Shugan Xiaozhi decoction protects mice against metabolic dysfunction associated steatohepatitis by modulating liver injury and intestinal flora.

Metabolic dysfunction associated steatohepatitis (MASH) is a pathological change of the liver that poses a major public safety challenge. Shugan Xiaozhi (SGXZ) decoction is specially developed for MASH. This study seeks to investigate whether SGXZ decoction could ameliorate MASH in vivo and its mechanism from the perspectives of intestinal flora. Through chemical analysis of SGXZ decoction, 30 effective components were initially obtained. The results of pathological and biochemical indexes analysis indicated that SGXZ decoction could effectively regulate the pathological state of MASH mice. It was manifested by the improvement of hepatic steatosis, inflammation, and lipid accumulation. The intestinal flora of MASH mice was significantly different from that of the control group in terms of diversity and richness. After SGXZ decoction intervention, the diversity and richness of intestinal flora in MASH mice returned to close to the control level. Moreover, SGXZ decoction intervention increased the abundance of beneficial bacteria (such as Bifidobacterium) and decreased the abundance of pathogenic bacteria (such as Bacillus cereus) in MASH. In addition, SGXZ decoction restored the expressions of intestinal tight junction proteins, including zonula occludens-1 (ZO-1), claudin-1 and occludin, and activated the farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) pathway in the intestine. Our results implied that SGXZ decoction could effectively alleviate MASH, and its mechanism included regulating intestinal flora, maintaining intestinal barrier function, activating FXR-FGF15 pathway, and improving liver injury and liver fat accumulation.