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

Background and Aim:  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 .
Methods:  Liver fibrosis was induced by carbon tetrachloride (CCl₄) injection in rats for 5 weeks. SM , ST or SM  +  ST was gavaged on day 1 of CCl₄ 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.
Results:  As compared with the CCL₄-only rats, serum ALT was significantly lower in CCl₄-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 CCL₄. Moreover, rats treated with ST had reduced protein expression of α-SMA both in prevention ( P  < 0.05) and in regression ( P  < 0.01) experiments. The double-color staining of α-SMA and TUNEL showed that ST increased HSC apoptosis. However, co-treatment of SM  +  ST did not increase the antifibrotic effect of ST .
Conclusions:  Stephania tetrandra safely and effectively prevents and reverses hepatic fibrosis through activating HSC apoptosis in rats.