Bioactive polysaccharide from Rosa roxburghii Tratt fruit ameliorates metabolic dysfunction-associated steatotic liver disease via AMPK and autophagy pathways.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder with limited therapeutic options. Here, we investigated the protective effects and underlying mechanisms of a polysaccharide extracted from Rosa roxburghii Tratt fruit (RTFP) in a high-fat/high-fructose diet (HFD)-induced MASLD mouse model, with a focus on the AMPK-autophagy-lipid metabolism axis. RTFP treatment for 8 weeks significantly reduced body weight gain, liver-to-body weight ratio, hepatic steatosis, and inflammatory infiltration. It also improved glucose tolerance, dyslipidemia (decreased TG and increased HDL-C), and liver injury markers (ALT and AST). Mechanistically, RTFP upregulated the expression of autophagy-related genes (Ampk, Ulk1, Atg5, Tfeb) and suppressed Mtor expression, while increasing the LC3-II/LC3-I ratio and decreasing p62 protein levels, indicating restored autophagic flux. These effects were accompanied by enhanced fatty acid oxidation (Pparα, Cpt1α), reduced de novo lipogenesis (Srebp-1, Fasn), and decreased cholesterol synthesis (Hmgcr). RTFP also increased AMPK phosphorylation, suggesting upstream activation of the AMPK pathway. Collectively, these findings demonstrate that RTFP ameliorates MASLD by reprogramming hepatic lipid metabolism toward catabolism via AMPK and autophagy activation. RTFP represents a promising dietary supplement for MASLD management.