The inhibition of Hippo/Yap signaling pathway is required for magnesium isoglycyrrhizinate to ameliorate hepatic stellate cell inflammation and activation.

Liver fibrosis is a reversible pathological process accompanied by abnormal inflammation, and its end-stage cirrhosis is responsible for high morbidity and mortality worldwide. This study was to investigate the effect of Magnesium isoglycyrrhizinate (MgIG) on liver fibrosis and inflammation, and to further clarify molecular mechanism. We found that MgIG treatment significantly alleviated carbon tetrachloride (CCl4)-induced liver fibrosis and HSC activation by regulating TGF-β signaling and MMP/TIMP systems. In addition, MgIG treatment significantly inhibited the inflammatory response of liver fibrosis in mice characterized by reduced pro-inflammatory factors expression and increased anti-inflammatory factors expression. Interestingly, experiments in vitro also showed that MgIG treatment significantly reduced the expression of hepatic stellate cell (HSC) activation markers. Besides, MgIG treatment not only inhibited the expression of pro-inflammatory factors, but also promoted the production of anti-inflammatory factors in activated HSCs. Importantly, treatment with MgIG inhibited Hippo/Yap signaling pathway, which was a potential mechanism for MgIG-induced anti-inflammatory effects. The overexpression of Hippo/Yap signaling effector YAP completely impaired MgIG-induced anti-inflammatory and anti-fibrotic effects. Taken together, these results provide novel implications to reveal the molecular mechanism of the anti-inflammatory properties induced by MgIG, by which points to the possibility of using MgIG to treat liver fibrosis.