Schisantherin A protects hepatocyte via upregulating DDAH1 to ameliorate liver fibrosis in mice

Abstract

Background: Hepatic fibrosis is the pivotal determinant in the progression of chronic liver diseases towards cirrhosis or advanced stages. Studies have shown that Schisantherin A (Sin A), the primary active compound from Schizandra chinensis (Turcz.) Baill., exhibits anti-hepatic fibrosis effects. However, the mechanism of Sin A in liver fibrosis remain unclear.

Purpose: To examine the effects and underlying mechanism of Sin A on hepatic fibrosis.

Study design and methods: The effects and mechanism of Sin A were investigated using liver fibrosis mouse models induced by carbon tetrachloride (CCl₄) or dimethylnitrosamine (DMN), as well as H₂O₂-induced hepatocyte injury in vitro.

Results: Sin A treatment ameliorated hepatocyte injury, inflammation, hepatic sinusoidal capillarization, and hepatic fibrosis in both CCl₄-induced and DMN-induced mice. Sin A effectively reversed the reduction of DDAH1 expression, the p-eNOS/eNOS ratio and NO generation and attenuated the elevation of hepatic ADMA level induced by CCl₄ and DMN. Knockdown of DDAH1 in hepatocytes not only triggered hepatocyte damage, but it also counteracted the effect of Sin A on protecting hepatocytes in vitro.

Conclusion: Our findings indicate that Sin A ameliorates liver fibrosis by upregulating DDAH1 to protect against hepatocyte injury. These results provide compelling evidence for Sin A treatment in liver fibrosis.

Keywords: DDAH1; Hepatic sinusoidal capillarization; Hepatocyte; Inflammation; Liver fibrosis; Schisantherin A.