[Pharmacology and toxicology of Guatteria gaumeri and alpha-asarone]

Guatteria gaumeri Greenman (Annonacease) has been used as bark infusion in the traditional mexican medicine for the treatment of hypercholesterolemia and cholelithiasis. The main component is alpha-asarone which has been isolated by different extraction procedures and subsequently synthetized, as well as 16 analogs, derivatives of 4-propenyl-1,2-dimethoxybenzenes 5-substituted. After daily dosing per os of 80 mg/kg of alpha-asarone and the amino and metoxi analogs for seven days to hypercholesterolemic male rats, cholesterol decreased 57.3, 37.5 and 46.9% and triglycerides diminished 42.5, 67.6 and 17.2% respectively. Some of the other analogs showed also important hypolipidemic activity. Similarly alpha-asarone decreased 80.6% the weight of gallstones in hamsters. Studies using adult rat hepatocytes suggest that at least part of the hypolipidemic effect of alpha-asarone could be due to a decrease in the secretion of lipids. Alpha-asarone did not produce any toxic effect after oral administration to rats of 10 or 50 mg/kg for 28 days, or genotoxicity by the dominant lethal test. However long-term exposure of cultivated hepatocytes to micromolar concentrations produced morphologic and ultrastructural alterations, triacylglycerol accumulation and inhibition of protein synthesis and secretion. At the same time both the Ames and sister-chromatid exchange tests showed genotoxic effect. No teratogenicity was observed in pregnant rats during organogenesis but in mice slight fetal toxicity was manifested by hydrocephaly, skeletal defects and fetal weight retardation. There are no data on the possible exposure levels in humans consuming the bark extract, but the toxic effects of alpha-asarone in animals suggest caution in the use of this plant.(ABSTRACT TRUNCATED AT 250 WORDS)