Hepatotoxic plants Pyrrolizidine

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). 

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... 

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. 

Alkaloids that contain pyrrolidine and pyrrolizidine ring systems are derived from the nonprotein amino acid, L-ornithine. Cocaine (Nl) and (—)-hyoscyamine, the two important pyrrolidine alkaloids that contain a tropane ring system, have been found to occur in coca (Erythroxylon coca, Erythroxylaceae) leaves and the whole plant of the deadly nightshade (Atropa belladonna, Solanaceae). The hepatotoxic alkaloid senecionine (N2) contains a bicyclic pyrrolizidine skeleton derived from two molecules of L-ornithine. 

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). 

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). 

In a study of toxicity of Sri Lankan traditional medicinal herbs, Arseculer-atne and co-workers evaluated 125 commonly used medicinal plants for the occurrence of hepatotoxic pyrrolizidine alkaloids (129,130). Crotolaria juncea, C. verrucosa, and Holarrhena antidysenterica were shown to contain pyrrolizidine alkaloids by TLC. When fed to rats, these plants produced hepatic lesions compatible with the action of pyrrolizidine alkaloids. 

Crotalaria sagittalis-. The roots of this fabaceous plant were considered to be avery strong narcotic by the Delaware-Okl Indians (lantaquic eon 1942). Dangerous hepatotoxic pyrrolizidine alkaloids are known from Crotalaria species, and their ingestion should thus be avoided assiduously (Turner Szczawinski 1991). 

Comfrey Symphytum officinale Anti-inflammatory gastritis diarrhea Hepatic veno-occlusive disease possible teratogen/carcinogen. (Note many other plants also contain hepatotoxic pyrrolizidine alkaloids-see Table 11-46). 

C,gH27NO Mr 337.42, mp. 129°C, [aJo -59° (C2H5OH). P. is a pyrrolizidine alkaloid from various genera of the Asteraceae, tribe Senecioneae (Adeno-styles, Senecio, Petasites). It exists in the plants as the (V-oxide. P. does not exhibit hepatotoxicity, isrelatively non-toxic, and has atropine-like activities. It was used in the former USSR for the treatment of stomach diseases. 

Pyrrolizidine alkaloids, a large group of plant bases, have been known for some considerable time to possess pharmacological activity, and in particular hepatotoxicity [34]. Recent studies have revealed that certain members of this class of alkaloids display antitumour activity against Walker 256, Ca 755, and S 180, and do not have significant cytotoxicity [35]. Structure-activity relationship studies have shown (a) that the active alkaloids include retronecine (Ila), mono- and di-esters of monobasic acids, cyclic esters of dibasic acids, and some iV-oxides of these alkaloids, and (b) that four cyclic diesters of retronecine and unesterified amino alcohols are inactive. From... 

Use discouraged due to potential presence of hepatotoxic pyrrolizidine alkaloids ubiquitous in Eupatorium species (newall). Abortion in cattle grazing on the plant is attributed to a high content of nitrate. Toxic principles are believed to include eupatorin (cytotoxic, emetic), bitter components (gastrointestinal irritants), and lactones (skin sensitizers) (brinker). 

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