Metabolic restoration: Rhubarb polysaccharides as a shield against non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) accounts for remarkable burden of death and costs worldwide with no recommended pharmacological intervention for the clinical management. This study aimed to investigate the efficacy and underlying mechanisms of rhubarb-derived polysaccharides (RP) in mitigating high-fat diet (HFD)-induced NAFLD and to analyze the primary monosaccharide components of RP. Forty male C57BL/6 mice were subjected to a dietary intervention consisting of either a high fat or chow diet for a duration of 12 weeks. RP (270, 540 mg·kg-1·d-1) was administered to the mice for 4 consecutive weeks from the 9th week. Various assessments were conducted, including histopathological examination, liver transcriptome analysis, non-targeted metabolomics analysis, and evaluation of protein expressions related to lipid and bile acid metabolism. This study found RP demonstrate a protective effect on the livers of NAFLD mice by inhibiting lipid accumulation and reducing hepatocyte inflammatory damage. The metabolomics analysis of multi-tissues revealed that the RP exert a hepatoprotective effect against NAFLD by restoring the altered bile acids (BAs) and fatty acids (FFAs) metabolism through the improvement of BA transporter, nucleus hormone receptor, lipogenesis protein, FFA transporter, and lipolysis proteins. Hence, RP may serve as a potential therapeutic agent for NAFLD.