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

Summary

Background

To investigate the potential mechanisms underlying the protective effects of 18α 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 18α GL group (25 mg/kg/d), intermediate-dose 18α GL group (12.5 mg/kg/d) and low-dose 18α GL group (6.25 mg/kg/d). The rat liver fibrosis model was induced by carbon tetrachloride (CCl4). The expressions of α-smooth muscle actin (αSMA) and NF-κB were determined by real-time PCR and immunohistochemistry.

Results

18αGL dose-dependently inhibited the CCl4-induced liver fibrosis. There were significant differences in the mRNA and protein expressions of αSMA between the fibrosis group and 18α-GL treatment groups, suggesting that 18α 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 18α-GL treatment groups increased HSC apoptosis. NF-κB was mainly found in the nucleus in the fibrosis group, while cytoplasmic expression of NF-κB was noted in the 18αGL groups. In the in vitro experiments, 18α GL promoted the proliferation of hepatocytes, but inhibited that of HSCs. HSCs were arrested in the G2/M phase following 18α GL treatment and were largely apoptotic.

Conclusions

18α-GL can suppress the activation of HSCs and induce the apoptosis of HSCs by blocking the translocation of NF-κB into the nucleus, which plays an important role in the protective effect of 18α-GL on liver fibrosis.