Acidic polysaccharide CP-2 from Dioscoreae Rhizoma ameliorated acute alcoholic liver injury through the gut-liver axis and AMPK/PPAR pathway.

Dioscoreae Rhizoma polysaccharides exhibit gastrointestinal protective properties, yet their efficacy against acute alcoholic liver injury (AALI) remains unexplored. This study identifies a novel acidic heteropolysaccharide (CP-2, Mw = 8.4 × 103 kDa) with galactose/galacturonic acid dominance and delineates its multimodal hepatoprotective mechanisms. In AALI mice, CP-2 attenuated liver injury by enhancing ADH and ALDH activities while restoring redox balance via SOD/CAT activation and MDA reduction, and suppressed inflammation by inhibiting IL-1β, IL-6, and TNF-α levels. Gut-liver axis modulation was achieved through intestinal barrier reinforcement (ZO-1, Occludin, Claudin-1) and microbiota rebalancing. CP-2 could reduce gram-negative bacteria ([Ruminococcus]_ torques_ group and Escherichia- Shigella) and Proteobacteria abundance while enriching Bacteroides and Akkermansia abundance, which collectively suppressed serum LPS level. In addition, CP-2 could activate the AMPK/PPAR signaling pathway to reduce the production of fatty acids and promote their degradation in AALI. CP-2 can improve AALI by adjusting the composition of gut microbiota, repairing intestinal barrier function, decreasing systemic inflammation and oxidative reactions, and regulating the AMPK/PPAR pathway. Our findings unveil CP-2 as a prebiotic candidate for AALI intervention and may advance functional food development for alcohol-related hepatopathies.