Revealing action mechanisms of Xiaoyaosan decoction for the treatment of nonalcoholic fatty liver in mice employing tandem mass tag quantitative proteomics.

Abstract

OBJECTIVE: To investigate the mechanism and pharmacological activity of (Xiaoyaosan decoction) XYSD in the treatment of NAFL (nonalcoholic fatty liver) by proteomic techniques. METHODS: C57BL/6 mice NAFL model was induced by HFD (high fat diet), and observed biochemical indicators and histopathological changes. We employed TMT (tandem mass tag) quantitative proteomics and conducted bioinformatics analysis. Additionally, an in vitro model using unsaturated FFA (free fatty acid)-induced lipid accumulation was established to discover the effect of XYSD on lipid accumulation in HepG2 cells. RESULTS: The results showed that XYSD improved liver index and biochemical indexes, and reversed the characteristics of liver steatosis in NAFL mice. Based on the results of in vivo proteomic enrichment analysis, we hypothesize that the activation of the PPARα signaling pathway may be a potential mechanism underlying the therapeutic effect of XYSD in treating NAFL. XYSD remarkably improved protein and gene expression of Fads2 (fatty acid desaturase 2), Hmgcs2 (3-hydroxymethylglutaryl-CoA synthase 2), Fabp1 (fatty acid-binding protein 1) and PPARα. This hypothesis has been further confirmed in our in vitro experiments. CONCLUSION: The study shows that XYSD improves lipid accumulation by activating PPARα signaling pathway, and finally achieves the effect of NAFL.