Plants Containing Pyrrolizidine Alkaloids Used in the Traditional Indian Medicine – Including Ayurveda
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REVIEW Pharmazeutisches Institut der Rheinischen Friedrich-Wilhelms-Universität, Bonn, Germany Plants containing pyrrolizidine alkaloids used in the Traditional Indian Medicine – including Ayurveda E. Roeder, H. Wiedenfeld Received July 11, 2012, accepted August 10, 2012 Prof. Dr.Dr.h.c. Erhard Roeder,Dr.Helmut Wiedenfeld, Pharmazeutisches Institut der Universität, An der Immenburg 4, D-53121 Bonn, Germany [email protected]; [email protected] Dedicated to Prof. Dr. Dr. h.c. Miroslawa Furmanowa on the occasion of her 85th birthday. Pharmazie 68: 83–92 (2013) doi: 10.1691/ph.2013.2706 Pyrrolizidine alkaloids (PAs) show a hazardous potential for humans and animals. They can possess mutagenic, teratogenic, cancerogenic and fetotoxic properties. One pathway of a human intoxication can be the use of medicinal plants which contain toxic PAs. The Traditional Indian medicine – in particular Ayurveda – is a popular and well-known healing system. Within this system several PA-containing plants are used which, on account of their PAlevel, represent a severe health risk. In general, it is not recommended to use plants containing those toxic compounds. 1. Introduction for the toxicity) which can result in mutagenic, genotoxic, can- cerogenic and fetotoxic effects (Fu et al. 2002, 2004, 2007; Xia The traditional medicine of India (TIM) consists of several et al. 2004, 2006; Wiedenfeld et al. 2008; Wiedenfeld and Edgar systems and enjoys great popularity worldwide. Within these 2011; Fig. 1). systems, especially “Ayurveda” is well-known and is practised in many countries; even hospital facilities can be found focused on an ayurvedic treatment. The first reports of TIM date back to 2000 BC. It influenced the 2. PA-containing plants in TIM Chinese and Tibetian and even Western medicine. Ageratum conyzoides L. (syn. Carelia conyzoides (L.) Kuntze., Although there are various studies demonstrating the successful syn. Eupatorium conyzoides (L.) Krause). [Asteraceae, sub- treatment by TIM e.g. in the case of heart diseases, asthma, family Asteroideae, tribe Eupatorieae]. Engl. name: bill goat, diabetes type II, rheuma, fistula-in-ano, there are hardly any goat weed; vernacular name: Ajagandha, Appa grass, Dochunty, evidence-based or double-blind studies which show the efficacy Uchunti, Gandhari, Schahadevi, Vishamushti (Nair et al. 1998; and importance of TIM preparations in modern medicine. This Samant et al. 1998; Khare 2007; Jadhav 2008; Enchanting may be caused by the frequent absence of a clear description of 2011). Distribution: whole India, especially southern India, up the active ingredients and/or the active principles. to an altitude of 1.800 m. Medicinal use: against haemorrhoids, No reports can also be found about possible long-term side dyspepsia, kidney stones, cuts, ulcers, wounds, diarrhoea and effects resulting from TIM treatment. However, these side- flatulence. The juice of the herb is used for rectal injections. effects are likely to be experienced if PA-containing plants or Intravaginal for uterine disorders. The leaves and stem have preparations from them are used. As already described for Euro- antiemetic, antitetanic and styptic properties. Contains the toxic pean and Chinese traditional medicines (Roeder 1995, 2000) alkaloids lycopsamine (15), and echinatine (30) (Wiedenfeld and for plants used in Mongolia, Nepal and Tibet (Roeder et al. et al. 1991). Alkanna tinctoria L. Tausch. [Boraginaceae, sub- 2009) and in Madagascar and the Mascarene islands (Roeder family Boraginoideae, tribe Lithospermeae]. et al. 2011) also in TIM different plants or preparations are used Engl. name: alkanet, dyers or Spanish bugloss. Distribution: which have already been described to contain toxic PAs or are natural in South Europe, cultivated in India. Medicinal use: suspected of containing them. adstringent, antimicrobial, used for indolent ulcers erysipelas Chemically, PAs are ester compounds deriving from a bicyclic (Khare 2007). In the traditional medicine of the Unani (located five-membered ring (necine) in form of mono-, di- or macro- in Kasmir) A. tinctoria can be replaced by Onosma echioides. cyclic diesters. In case the necine shows a double-bond in Contains the toxic pyrrolizidine alkaloids O7-angeloyl- position 1,2 and a non-substitution adjacent to the bridge nitro- retronecine (9), triangularine (19), dihydroxytriangularine (20) gen atom, the resulting PAs can be toxic for humans and (Roeder et al. 1984). domestic animals. Although showing no or only low active toxi- Anchusa italica Retz. (syn. A. azurea Mill) [Boraginaceae, sub- city, PAs can undergo a 3-step metabolic toxication to alkylating family Boraginoideae, tribe Boragineae]. Engl. name: alkanet, agents in the human or animal liver (being the first target organ cow’s tongue plant. Distribution: in Indian gardens and hills. Pharmazie 68 (2013) 83 REVIEW Fig. 1: Metabolism of toxic PAs Medicinal use: stimulant, tonic, demulcent used in bilious com- Chromolaena odorata (L.) King & Robinson (syn. Eupatorium plaints, fever, cough, asthma, as diuretic in bladder and in case odoratum L., syn. Osmia odorata (L.) Sch. Bip.). [Aster- of kidney stones (Khare 2007). aceae, subfamily Asteroideae, tribe Eupatorieae]. Engl. name: The botanically related species A. strigosa contains 3 nontoxic Siam weed, bitter bush, goat weed; vernacular name: Ropani, alkaloids (2, 3, 4) as well as 4 toxic ones (23–26) (Braca et al. Seekhrasarpi. Distribution: throughout India, growing in waste- 2003; Siciliano et al. 2005). lands as a weed. Medicinal use: juice of the leaves applied to cuts Arnebia benthami (Wall. ex G. Don) Johnston. (syn. Macroto- and wounds, burns, haemorrhages, indigestion, skin diseases, mia benthami Wall ex G.Don; syn. Lithospermum benthamii traumatic injury, edema, fracture and infections (Nair et al. 1998; (Wall ex G. Don). [Boraginaceae, subfamily Boraginoideae, Samant et al. 1998; Enchant 2011). Contains the toxic alkaloids tribe Lithospermeae] Engl. name: Himalayan arnebia. Distri- O7-angeloylretronecine (9), O9-angeloylretronecine (10), inter- bution: In alpine Himalayas from Kashmir to Kumaon, at an medine (11), rinderine (27), O7,O3 -diacetylrinderine (28) and altitude of 3.000–3.900 m. Medicinal use: stimulant, diuretic, supinine (36) (Biller et al. 1994; Prasad et al. 2005). used in diseases of the mouth and throat, also in the treatment of Cordia dichotoma Forst. (syn. C. myxa L., syn. C. latifolia fevers and debility; antiseptic (Samant et al. 1998; Khare 2007; (Roxb.), syn. C. obliqua Willd., syn. C. wallichii G. Don. [Bor- Sharma et al. 2009). aginaceaeeee, subfamily Cordioideae, tribe Cordieae]. Engl. Arnebia euchroma (Royle) Johnst. (syn. Macrotomia euchroma name: Indian sherry, Sebestan plum; vernacular name: Shlesh- Royle) [Boraginaceae, subfamily Boraginoideae, tribe Lithos- maataka, Shelu, Bahuvaara, Bhuutvaaraka, Uddaalaka, Shita, permeae]. Distribution: in alpine Himalayas from Kashmir to Picchila, Lisodaa, Bahuvarkara. Distribution: all over India, wild India, at an altitude of 3.400–4.500 m. Medicinal use: induces and often planted up to 1.500 m. Medicinal use: rheumatism, apoptosis and exerts antitumor effects and is used to treat asthma, expectorant, leprosy, ulcers; leaves and fruits as diuretic cancer (Huang et al. 2005; Bhatia et al. 2011). The plant expectorant, demulcent and against stomach-aches. Used medi- contains the toxic alkaloids O7-angeloylretronecine (9) and O9- cally in pectoral diseases, ulcers, headache, respiratory system, angeloylretronecine (10) (Roeder et al. 1993b). asthma, cough, cold, allergic bronchitis, antispasmodic, leprosy Arnebia nobilis Rech f. [Boraginaceae, subfamily Boragi- and ulcers (Nair et al. 1998; Kapoor 2001; Drury 2006; Khare noideae, tribe Lithospermeae]. Distribution: whole India. 2007; Singh 2008; Jadhav 2008; Sharma et al. 2009; Enchanting Medicinal use: antitumor plant (Rastogi et al. 1990; Arora et al. 2011). It contains the alkaloid macrophylline (8) (Wassel et al. 2009; Bhatia et al. 2011). The plant contains alkaloids with 1987). unknown structure. It can be expected that there exists a similar Cordia rothii Roem & Schult. [Boraginaceae, subfamily content like in A. euchroma. Cordioideae, tribe Cordieae]. Engl. name: Sebestan; vernacu- 84 Pharmazie 68 (2013) REVIEW lar name: Laghu-shleshmaataka, Shelu, Lisodaa. Distribution: Ehretia buxifolia Roxb. (syn. Carmona microphylla (Lam.) Rajastan, Gujarat, Deccan, and Karnataka. Medicinal use: An G. Don.) [Boraginaceae, subfamily Ehretioideae, tribe adstringent decoction is used as gargle (Khare 2007; Singh 2008; Eritrichieae]. Distribution: common in dry scrub forests of Sharma et al. 2009). The alkaloidal content should be similar to India. Medicinal use: Root is used of cachexia and venereal C. dichotoma. affections of long standing and is an antidote to vegetable Crotalaria burhia Buch-Ham. ex Benth. [Fabaceae, subfamily poisons (Nair et al. 1998; Drury 2006; Khare 2007). The Faboideae, tribe Crotalarieae]. Distribution: Southern part of closely related E. aspera Willd. contains the non-toxic alkaloid India. Medicinal use: anticancer activities (Rastogi et al. 1990). ehretinine (5). (Suri et al. 1980). Contains the toxic alkaloids monocrotaline (39), croburhine Ehretia laevis Roxb. var. aspera (Willd.) C.B. Clarke (syn. E. (44), crosemperine (63) (Ali et al. 1973; Rao et al. 1975; Ahmad aspera Wiild., syn. E. obtusifolia Hochst ex DC) [Boraginaceae, et al. 1986). subfamily Ehretioideae, tribe Eritrichieae]. Vernacular name: Crotalaria juncea L. [Fabaceae,