A polysaccharide-rich preparation from Moutan Cortex alleviates non-alcoholic fatty liver disease by ameliorating intestinal flora and bile acid metabolism.

BACKGROUND: Moutan Cortex (MC), the dried root bark of Paeonia × suffruticosa Andrews, is used as both a medicinal and edible product and possesses hepatoprotective and anti-inflammatory properties. It is rich in bioactive polysaccharide components. However, the role of a polysaccharide-rich preparation from Moutan Cortex (MC-Pa) in alleviating non-alcoholic fatty liver disease (NAFLD) has not been sufficiently investigated. PURPOSE: This study aimed to evaluate the effect of MC-Pa on NAFLD and clarify the mechanisms associated with this effect. METHODS: A methionine- and choline-deficient (MCD) diet was used to establish the NAFLD model. Liver pathological changes were evaluated using H&E and Oil Red O staining, together with measurements of serum transaminases (ALT/AST). Hepatic lipid homeostasis, redox status, and inflammatory responses were further assessed. The intestinal microbiota composition was investigated through 16S rRNA sequencing, whereas hepatic bile acid profiles were examined using targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). The protein expression levels of CD36, FXR, CYP7A1, and TGR5 were determined by Western blotting. RESULTS: MC-Pa treatment substantially reduced hepatic steatosis, inflammation, and oxidative stress in MCD-fed mice and lowered serum ALT/AST levels. MC-Pa favorably modulated the gut microbiota by reducing the Firmicutes/Bacteroidota ratio and increasing the abundance of Muribaculaceae and Akkermansia. Moreover, MC-Pa regulated bile acid-related signaling, as indicated by altered expression of hepatic FXR, CYP7A1, and TGR5. CONCLUSION: MC-Pa alleviates hepatic steatosis, inflammation, and oxidative stress in MCD-induced NAFLD mice, and these effects are associated with modulation of gut microbiota and bile acid metabolism, potentially involving the FXR/CYP7A1-related signaling pathway.