Protective effect of α- and β-amyrin, a triterpene mixture from Protium heptaphyllum (Aubl.) March. trunk wood resin, against acetaminophen-induced liver injury in mice

In the search of hepatoprotective agents from natural sources, alpha- and P-amyrin, a triterpene mixture isolated from the trunk wood resin of folk medicinal plant, Protium heptaphyllum was tested against acetaminophen-induced liver injury in mice. Liver injury was analysed by quantifying the serum enzyme activities and by histopathological observations. In mice, acetaminophen (500 mg/kg, p.o.) caused fulminant liver damage characterized by centrilobular necrosis with inflammatory cell infiltration, an increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, a decrease in hepatic glutathione (GSH) and 50% mortality. Pretreatment with alpha- and beta-amyrin (50 and 100 mg/kg, i.p. at 48, 24, and 2 h before acetaminophen) attenuated the acetaminophen-induced acute increase in serum ALT and AST activities, replenished the depleted hepatic GSH, and considerably reduced the histopathological alterations in a manner similar to N-acetylcysteine, a sulfhydryls donor. Also, the acetaminophen-associated mortality was completely suppressed by terpenoid pretreatment. Further, alpha- and beta-amyrin could potentiate the pentobarbital (50mg/kg, i.p.) sleeping time, suggesting the possible suppression of liver cytochrome-P450. These findings indicate the hepatoprotective potential of alpha- and beta-amyrin against toxic liver injury and suggest that the diminution in oxidative stress and toxic metabolite formation as likely mechanisms involved in its hepatoprotection. In conclusion, this study supports the traditional use of Protium heptaphyllum, resin as a medicinal agent and suggests the feasibility of developing herbal drugs for treatment of liver disorders. (c) 2005 Elsevier Ireland Ltd. All rights reserved.