Schisandrin B improves non-alcoholic fatty liver disease by impacting intestinal mucosal barrier function

In recent years, the prevalence of non-alcoholic fatty liver disease (NAFLD) has been dramatically increased in China and specific targeted therapy is still unavailable. The purpose of this research was to investigate whether schisandrin B (SchB) improves NAFLD and the potential mechanisms. Wildtype mice with C57BL/6J background were treated with special high fat diet (containing 40% fat, 22% fructose, 10% sucrose, and 2% cholesterol) for 16 weeks to induce NAFLD. Then SchB (120 mg·kg^-1) were used to treat NAFLD mice for 6 weeks. Body weight, food intake, glucose tolerance, insulin resistance, serum level of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assayed and histopathological analysis were performed to evaluate the improvement of NAFLD induced by SchB. Furthermore, the level of lipopolysaccharide (LPS) in serum, intestinal permeability, and the expression of genes and proteins associated with mucosal defense were evaluated, intestinal flora composition in fresh cecal contents were analyzed and differential flora were identified to explore the potential mechanism. All animal experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. These results showed that SchB significantly reduced the body weight of NAFLD mice without changing food intake, and effectively reduced serum level of TC, ALT, and AST. SchB also significantly altered the composition of the microflora in NAFLD mice, increased the abundance of the Akkermansia muciniphila (A. Muciniphila) and elevated the expression of genes and proteins associated with the mucosal defense in ileum and colon, restored the permeability of intestinal barrier. In summary, SchB improves NAFLD by regulating the composition of the microflora and enhancing the function of intestinal barrier to further reduce the excessive lipids accumulation and hepatic inflammation.