Dihydromyricetin, a flavonoid from vine tea ( Ampelopsis grossedentata) provides hepatoprotection by modulating gut microbiota-mediated bile acid homeostasis

Vine tea is a traditional Chinese tea that has been used for centuries. It is rich in flavonoids and has excellent health benefits, especially for liver. The aim of this study was to investigate the hepatoprotective mechanism of dihydromyricetin (DMY), a flavonoid mainly contained in vine tea. Six-week-old male C57BL/6J mice were administered different doses of DMY by oral gavage for two weeks. Liver function and physiological indices of mice were assessed, while changes in gut microbiota following DMY treatment were monitored through 16S rDNA gene sequencing. Additionally, metabolic pathways and mechanisms were further explored using RT-qPCR and Western blot analysis. The results showed that aspartate aminotransferase and alanine aminotransferase levels were significantly reduced after DMY intervention in mice. Meanwhile, the diversity and abundance of gut microbiota was increased by DMY. Moreover, DMY enhanced gut microbiota-mediated primary and secondary bile acid synthesis pathways. It inhibited the expression of bile acid synthesis rate-limiting enzymes, such as cyp7a1 and cyp27a1, in mouse liver tissue. However, bile acid-related receptors including fxr, FGFR4, and TGR5 were significantly activated, indicating that DMY inhibited bile acid synthesis in the liver. This negative feedback regulation mechanism, in which DMY participated, maintained bile acid homeostasis in the liver and intestine of mice. In conclusion, DMY modulated the composition of intestinal microbiota and its mediated bile acid homeostasis in mice, thereby exhibiting a protective effect on liver tissue.