PHARMACOLOGY AND TOXICOLOGY OF GUATTERIA- GAUMERI

Guatteria gaumeri Greenman (Annonacease) has been used as bark infusio n in the traditional mexican medicine for the treatment of hypercholes terolemia and cholelithiasis. The main component is alpha-asarone whic h has been isolated by different extraction procedures and subsecuentl y synthetized, as well as 16 analogs, derivatives of 4-propenyl-1,2-di methoxybenzenes 5-substituted. After daily dosing per os of 80 mg/kg o f alpha-asarone and the amino and metoxi analogs for seven days to hyp ercholesterolemic 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. Si milarly alpha-asarone decreased 80.6% the weight of gallstones in hams ters. Studies using adult rat hepatocytes suggest that at least part o f the hypolipidemic effect of alpha-asarone could be due to a decrease in the secretion of lipids. Alpha-asarone did not produce any toxic e ffect after oral administration to rats of 10 or 50 mg/kg for 28 days, or genotoxicity by the dominant lethal test. However long-term exposu re of cultivated hepatocytes to micromolar concentrations produced mor phologic and ultraestructural alterations, triacylglycerol accumulatio n and inhibition of protein synthesis and secretion. At the same time both the Ames and sister- chromatide exchange tests showed genotoxic e ffect. No teratogenicity was observed in pregnant rats during organoge nesis but in mice slight fetal toxicity was manifested by hidrocephaly , 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. It is interesting to carry out other investigations on alpha-asarone especially the toxicologic screening of the new anal ogs.