Sage Leaf, Three-Lobed 2014

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Salviae trilobae folium Sage Leaf, Three-lobed 2014

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SALVIAE TRILOBAE FOLIUM Sage Leaf, Three-lobed

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 SERIES ISBN 978-1-901964-14-1

Salviae trilobae folium - Sage Leaf, Three-lobed

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

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

Edited by Simon Mills and Roberta Hutchins Cover photograph by Professor Salvador Cañigueral Folcara (Salvia fruticosa) Cover and text design by Martin Willoughby Typeset in Optima by Roberta Hutchins

Plant illustrated on the cover: Salvia fruticosa FOREWORD

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

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

Liselotte Krenn Chair of the Board of ESCOP

PREFACE

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

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

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

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

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

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

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

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

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

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

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

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

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

LTB 4 leukotriene B4 M molar (concentration) MAO monoamine oxidase MBC minimum bactericidal concentration MDA malondialdehyde MFC minimum fungicidal concentration MIC minimum inhibitory concentration Mr molecular MRS Menopause Rating Scale MRSA methicillin-resistant Staphylococcus aureus MTD maximum tolerated dose MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MW molecular weight NBT nitro blue tetrazolium NF-kB necrosis factor kappa-B NO nitric oxide NOS nitric oxide synthase n.s. not significant NSAID non-steroidal anti-inflammatory drug ovx ovariectomy or ovariectomized ORAC oxygen radical absorbance capacity PA pyrrolizidine alkaloid PAF platelet activating factor PCR polymerase chain reaction PEG polyethylene glycol PGE prostaglandin E PHA phythaemagglutinin p.o. per os POMS profile of mood states PVPP polyvinylpolypyrrolidone RANKL receptor activator of nuclear factor kappa-B ligand RNA ribonucleic acid RT-PCR reverse transcription polymerase chain reaction s.c. subcutaneous SCI spinal cord injury SERM selective oestrogen receptor modulator SGOT or GOT serum glutamate oxalacetate transaminase (= ASAT or AST) SGPT or GPT serum glutamate pyruvate transaminase (= ALAT or ALT) SHBG sex hormone binding globulin SOD superoxide dismutase SSRI selective serotonin reuptake inhibitor STAI state-trait anxiety inventory t1/2 elimination half-life TBARS thiobarbituric acid reactive substances TGF-b transforming growth factor-beta TNF tumour necrosis factor TPA 12-O-tetradecanoylphorbol-13-acetate URT upper respiratory tract URTI upper respiratory tract infection UTI urinary tract infection VAS visual analogue scale VLDL very low density lipoprotein SALVIAE TRILOBAE FOLIUM 2014 Sage Leaf, Three-lobed

DEFINITION

Three-lobed sage leaf consists of the whole or cut, dried leaves of Salvia fruticosa Mill. [syn. S. triloba L.fil.]. It contains not less than 18 ml/kg of essential oil in the whole drug, and not less than 12 ml/kg of essential oil in the cut drug, both calculated with reference to the dried material.

The material complies with the monograph of the European Pharmacopoeia [Sage leaf, three-lobed].

CONSTITUENTS

1.5-3.5% of essential oil consisting mainly of terpenes with cineole (40-67%), a- and b-thujone (2-6%), camphor (1-24%), camphene (0.3-5%), borneol (1%), b-caryophyllene, a- and b-pinene, bornyl acetate, limonene, linalyl acetate and viridoflorol [Länger 1996; Stahl-Biskup 2008; Pitarokili 2003; Brand 2008; Papageorgiou 2008].

Other characteristic constituents include phenolic acids (1-4%) such as 3,4-dihydroxybenzoic, rosmarinic and caffeic acids [Brand 2008; Papageorgiou 2008]; flavonoids such as salvigenin, glucosides and glucuronides of apigenin, chrysoeriol, hispidulin, luteolin, 6-methoxyluteolin and jaceosidin [Abdalla 1983; Brand 2008]; diterpenes such as carnosol and triterpenes such as ursolic and oleanolic acids (< 8%) [Stahl-Biskup 2008; Brand 2008].

CLINICAL PARTICULARS

Therapeutic indications

Inflammations and infections of the mouth and throat such as stomatitis, gingivitis and pharyngitis [Stahl-Biskup 2008; Benedum 2006]; digestive disorders such as dyspepsia [Benedum 2006].

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

Posology and method of administration

Dosage

Topical use Adult daily dose: An infusion of 3 g of dried drug in 125 ml of water as a mouthwash or gargle [Stahl-Biskup 2008; Böhme 2010].

Oral use Adult dose: 1-1.5 g of dried drug as an infusion in 150 ml of water, once or several times daily [Stahl-Biskup 2008; Böhme 2010].

Method of administration For oral administration.

Duration of administration No restriction. If symptoms persist or worsen, medical advice should be sought.

Contraindications None known.

Special warnings and special precautions for use None required.

Interaction with other medicaments and other forms of interaction None reported [Williamson 2009].

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Pregnancy and lactation between free radical scavenging activity and concentrations No data available. In accordance with normal medical practice, of oxygenated sesqui- and diterpenes [Papageorgiou 2008]. three-lobed sage leaf should not be used during pregnancy and lactation without medical advice. Acetyl- and butyrylcholinesterase inhibitory activity A dichloromethane dry extract (13.4:1) inhibited acetylcholin- Effects on ability to drive and use machines esterase activity by 27% at 25 µg/ml and 51% at 100 µg/ml None known. [Senol 2010].

Undesirable effects In another study, a 75%-hydroethanolic dry extract (1 g/60 ml; None reported. 1% total phenols) inhibited acetylcholinesterase activity with

an IC50 of 0.71 mg/ml [Orhan 2009]. Overdose No toxic effects reported. An ethyl acetate dry extract (1 g/20 ml) slightly inhibited acetylcholinesterase activity, by 28% at 1.0 mg/ml and 11% at 0.25 mg/ml, while a dry aqueous extract (1 g/20 ml) was inactive PHARMACOLOGICAL PROPERTIES [Salah 2005].

Data relating to the essential oil and lipophilic extracts are In an assessment of the inhibition of human cholinesterases included below for completeness, although their components by three-lobed sage leaf essential oil, contradictory results are present to only a minor extent in aqueous preparations such were obtained in the case of butyrylcholinesterase, whereas as those recommended under Dosage. IC50 values of 0.04-0.06 mg/ml were reported for inhibition of acetylcholinesterase. The most pronounced acetylcholin- Pharmacodynamic properties esterase inhibition by individual components of the oil was

observed for 1,8-cineole (IC50: 0.06 mg/ml), b-caryophyllene In vitro experiments (IC50: 0.03 mg/ml), a-pinene (IC50: 0.1 mg/ml) and b-pinene (IC50: 0.2 mg/ml); a-thujone and camphor at 0.5 mg/ml inhibited Antioxidant and radical-scavenging activity the enzyme by 37% and 13% respectively. No or only low An aqueous extract (0.25 g/10 ml, 1.4% polyphenols) showed butyrylcholinesterase inhibition was observed with all tested antioxidant activity of 53.5 µmol trolox equivalents per g of dry compounds [Savelev 2004]. plant material and an 80% methanolic extract (0.25 g/10 ml, 2.4% polyphenols) 175 µmol trolox equivalents per g of dry plant Cytotoxic activity material in the 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic An aqueous dry extract (2 g/150 ml, 71.5 µg/ml rosmarinic acid, acid) diammonium salt (ABTS) radical cation decolourisation 28.6 µg/ml 6-hydroxyluteolin-7-glucoside, 29.4 µg/ml other test [Tawaha 2007]. phenolic compounds, lyophilised) at 50 µg/ml significantly inhibited cell proliferation in the human colon cancer cell line In the deoxyribose assay an infusion (1 g/25 ml) exhibited HCT15 (from 26.2% in the control to 4.7%, p ≤ 0.001). No antioxidant activity in the presence or absence of digestive significant effect was observed in CO115 cells; rosmarinic acid enzymes and bile salts. The amount of total dialysable iron at 10-100 µg/ml was inactive in both cell lines. The extract and was increased compared to the Fe(III) control under simulated rosmarinic acid induced apoptosis in a concentration-dependent gastric conditions [Matsingou 2000]. manner. In HCT15 cells the extract increased the proportion of apoptotic cells from 0.4% in the control to 6.6% at 50 µg/ An acidic aqueous methanolic dry extract (30% V/V, 3.4-5.2:1) ml, rosmarinic acid increased numbers to 2.5% (p ≤ 0.001). In had an IC50 value of 0.021-0.046 g/litre in the DPPH assay and CO115 cells, the proportion of apoptotic cells increased from was also active in the ABTS cation decolourisation assay. The 1.8% in the control to 6.8% after treatment with the extract free radical scavenging activity in both assays was correlated and to 3.6% by rosmarinic acid at the same concentrations. with the total phenolic content (6.4-14.4%) determined by a No cleaved caspase-9 and caspase-3 were observed 24 hours colorimetric method [Papageorgiou 2008]. after treatment.

An ethanolic dry extract (1.6:1) and an acetone dry extract Both the extract and rosmarinic acid inhibited the mitogen- (4.2:1) reduced DPPH by 98.5% and 97.6% respectively. activated protein kinase / extracellular signal-regulated kinase Antioxidant activity of these extracts was also observed in the (MAPK/ERK) pathway in HCT15 cells by 50% (p ≤ 0.001) and phosphatidylcholine liposome assay. The protective effect of the had no effects in CO115 cells. No inhibition on Akt (a serine/ extracts against oxidation of sunflower oil under accelerated threonine kinase) phosphorylation was observed. Both pathways conditions (120°C) was evaluated in a Rancimat apparatus using are commonly altered in colorectal carcinoma, and lead to 0.02% (w/w) of extract in bulk oil; the ethanolic and acetone increased proliferation and inhibition of apoptosis [Xavier 2009]. extracts protected the oil by factors of 1.7 and 2.2 compared to a blank control [Exarchou 2002]. In another study using the Three-lobed sage leaf essential oil and its main components Rancimat method a methanolic dry extract (3.8:1) protected exhibited cytotoxic activity against African green monkey sunflower oil from oxidation by a factor of 1.08 at 0.02% and kidney (Vero) cells. The essential oil caused complete cell death 3.03 at 1% [Bozan 2002]. within 24 hours of exposure at a dilution of 1/500 (V/V) and within 48 hours at 1/1000. At 1/2000 a transient decrease in Free radical scavenging activity of the essential oil of three-lobed cell viability was initially observed, but this had been overcome sage leaf harvested during different seasons, and some of its after 48 hours. Among the main components at dilutions of components, was determined in the DPPH assay. IC50 values 1/1000 (i.e. 0.10%), thujone was the most cytotoxic causing of the essential oils were between 2.4 and 5.2 g/litre, while 95% reduction in viability, and camphor showed moderate that of b-caryophyllene was 18.6 g/litre, and 1,8-cineole and activity (40% reduction), whereas 1,8-cineole was less active a-pinene were inactive; IC50 values of the positive controls, (5% reduction) [Sivropoulou 1997]. ascorbic acid and butylated hydroxytoluene, were 0.06 g/litre and 0.08 g/litre respectively. A positive correlation was found In another evaluation of cytotoxic activity, the IC50 values for

2 SALVIAE TRILOBAE FOLIUM

an undefined dichloromethane-methanol dry extract were main components was evaluated against HSV-1, an ubiquitous 180 µg/ml in mouse fibrosarcoma cells, 250 µg/ml in a human pathogen. At a concentration of 0.2% the essential benign human breast carcinoma cell line and 290 µg/ml in oil inactivated 80% of infectious virus within 30 minutes a metastatic human breast carcinoma cell line [Kaileh 2007]. and thujone at 0.1% inactivated 95%, whereas 1,8-cineole and camphor at 0.1% inactivated 35% and 0% respectively Spasmolytic activity [Sivropoulou 1997]. A decoction and an infusion from three-lobed sage leaf, and corresponding fractions obtained by partitioning these between Other effects benzene and water, as well as a fluid extract (1:2, 70% ethanol), Pretreatment of murine fibrosarcoma cells with a dichloro- had varying effects on the tone and phasic contractile activity methane-methanol dry extract at 62.5 µg/ml revealed a weak of isolated segments from guinea pig ileum. The decoction, inhibitory effect on the IL-6 promoter and the recombinant and the aqueous fraction of the infusion, caused contraction NFkB promoter construct [Kaileh 2007]. of the smooth muscle preparation without affecting phasic contractions, the aqueous fraction of the decoction decreased the An ethanolic extract showed moderate binding affinity at the tone and caused relaxation, while the fluid extract potentiated GABAA-benzodiazepine receptor site [Salah 2005]. phasic activity but did not affect the tone. The infusion caused contraction of the intestinal segments and intensified phasic In vivo experiments contractions. All the extracts inhibited contractions induced by acetylcholine (10-7 M), barium chloride (10-4 M), histamine Antidiabetic activity (10-5 M) and serotonin (10-5 M) by 20-90% [Todorov 1984]. The hypoglycaemic activity of a 10% infusion was evaluated in normoglycaemic rabbits and rabbits with alloxan-induced Antimicrobial and antiviral activity of the essential oil diabetes. A single oral dose of 2.5 ml/kg b.w. (corresponding The essential oil of three-lobed sage leaf exhibited slight to 0.25 g/kg of dried leaf) had no acute effect on blood glucose inhibitory activity against growth of Fusarium moniliforme, levels in either group. Repeated oral administration at 2.5 ml/ Rhizoctonia solani, Phytophthora capsici [Müller-Riebau 1997], kg/day over a period of 7 days produced a significant reduction Botrytis cinerea, Fusarium solani var. coeruleum [Daferera of blood glucose levels in hyperglycaemic rabbits but had no 2003], Trichophyton rubrum and Trichosporon beigelii [Adam effect in normoglycaemic animals. Compared to hyperglycaemic 1998]. In tests of the antifungal activity of the essential oil, control animals, blood glucose levels in treated hyperglycaemic 1,8-cineole and camphor against 13 other fungal species (type rabbits were 20.2% lower 60 minutes after the last administ- cultures and isolates), such as Aspergillus sp., Penicillium sp., ration of infusion (p<0.05), 24.9% lower after 90 minutes Phomopsis, Alternaria, Microsporum and Epidermophyton (p<0.01) and 25.7% lower after 120 minutes (p<0.01). sp., minimium inhibitory concentrations (MIC) and minimum After oral glucose loading at 1 g/kg, administration of a single fungicidal concentrations (MFC) respectively were found to be: oral dose of the infusion at 0.25 ml/kg significantly reduced 5.0-15.0 µl/ml and 5.0-20.0 µl/ml for the essential oil, 4.0-9.0 blood glucose levels in both normo- and hyperglycaemic µl/ml and 5.0-15.0 µl/ml for 1,8-cineole, and 3.0-5.0 µl/ml and animals, the effect being more evident in the latter. In treated 3.0-10.0 µl/ml for camphor [Sokovic 2002]. hyperglycaemic rabbits the increase in blood glucose was only 19.2% (p<0.05), 7.8% (p<0.01) and 7.1% (p<0.01) after 60, 90 Three-lobed sage leaf essential oil exhibited low activity against and 120 minutes, compared to 78.2%, 73.1% and 55.5% in Erwinia herbicola (MIC: 2 mg/ml) and was inactive against hyperglycaemic control animals receiving water only. Pseudomonas syringae, whereas leaf surface phenolics extracted A single oral administration of the infusion had no significant with dichloromethane inhibited both bacterial strains. Camphor, effects on plasma insulin levels in any group of rabbits following with an MIC and MBC (minimum bactericidal concentration) oral glucose loading, nor on blood glucose levels in normo- of 2 mg/ml, was more effective than 1,8-cineole (both values glycaemic animals after intravenous glucose loading. The ≥ 2 mg/ml) [Karamanoli 2000]. results suggested that three-lobed sage leaf does not influence glucose metabolism; the hypoglycaemic activity might be due Essential oil of three-lobed sage leaf cultivated in Brazil inhibited to inhibition of intestinal absorption of glucose [Perfumi 1991]. the growth of Escherichia coli, Proteus mirabilis, Salmonella typhimurium, Aeromonas sp., Klebsiella oxytoca, Citrobacter In another study, the effect of an infusion (5:1) in streptozotocin sp., Serratia marcescens, Bacillus sp., Pseudomonas sp. and (STZ)-induced diabetic rats was investigated. One week after Staphylococcus sp. The MICs (0.1 to 10 mg/ml) and MBCs (0.1 i.p. injection of a single dose of 45 mg/kg b.w. STZ, the glucose to >10 mg/ml) indicated that the essential oil of Salvia triloba level was 311 ± 25 mg/dL in diabetic rats (n=12) compared was generally more effective than that of S. officinalis against to 119 ± 4 mg/dL in healthy rats (n=12). In water drinking these bacterial strains. The activity was more pronounced against STZ-diabetic animals (n=6), plasma glucose levels continued Gram-negative bacteria [Delamare 2007]. to increase throughout the 14-day experimental period but remained stable in STZ-diabetic animals (n=6) drinking the In the disk diffusion assay the essential oil, 1,8-cineole and infusion (0.28% w/v, ad libidum) (p<0.01 on day 14). In non- thujone showed moderate activity against a selection of eight diabetic animals glucose levels were not influenced by drinking bacteria, Salmonella typhimurium being the most resistant the infusion (n=6). The administration of the infusion did not and Pseudomonas aeruginosa being the most sensitive, while significantly change the liver glycogen content or induce liver camphor was almost inactive. The essential oil was bactericidal toxicity or increase the regeneration of b-cell mass. The increase against Staphylococcus aureus at 1/4000 dilution, while dilutions in intestinal Na+/glucose cotransporter-1 (SGLT1), localized up to 1/10000 caused a considerable decrease in bacterial to the enterocyte brush-border membrane, was significantly growth rates [Sivropoulou 1997]. abrogated by treatment with the infusion (30% compared to untreated animals, p<0.01) without changes in total cellular Hydrosols of three-lobed sage leaf (the aqueous phases obtained transporter protein levels. Comparable results were obtained by 1 hour of steam distillation) were inactive against fifteen in rats with high carbohydrate diet-induced diabetes (n=6) bacterial strains such as E. coli or S. aureus [Sagdic 2003]. drinking the infusion (32%, p<0.05) when compared to a water drinking group (n=6). Rosmarinic acid (0.58 mg/mL) in the The virucidal activity of three-lobed sage leaf essential oil and its drinking water inhibited SGTL1 to 50% (p<0.01). No effects

3 SALVIAE TRILOBAE FOLIUM

were observed on glucose transporter 2, Na+/K+-ATPase or 400 mg/kg also had no effect on the number of pregnancies glucagon-like peptide-1 levels by the treatment [Azevedo 2011]. or implantations; however, the number of viable fetuses decreased (p<0.005) and the number of resorptions increased Antihypertensive activity (p<0.005). A dry decoction, administered intraperitoneally to nembutal- In contrast, intragastric administration of the aqueous dry anaesthetized, spontaneously hypertensive rats as a single dose extract at 800 mg/kg or the ethanolic dry extract at 400 mg/kg of 50 mg/kg b.w., reduced blood pressure by 31% compared to adult female rats for 30 consecutive days had no effect on to saline controls after 120 minutes [Todorov 1984]. the occurrence of pregnancy, but the number of implantations (p<0.05) and viable fetuses (p<0.01) decreased and the Anti-inflammatory activity number of resorptions increased (p<0.01 for aqueous dry Three-lobed sage leaf was successively extracted with chloroform extract, p<0.005 for ethanolic dry extract). Ingestion of the (dry yield: 6.75%), ethanol (4%), butanol (1%) and water (> same extracts at the same dosage levels for 30 consecutive 20%, viscous extract). Oral administration of the chloroform days by adult male rats had no effect on the final proportion fraction at 25 mg/kg b.w. significantly inhibited carrageenan- of pregnant females impregnated by these males; however induced rat paw oedema by 17% (p<0.01) compared to 47% the number of implantations and viable fetuses were reduced by diclofenac at 10 mg/kg as positive control (p<0.01); the other in such females (p<0.01 for aqueous dry extract, p<0.001 fractions were less effective. In the cotton pellet granuloma assay for ethanolic dry extract), whereas the number of resorptions the chloroform fraction inhibited chronic mean gain in pellet increased (p<0.005). Prenatal exposure of male and female weight by 18 mg compared to 29 mg by diclofenac (p<0.01) rat offspring to the ethanolic dry extract at 400 mg/kg had no [El-Sayed 2006]. effect on the timing of testicular descent or vaginal opening [Al-Hamood 1998]. Central effects A dry decoction and the dry benzene fraction from an infusion, Ulcerogenicity administered subcutaneously to mice at 100 mg/kg b.w. 10 Three-lobed sage leaf was successively extracted with chloroform minutes before administration of hexobarbital (80 mg/kg b.w.), (dry yield: 6.75%), ethanol (4%), butanol (1%) and water (> 20%, delayed the onset of sleep [Todorov 1984]. viscous extract), and each fraction was orally administered to rats at 25 mg/kg b.w. The ulcer indices were 0 for the ethanol fraction, In another study, a 75%-hydroethanolic dry extract (1g/60 ml; 1.2 for the water fraction (p<0.01) and 1.3 for the chloroform total phenolic content: 10.9 mg/g, expressed as gallic acid fraction (p<0.01), compared to 12.3 for acetylsalicylic acid at equivalent) exerted dose-dependent anti-amnesic activity in 1 mg/kg (p<0.01) [El-Sayed 2006]. mice. A passive avoidance apparatus (step-through type) was used to investigate long-term memory; amnesia was induced by Toxicity of thujone scopolamine (1 mg/kg, given intraperitoneally 30 minutes after Although a-thujone is present in the essential oil of three-lobed oral administration of the extract) and donezepil was used as a sage leaf, the proportion is far less than in essential oils of Salvia positive control. The extract had a relative memory-enhancing officinalis or Artemisia absinthium; aqueous preparations are effect of 57.1 and 71.4% at 200 and 400 mg/kg b.w. respectively unlikely to contain toxic amounts of a-thujone. (control group 0%, donezepil group set to 100%) [Orhan 2009]. Clinical safety data Clinical studies No data available. No clinical studies have been published on mono-preparations of three-lobed sage leaf. REFERENCES

Pharmacokinetic properties Abdalla MF, Saleh NAM, Gabr S, Abu-Eyta AM, El-Said H. Flavone No data available. glycosides of Salvia triloba. Phytochemistry 1983;22:1057-60. http:// dx.doi.org/10.1016/0031-9422(83)80044-2 Preclinical safety data Adam K, Sivropoulou A, Kokkini S, Lanaras T, Arsenakis M. Antifungal Mutagenicity activities of Origanum vulgare subsp. hirsutum, Mentha spicata, An aqueous dry extract (1 g/100 ml, extracted at 50°C) at 40 Lavandula angustifolia and Salvia fruticosa essential oils against human and 80 µg per plate showed no mutagenic potential in the Ames pathogenic fungi. J Agric Food Chem 1998;46:1739-45.http://dx.doi. test using Salmonella typhimurium strains TA98 and TA100 org/10.1021/jf9708296 with and without metabolic activation. In the alkaline single cell gel electrophoresis (COMET) assay in human lymphocytes Al-Hamood MH, Elbetieha A, Alkofahi A, Bataineh H. Reproductive treatment with 40 µg of the aqueous dry extract produced a toxicity potentials of Salvia fruticosa (Labiatae) in rats. J Ethnopharmacol significant increase in COMET tail moments when compared 1998;61:67-74. Erratum: ibid. 1998;63:265. to the positive control, 4 mM hydrogen peroxide (22.0 vs 13.2, Azevedo MF, Lima CF, Fernandes-Ferreira M, Almeida MJ, Wilson JM, p<0.01) [Basaran 1996]. Pereira-Wilson C. Rosmarinic acid, major phenolic constituent of Greek sage herbal tea, modulates rat intestinal SGTL1 levels with effects on Essential oil of three-lobed sage leaf at concentrations of 250- blood glucose. Mol Nutr Food Res 2011;55:S15-S25. http://dx.doi. 2000 ppm did not exhibit any mutagenic activity in the Ames org/10.1002/mnfr.201000472 test using S. typhimurium strains TA97, TA98, TA100 and TA102 in [Adam 1998]. Basaran AA, Yu T-W, Plewa MJ, Anderson D. An investigation of some Turkish herbal medicines in Salmonella typhimurium and in the COMET Effects on fertility Assay in human lymphocytes. Teratog Carcinog Mutagen 1996;16:125- Ingestion of an aqueous dry extract by female rats at 200, 400 38. http://dx.doi.org/10.1002/(SICI)1520-6866(1996)16:2<125::AID- and 800 mg/kg b.w. from days 1 to day 6 of pregnancy had no TCM6>3.0.CO;2-K significant effects on the number of pregnancies, implantations, viable fetuses or resorptions when compared to the control. Benedum J, Loew D, Schilcher H. SALVIAE TRILOBAE FOLIUM (Greek Intragastric administration of a 95%-ethanolic dry extract at sage leaves). In: Medicinal Plants in Traditional Medicine, 4th ed. Bonn:

4 SALVIAE TRILOBAE FOLIUM

Kooperation Phytopharmaka, 2006:322. Papageorgiou V, Gardeli C, Mallouchos A, Papaioannou M, Komaitis M. Variation of the chemical profile and antioxidant behaviour of Böhme H (founder), Bracher F, Heisig P, Langguth P, Mutschler E, Rücker Rosmarinus officinalis L. and Salvia fruticosa Miller grown in Greece. G, Scriba G, Stahl-Biskup E, Troschütz R (editors). Dreilappiger Salbei. In: J Agric Food Chem 2008;56:7254-64. http://dx.doi.org/10.1021/ Kommentar zum europäischen Arzneibuch. Stuttgart: Wissenschaftliche jf800802t Verlagsgesellschaft, 2010. Perfumi M, Arnold N, Tacconi R. Hypoglycemic activity of Salvia Bozan B, Ozturk N, Kosar M, Tunalier Z, Baser KHC. Antioxidant and fruticosa Mill. from Cyprus. J Ethnopharmacol 1991;34:135-40. http:// free radical scavenging activities of eight Salvia species. Chem Nat dx.doi.org/10.1016/0378-8741(91)90030-H Prod 2002;38:198-200. Pitarokili D, Tzakou O, Loukis A, Harvala C. Volatile metabolites from Brand N. SALVIA. In: Blaschek W, Ebel S, Hackenthal E, Holzgrabe Salvia fruticosa as antifungal agents in soilborne pathogens. J Agric U, Keller K, Reichling J, Schulz V, editors. Hagers Enzyklopädie der Food Chem 2003;51:3294-301. http://dx.doi.org/10.1021/jf0211534 Arzneistoffe und Drogen, 6th ed. Volume 14. Berlin-Heidelberg-New York-London: Springer-Verlag, 2007:125-70. Sagdic O, Özcan M. Antibacterial activity of Turkish spice hydrosols. Food Control 2003;14:141-3. http://dx.doi.org/10.1016/S0956- Daferera DJ, Ziogas BN, Polissiou MG. The effectiveness of plant essential 7135(02)00057-9 oils on the growth of Botrytis cinerea, Fusarium sp. and Clavibacter michiganensis subsp. michiganensis. Crop Protection 2003;22:39-44. Sage leaf, three-lobed - Salviae trilobae folium. European Pharmacopoeia, http://dx.doi.org/10.1016/S0261-2194(02)00095-9 Council of Europe.

Delamare APL, Moschen-Pistorello IT, Artico L, Atti-Serafini L, Salah SM, Jäger AK. Screening of traditionally used Lebanese herbs for Echeverrigaray S. Antibacterial activity of the essential oil of Salvia neurological activities. J Ethnopharmacol 2005;97:145-9. http://dx.doi. officinalis L. and Salvia triloba L. cultivated in South Brazil. Food Chem org/10.1016/j.jep.2004.10.023 2007;100:603-8. http://dx.doi.org/10.1016/j.foodchem.2005.09.078 Savelev SU, Okello EJ, Perry EK. Butyryl- and acetylcholinesterase Dreilappiger Salbei - Salvia trilobae folium. Kommentar zum inhibitory activities in essential oils of Salvia species and their Europäischen Arzneibuch, Stuttgart : Deutsche Verlagsgesellschaft, constituents. Phytother Res 2004;18:315-24. http://dx.doi.org/10.1002/ Eschborn: Govi-Verlag. 23. Lfg. 2006 ptr.1451

El-Sayed NH, El-Eraky W, Ibrahim MT, Mabry TJ. Antiinflammatory and Senol FS, Orhan I, Celep F, Kahraman A, Dogan M, Yilmaz G, Sener B. ulcerogenic activities of Salvia triloba extracts. Fitoterapia 2006;77:333- Survey of 55 Turkish Salvia taxa for their acetylcholinesterase inhibitory 5. http://dx.doi.org/10.1016/j.fitote.2006.04.002 and antioxidant acitivities. Food Chem 2010;120:34-43. http://dx.doi. org/10.1016/j.foodchem.2009.09.066 Exarchou V, Nenadis N, Tsimidou M, Gerothanassis IP, Troganis A, Boskou D. Antioxidant and phenolic composition of extracts from Sivropoulou A, Nikolaou C, Papanikolaou E, Kokkini S, Lanaras T, Greek oregano, Greek sage and summer savory. J Agric Food Chem Arsenakis M. Antimicrobial, cytotoxic and antiviral activities of Salvia 2002;50:5294-9. http://dx.doi.org/10.1021/jf020408a fruticosa essential oil. J Agric Food Chem 1997;45:3197-201. http:// dx.doi.org/10.1021/jf970031m Kaileh M, Berghe WV, Boone E, Essawi T, Haegeman G. Screening of indigenous Palestinian medicinal plants for potential anti- Sokovic M, Tzakou O, Pitarokili D, Couladis M. Antifungal activities of inflammatory and cytotoxic activity. J Ethnopharmacol 2007;113:510- selected aromatic plants growing wild in Greece. Nahrung 2002;46:317- 6. http://dx.doi.org/10.1016/j.jep.2007.07.008 20. http://dx.doi.org/10.1002/1521-3803(20020901)46:5<317::AID- FOOD317>3.0.CO;2-B Karamanoli K, Vokou D, Menkissoglu U, Constantinidou HI. Bacterial colonization of phyllosphere of Mediterranean aromatic plants. J Stahl-Biskup E, Wichtl M, Loew D. Salviae trilobae folium. Teedrogen Chem Ecol 2000;26:2035-48. http://dx.doi.org/10.1023/A:100555601 und Phytopharmaka - Ein Handbuch für die Praxis auf wissenschaftlicher 3314 Grundlage, 5th ed. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 2008:596-7. Länger R, Mechtler C, Jurenitsch J. Composition of the essential oils of commercial samples of Salvia officinalis L. and S. fruticosa Miller: Tawaha K, Alali FQ, Gharaibeh M, Mohammad M, El-Elimat T. a comparison of oils obtained by extraction and steam distillation. Antioxidant activity and total phenolic content of selected Jordanian Phytochem Anal 1996;7:289-93. http://dx.doi.org/10.1002/(SICI)1099- plant species. Food Chem 2007;104:1372-8. http://dx.doi.org/10.1016/j. 1565(199611)7:6<289::AID-PCA318> 3.0.CO;2-7 foodchem.2007.01.064

Matsingou TC, Kapsokefalou M, Salifoglou A. In vitro antioxidant activity Todorov S, Philianos S, Petkov V, Harvala C, Zamfirova R, Olimpiou H. of black tea and Mediterranean herb infusions toward iron under simulated Experimental pharmacological study of three species from the genus gastrointestinal conditions. J Food Sci 2000;65:1060-5. http://dx.doi.org/ Salvia. Acta Physiol Pharmacol Bulg 1984;10:13-20. 10.1111/j.1365-2621.2000.tb09418.x Williamson E, Driver S and Baxter K. SAGE. In: Stockley’s Herbal Müller-Riebau F, Berger BM, Yegen O, Cakir C. Seasonal variation in Medicines Interactions - A guide to the interactions of herbal medicines, the chemical compositions of essential oils of selected aromatic plants dietary supplements and nutraceuticals with conventional medicines. growing wild in Turkey. J Agric Food Chem 1997;45:4821-5. http:// London-Chicago: Pharmaceutical Press, 2009:343. dx.doi.org/10.1021/jf970110y Xavier CPR, Lima CF, Fernandes-Ferreira M, Pereira-Wilson C. Salvia Orhan I, Aslan M. Appraisal of scopolamine-induced antiamnesic fruticosa, Salvia officinalis, and rosmarinic acid induce apoptosis and effect in mice and in vitro antiacetylcholinesterase and antioxidant ihibit proliferation of human colorectal cell lines: the role in MAPK/ activities of some traditionally used Lamiaceae plants. J Ethnopharmacol ERK pathway. Nutrition and Cancer 2009;61:564-571. http://dx.doi. 2009;122:327-32. http://dx.doi.org/10.1016/j.jep.2008.12.026 org/10.1080/01635580802710733

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CUM FLORE Wild Pansy Supplement 2009 VITIS VINIFERAE FOLIUM Red Vine Leaf Supplement 2009 ZINGIBERIS RHIZOMA Ginger Supplement 2009 Online Series Monographs The Scientific Foundation for Herbal Medicinal Products

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.