Prunus cerasifera Ehrhart (P. cerasifera) flourishes uniquely in the arid landscapes of Xinjiang, China. Preliminary studies have revealed the therapeutic potential of its polyphenol extract (PPE) in mitigating liver lipid accumulation in mice fed a high-fat diet. We established a mouse model that was subjected to a continuous high-fat diet for 24 weeks and administered PPE to investigate the effects of PPE on cholesterol and BA metabolism in NAFLD mice. The results showed that PPE administration (200 and 400 mg/kg/day, BW) led to a reduction in liver TC, an increase in liver T-BAs, and normalization of the disrupted fecal BA profile. Concurrently, it decreased levels of lipotoxic BAs and inhibited hepatic cholesterol synthesis (evidenced by reduced HMGCR activity) and intestinal cholesterol absorption (indicated by lower ACAT2 levels) while enhancing intestinal cholesterol efflux (via LXRα, ABCA1, ABCG5, and ABCG8) and stimulating hepatic BA synthesis (CYP7A1, CYP27A1) and secretion (BSEP). PPE thus led to a significant reduction in lipotoxic BAs metabolized by gut microbiota and a downregulation of the BA secretion pathway under its influence. Our findings reveal the therapeutic effect of PPE on NAFLD mice via regulating cholesterol and BA metabolism, providing a theoretical basis for exploring the potential functions of P. cerasifera.
Keywords: Prunus cerasifera Ehrhart; bile acid metabolism; drought environments; non-alcoholic fatty liver disease; polyphenol extracts.