Effect of tetrandrine on experimental hepatic fibrosis induced by bile duct ligation and scission in rats

Tetrandrine, an alkaloid isolated from the Chinese medicinal herb Stephania tetrandra, has been shown to elicit antifibrotic effects in various cell t ypes. In the present study, the effect of tetrandrine on liver fibrosis was investigated by using bile duct ligation and scission in rats as a model o f hepatic fibrosis. Treatment with tetrandrine in fibrotic rats reduced ser um aspartate aminotransferase, alanine aminotransferase, and alkaline phosp hatase levels to 72%, 52% and 51% that of controls at 10 mg/kg/day, respect ively. Liver hydroxyproline contents in tetrandrine-treated rats with bile duct ligation and scission were also reduced to 65% of that of control rats with bile duct ligation and scission at 10 mg/kg/day. The morphological ch aracteristics of fibrotic liver, which appeared in control bile duct ligati on and scission group, were improved in tetrandrine-treated bile duct ligat ion and scission group. We also examined the effect of tetrandrine on cultu red rat hepatic stellate cells, which plays an important role in the pathog enesis of hepatic fibrosis, activation to investigate whether it could act mainly by direct action on rat hepatic fibroblastic cells. In cultured rat hepatic stellate cells, tetrandrine reduced DNA synthesis to 57% of control hepatic stellate cells at 10 mug/ml without affecting cell viability Smoot h muscle-cc-actin expression, the phenotypic marker of activated hepatic st ellate cells, was also decreased. We conclude that tetrandrine has an antif ibrotic effect on liver fibrosis in rats induced by bile duct ligation and scission, indicating that it might exert a direct effect on rat hepatic ste llate cells.