Anoectochilus roxburghii polysaccharide alleviates DSS-induced ulcerative colitis by modulating the MAPK/NF-κB signaling pathway and gut microbiota

Ulcerative colitis (UC) involves mucosal barrier disruption, immune dysregulation, and gut dysbiosis, with current therapies limited by cost and side effects. This study evaluated the effects of Anoectochilus roxburghii polysaccharide (ARP)—a glucan-rich heteropolysaccharide (888 Da–2.43 × 10 6 Da)—on dextran sulfate sodium (DSS)-induced murine colitis model. ARP (150–300 mg/kg) markedly alleviated colitis by reducing the disease activity index, restoring colon length, and improving histopathology. ARP enhanced intestinal barrier integrity by upregulating ZO-1, OCLN, and MUC2, while suppressing pro-inflammatory cytokines (IL-1 β , IL-6, and TNF- α ), M1 macrophage polarization, and MAPK/NF- κ B signaling. Transcriptomic and immunoblot analyses confirmed the downregulation of key inflammatory mediators, including phosphorylated p38, JNK, and I κ Bα. ARP also modulated gut microbiota, increasing Bacteroidota and decreasing Proteobacteria abundance . These results provide integrated evidence that ARP exerts multimodal protective effects in UC by targeting barrier dysfunction, immune hyperactivation, and microbial dysbiosis, establishing a mechanistic basis for developing ARP as a functional food and natural dietary intervention for UC.