Schisandrin B inhibits hepatic inflammation and steatosis via activation of pregnane X receptor signaling in methionine and choline-deficient high fat diet-induced steatohepatitis mouse model.

Abstract

Schisandrin B (Sch B), a key bioactive lignan extracted from Schisandra chinensis (Turcz.) Baill, exhibits lipid lowering and anti-inflammatory properties in vivo and in vitro. However, few studies investigate the anti-metabolic dysfunction associated steatohepatitis (MASH) effect of Sch B. In this study, we employed a methionine and choline-deficient high fat diet (MCDHF)-induced MASH mouse model and palmitate acid (PA)-induced MASH cell models to evaluate the anti-inflammatory and anti-steatosis effects of Sch B. We also explore the molecular targets of Sch B for its anti-MASH effect. The results showed that Sch B treatment markedly suppressed the production of inflammatory factors and lipid accumulation in MASH mice, as well as in PA-exposed HepG2 cells and mouse primary hepatocytes (MPHs). It also reduced the content of hepatic lipid profiles and the serum levels of AST and ALT in MASH mice. Mechanistic studies revealed that Sch B treatment activated the PXR signaling pathway. Sch B treatment also suppressed the phosphorylation of key proteins involved in NF-κB signaling in PA-treated HepG2 cells, and modulated the expression of lipid metabolism related enzymes in PA-treated MPHs. PXR inhibitor reversed the lipid reducing effect of Sch B in PA-exposed MPHs. Our results suggest that Sch B could ameliorate the hepatic steatosis and inflammation via activation of the PXR signaling.