Sanye tablet regulates gut microbiota and bile acid metabolism to attenuate hepatic steatosis.

ETHNOPHARMACOLOGICAL RELEVANCE

Sanye Tablet (SYT), a patent traditional Chinese prescription, is commonly used in treating type 2 diabetes mellitus and hyperlipidemia. Both clinical and animal studies suggest that SYT effectively regulates lipid metabolism. However, its mode of action on hepatic steatosis has yet to be fully elucidated.

AIM OF STUDY

This study investigates the lipid-regulating effects and underlying mechanism of SYT in high-fat diet (HFD)-induced hepatic steatosis mice.

MATERIAL AND METHODS

The inhibitory effects of SYT on developing hepatic steatosis were investigated in HFD-fed C57BL/6N mice. Biochemical markers, including total cholesterol (TC) and triglycerides (TG), were measured using specific kits. Hepatic histological alterations were determined by Hematoxylin and Eosin (H&E) and Oil Red O staining. Hepatic, fecal, and systemic bile acids (BAs) profiles were detected by UPLC-MS. mRNA and protein levels of BAs synthesis-related enzymes and critical nodes of farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF15)/fibroblast growth factor receptor 4 (FGFR4) signaling were detected. Fecal microbial composition was analyzed by 16S rRNA gene sequencing and the antimicrobial activity of SYT was further evaluated in vitro.

RESULTS

SYT alleviated HFD-induced hepatic steatosis by decreasing TG and TC levels, relieving hepatocyte ballooning, and promoting hepatic BAs synthesis. Moreover, SYT significantly increased the levels of taurine-conjugated BAs in the liver and feces, which in turn inhibited the FXR/FGF15/FGFR4 signaling. Consequently, the hepatic BAs synthesis-related enzyme expression was promoted to reduce lipid accumulation. Notably, SYT remodeled the gut microbiota composition of HFD-fed mice, especially inhibiting the growth of bile salt hydrolase (BSH)-producing bacteria, such as Lactobacillus murinus, Lactobacillus johnsonii, and Enterococcus faecalis.

CONCLUSION

The findings illustrated that SYT prevented hepatic steatosis by improving hepatic lipid accumulation, which is reflected in modulating the gut-liver axis. SYT corrects BAs profile, restores perturbed FXR/FGF15/FGFR4 signaling and promotes hepatic BAs synthesis, which is associated with modulation on certain BSH-producing bacteria.