Leonurus – Motherwort (Leonuri cardiacae herba)
|Latin name of the genus:||Leonurus|
|Latin name of herbal substance:||Leonuri cardiacae herba|
|Botanical name of plant:||Leonurus cardiaca l.|
|English common name of herbal substance:||Motherwort|
Latin name of the genus: Leonurus
Latin name of herbal substance: Leonuri cardiacae herba
Botanical name of plant: Leonurus cardiaca L.
English common name of herbal substance: Motherwort
2.2.Information on traditional/current indications and specified substances/preparations . 15
2.3.Specified strength/posology/route of administration/duration of use for relevant
- 1. Introduction
- 2. Historical data on medicinal use
- 3. Non-Clinical Data
- 3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- 3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- 3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
- 3.4. Overall conclusions on non-clinical data
- 4. Clinical Data
- 4.1. Clinical Pharmacology
- 4.1.1. Overview of pharmacodynamic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
- 4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
- 4.2. Clinical Efficacy
- 4.2.1. Dose response studies
- 4.2.2. Clinical studies (case studies and clinical trials)
- 4.2.3. Clinical studies in special populations (e.g. elderly and children)
- 4.3. Overall conclusions on clinical pharmacology and efficacy
- 5. Clinical Safety/Pharmacovigilance
- 6. Overall conclusions
1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof
Leonuri cardiacae herba, Motherwort Ph. Eur. 6.0: Whole or cut, dried flowering parts of Leonurus cardiaca L. Content: minimum 0.2% of flavonoids, expressed as hyperoside (Ph. Eur. 01/2008:1833 corrected 6.0).
Herba Leonuri cardiacae EB6: Dried
Motherwort, Leonuri cardiacae herba (BHP 1974, 1990, 1994):
The dried aerial parts of Leonurus cardiaca L. collected when the plant is in flower. This definition is covered by the Ph. Eur.
powdered herbal substance (BHP 1994)
tincture 1:5, ethanol 70% V/V (Latvia, Mashkovskij 1972, Krylow 1993, Sokolov 1984)
tincture 1:5, ethanol 45% V/V (BHP 1974, Barnes 2007)
liquid extract 1:1, ethanol 25% V/V (Wichtl 2002, 2009, Bradley 1992, BHP 1974, Barnes 2007)
tincture 1:5, ethanol 34% V/V (Wichtl 2002, 2009)
tincture 1:5, ethanol 25% V/V (Bradley 1992)
Combinations of herbal substance(s) and/or herbal preparation(s) including a description of vitamin(s) and/or mineral(s) as ingredients of traditional combination herbal medicinal products assessed, where applicable.
Other related herbal substances used in traditional medicine:
Leonurus japonicus HOUTT.:
Leonurus japonicus HOUTT., herba
Fresh or dried above earth parts of Leonurus heterophyllus SWEET (= L. japonicus HOUTT.) (chin. yimucao) (Stöger 2009)
Dried above earth parts of Leonurus japonicus HOUTT., collected during flowering (BfArM)
Leonurus japonicus HOUTT., fructus
Dried fruits of Leonurus japonicus HOUTT. (chin.: Chong Wei Zi) (Körfers 2009)
Dried, ripe fruits of Leonurus heterophyllus SWEET (= L. japonicus HOUTT). (chin. chongweizi) (Stöger 2009)
Leonurus sibiricus L.
Leonus sibiricus L., semen( Korean: 충위자, 익모초자)
Leonuri Semen is the seed of Leonurus sibiricus L. (Korean FDA).
1.1.1. Botanical and phytochemical characteristics
The genus Leonurus L. sensu stricto (Lamiaceae) comprises 24 species, divided in 3 sections and in 5
Leonurus, ser. Leonurus comprises Leonurus cardiaca L. and Leonurus quinquelobatus GILIB. (Kartnig 2006).
The taxonomy of Leonurus is still controversial and any allocation of bibliographic information to a defined species may be questioned under this aspect.
Although L. sibiricus is mentioned in the Korean Herbal Pharmacopoeia 2002 and some authors refer expressly to L. sibiricus L., it cannot be excluded that L. japonicus HOUTT. (syn L. sibiricus auct. non L.) has been used in the studies. Doubts may come from the fact that the authors usually refer to the traditional use in TCM, without addressing the fact that L. japonicus HOUTT. is used in TCM and not L. sibiricus L.
According to Bomme (2006) commercial seed material labelled as L. sibiricus represents in reality L. japonicus HOUTT. Individual plants of L. japonicus with small flowers that were collected in Siberia were falsely named L. sibiricus L.
Synonyms of L. cardiaca L:
Leonurus villosus DESF. et SPRENG. (Wichtl 2002, 2009)
Leonurus campestris ANDRZ. (Kartnig 2006)
Leonurus canescens DUMORT (Kartnig 2006)
Leonurus trilobatus (LAM.) DULAC (Kartnig 2006)
Cardiaca vulgaris MOENCH (Penso 1983)
Cardiaca trilobata LAM. (Kartnig 2006)
Cardiaca vulgaris MOENCH (Kartnig 2006)
Synonyms of Leonurus cardiaca L. var. villosus DESF:
Leonurus quinquelobatus GILIB. (Penso 1983)
Leonurus quinquelobatus DESF. (Penso 1983)
Synonyms of Leonurus japonicus HOUTT.:
Leonurus artemisia (LOUR.) S.Y. HU (Kartnig 2006)
Leonurus heterophyllus SWEET (Kartnig 2006, Harley 2001)
Leonurus sibiricus auct. non L. (Kartnig 2006, Harley 2001)
Leonurus sibiricus var. albiflora MIQUEL (Lin 2007)
Phytochemical characteristics of L. cardiaca, herba:
Characteristic constituents are bitter tasting (Wichtl 2002, 2009) furanic diterpenens of the labdane type such as leocardin (Kartnig 2006) or leosibiricin (Knoess 1996):
The main furanic labdane diterpene is leosibiricin that occurs mostly in flowers and young, fully developed leaves
Diterpenes of the clerodane type that had been found in investigations conducted by Brieskorn (1972, 1979) were neither found in the samples analysed by Knoess 1996 nor in other investigations, e.g. Agnihotri (2008), Cai (2006), Malakov (1985), Papanov (1997a, 1997b). A literature review covering investigations until 2006 stated that no other publications on the
0.35% stachydrine in the herb (Van Eijk 1952, Barnes 2007). Samples tested by HPTLC did contain
0.0068% of leonurin
Leonurin (Lin 2007)
Approximately 1% of lavandulifolioside was isolated from L. cardiaca herb collected in Poland
The herb is reported to contain “small amounts” of essential oil (Kartnig 2006); Iridoids: ajugosid (= leonurid =
Samples from Lithuania did contain
Ali et al. (2007) isolated 25 mg of ursolic acid from 2 kg of L. cardiaca herb. Interestingly, the samples tested by Brieskorn (1952) did not contain any ursolic acid.
Herbal material cultivated in Italy and in Poland did contain 0.032 and 0.28% sterols, mainly ß- sitosterol and stigmasterol (Senatore 1991).
The presence of cardiac glycosides is controversial. Old studies (Schultz 1961a, 1961b) were not confirmed by other groups or more recent investigations (Reuter 1970). No glucosides were found (Romanowski 1960).
2.03 µg/g nickel and 0.6 µg/g chromium were found in the herb by atom absorption spectrometry. 65% of the Nickel and 51% of the chromium were extracted by tea infusion (Bloniarz 2008). A “high amount” of potassium nitrate was found (Kozlowa 1964). In herbal substance imported from Poland, 27.5 +/- 11.4 mg/kg x
Water soluble extractives (BHP 1990, 1994): not less than 15%
Tincture (1:5), ethanol 70% V/V
By a photometric method
The optimum extraction parameters for a tincture were investigated by Bernatoniene (2003, 2004). The yield of total flavonoids, calculated as quercetin was 0.0095%, 0.0193%, 0.0267%, 0.0269% and 0.0301% for ethanol 50, 60, 70, 80 and 90% V/V respectively. The dry residue increased from 2.4% (ethanol 50%), to 2.99% (ethanol 60%) to
About 14.5% of lead and cadmium that were present in the herbal substance were transferred into a tincture prepared with ethanol 70% V/V (Zitkevicius 2003).
Other parts of Leonurus cardiaca L.
A lectin from L. cardiaca seeds agglutinates red blood cells with a CAD marker in a highly specific way. The lectin is proposed as a specific reagent for the elucidation of red blood cell polyagglutinability (Bird 1979, Leger 1996).
The seeds contain 34.5% fat. 11.7% of the fatty acids are laballenic acid (18:2delta5,6 allene), 0.7% 20:1delta9c acid and 0.2% phlomic acid (Aizetmüller 1998).
Other related herbal substances used in traditional medicine:
1.Leonurus japonicus HOUTT.:
Leonurus japonicus HOUTT., herba
Stachydrine: > 0.50%, calculated as
Stachydrine hydrochloride (Stöger 2009)
The method of the Chinese Pharmacopoeia for determination of stachydrine was found “unreliable” by Bomme (2006)
L. japonicus HOUTT, herba that had been cultivated in Germany (Bomme 2003), did contain 0.5 – 1.5% (Bomme 2006),
Minimum of 0.3% of flavonoids, calculated as hyperosid (BfArM).
The above earth parts of L. japonicus are reported to contain
Diterpenes of the
Commercial samples of the herb originating from Asia complied with pharmacopoeial standards when tested for lead, cadmium, mercury and pesticides (Heuberger 2008b).
Leonurus japonicus HOUTT., fructus
Cycloleonurinin (Kinoshita 1991)
2.Leonurus sibiricus L.
The main components of the essential oil from the herb were identified by
The herb contains furanic labdane diterpenes (Savona 1982, Satoh 2003).
The occurrence of leonurin,
The seeds contain 28.5% fat. 18.1% of the fatty acids are laballenic acid
It seems that the different Leonurus species, except L. marrubiastrum L., present a similar phytochemical profile, especially when it comes to the presence of furanic diterpenes of the labdane- type. L.marrubiastrum L. is the only species where
1.2. Information about products on the market in the Member States
Crataegi liquid extract 40 ml, Passiflorae tincture 10 ml, Valerianae tincture 15 ml, Avenae liquid extract 10 ml, Melissae liquid extract 10 ml, Leonuri cardiacae tincture 15 ml; oral use; in cases of palpitations: Adults 15 drops 3 times daily, in cases of sleep disorders: Adults 15 drops 2 times daily, Children over 6 years: 6 drops 2 times daily; traditionally used to reduce nervousness in adults, particularly in the case of exaggerated awareness of heartbeat (palpitations) after any heart disease has been shown to be absent; traditionally used to reduce nervousness in adults and children, notably in cases of disorders of sleep.
Single ingredient products
150 mg Leonuri herba, powder, 160 mg dry extract from Equiseti herba
Four combinations with
0.24g Leonuri cardiacae herba, 0.24 g Plantaginis folium, 0.12 g Menthae piperitae folium, 0.12 g Visci albi stipes) / 1 filter tasak (1.2 g teamixtures); 7 years of use;
0.36g Melissae herba, 0.36 g Visci albi stipes, 0.06 g Valerianae radix/1 filter; 9 years of use; 1 filter sachet 3 times per day; For relieve cardiac complaints due to overload, exhaustion, nervousness and for relive of senile cardiovascular complaints. As adjuvant therapy of mild cases of hypertension and angina pectoris.
Single ingredient products
Comminuted herbal substance, in use for 38 years, herbal tea, oral use, infusion of 2 teaspoons comminuted herbal substance with 1 glass of boiling water, allow to infuse 20 minutes, 1/3 of glass 3 times per day, as a sedative in cases of hypersensitivity of central nervous system, treatment of heart and blood system neurosis, early stages of hypertension.
Tincture 1:5, ethanol 70% V/V, in use for 40 years, oral use, adults and adolescents:
functional heart disorders (heart neurosis, manifested as palpitations, intermission, short term stitchy or long term pressure pain in heart) if there is no organic disease, but symptoms are caused by stress, anxiety, hypersensitivity of nervous system. Also used to reduce heart symptoms (for example, palpitations) caused by hyperthyreodism or hormonal changes during menopause.
Eight combination products. Two contain vitamins and minerals; three combinations of Leonuri tinctura with Valerianae tinctura, Crataegi tinctura or fluid extract and Menthae piperitae tincture as heart function improving drops; two combinations of Leonuri herba with Valerianae radix, Lupuli flos, Mentha piperitae folium, Melissae folium as sedative; one combination of Leonuri herba with Crataegi inflorescentia, Crataegi fructus, Meliloti herba – as additional treatment of functional disorders of heart function and blood system.
According to the database of Latvian Food Centre: three food supplements containing a single ingredient; several combination products.
Single ingredient products
Comminuted herbal substance, in use for 55 years, herbal tea, oral use, 4.5 g of herbal substance 1 – 3 times per day, to make an infusion, pour
Tincture (1:5, extraction solvent ethanol 70% V/V), in use for 55 years, oral liquid,
Combination products contain
Single ingredient products
Leonuri herba, in use for 30 years, herbal tea, oral use,
1.Leonuri herba + Melissae folium + Violae herba + Crataegi inflorescentia, 22 years of use, herbal tea, oral use, 3.6 g 4 times per day, nervous heart complaints.
2.Crataegi folium cum flore + Crataegi fructus + Leonuri cardiacae herba + Meliloti herba, 6 years of use, herbal tea, oral use, 1 g
3.Lupuli strobulus + Melissae folium + Leonuri cardiacae herba + Lavandulae flos + Archangelicae radix + Rosae fructus, 19 years of use, herbal tea, oral use, 2 g 4 times per day, excessive nervous excitability.
4.Chamomillae anthodium + Melissae folium + Valerianae radix + Leonuri cardiacae herba + Crataegi inflorescentia + Lupuli strobuli, 15 years of use, herbal tea, oral use, 5 g
5.Solidaginis herba + Crataegi inflorescentia + Leonuri herba + Valerianae radix + Melissae folium + Polygoni avicularis herba + Lupuli strobuli, 15 years of use, herbal tea, oral use, 5 g
6.Extractum compositum (1:3.5) ex: Leonuri herba, Lupuli strobilo, Melissae folio, Lavandulae flore; extraction solvent – ethanol 70%(v/v), 7 years of use, oral liquid, 7.5 ml 3 times per day, increased nervous tension; difficulty in falling asleep.
7.Melissae herbae intractum + Lupuli strobuli tinctura + Chamomillae anthodii tinctura + Leonuri herbae tinctura (extraction solvent – ethanol 70%(v/v)) + Crataegi inflorescentiae tinctura + Valerianae radicis tinctura, 14 years of use, oral liquid, 2.5 ml
8.Crataegi folium cum flore + Crataegi fructus + Leonuri cardiacae herba + Meliloti herba, 16 years of use, tablet, 2 tablets
9.Valerianae radix + Lupuli strobilus + Melissae folium + Leonuri herba, 18 years of use, tablet, 2 tablets 3 times per day, temporary mild nervous tension; temporary difficulty in falling asleep.
Motherwort is included in the General sales List. Nine products that contain motherwort are reported for the UK market (Barnes 2007). No further details on these products could be retrieved. None of these is authorised or registered (see section I).
Regulatory status overview
MA: Marketing Authorisation TRAD: Traditional Use Registration
Other TRAD: Other national Traditional systems of registration Other: If known, it should be specified or otherwise add ’Not Known’
This regulatory overview is not legally binding and does not necessarily reflect the legal status of the products in the MSs concerned.
1.2. Search and assessment methodology
The term “Leonurus” has been searched on 28 December 2009 in following databases:
CC00 – CCMED copyright ZBMED
CDSR93 – Cochrane Library – CDSR copyright Cochrane
AR96 – Deutsches Ärzteblatt copyright DAEB
GA03 – gms copyright gms
GM03 – gms Meetings copyright gms
ME60 – MEDLINE copyright NLM
ED93 – ETHMED copyright IDEM 2009 HN69 – HECLINET copyright IFG 2002 CV72 – CAB Abstracts copyright CAB
CB85 – AMED copyright THE BRITISH LIBRARY 2009 NHSEED –
AZ72 – GLOBAL Health copyright CAB IA70 – IPA copyright Thomson Reuters
BA26 – BIOSIS Previews copyright Thomson Reuters EM74 – EMBASE copyright 2009 Elsevier B.V.
DH64 – Derwent Drug Backfile copyright Thomson Reuters EA08 – EMBASE Alert copyright 2009 Elsevier B.V.
DD83 – Derwent Drug File copyright Thomson Reuters II78 – ISTPB + ISTP/ISSHP copyright Thomson Reuters IS74 – SciSearch copyright Thomson Reuters
T165 – XTOXLINE copyright NLM 2006 TB69 – TOXBIO copyright Thomson Reuters
AN83 – Adis Newsletters copyright Wolters Kluwer Health – Adis International
748 documents have been retrieved from this search. No further restrictions of search terms have been used.
The RTECS database was consulted for toxicological facts. No additional information was found.
Literature and data submitted by the company Valentis, Vilnius, and by AESGP were consulted. Articles and data that were found to be relevant for assessment are included in the list of references.
2. Historical data on medicinal use
2.1. Information on period of medicinal use in the Community
The continous medicinal use of Leonuri cardiaca herba in Europe is documented for several centuries: Mattiolius (1626), Lonicerus (1679), Schröder (1685), Benedum (2006), Wittstein (1882), Hoppe (1949), Hoppe (1957), Hoppe (1975), Weiss (2009).
The comminuted herbal substance and the powder are described in EB6 for more than 50 years (EB6). The comminuted herbal substance, “Herba Leonuri cardiacae conc.”, has been continuously sold
for more than 30 years in Germany as a herbal tea delivered to pharmacies and drug stores (Caelo 1979, Caelo 1994, Caelo 1997, Caelo 2003, Caelo 2009). The use of the herbal substance in tea infusions in UK is documented by the BHP (1974), BHP (1990) and Bradley (1992). The comminuted herbal substance has been used an herbal tea in Poland for more than 30 years (see above) and in Lithuania for 55 years. A monograph from the Russian Pharmacopoeia 9th edition has been the basis for marketing of the comminuted herbal substance in Lithuania; since 2000 in the Drug Register of Latvia, however on the market since 1972 (Latvia).
A tincture 1:5 with ethanol 70% V/V has been on the market in Lithuania for 55 years and has been registered in 1994 (registration certificate 94/843/9 issued by the Ministry of Health). Before 1994, the liquid extract was distributed to Lithuania from manufacturers originating from the former UdSSR (Mashkovskij 1972, Krylow 1993, Sokolov 1984). According to a PSUR submitted by one company, more than 380.000 packages (30 ml or 50 ml) of the liquid extract have been distributed in both countries from 2003 to 2009.
Since 1993 in the Drug Register of Latvia, however on the market since 1970s when Motherwort tincture was included in the register of the former USSR and therefore was on the market in Latvia as its former part (Latvia).
A liquid extract 1:1, ethanol 25% V/V has been in continuous use for more than 30 years (Wichtl 2002, 2009, Bradley 1992, BHP 1974).
The limited information on a medicinal use of the powdered herbal substance makes it difficult to establish a plausible traditional use. Although the powder is mentioned in EB6, limited evidence of medicinal use as a single ingredient product could be found. The powdered herbal substance is included in BHP (1994). However, a fixed combination with two ingredients has been marketed in Germany for more than 34 years (see II.1.2.). As the combination of only two very distinct ingredients, 150 mg Leonuri herba, powder, 160 mg dry extract from Equiseti herba
A tincture 1:5, ethanol 45% V/V has been mentioned in BHP (1974) and in Barnes (2007), but no additional information of use could be retrieved.
No information on more than 30 years of traditional use has been found for the following preparations that were found in literature and data submitted by AESGP:
Tincture 1:5, ethanol 34% V/V (Wichtl 2002, 2009)
Tincture 1:5, ethanol 25% V/V (Bradley 1992)
It might be questioned if the reported figures relating to the
2.2. Information on traditional/current indications and specified substances/preparations
(comminuted) herbal substance:
reported to have cardiac activity, especially in neurosis (Hoppe 1957),
used as a sedative in neurogenic and functional heart complaints (Hoppe 1957),
nervous cardiac complaints, feeling of anxiety, cardiac palpitations, vegetative “heart neurosis” (Schulze 1944),
trembling and palpitations of the heart (Mattiolius 1626),
relieves cardiac pain (Lonicerus 1679),
improves cardiac blood flow (Lonicerus 1679),
cardiac irregularities (Lonicerus 1679),
angina pectoris (Lonicerus 1679),
cardiac complaints, esp. in children (Schröder 1685),
nervous cardiac disorders (Wichtl 2002, 2009, Kommission E 1986, Thomson 1978),
traditionally used to support cardiovascular function (Kommission E from Wichtl 2002, 2009),
sedative in nervous heart complaints (Poland),
nervous cardiac disorders (Weiß 1938),
sedative, vegetative neurosis,
functional heart complaints (Kraft 2009),
heart disorders caused by anxiety and stress (no difference to L. japonicus HOUTT.) (Balch 2002),
sedative, cardiotonic, hypotensive (Bradley 1992),
neuropathic cardiac disorders, cardiac complaints of nervous origin (Bradley 1992),
palpitation of the heart arising from hysteric cause (Steinmetz 1954),
sedative, antispasmodic, cardiac debility, simple tachycardia, effort syndrome, amenorrhoea, specifically for cardiac symptoms associated with neurosis (Barnes 2007),
originally used in cardiovascular neurosis, angina pectoris, hypertonia, since the beginning of the 20th century as a sedative, e.g. in nervous conditions, psychasthenia, neurasthenia with insomnia, stress, hyperreactivity,
nervous symptoms, cardiovascular neurosis, early stages of hypertension (Mashkovskij 1972, Krylow 1993),
neuroregulatory related disorder of heart function (e. g. thyroid hyperfunction, climacteric period etc.), in absence of organic cardiovascular disease (Lithuania),
treatment of heart and blood system neurosis, early stages of hypertension (Latvia),
as a sedative in cases of hypersensitivity of central nervous system (Latvia),
traditionally as a sedative (Wichtl 2002, 2009),
hysterical complaints (Steinmetz 1954),
relieves nervous irritability, calming action (Steinmetz 1954),
used in many traditions in trouble with concentrating,
climacteric disorders (Hoppe 1957),
traditionally in climacteric complaints, (Wichtl 2002, 2009),
to facilitate menstruation, “emenagogum”, (Hoppe 1957),
traditionally in amenorrhoe (Wichtl 2002, 2009),
used in many traditions in “uterine weekness” (Abascal 2004),
premenstrual syndrome (no difference to L. japonicus HOUTT.) (Balch 2002),
India: in Unani medicine (“Baranjaasif”, name also used for Artemisia vulgaris L. and Achillea millefolium L.) in absent or painful menstruation, premenstrual tension, menopausal flushes (Khare 2007),
spasms (Mattiolius 1626),
paralysis of the limbs (Mattiolius 1626),
historically (!) for the treatment of wounds, to expell phlegm from the lungs, to support gastric function (Wittstein 1882),
pain of the stomach, pain caused by
adjuvant in hyperactivity of the thyroid (Wichtl 2002, 2009), (Kommission E 1986),
tachycardia associated with hyperthyreosis (Weiss 1974, Weiss 1980), but: “L. cardiaca has no thyreostatic acitivity” (Weiss 1997).
Uses in US eclectic medicine:
Infusions in hysterical affections, sleeplessness, delirium, uterine pain and
Tincture (1:5), ethanol 70% V/V
Reduction of mild nervous tension, in cases of functional heart disorders; in cases of pre- hypertension, isolated clinical hypertension, borderline hypertension; treatment of functional heart disorders (heart neurosis, manifested as palpitations, intermission, short term stitchy or long term pressure pain in heart) if there is no organic disease, but symptoms are caused by stress, anxiety, hypersensitivity of nervous system. Also used to reduce heart symptoms (for example, palpitations) caused by hyperthyreodism or hormonal changes during menopause (Latvia)
Liquid extract 1:1, ethanol 25% V/V
sedative, cardiotonic, hypotensive (Bradley 1992)
sedative, antispasmodic; cardiac symptoms associated with neurosis (BHP 1974)
neuropathic cardiac disorders, cardiac complaints of nervous origin (Bradley 1992)
sedative, antispasmodic,; cardiac debility, simple tachycardia, effort syndrome, amenorrhoea, specifically for cardiac symptoms associated with neurosis (Barnes 2007)
Tincture 1:5, ethanol 45% V/V
sedative, antispasmodic; cardiac symptoms associated with neurosis (BHP 1974)
sedative, antispasmodic; cardiac debility, simple tachycardia, effort syndrome, amenorrhoea, specifically for cardiac symptoms associated with neurosis (Barnes 2007)
Tincture 1:5, ethanol 25% V/V
sedative, cardiotonic, hypotensive (Bradley 1992)
neuropathic cardiac disorders, cardiac complaints of nervous origin (Bradley 1992)
Traditional uses of other Leonurus species:
Leonurus japonicus HOUTT., herb:
The first reported use “to expel dead fetus and retained placenta” is described in the first official Chines Pharmacopoeoa Tang Peng Ts’ao (659 A.D.) (Blancafort 1977).
Current TCM: Menstrual disorders, painful menstruation, amenorrhoea, prolonged menorrhoea, edema with reduced elimination of urine, oedema in acute nephritis (Stöger 2009). Most frequently used as an emenagogue in form of a decoction. In eastern parts of China to promote uterine recovery after delivery (Kong 1976, Bensky 2004).
Premenstrual syndrome, heart disorders caused by anxiety and stress (no difference to L. cardiaca L.) (Balch 2002).
In a retrospective study in Taiwan, L. japonicus, herba was the most commonly prescribed herbal substance for the treatment of symptoms related to menopause. The study investigated records of 3432 that were treated in the time period between January 2003 and December 2006 (Chen 2010).
Leonurus japonicus HOUTT., fruit:
Current TCM: To activate blood circulation and regulate menstruation, to subdue hyperactivity of the liver and to clear the eye from opacity. Used in menstrual disorders, amenorrhea, hysmenorrhea, inflammation of the eye with formation of corneal opacity; dizziness and headache (Pharm. Commission Chin. 1996).
Menstrual disorders, amenorrhoea, painful menstruation, inflammation of eye, corneal opacity, dizziness, pain and sensation of tension (Stöger 2009, Jia 2006).
The daily dose should not exceed 15 g for because of possible toxicity (Bensky 2004).
Leonurus sibiricus L., herb (see general comment in 1.1.1.)
Used in Korean traditional medicine for the treatment of uterine leiomyoma (Bajracharya 2009).
2.3. Specified strength/posology/route of administration/duration of use for relevant preparations and indications
Posology (oral use)
As an herbal tea:
single dose 1.5 g (EB6)
single dose 1.5 g, daily dose 4.5 g (Wichtl 2002, 2009; Kommission E 1986)
single dose 1.5 – 2.5 g,
single dose 3 g, for a decoction,
single dose 2 g, twice a day (Weiss 1944, Weiss 1974, Weiss 1980, Weiss 1997, Weiss 2009)
single dose 1 g,
single dose 4.5 g,
15 g/200 ml boiling water, take 1/3 of the tea preparation twice a day; if CNS suppression occurs, doses are either reduced or treatment is interrupted for
15 g/200 ml boiling water, 1
2 teaspoons comminuted herbal substance with 1 glass of boiling water, allow infusing 20 minutes, 1/3 of glass 3 times per day (Latvia). Presuming that a teaspoon would correspond to
single dose 1 tea spoon
single dose: 2 teaspoons
The majority of posologies proposed by authors would be covered by a single dose of 1.5 to 4.5 g, and a daily dose of 3 to 10 g.
Powdered herbal substance:
The posology of the powder as part of the comparable fixed combination is 150 mg,
Tincture 1:5, ethanol 70% V/V:
According to DAB 7, 1 drop of ethanol 70% corresponds to 18 mg, 55 drops=1 g
single dose approx.
Liquid extract 1:1, ethanol 25% V/V:
Tincture 1:5, ethanol 45% V/V:
Posologies of preparations without traditional use over at least 30 years:
tincture 1:5, ethanol 34% V/V single dose
tincture 1:5, ethanol 25% V/V single dose
Duration of use:
3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
In vitro experiments
Action on free radicals / antioxidant action
A radical scavenging action in ABTS
According to Masteikova (2008) the antioxidant activity of L. cardiaca tincture, as compared to a tincture from hawthorn fruits, does not correlate with the total phenol content and is mainly related to the presence of rutoside (55 µg/ml). An antioxidant effect in vitro was found with an extract prepared with methanol 60% from the herb, which was extracted first with chloroform (Matkowski 2006).
A dry extract of the herb with chloroform inhibited the growth of St. aureus in the agar diffusion test and in the serial dilution test (MIC 500 µg/ml) (Sattar 1995).
Aqueous extracts from L. cardiaca herb inhibited almost completely
Ali et al (2007) investigated a potential
A purified extract with water from L. cardiacae herba was investigated in the isolated rabbit heart in vitro. 0.1 to 3.0 mg/ml of the extract were applied intracoronarily. The extract reduced significantly and in a
The extract was subject of a patent application in 2005. According to the application, the extract is prepared by purifying a lyophylized extract with water with lipophilic organic solvents, redissolving the water soluble part in water, precipitating the solution with methanol and using the supernatant fluid. This purified extract may be further purified by elimination of potassium (Dhein 2005, Ritter 2009). The refined extract contained approximately 6% stachydrine, 0.1% rutosid, 0.2% verbascosid, 0.3% lavandulifolioside (Kuchta 2009, Ritter 2009). Furanic diterpenes that were toxic to the isolated heart preparation and resulted in cardiac arrest were eliminated by prior extraction with dichloromethane (Ritter 2009). The refined extract was applied intracoronarily in isolated rabbit hearts perfused according to the Langendorff technique. Mapping experiments with 256 electrodes on the heart surface showed a reduction of left ventricular pressure and an increase of relative coronary flow at concentrations of 1.0 and 2.0 mg/ml. Furthermore, the
however a proarrhytmogenic activity and a potential to induce torsade de points was not observed, even at 2 mg/ml. In summary, a bradycardic action of
Other actions on isolated organs
Isolated small intestine of guinea pigs: Ashes/minerals from L. cardiaca herb resulted in a strong increase of the tonus, whereas a decoction or an ethanolic extract (see sedative action) resulted in a week increase of tonus (Erspamer 1947).
Isolated small intestine of dogs: A decoction resulted in an increase of tonus that returned slowly back to normal, an ethanolic extract resulted in an increase that was hardly reversible, whereas the ashes induced an immediate increase in tonus easily reversible (Espamer 1947).
Isolated uterus of guinea pigs: 0.2 ml/8 ml of a 10% decoction; an ethanolic extract corresponding to 0.4 g herb/8ml and ashes corresponding to 0.4 g herb/8 ml resulted in a clear increase of the tonus (Erspamer 1947).
Espamer (1947) concludes that L. cardiaca herb has a minor, mostly excitant action on the small intestine and uterus that is, in part, associated with the minerals present in the herb.
In vivo experiments
10 mg/kg of
An aqueous and an ethanolic extract are reported to have analgetic effects in the hot plate test in mice. No further details are given (Szocs 1999).
The aerial parts of plant material collected in Poland were extracted first with chloroform and then with methanol. The dry extract with methanol was further fractionated into ethyl ether, ethyl acetate and n- butanol. From the
In a dog, i.v. injection of an ethanolic extract (corresponding to
Erspamer (1948) investigated potential sedative actions of L. cardiacae herba in frogs and mice. A comparison between the effects of a 5% decoction (delivering
1 ml/ animal s.c. resulted in a higher amperage necessary to induce contraction (Polyakov 1962). No conclusions on sedative actions can be drawn from this model.
800 and 1600 mg/kg b.w., intragastrically of lavandulifolioside did not influence the locomotor activity in mice. 800 mg/kg b.w. of a
0.5 ml/mouse i.p. of an extract of the aerial parts of Leonurus cardiaca L. var. villosus DESF. with water (10%) is reported to reduce the motor acitivity by 50% after 3h. The extract antagonized the hypermotility induced by s.c. methyl phenidate (20 mg/kg b.w.), prolonged the
3.5 ml/kg b.w., p.o. of an extract with ethanol (concentration not given) slightly prolonged the hexobarbital sleeping time in female NMRI mice. 1.75 ml/kg b.w. had no significant effect (Weischer 1994).
Studies on related herbal substances/preparations
Leonurus japonicus HOUTT., herba
An extract with
The activity prostaglandin E
2 mg/10 ml of a dry extract prepared with methanol inhibited the
Leonurin isolated from the herb, inhibited rabbit platelet aggregation induced by thrombine (IC50 97.22 µM), arachidonic acid (IC50 31.03 µM) and collagen (IC50 44.48 µM) in vitro (Lin 2007).
A furanic diterpene, prehispanolone, isolated from the herb inhibited the binding of
Actions on the endocrine system
Prolonged administration of the herb in pigs and rats is reported to decrease the level of estrogene in the urine and in the serum with no change in the menstrual cycle (Chen 1982).
No estrogenic or antiestrogenic activity was observed with a dry extract prepared from the herb with ethanol 95% in a recombinant yeast system featuring both a human estrogene receptor expression plasmid and a reporter plasmid (Kim 2008).
An extract of the herb with acetone 70% has shown
Pretreatment with 400 mg/kg b.w./day with a dry extract prepared with water (approx. 5:1) that did contain stachydrine, quercetin and kaempferol as main constituents did not influence the survival rate of rats with a myocardial infarction caused by ligation of the coronary artery. An antioxidant effect is attributed to the presence of flavonoids (Sun 2005).
Pretreatment over two weeks with 400 mg/kg b.w./day with a dry extract prepared with water (approx. 5:1) that did contain stachydrine, quercetin and kaempferol as main constituents reduced significantly the volume of cerebral infarction induced in rats by middle cerebral artery occlusion. A neurological deficit score was reduced, although no significant effect is described. The pretreatment antagonized significantly the drop in antioxidant capacity of the rat serum after induction of the cerebral infarction. DNA oxidative damage was significantly reduced (Loh 2009).
In anesthetised rats with myocardial ischemia induced by ligature of the coronary artery, i.v. injection of an extract (no details given) significantly reduced plasma fibrinogen, lowered platelet aggregation rate induced by ADP and collagen (Yin 2003).
Actions on smooth muscle
Leonurin from L. japonicus stimulated in vitro the contraction of uterine smooth muscle from mice, pretreated with oestrogen. Significant effects on frequency and amplitude are reported for 40 µg /ml and 90 µg/ml. In smooth muscle from portal veins from rats, a dose dependent reduction of the amplitude by
Leonurin (0.4 µg/ml) isolated from the herb, induced regular contractions of large amplitude in uterine preparations from rats. Actively contracting uterine preparations from estrous rats responded by an increased rate of contraction (Yeung 1977).
An extract prepared with water (0.3 mg/ml) stimulated slightly contractions of the the isolated rat aorta with endothelium. Contractions induced by
The effects of a
Cytotoxicity of a dry extract from the aerial parts with 70% ethanol (approx. 28:1) was analyzed with MTT assay on ER negative
The essential oil from L. japonicus from Brazil, up to 700 mg/kg b.w i.p., was not effective in preventing
Actions on the uterus
Leonurin isolated from the herb increased the frequency and amplitude of contractions in uterine strips from proestrous rats or ovarectomised rats pretreated with estradiol. In a concentration range of 0.2- 1.0 µg/ml a
In myometrium samples of patients undergoing total hysterectomy, an increase in frequency and amplitude in uterine contractions was recorded in vitro after adding a dry extract prepared with
methanol from the herb to the organ bath. 4 samples from patients well beyond menopause did not react (Kong 1974).
Leonurin, isolated from the herb, inhibited in vitro rabbit muscle creatine kinase activity in concentration- and
Protective effects of synthetic leonurin against doxycycline
Leonurus japonicus HOUTT., fructus
Cycloleonurinin isolated from the fruits did not present any activity on the isolated guinea pig ileum, the isolated rat aorta (up to 3 x
Cycloleonurinin inhibited the mitogen (concanavalin A) induced response of human
Cycloleonuripeptide B and C showed growth inhibition in
Leonurus sibiricus L. (see comment in 1.1.1.):
The aqueous extract of Leonurus sibiricus L., herba was examined for its reducing power, scavenging ability toward superoxide and hydroxyl radicals, and their inhibitory effect on lipid peroxidation. The extract was found to be active on scavenging of superoxide radicals. The level of hydroxyl radical scavenging activity tended to be lower than that for superoxide radicals. Inhibitory effects on lipid peroxidation were examined using a rabbit
Inhibition of the cytochromes
Lyophilised extracts with water from “Leonuri herba” commonly used in Korea (species not specified; L. sibiricus L. or L. japonicus HOUTT.), were tested for inhibition of several cytochrome P450 (CYP) isoforms and microsomal
CYP 1A2 830.9 (1.25), CYP 2C9 698.8 (19.2), CYP 2C19 342.1 (>30), CYP 2D6 >1000 (>30), CYP 2E1 >1000 (>30), CYP 3A4 712.9 (>30),
The MeOH extract, CH2Cl2 fraction, EtOAc fraction,
An in vitro antimicrobial action against St. aureus, S. epidermis, Strepotococcus pyogenes, E. coli,
Vibrio colerae, Shigella dysenteriae, and S. boydii has been found for CCl4 and chloroform extracts of the aerial parts. The zone of inhibition of 500 µg/disc of extract has been similar to 30 µg/disc of kanamycin. No or a minor inhibition was observed with extracts prepared with methanol or acetone (Ahmed 2006).
A methanolic extract from L. sibiricus herb from Brazil presented in vitro an inhibition of B. subtilis. No inhibitory effect was observed in St. aureus, St. epidermidis, E. coli, Micrococcus luteus, C. albicans, S. cerevisiae (Coelho de Souza 2004).
Dry extracts prepared by stepwise extraction with ethanol 96% and ethanol 70% were reported to have a significant antifungal activity in vitro (< 2 µg/spot) Heinrich (1991).
An extract with ethanol 70% was reported to be active in vitro against C. albicans, St aureus and Ps. aeruginosa (Wadt 1996).
A lyophilised water extract from L. sibiricus L., herba, (0.1 mg/mL) did not have any significant effect on the growth of human myometrial or leiomyomal cells in vitro. The study could not confirm prior results reported by Baek (2006) (Bajracharya 2009).
Furanic diterpenes, isolated from the herb, showed weak cytotoxic activity against L1210 leukaemia cells in vitro (IC50
Action on endogenous mediators (NO,
200 mg/kg and 400 mg/kg, i.p., of a dry extract (approx. 10:1) prepared with methanol 90% are reported to reduce the onset of sleep and to prolong the sleeping ime in pentobarbital induced sleep in mice. The same doses of the extract caused a significant decrease of scores in different exploratory behaviour tests (open field test, hole cross test, hole board test) in mice (Ahmed 2005).
250 and 500 mg/kg i.p. of a dry extract from the herb prepared with methanol showed a significant analgesic effect in acetic
Permanent feeding of multiparous GR/A mice with 0.5% of an dry extract prepared with methanol 60% in drinking water over several litters enhanced the development of both
3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
No studies have been performed. In absence of constituents with known therapeutic activity, kinetic studies are not required.
3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
L. cardiaca L. var. villosus DESF., herba
Extract with water (1ml=1 g dry material): LD50 i.p., mouse, 10,800 mg/kg b.w. (Racz 1989).
L. cardiaca, herba:
Related herbal substances and isolated constituents
Acute / subchronic toxicity
The toxicity of the dried herb of L. sibiricus L. on Sprague Dawley male and female rats was evaluated through
when compared with the control and the low dose groups. A decrease of alkaline phosphatase (ALP) was observed in the medium and in the high dose groups. The haematology study revealed a statistically significant mild anaemia in rats from the medium and high dose groups as indicated by decreases in haemoglobin, red blood cell count and packed cell volume (haematocrit value). Administration of the herb at medium and high dose was also found to cause adverse effects in histopathological structure of the liver
Extract from L. japonicus herb (not specified), LD50, i.v., mice:
Adult male rats fed on a diet with 50% L. japonicus herb for 80 days showed no toxic effects or change in fertility (Kong 1976, Chinwala 2003).
Total alkaloids from L. japonicus herb (not specified), i.v., mice, 572 mg/kg b.w. (Chinwala 2003).
Lavandulifolioside isolated from L. cardiaca: LD50 i.v. approx. 1000 mg/kg b.w., p.o. > 2000 mg/kg b.w.
No adverse effects in rats after 2 mg/rat leonurin i.p. for 4 days (Kong 1976, Chinwala 2003).
30 mg/kg b.w. per day of leonurin, s.c., in rabbits over 2 weeks did not affect food intake, faecal and urinary excretions and body weight (Chinwala 2003).
Leonurin of synthetic origin is reported to be
Toxicity on reproduction
A fed containing 50% of powdered L. japonicus herb did not affect fertility in male rats (Chinwala 2003).
The milk production in rats fed a diet with 1% of the herb, starting on day 18 of gestation, was significantly increased on day 8, 13 and 18 of lactation by 15.22, 19.11 and 19.25% as compared to
Rats given 0.5 mg/ml leonurin of synthetic origin as the only water source over 3 generations and
3.4. Overall conclusions on
Pharmacodynamic studies on Asian and European Leonurus species follow the different traditional uses: sedative and cardiovascular effects for L. cardiaca were investigated in Europe whereas effects of L. japonicus on reproductive organs and haematological parameters were focused in Asia. There is some overlap between the effects of both species, although it remains an open question if the different studies reflect a different pharmacological profile or simply a different area of interest.
From a perspective of safety the bradycardic actions, renal and liver toxicity and the activity on the uterus deserve attention. Water soluble components exert in vitro in relatively high doses of
The finding of renal and liver toxicity in animals after prolonged feeding of high doses of L. sibiricus powder is not considered relevant for the use of the herbal tea or the tincture under the conditions proposed in the monograph. The maximum dose for preparation of an herbal tea is 10 g/day, representing an additional safety margin of 2.5 (50 kg person) compared to the dose of powder that is considered safe in the feeding experiment. The maximum daily doses of the liquid extract 1:1 (12 ml) would result in a safety margin of 2 and of the powder (450 mg) in a safety factor of > 50. In addition to that, the duration of use under OTC conditions is limited to 4 weeks vs. 90 days in the feeding study. As
Although no studies have been performed with L. cardiaca on toxicity in reproduction, the data on leonurin (present in L. cardiaca) and the studies in Asian Leonurus species point to a risk and confirm the contraindication in pregnancy that is widely and consistently found in several handbooks.
No studies on genotoxicity and carcinogenicity have been found.
The data on sedative actions, although limited, contribute to the plausibility of the traditional use of L. cardiaca in the indication covered by the monograph.
4. Clinical Data
4.1. Clinical Pharmacology
4.1.1. Overview of pharmacodynamic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
According to Ovanesov (2005) enhanced anxiety state is accompanied by a limitation of the color- discrimination function of the retina in young humans. Chronic administration of tofisopam (grandaxin) or tinctura leonuri is reported to have decreased anxiety and significantly improved the colour discrimination function of retina with respect to all four colours studied. The author suggests that this improvement may be related to an action upon the GABAergic processes both in the retina and in the related cerebral structures. No details are presented.
After repeated administration of melatonin (0.75 mg at night, 10 days) a significant decrease in the thresholds of retinal brightness sensitivity and an improved emotional state in anxious young subjects have been observed. Similar, but less pronounced effects were observed after the treatment with Leonurus cardiaca tincture. The authors suggest that there might be a relation between the limitation of anxiety and the improvement of visual function (sensitivity). No details are presented (Ovanesov 2006).
Other Leonurus species:
L. japonicus HOUTT.:
The results of a clinical study, involving 105 men with “blood hyperviscosity” (hypertension 60, atherothrombotic brain infarction 21, brain atherosclerosis 9, diabetes 3) are reported. The patients did receive 10 ml of a preparation consisting of a decoction of the herb (5 g/ml) in 250 ml 5% glucose i.v. per day for 15 days. No details on the preparation are available. Improvement of symptoms such as vertigo, headache, insomnia, numbness in limbs, ability to stand on one leg with closing eyes, is
reported for the majority of patients. Platelet aggregation that was investigated in 65 patients was significantly reduced (Zou 1989).
52 Patients with thrombocytopenic purpurea were treated by TCM “Huo Xue Hua Yu” medications, i.e., agents that are traditional associated with “activated blood flow and elimination of blood stasis”, among them Leonurus japonicus. An overall response rate of 88%, with platelet and megakaryocyte recovery is reported. The elevated PAIgG and the platelet count felt to normal levels in the majority of cases. No detailed information could be found (Deng 1993).
The effect of an infusion of the herb was investigated in 141 fertile women. A single dose of 150 ml of a decoction prepared from 30 g of herb was administered orally.
4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
No clinical studies have been performed. In absence of constituents with known therapeutic activity, pharmakokinetic studies are not required.
4.2. Clinical Efficacy
4.2.1. Dose response studies
No information on
4.2.2. Clinical studies (case studies and clinical trials)
Fifty male and female patients with arterial hypertension stage 1 (n=22; bp
Due to the short duration of the study and due to the absence of a control group, no conclusion on efficacy can be drawn from this study. However, the results add to the plausibility of the traditional use.
Studies with combination products
Fifty male alcohol abusers (mean age 45.6 years) with sleep disturbances were enrolled in a cross- over, placebo controlled study with a fixed combination product. On 2 consecutive nights, the volunteers were given tablets containing 170 mg valerian (Valeriana officinalis) root, 50 mg hop cones, 50 mg balm (Melissa officinalis) leaves and 50 mg motherwort (Leonurus officinalis [sic]) herb, or the placebo, which contained 5 mg valerian root. Treatments were taken orally 1 hour before bed. The following morning a questionnaire was completed by the volunteers, concerning sleep quality, dream recall, frequency of night awakenings, and fatigue and sleepiness in the morning. Statistical analysis using the Wilcoxon
Studies with preparations from L. japonicus, herba
85 patients with acute cerebral ischemic infarction were randomized to receive either 10 ml of a “Leonurus injection” plus 500 ml 0.9% NaCl solution i.v. drip q.d. for 15 days or 20 ml of a “Salvia miltiorrhiza injection” plus 500 ml 0.9% NaCl solution i.v. drip q.d. for 15 days. No details on the extract are given. As compared to the start of the study, there was a significant difference favouring the Leonurus preparation in the curative rate (neurological deficit status; 70% improvement vs. 31%). The Leonurus preparation reduced serum lipids, fibrinogen and had an anticoagulant action (Xu 2002).
An injection prepared from L. japonicus herb (no details on the extract) was tested for preventing postpartum haemorrhage after caesarean section in a prospective, randomized and single blinded
observed. The authors conclude that combined use of motherwort injection and oxytocin to prevent postpartum haemorrhagia during or after caesarean section is safe and effective (Lin 2009).
4.2.3. Clinical studies in special populations (e.g. elderly and children)
No clinical studies of good quality have been found. The statement in a very old textbook (Schröder 1685) that preparations from L. cardiaca are “especially useful for the treatment of cardiac complaints in children” is not substantiated by new studies, although the use of a combination product in France that has been in use since 1953 points to the same direction.
A collection of case reports has been published by Orlandi (1950): 11 children were treated with a dry extract prepared with water incorporated in granules. 6 g of granules per day, containing 0.03 g of dry extract, were administered in three single doses. No further details on the extract are given. One infant (15 months) presented complex symptoms associated with rachitis and central seizures among them restlessness, irritability, and spasms. After treatment with Leonurus extract for one week, a general improvement of the nervous symptoms is reported. Ten children (2.5 to 9 years) presenting heterogeneous symptoms such as heart palpitations, extrasystolic tachycardia, vasomotoric complaints, irritability, sleep disorders, nervousness, anxiety. Treatment for 5 days to 1 month resulted in an improvement of nervous symptoms and heart palpitations. The author concludes that the extract has a sedative action in children. In view of the small number of cases, the heterogeneity of conditions and the limited availability of information on medication and other interventions applied no conclusion on the safety and efficacy of L. cardiaca in the paediatric population can be drawn.
4.3. Overall conclusions on clinical pharmacology and efficacy
The summary statement by Benedum (2006) that “traditionally the effects of the drug on palpitations, anxiety attacks, cardiac asthenia, labile pulse, and altogether on nervous cardialgia are excellently substantiated” cannot be fully endorsed. No studies on efficacy have been retrieved from literature searches. The use as an adjuvant in hyperthyreosis (Kommission E 1986, Wichtl 2002, 2009) is not supported by any clinical data. Initiation of treatment for any type of thyroid disorder should be considered only under the supervision of an experienced medical doctor (American Botanical Council 2008). In absence of clinical studies, an indication in the area of
As other specific expressions of symptoms of nervous tension such as hyperthyroidism, or other indications such as anxiety may indicate a serious condition and require intervention by a medical doctor for diagnosis, treatment and
5. Clinical Safety/Pharmacovigilance
5.1. Overview of toxicological/safety data from clinical trials in humans
No clinical studies with single ingredient products were found.
5.2. Patient exposure
The herbal substance has been continuously distributed in the EU for more than 30 years, it is present in official pharmacopoeias for more than 50 years and the continuous use of the herbal tea is documented for nearly 400 years (see above).
98.000 packages of 25 ml tincture have been sold in Lithuania in 2008. More than 350.000 packages were distributed from 2003 until March 2009 (Valentis 2009).
5.3. Adverse events and serious adverse events and deaths
Unknown (Krylow 1993).
A 94 year old woman was admitted at hospital for heart failure and bradyarrhytmia. She had been treated before over three days with spironolactone and a combination product that contains L. cardiaca herb. ECG showed complete AV block, prolonged QTC, and late ventricular premature beats. As the authors suspected a wrong OTC use of cardiac glycosides, digoxin plasma level was assessed (0.73 µg/l). The authors assume that glycosides present in L. cardiaca may have
The following information on adverse events is labelled for a tincture marketed in Lithuania and Latvia: Very rarely hypersensitivity may occur;
No case reports of allergic reactions, including contact allergy, were found in literature. The occurrence of gastric complaints may be associated with the tannins or the bitter taste of the herbal preparations. As such a “class labelling” is absent in monographs on Centaurii herba, or Hamamelidis cortex, the inclusion of an ADR is in absence of any case reports not appropriate.
5.4. Laboratory findings
5.5. Safety in special populations and situations
Potential for interactions:
None documented (Barnes 2007).
Abebe (2002) has claimed that Leonurus cardiaca L would contain “coumarin” and might interfer with NSAIDs with respect to decrease in blood coagulation/increased bleeding. Appropriate precautionary mesures when taken with NSAIDs or in coagulation disorders are recommended. However, coumarin does not interfer directly with
Miller (1998) and Harkness (2003) have reported that motherwort would contain cardiac glycosides and significant interactions may occur. Although the presence of glycosides with “cardiac action” was
reported in old literature, no digitalis like cardiac glycosides has been found. The recommendation to avoid taking motherwort for this reason has no scientific basis.
Potentiates the effects of hypnotics and analgetics (Krylow 1993). For studies on effects on the
A dose of 3000 mg of solid extract per day, taken in capsule or tablet form, is likely to cause diarrhoea, stomach irritation, or uterine bleeding (Balch 2002). This statement seems to refer to an earlier statement from Van Hellemont (1986) that a dose in excess of 3.0 grams of a powdered extract may cause diarrhoea, uterine bleeding, and stomach irritation. No details on the extract are recorded.
Because of the traditional use for uterine stimulation, motherwort should not be used by pregnant women (Balch 2002).
Contraindicated in pregnancy (Bradley 1992).
Not to be used during pregnancy; emenagogue / uterine stimulant (McGuffin 1997). The use during pregnancy and lactation should be avoided (Barnes 2007).
Other Leonurus species:
L. japonicus Houtt., herba:
L. japonicus Houtt., herba is contraindicated during pregnancy (Stöger 2009) for uterotonic effect (see 4.1.1.)
Precautions for use:
L. japonicus Houtt., fructus:
To be used with special care in patients with wide pupils (Stöger 2009).
L. japonicus Houtt., fructus:
After ingestions of
5.6. Overall conclusions on clinical safety
Preparations of L. cardiaca are safe under the conditions of use included in the monograph. Preclinical data, a clinical study with L. sibiricus and consistent information from handbooks are the basis for establishing a
The adverse events mentioned for the tincture seem to be of a hypothetical nature. No case reports have been found.
The duration of use should be limited to 4 weeks because of the clinical condition that would need a medical diagnosis after that period of time and because of inconclusive signals for risks at higher doses/prolonged use from animal experiments. Information with respect to interaction with sedatives has not been included, although it is reported in a general way without any case reports.
The potential for interaction with substances such as warfarin deserves careful consideration. Warnings that can be found in handbooks are based on the wrong assumption that L. cardiaca may contain relevant amounts of “coumarins” with an
preparations of Asian L. japonicus are reported to have influenced blood aggregation. As no case reports were found for L. cardiaca preparations and the posologies included in the monograph, no warning is included.
6. Overall conclusions
In absence of clinical studies, an indication in the area of
Taking into account the pharmacological data and the continuous, long standing use of the herbal substance and preparations thereof in symptoms of nervous tension the traditional use in this indication is plausible. There is no need to consult a physician for diagnosis of this condition or for follow up within the period of time foreseen in the monograph.
The indication may cover gynaecological, cardiovascular or
Cardiac complaints are consistently and widely mentioned in the literature and such use may even be reflected by the plant’s name. Although the indication is already covered by the broader term, nervous cardiac complaints were included under the condition that initial diagnosis by a doctor has ruled out any serious condition such as arrhythmia, hyperthyreosis, organic heart diseases, etc.
As other specific expressions of symptoms of nervous tension such as hyperthyreosis, or other indications such as anxiety may indicate a serious condition and require intervention by a medical doctor for diagnosis, treatment and
In absence of adequate data on genotoxicity, a list entry cannot be proposed.