18?-Glycyrrhizin induces apoptosis and suppresses activation of rat hepatic stellate cells.

ABSTRACT: BACKGROUND: To investigate the potential mechanisms underlying the protective effects of 18? Glycyrrhizin (GL) on rat hepatic stellate cells (HSCs) and hepatocytes in vivo and in vitro. MATERIAL/METHODS: Sprague-Dawley (SD) rats were randomly divided into 5 groups: normal control group, liver fibrosis group, high-dose 18? GL group (25 mg/ kg/d), intermediate-dose 18? GL group (12.5 mg/kg/d) and low-dose 18? GL group (6.25 mg/ kg/d). The rat liver fibrosis model was induced by carbon tetrachloride (CCl4). The expressions of alpha-smooth muscle actin (?SMA) and NF-kappaB were determined by real-time PCR and immunohistochemistry. RESULTS: 18?GL dose-dependently inhibited the CCl4-induced liver fibrosis. There were significant differences in the mRNA and protein expressions of ?SMA between the fibrosis group and 18?-GL treatment groups, suggesting that 18? GL can suppress the proliferation and activation of HSCs. Few HSCs were apoptotic in the portal area and fibrous septum in the liver fibrosis group. However, the double-color staining of a-SMA and TUNEL showed that 18?-GL treatment groups increased HSC apoptosis. NF-kappaB was mainly found in the nucleus in the fibrosis group, while cytoplasmic expression of NF-kappaB was noted in the 18?GL groups. In the in vitro experiments, 18? GL promoted the proliferation of hepatocytes, but inhibited that of HSCs. HSCs were arrested in the G2/M phase following 18? GL treatment and were largely apoptotic. CONCLUSIONS: 18?-GL can suppress the activation of HSCs and induce the apoptosis of HSCs by blocking the translocation of NF-kappaB into the nucleus, which plays an important role in the protective effect of 18?-GL on liver fibrosis.

SUBMITTER: Qu Y 

PROVIDER: S-EPMC3560665 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature