Motherwort

Summary and Pharmaceutical Comment

The common name motherwort may be applied to one of many Leonurus species. L. cardiaca is the typical European species utilised, whereas Leonurus japonicus Houtt is commonly used in traditional Chinese medicine. Other species referred to as motherwort include Leonurus sibirious and L. heterophyllus. The chemistry of L. cardiaca is well studied although the presence of the uterotonic principle leonurine has been disputed. Cardioactivity in vitro has been reported for motherwort (L. cardiaca), although the clinical relevance of this is not clear. There is a lack of clinical research assessing the efficacy and safety of motherwort, and any symptoms of cardiac disorder are not suitable for selfdiagnosis and treatment with a herbal remedy. In view of the lack of toxicity data, excessive use of motherwort and use during pregnancy and lactation should be avoided.

Species (Family)

Leonurus cardiaca L. (Labiatae/Lamiaceae)

Synonym(s)

Leonurus

Part(s) Used

Herb

Pharmacopoeial and Other Monographs

BHC 1992(G6)

BHP 1996(G9)

BP 2007(G84)

Complete German Commission E(G3)

Martindale 35th edition(G85)

Ph Eur 2007(G81)

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General Reference G6.

Alkaloids 0.35%. Stachydrine (a pyrrolidine-type alkaloid), betonicine and turicin (stereoisomers of 4-hydroxystachydrine), leonurine 0.0068% (a guanidine derivative),(1) leonuridin, leonurinine. The presence of leonurine in L. cardiaca has been disputed, although it has been documented for other Leonurus species.

Flavonoids Glycosides of apigenin, kaempferol, and quercetin (e.g. hyperoside, kaempferol-3-D-glucoside, genkwanin, quinqueloside, quercitrin and rutin).(2, 3)

Iridoids Ajugol, ajugoside, galiridoside, leonuride and three or four more unidentified glycosides.(4)

Tannins 2–8%. Type not specified. Pseudotannins (e.g. pyrogallol, catechins).

Terpenoids Volatile oil 0.05%, resin, wax, ursolic acid, leocardin (a labdane diterpene)(5) as an epimeric mixture, and a diterpene lactone similar to marrubiin.(2) Cardiac glycosides (bufadienolide/ bufanolide type) have been documented although their presence in motherwort has not been confirmed.

Other constituents Citric acid, malic acid, oleic acid, bitter principles,(6, 7) carbohydrates 2.89%, choline and a phenolic glycoside (caffeic acid 4-rutinoside).(8)

A Cad-specific lectin has been isolated from the seeds.(9)

Food Use

Motherwort is not used in foods. Previously, motherwort has been listed by the Food and Drugs Administration (FDA) as a Herb of Undefined Safety.(G22)

Herbal Use

Figure 1 Selected constituents of motherwort.

448 Motherwort

Dosage

Dosages for oral administration (adults) for traditional uses recommended in standard herbal reference texts are given below.

Dried herb 2–4 g as an infusion three times daily.(G6, G7)

Liquid extract 2–4 mL (1 : 1 in 25% alcohol) three times

daily.(G6, G7)

Tincture 2–6 mL (1 : 5 in 45% alcohol) three times daily.(G6, G7)

Pharmacological Actions

In vitro and animal studies

The uterotonic principle in motherwort is unclear, although leonurine is reported to be the utero-active constituent in various Leonurus species. In addition, oxytocic activity documented for L. cardiaca has been attributed to another alkaloid constituent, stachydrine.(G30) Uterotonic activity has been reported for leonurine in various in vitro preparations including human myometrial strips and isolated rat uterus.(10, 11)

In vitro cardioactivity has been documented for motherwort.(12) An alcoholic extract was found to have a direct inhibitory effect on myocardial cells: antagonistic action towards calcium chloride (provided that the extract was administered before calcium chloride), and towards both a- and b-adrenoceptor stimulation was observed. No significant effect on the cardiac activity of the isolated guinea-pig heart was noted for caffeic acid 4-rutinoside.(8)

Ursolic acid has been reported to possess antiviral, tumourinhibitory and cytotoxic activities.(13, 14) Ursolic acid was found to

Minhibit the Epstein–Barr virus in vitro and to inhibit tumour production by 12-O-tetradeconoyl phorbol (TPA) in mouse skin,

with activity comparable to that of retinoic acid, a known tumourpromoter inhibitor.(14) In vitro cytotoxicity was documented in lymphocytic leukaemia (P-388, L-1210), human lung carcinoma

(A-549), KB cells, human colon (HCT-8) and mammary tumour (MCF-7).(13)

Clinical studies

There is a lack of clinical research assessing the effects of motherwort and rigorous randomised controlled clinical trials are required.

Side-effects, Toxicity

Clinical data

There is a lack of clinical safety and toxicity data for motherwort and further investigation of these aspects is required.

It has been stated that the leaves of motherwort may cause

contact dermatitis and that the lemon-scented oil may result in photosensitisation.(G51)

Preclinical data

No documented toxicity studies were located. Cytotoxic activities have been reported for ursolic acid (see Pharmacological Actions, In vitro and animal studies).

Contra-indications, Warnings

Sensitive individuals may experience an allergic reaction.

Drug interactions None documented. However, the potential for preparations of motherwort to interact with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered.

Pregnancy and lactation Motherwort is reputed to affect the menstrual cycle.(G22) In view of the lack of toxicity data and the

documented in vitro uterotonic activity,(G30) the use of motherwort during pregnancy and lactation should be avoided.

Preparations

Proprietary multi-ingredient preparations

Australia: Pacifenity; Valerian. Austria: Thyreogutt. France: Biocarde. Germany: Biovital Aktiv; Biovital Classic; Mutellon; Oxacant-sedativ. Hungary: Biovital; Biovital. Switzerland: Tisane pour le coeur et la circulation. UK: Fenneherb Prementaid; Menopause Relief; Modern Herbals Stress; Period Pain Relief; Prementaid; Quiet Life; Roberts Alchemilla Compound Tablets; SuNerven; Wellwoman.

References

1 Gulubov AZ. Structure of alkaloids from Leonurus cardiaca. Nauch Tr Vissh Predagog Inst Plovdiv Mat Fiz Khim Biol 1970; 8: 129–132.

2Scott JH et al. Components of Leonurus cardiaca. Sci Pharm 1973; 41: 149–155.

3 Kartnig T et al. Flavonoid-O-glycosides from the herbs of Leonurus cardiaca. J Nat Prod 1985; 48: 494–507.

4Buzogany K, Cucu V. Comparative study between the species of

Leonurus quinquelobatus. Part II Iridoids. Clujul Med 1983; 56: 385– 388.

5Malakov P et al. The structure of leocardin, two epimers of a diterpenoid from Leonurus cardiaca. Phytochemistry 1985; 24: 2341– 2343.

6 Brieskorn CH, Hofmann R. Labiatenbitterstoffe: Ein clerodanderivat aus Leonurus cardiaca L. Tetrahedron Lett 1979; 27: 2511–2512.

7Brieskorn CH, Broschek W. Bitter principles and furanoid compounds of L. cardiaca. Pharm Acta Helv 1972; 47: 123–132.

8 Tschesche R et al. Caffeic acid 4-rutinoside from Leonurus cardiaca.

Phytochemistry 1980; 19: 2783.

9 Bird GWG, Wingham J. Anti-Cad lectin from the seeds of Leonurus cardiaca. Clin Lab Haematol 1979; 1: 57–59.

10Yeung HW et al. The structure and biological effect of leonurine – a uterotonic principle from the Chineses drug, I-mu Ts'ao. Planta Med 1977; 31: 51–56.

11Kong YC et al. Isolation of the uterotonic principle from Leonorus artemisia, the Chinese motherwort. Am J Chin Med 1976; 4: 373–382.

12Yanxing X. The inhibitory effect of motherwort extract on pulsating myocardial cells in vitro. J Trad Chin Med 1983; 3: 185–188.

13Kuo-Hsiung L et al. The cytotoxic principles of Prunella vulgaris,

Psychotria serpens, and Hyptis capitata: Ursolic acid and related derivatives. Planta Med 1988; 54: 308.

14Tokuda H et al. Inhibitory effects of ursolic and oleanolic acid on skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. Cancer Lett 1986; 33: 279–285.

Summary and Pharmaceutical Comment

The volatile oil, gum and resin components of myrrh are well documented. The anti-inflammatory and antipyretic activities documented in animals support some of the traditional uses. Phenol components of the volatile oil may account for the antimicrobial properties of myrrh, although no documented studies were located. Lipid-lowering properties via a stimulant action on the thyroid gland have been documented for C. mukul both in animals and, to a limited extent, in humans. However, robust clinical research assessing the efficacy and safety of myrrh is lacking. In view of the lack of toxicity data, excessive use of myrrh and use during pregnancy and lactation should be avoided.

Species (Family)

Commiphora myrrha (Nees) Engl. (Burseraceae)

Synonym(s)

African Myrrh, Arabian Myrrh, Balsamodendron Myrrha, Balsamodendron myrrha (Nees), Bitter Myrrh, Commiphora,

Commiphora molmol (Engl.) Engl., C. coriacea Engl., C. cuspidata Chiov., C. habessinica (O. Berg) Engl. var. grossedentata

Chiov., C. myrrha (Nees) Engl. var. molmol Engl., C. playfairii (Oliv.) Engl. var. benadirensis Chiov., C. rivae Engl., Diddin, Didin, Male Myrrh, Malmal, Mohmol, Molmol, Murr, Myrrh, Somali Myrrh, Yemen Myrrh

Part(s) Used

Oleo-gum-resin

Pharmacopoeial and Other Monographs

BHC 1992(G6)

BHP 1996(G9)

BP 2007(G84)

Complete German Commission E(G3)

ESCOP 2006(G76)

Martindale 35th edition(G85)

Ph Eur 2007(G81)

USP29/NF24(G86)

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General References G2, G6 and G52.

Carbohydrates Up to 60% gum yielding arabinose, galactose, xylose, and 4-O-methylglucuronic acid following hydrolysis.

Resins Up to 40% (average 20%) consisting of a-, b- and g- commiphoric acids, commiphorinic acid, a- and b-heerabomyr- rhols, heeraboresene and commiferin.

Steroids Campesterol, cholesterol and b-sitosterol.

Terpenoids a-Amyrin. Furanosesquiterpenes, including furaneu- desma-1,3-diene (major), furaneudesma-1,4-diene-6-one, lindes-

trine, curzerenone, furanodiene, 2-methoxyfuranodiene and 4,5- dihydrofuranodiene-6-one.(1, G52)

Volatile oils 1.5–17%. Main constituents are furanosesquiterpenes. Dipentene, cadinene, heerabolene, limonene, pinene, eugenol, m-cresol, cinnamaldehyde, cuminaldehyde, cumic alcohol and others.

Figure 1 Selected constituents of myrrh.

450 Myrrh

Pharmacological Actions

In vitro and animal studies

Anti-inflammatory activity Anti-inflammatory (carrageenaninduced inflammation and cotton pellet granuloma)(2) and antipyretic activities in mice(2, 3) have been documented for C. molmol.

Hypoglycaemic activity Hypoglycaemic activity in both normal and diabetic rats has been reported for a myrrh extract.(4, 5) Together with an aloe gum extract, myrrh was found to be an active component of a multi-plant extract that exhibited antidiabetic activity. The mode of action was thought to involve a decrease in gluconeogenesis and an increase in peripheral utilisation of glucose in diabetic rats.

Myrrh is stated to have astringent properties on mucous membranes(G45) and to have antimicrobial activities in vitro.(G41)

Anti-inflammatory activity Anti-inflammatory activities have been reported for an Indian plant, Commiphora mukul, commonly known as guggulipid. Anti-inflammatory activity was described for a crystalline steroidal fraction of guggulipid in both acute (carrageenan-induced rat paw oedema test) and chronic (adjuvant arthritis) models of inflammation.(6)

Lipid-lowering effects A ketosteroid has been identified as the active hypocholesterolaemic principle in guggulipid.(7) In some animal species, thyroid suppression is required as well as cholesterol administration in order to achieve experimental hypercholesterolaemia. Results of studies in chicks administered

Ma thyroid suppressant and cholesterol indicated that guggulipid prevents endogenous hypercholesterolaemia via stimulation of the thyroid gland.(7) When fed to rabbits, guggulipid has been found to reverse the decrease in catecholamine concentrations and

dopamine-b-decarboxylase activity that are associated with hyperlipidaemia.(8)

Stimulation of phagocytosis Stimulation of phagocytosis has

been documented in mice innoculated with Escherichia coli and given with extracts of myrrh by intraperitoneal injecton.(G52)

Cytoprotective activity An aqueous suspension of myrrh administered to rats at oral doses of 250–1000 mg/kg gave

significant and dose-dependent protection to gastric mucosa against various ulcerogenic agents.(G52)

Analgesic activity In mice, powdered myrrh (1 mg/kg, orally)

had significant analgesic activity in the hotplate test.(G52) Isolated furanoeudesma-1,3-dione (50 mg/kg, orally) was significantly more effective than control (p < 0.01) in the mouse writhing

test, and the effective dose was reversed by naloxone (1 mg/

kg).(G52)

Anti-tumour and cytotoxic activities In mice with Ehrlich solid tumours, an aqueous suspension of myrrh (250 or 500 mg/kg,

orally) produced significant decreases in tumour weight (p < 0.05) after 25 days.(G52) Aqueous suspension of myrrh increased survival

time in mice with Ehrlich ascite tumours.

Clinical studies

There is a lack of clinical research assessing the effects of myrrh and rigorous randomised controlled clinical trials are required.

Guggulipid has been reported to lower the concentration of total serum lipids, serum cholesterol, serum triglycerides, serum phospholipids and b-lipoproteins in 20 patients.(9) This effect was

reported to be comparable to that of two other known lipidlowering drugs also used in the study.

Side-effects, Toxicity

There is a lack of clinical safety and toxicity data for myrrh and further investigation of these aspects is required.

No reported side-effects were located for C. molmol or C. abyssinica. Hiccup,(9) diarrhoea,(7) restlessness and apprehension,(9) were documented as side-effects for guggulipid when administered to 20 patients.(9) Myrrh has been reported to be nonirritating, non-sensitising and non-phototoxic to human and animal skins.(G41)

Contra-indications, Warnings

Drug interactions None documented. However, the potential for preparations of myrrh to interact with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered. There is limited evidence from preclinical studies that myrrh has hypoglycaemic activity.

Pregnancy and lactation In view of the lack of safety information, use of myrrh during pregnancy and lactation should be avoided.

Preparations

Proprietary single-ingredient preparations

Germany: Inspirol P.

Proprietary multi-ingredient preparations

Argentina: Parodontax Fluor. Australia: Eczema Relief. Austria: Brady's-Magentropfen; Dentinox; Original Schwedenbitter; Paradenton; Parodontax; Parodontax. Brazil: Paratonico; Parodontax. Canada: Chase Coldsorex; Cold Sore Lotion. Chile: Astrijesan. Czech Republic: Dr Theiss Rheuma Creme; Dr Theiss Schweden Krauter; Dr Theiss Schwedenbitter. Denmark: Dolodent. Germany: Ad-Muc; Mint-Lysoform; Myrrhinil-Intest; Repha-Os. Hong Kong: Ad-Muc. Italy: Gengivario. Russia: Original Grosser Bittner Balsam (Ориги-

нальный Большой Бальзам Биттнера). South Africa: Helmontskruie; Lewensessens. Spain: Buco Regis. Switzerland: Pommade au Baume; Sanogencive. UK: Golden Seal Indigestion Tablets; Herbal Indigestion Naturtabs; HRI Golden Seal Digestive; Indigestion and Flatulence; Napiers Digestion Tablets; Nervous Dyspepsia Tablets; Vocalzone; Wind & Dyspepsia Relief. Venezuela: One Drop Spray.

References

1Brieskorn CH, Noble P. Constituents of the essential oil of myrrh. II: Sesquiterpenes and furanosesquiterpenes. Planta Med 1982; 44: 87–90.

2Tariq M et al. Anti-inflammatory activity of Commiphora molmol. Agents Actions 1986; 17: 381–382.

3Mohsin A et al. Analgesic, antipyretic activity and phytochemical screening of some plants used in traditional Arab system of medicine. Fitoterapia 1989; 60: 174–177.

4Al-Awadi FM, Gumaa KA. Studies on the activity of individual plants of an antidiabetic plant mixture. Acta Diabetol Lat 1987; 24: 37–41.

5Al-Awadi FM et al. On the mechanism of the hypoglycaemic effect of a plant extract. Diabetologia 1985; 28: 432–434.

6Arora RB et al. Anti-inflammatory studies on a crystalline steroid isolated from Commiphora mukul. Indian J Med Res 1972; 60: 929–

931.

7Tripathi SN et al. Effect of a keto-steroid of Commifora mukul L. on hypercholesterolemia and hyperlipidemia induced by neomercazole and cholesterol mixture in chicks. Indian J Exp Biol 1975; 13: 15– 18.

Myrrh 451

8 Srivastava M et al. Effect of hypocholesterolemic agents of plant origin on catecholamine biosynthesis in normal and cholesterol fed rabbits. J Biosci 1984; 6: 277–282.

9Malhotra SC, Ahuja MMS. Comparative hypolipidaemic effectiveness of gum guggulu (Commiphora mukul) fraction 'A', ethyl-p- chlorophenoxyisobutyrate and Ciba-13437-Su. Indian J Med Res 1971; 59: 1621–1632.