváth G, Pluhár Z, Kilár F, Felinger A. Determination of polyphenolic compounds by liquid chromatography-mass spectrometry in Thymus species. J Chromatogr A 2010;1217:7972-80. http://dx.doi.org/10.1016/j.chroma.2010.07.042

Bozkurt E, Atmaca H, Kisim A, Uzunoglu S, Uslu R, Burcak K. Effects of Thymus serpyllum extract on cell proliferation, apoptosis and epigenetic events in human breast cancer cells. Nutr Cancer 2012;64:1245-50. http://dx.doi.org/10.1080/01635581.2012.719658

Bulut C, Altiok E, Bayraktar O, Ülkü S. Antioxidative and antimicrobial screening of 19 commercial essential oils in Turkey. Acta Hort 2009;826:111-6.

Ćavar S, Maksimović M, Vidic D.The essential oil of Thymus aureopunctatus (Beck) K. Maly. Nat Prod Commun 2009;4:415-20.

Fecka I, Turek S. Determination of polyphenolic compounds in com-mercial herbal drugs and spices from Lamiaceae: thyme, wild thyme

and sweet marjoram by chromatographic techniques. Food Chem 2008;108:1039-53. http://dx.doi.org/10.1016/j.foodchem.2007.11.035

Hussain AI, Anwar F, Chatha SAS, Latif S, Sherazi STH, Ahmad A, Worthington J, Sarker SD. Chemical composition and bioactivity studies of the essential oils from two Thymus species from the Pakistani flora. LWT Food Sci Technol 2013;50:185-92. http://dx.doi.org/10.1016/j.lwt.2012.06.003

Inouye S, Uchida K, Abe S. Vapor activity of 72 essential oils against a Trichophyton mentagrophytes. J Infection & Chemotherapy 2006;12:210-6. http://dx.doi.org/10.1007/s10156-006-0449-8

Janicsak G, Veres K, Kakasy AZ, Mathe I. Study of the oleanolic and ursolic acid contents of some species of the Lamiaceae. Biochem Syst Ecol 2006;34:392-6. http://dx.doi.org/10.1016/j.bse.2005.12.004

Jänicke C, Grünwald J, Brendler T. In: Handbuch Phytotherapie. Stuttgart: Wissenschaftliche Verlagsgesellschaft mbH, 2003:428.

Katalinic V, Milos M, Kulisic T, Jukic M. Screening of 70 medicinal plant extracts for anti-oxidant capacity and total phenols. Food Chem 2006;94:550-7. http://dx.doi.org/10.1016/j.foodchem.2004.12.004

Komes D, Belščak-Cvitanović A, Horžić D, Rusak G, Likić S, Berendika M. Phenolic composition and antioxidant properties of some tradition-ally used medicinal plants affected by the extraction time and hydrolysis. Phytochem Anal 2011;22:172-80. http://dx.doi.org/10.1002/pca. 1264

Kulisic T, Dragovic-Uzelac V, Milos M. Antioxidant activity of aqueous tea infus-ions prepared from oregano, thyme and wild thyme. Food Technol Biotechnol 2006;44:485-92.

Kulisic T, Krisko A, Dragovic-Uzelac V, Milos M, Pifat G. The effects of essential oils and aqueous tea infusions of oregano (Origanum vulgare L. spp. hirtum), thyme (Thymus vulgaris L.) and wild thyme (Thymus serpyllum L.) on the copper-induced oxidation of human low-density lipoproteins. Int J Food Sci Nutr 2007;58:87-93. http://dx.doi.org/10.1080/09637480601108307

Loziene K Vaiciuniene J, Venskutonis PR. Chemical composition of the essential oil of creeping thyme (Thymus serpyllum s.l.) growing wild in Lithuania. Planta Med 1998;64:772-3. http://dx.doi.org/10.1055/s-2006-957582

Mata AT, Proenca C, Ferreira AR, Serralheiro MLM, Nogueira JMF, Araujo MEM. Antioxidant and antiacetylcholinesterase activities of five plants used as Portuguese food spices. Food Chem 2007;103:778-86. http://dx.doi.org/10.1016/j.foodchem.2006.09.017

Mazulin GV, Mazulin OV, Koloshina NO. A new approach to the study of amino acids in the plants Thymus, Origanum and Majorana. Farmatsevtichnii Zhurnal (Kiev) 2002;(1):65-7.

Miron TL, Plaza M, Bahrim G, Ibánez E, Herrero M. Chemical comp-osition of bioactive pressurized extracts of Romanian aromatic plants. J Chromatogr A 2011;1218:4918-27. http://dx.doi.org/10.1016/j.chroma.2010.11.055

Mockute D, Bernotiene G. 1,8-Cineole – Caryophyllene oxide chemotype of essential oil of Thymus serpyllum L. growing in Vilnius (Lithuania). J Essent Oil Res 2004;16:236-8. http://dx.doi.org/10.1080/10412905.2004.9698708

Nedorostova L, Kloucek P, Urbanova K et al. Antibacterial effect of essential oil vapours against different strains of Staphylococcus aureus, including MRSA. Flavour Frag J 2011;26:403-7. http://dx.doi.org/10.1002/ffj.2068

Oussalah M, Caillet S, Saucier L, Lacroix M. Inhibitory effects of selected plant essential oils on the growth of four pathogenic bacteria:

4

SERPYLLI HERBA

E. coli O157:H7, Salmonella typhimurium, Staphylococcus aureus and Listeria monocytogenes. Food Control 2007;18:414-20. http://dx.doi.org/10.1016/j.foodcont.2005.11.009

Paaver U, Orav A, Arak E, Maeorg U, Raal A. Phytochemical analysis of the essential oil of Thymus serpyllum L. growing wild in Estonia. Nat Prod Res 2008;22:108-15.http://dx.doi.org/10.1080/14786410601035118

Raal A, Paaver U, Arak E, Orav A. Content and composition of the essential oil of Thymus serpyllum L. growing wild in Estonia. Medicina (Kaunas, Lithuania) 2004;40:795-800. Rahman MU, Gul S. Mycotoxic effects of Thymus serpyllum oil on the asexual reproduction of Aspergillus species. J Essent Oil Res 2003;15:168-71. http://dx.doi.org/10.1080/10412905.2003.9712104

Rasooli I, Mirmostafa SA. Antibacterial properties of Thymus pubescens and Thymus serpyllum essential oils. Fitoterapia 2002;73:244-50. http://dx.doi.org/10.1016/S0367-326X(02)00064-3

Sagdic O. Sensitivity of four pathogenic bacteria to Turkish thyme and oregano hydrosols. Lebensm-Wiss u -Technol 2003;36:467-73.

Schilcher H, Kammerer S, Wegener T. In: Leitfaden Phytotherapie, 4rd ed. München: Urban & Fischer, 2010:261-2.

Sefidkon F, Dabiri M, Mirmostafa SA. The composition of Thymus serpyllum L. oil. J Essent Oil Res 2004;16:184-5. http://dx.doi.org/10.1080/10412905.2004.9698691

Sourgens H, Winterhoff H, Gumbinger HG, Kemper FH. Antihormonal effects of plant extracts. Planta med 1982;45:78-86. http://dx.doi.

org/10.1055/s-2007-971251

Stahl-Biskup E. Thymus. In: Blaschek W, Ebel S, Hackenthal E, Holzgrabe U, Keller K, Reichling J, Schulz V, editors. Hager Enzyklopädie der Arzneistoffe und Drogen. 6th ed. Vol. 15. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 2007:729-759.

Stahl-Biskup E, Hiller K, Loew D. Serpylli herba. In: Wichtl M, editor. Teedrogen und Phytopharmaka. 5th ed. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 2009:624-6.

Teissedre PL, Waterhouse AL. Inhibition of oxidation of human low-density lipoproteins by phenolic substances in different essential oils varieties. J Agric Food Chem 2000;48:3801-5. http://dx.doi.org/10.1021/jf990921x

Topal U, Sasaki M, Goto M, Otles S. Chemical compositions and antioxidant properties of essential oils from nine species of Turkish plants obtained by supercritical carbon dioxide extraction and steam distillation. Int J Food Sci Nutrition 2008; 59:619-34. http://dx.doi.org/10.1080/09637480701553816

Washington JS, Saxena VK.Scutellarein-7-O-a-D-glucopyranosyl(1→4)-O-a-L-rhamnopyranoside from the stems of Thymus serpyllum. J Indian Chem Soc 1986;63:226-7.

Wild thyme – Serpylli herba. European Pharmacopoeia, Council of Europe.

Ziakova A, Brandsteterova E. Validation of HPLC determination of phenolic acids present in some Lamiaceae family plants. J Liqu Chromatogr & Rel Technol 2003;26:443-53. http://dx.doi.org/10.1081/JLC-120017181

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 978-1-901964-16-5

onlineseries