Anti-cancer cachexia-induced muscle atrophy potential evaluation of polysaccharides from Pleurotus citrinopileatus in vitro and in vivo

• An acidic polysaccharide (PCP1) was isolated and purified from Pleurotus citrinopileatus. • In vitro experiments, PCP1 can inhibit DEX-induced apoptosis in L6 myoblasts. • In vivo experiments, PCP1 can antagonize muscle attenuation and enrich the butyric acid-producing microbiota in mice with cancer cachexia-induced muscle atrophy. In this study, an acidic polysaccharide (PCP1) was purified from Pleurotus citrinopileatus with a molecular weight of 17.186 kDa, primarily composed of glucose, glucuronic acid, galactose, and mannose. Structural characterization revealed a triple-helix conformation with low crystallinity and excellent thermal stability. In vitro experiments demonstrated that PCP1 alleviated dexamethasone-induced oxidative stress and mitochondrial dysfunction, significantly mitigating cell cycle arrest and apoptosis in L6 myoblasts. In vivo studies further confirmed that PCP1 ameliorated cancer cachexia-induced muscle atrophy in mice, as evidenced by increased body weight, restored gastrocnemius muscle mass, reduced serum levels of IL-6 and TNF-α, and downregulated expression of muscle atrophy markers Atrogin-1 and MuRF-1. Gut microbiota sequencing analysis indicated that PCP1 enriched butyrate-producing genera, including norank_f_Muribaculaceae, Bacteroides, Lactobacillus , and unclassified_f_Prevotellaceae , thereby modulating secondary bile acid metabolism to combat muscle wasting. These findings highlight the therapeutic potential of PCP1 in alleviating cancer cachexia-associated muscle atrophy through both in vitro and in vivo mechanisms.