Pyrrolizidine alkaloids, hepatotoxicity

Borage Anti-inflammatory diuretic Pyrrolizidine alkaloids, hepatotoxicity Avoid... 

Coltsfoot Upper respiratory tract infections Pyrrolizidine alkaloids, hepatotoxicity Avoid ingestion of any parts of plant leaves may be used topically for anti-inflammatory effects for up to 4-6 weeks... 

Comfrey Symphytum species Leaves and roots Internal digestive aid, topical for wound healing Pyrrolizidine alkaloids, hepatotoxicity Avoid internal ingestion topical use should be limited to 4-6 weeks... 

Borage Borago officinalis Tops, leaves Anti -i nfl ammatory, diuretic Pyrrolizidine alkaloids, hepatotoxicity Avoid... 

Pride of India Pride-of-Madeira Echlum spp 1 Pyrrolizidine alkaloids hepatotoxicity... 

Lin G, Cui Y-Y, Liu X-Q and Wang Z-T (2002b), Species differences in the in vitro metabolic activation of the hepatotoxic pyrrolizidine alkaloids clivorine , Chem Res Toxicol, 15, 1421-1428. 

We knew Utetheisa to feed on poisonous plants as a larva (Figure 1B). The plants, of the genus Crotalaria (family Leguminosae), were known to contain pyrrolizidine alkaloids (henceforth abbreviated as PAs), intensely bitter compounds potently hepatotoxic to mammals (7). Other species of Utetheisa were known to sequester PAs (8). We found this to be true for U. ornatrix as well. Adult Utetheisa raised on Crotalaria spectabilis, one of the principal foodplants available to the moth in the United States, contain on average about 700 p,g of monocrotaline (1), the principal PA in that plant (9, 10). 

Comfrey (Symphytum officinale) Uses Topical treatment of wounds, bruises, sprains, inflammation Action Multiple chemical components, allantoin promotes cell division, rosmarinic acid has anti-inflammatory effects, tannin possesses astringent effects, mucilage is a demulcent w/ anti-inflammatory properties, pyrrolizidine alkaloids cause hepatotox Available forms Topical application w/ 5—20% of herb applied on intact skin for up to 10 d Contra Do not take orally d/t hepatotox, do not use if PRG or w/ lactation Notes/SE N/V, exfoliative dermatitis w/ topical use Interactions T Risk of hepatotox W/ ingestion of borage, golden ragwort, hemp, Petasites EMS None... 

Mattocks, A. R. (1971). Hepatotoxic effects due to pyrrolizidine alkaloid /V-oxides. Xenobiotica 1 563-565. 

Russian comfrey (Symphytum x uplandicum Nyman) is widely recommended as a medicinal herb and an item of human diet. A previous investigation of this species led to the isolation of three alkaloids which were not fully characterized (cf. Vol. 7, p. 57). Culvenor and co-workers have separated eight pyrrolizidine alkaloids from the leaves of this perennial plant by counter-current distribution.21 The known alkaloids echimidine (51), symphytine (52), lycopsamine (53), and intermedine (54) were present. In addition, four new alkaloids, i.e. 7-acetyl-lycopsamine (55), 7-acetylintermedine (56), symlandine (57), and uplandicine (58), were characterized by spectroscopic methods, and by hydrolysis. The total alkaloidal extract caused chronic hepatotoxic effects in rats, and the authors... 

Pyrrolizidine alkaloids (PAs) are a typical class of plant secondary metabolites, which certain butterflies and moths in particular groups, that is, Danainae, Ithomiinae (Nymphalidae), and Arctiidae, sequester as larvae or adults and utilize as chemical defensive substances against predatory enemies, probably due to their bitter taste and hepatotoxicity.13 PAs also serve as precursors of male pheromones of PA-storing lepidopterans. 

Mattocks, A.R. (1972) Acute hepatotoxicity and pyrrolic metabolites in rats dosed with pyrrolizidine alkaloids. Chem. Biol. Interact., 5, 227-42. 

There are no drugs based on the pyrrolizidine alkaloids of the Asteraceae (e.g., Senecio and Symphytum) and Boraginaceae (Crotolaria). However, these alkaloids pose a great threat to human and animal health because of their potential for inadvertent consumption. In the case of 1,2-dehydro derivatives, such as senecio-nine, ingestion leads to non-reversible hepatotoxicity. Pyrrolizidine nucleus formation from two units of ornithine is shown (Fig. 24). 

Petasites species have hepatotoxic potential, owing to the presence of pyrrolizidine alkaloids, which are covered in a separate monograph. Extracts of Petasites hybridus (blat-terdock, bog rhubarb, butterbur, butterdock) contain ht-tle in the way of these alkaloids (31). Butterbur has been used to treat allergic rhinitis and asthma and in the prevention of migraine. 

Many species of Senecio, such as Senecio jacobaea (ragwort) and Senecio longilobus (thread leaf groundsel), contain hepatotoxic amounts of pyrrolizidine alkaloids (which are covered in a separate monograph). Honey made from Senecio plants also contains pjrrolizidine alkaloids (32). 

Tussilago farfara (coltsfoot) has hepatotoxic potential owing to the presence of pyrrolizidine alkaloids (see separate monograph). 

Symphytum officinale (black wort, boneset, bruise wort, comfrey, knitback, knitbone, slippery root) contains pyrrolizidine alkaloids, such as lasiocarpine and symphytine, and their N-oxides, and has repeatedly been associated with hepatotoxicity. 

Most of the members of the Crotalaria (rattlebox) species contain pyrrolizidine alkaloids, such as crotaline and monocrotaline, and therefore have hepatotoxic potential (18). These alkaloids are covered in a separate monograph. 

Unfortunately, persistent misconceptions about botanical safety become part of the conventional wisdom about herbs, as the original case reports are repeatedly cited without any acknowledgement of the explicatory letters that follow in subsequent volumes of the journals in which the original reports or letters appeared. In addition to this unfortunate situation, adverse effects of particular herbs have been predicted, in the absence of case reports or even in vitro studies, on the basis of the chemical composition of the herb in question. For instance, Miller (1998) warned about the expected hepatotoxicity of Echinacea spp. based on the occurrence of the pyrrolizidine alkaloids tussilagine and isotussilagine. These compounds are indeed present (at 0.006%) in Echinacea root, but they are nontoxic because they lack the structural features (1,2 unsaturation in the pyrrolizidine ring) mentioned above necessary for hepatic activation into reactive pyrroles. 

Armstrong, B. and Doll, R. 1975. Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Intern. J. Cancer 15, 617-631. Arseculeratne, S., Gunatilaka, A., and Panabokke, R. 1981. Studies on medicinal plants of Sri Lanka Occurrence of pyrrolizidine alkaloids and hepatotoxic properties in some traditional medicinal herbs. J. Ethnopharmacol. 4, 159-177. 

Biller et al. (22) isolated the pyrrolizidine alkaloids 7-and 9-angeloylretronecine, intermedine, rinderine and 3 -acetylrinderine. The concentrations of these hepatotoxic alkaloids were high in the roots and mature flower heads, but negligible in the leaves and stems. This finding is noteworthy since the leaves are mostly used in traditional medicine. Phenolic acids including protocatechuic, />-hydroxybenzoic, />-coumaric, femlic and vanillic acids have also been isolated from the plant (29). 

Comfrey is a perennial herb used for the prevention of kidney stones nourishing and repairing bone and muscle and for the treatment of injuries such as burns and bruises. In Australia, comfrey is classified as a poison and its sales have been restricted in several regions. Many different commercial forms of comfrey are marketed, including oral and external products. Commercial comfrey is usually derived from the leaves or roots of Symphytum officinale (common comfrey). However, some products are also derived from Russian comfrey. Russian comfrey contains a very toxic pyrrolizidine alkaloid, echimidine, which is not found in common comfrey. However, common comfrey contains other hepatotoxic alkaloids, namely 7-acetylintermedine, 7-acetyllycopsamine and symphytine. The metabolites of these alkaloids are very toxic to the liver. Ridker et al. documented hepatic venocclusive disease associated with consumption of comfrey root. Long-term smdies in animals have also confirmed the carcinogenicity of comfrey in animal models. ... 

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