Stephania tetrandra prevents and regresses liver fibrosis induced by carbon tetrachloride in rats

Abstract

There is currently no safe and effective treatment for liver fibrosis. We have previously shown that Stephania tetrandra (ST) and Salvia miltiorrhiza (SM) suppress cell proliferation and enhance apoptosis of hepatic stellate cell (HSC) in vitro. In this study, we aimed to investigate the anti-fibrotic effect of these two herbs in vivo. Liver fibrosis was induced by carbon tetrachloride (CCl(4)) injection in rats for 5 weeks. SM, ST or SM + ST was gavaged on day 1 of CCl(4) administration to study the preventive effects of herbs on hepatic fibrosis. In a separate study designed to assess possible fibrosis regression, rats were randomly allocated to be treated with SM, ST or SM + ST when fibrosis was established. Liver injury and collagen content were assessed. HSC activation and apoptosis were determined. As compared with the CCL(4)-only rats, serum ALT was significantly lower in CCl(4)-treated rats that received either SM (P < 0.01) or ST (P < 0.01). Administration of ST significantly prevented (P < 0.01) or reversed the hepatic fibrosis (P < 0.01) induced by CCL(4). Moreover, rats treated with ST had reduced protein expression of alpha-SMA both in prevention (P < 0.05) and in regression (P < 0.01) experiments. The double-color staining of alpha-SMA and TUNEL showed that ST increased HSC apoptosis. However, co-treatment of SM + ST did not increase the antifibrotic effect of ST. Stephania tetrandra safely and effectively prevents and reverses hepatic fibrosis through activating HSC apoptosis in rats.