Different polarity polyphenol extracts from Prunus cerasifera fruits ameliorate non-alcoholic fatty liver disease via bile acid metabolism and gut microbiota

Abstract Non-alcoholic fatty liver disease (NAFLD) is a global metabolic disease caused by abnormal accumulation of lipids in the liver, for which effective therapeutic targets and drugs are scarce. Prunus cerasifera polyphenol extract (PPE) has been proven to be able to alleviate NAFLD via the “gut microbiota-bile acid” signaling pathway, but its active ingredients that exert anti-NAFLD effects are still unclear. In this study, PPE was separated according to different polarities, and the optimal components for exerting anti-NAFLD effects based on the “gut microbiota-bile acid” signaling pathway were explored. Different polarity polyphenol extracts from P. cerasifera, especially aqueous PPE (APPE) enhanced hepatic bile acid synthesis and alleviated liver injury in NAFLD mice. Meanwhile, APPE significantly reduced the levels of bile salt hydrolase (BSH)-producing bacteria, in particular Bacteroides, and reduced the presence of endogenous farnesoid X receptor (FXR) ligands (chenodeoxycholic acid (CDCA); lithocholic acid (LCA); and deoxycholic acid (DCA)) in the intestines of NAFLD mice, thereby inhibiting the ileal FXR-FGF15 axis. In addition, activation of the hepatic FXR-small heterodimer partner (SHP) axis by APPE also supported cholesterol 7-alpha hydroxylase (CYP7A1)- and cytochrome P450 27A1 (CYP27A1)-mediated bile acid synthesis. The data suggested that APPE demonstrated a notable anti-NAFLD effect through the “gut microbiota-bile acid” signaling pathway, indicating the potential for isolating individual compounds from APPE for the treatment of NAFLD.