Salvianolic acid B attenuates hypercholesterolemia via modulating the gut microbiota and bile acid metabolism.

Regulation of bile acid metabolism offers an effective approach of reducing hypercholesterolemia. Salvianolic acid B, a phenolic acid compound found in salvia miltiorrhiza Bge, has therapeutic effects on cardiovascular diseases. Nevertheless, insufficient is known concerning the impact on hypercholesterolemia. This study has investigated the cholesterol-lowering effect of salvianolic acid B and delved into its potential mechanism. Hypercholesterolemia mice model was induced by a high-cholesterol diet. We evaluated lipid parameters in serum and liver and examined pathology changes and gene expression alterations in liver. In addition, we examined the effect of salvianolic acid B on gut microbiota in colonic contents utilized 16S rRNA. Salvianolic acid B significantly decreased the levels of lipids in serum, improved lipid accumulation in liver, and significantly increased the feces bile acid content. RNA-seq analysis results showed that salvianolic acid B exerts a significant influence on primary bile acid biosynthesis. In addition, Salvianolic acid B enhanced the expression of cholesterol 7α-hydroxylase (CYP7A1) and sterol 27-hydroxylase(CYP27A1). Furthermore, salvianolic acid B inhibited the abundance of BSH-producing bacteria, and decreased the expression levels of farnesoid X receptor (FXR), fibroblast growth factor 15 (FGF-15), apical sodium-dependent bile acid transporter (ASBT) and ileum bile acid binding protein (I-BABP). Taken together, this study demonstrated that salvianolic acid B improved hypercholesterolemia by inhibiting the abundance of BSH-producing bacteria and ileum FXR/FGF-15 signaling to enhance the synthesis and excretion of bile acids.