Phosphorylated Cyclocarya paliurus polysaccharide alleviates DSS-induced ulcerative colitis by improving intestinal barrier function, inhibiting inflammation and regulating gut microbiota.

Ulcerative colitis (UC) is a chronic and idiopathic inflammatory bowel disease with limited therapeutic options, high relapse rates, and potential adverse effects. Although natural polysaccharides have shown promise in alleviating colitis-associated inflammation, the impact of structural modification on their bioactivity and underlying mechanisms remains insufficiently explored. In this study, the pharmacological activities and mechanisms of phosphorylated Cyclocarya paliurus polysaccharides (P-CPPs) were systematically investigated in a dextran sulfate sodium (DSS)-induced murine colitis model. The results demonstrated that P-CPPs significantly improved colitis-associated pathological features and preserved intestinal barrier function, upregulated expression of the mucus barrier protein MUC-2, occludin, and claudin-1. Enhancement of barrier integrity was accompanied by a marked reduction in oxidative stress in both intestinal tissue and the liver. Moreover, P-CPPs effectively suppressed inflammation-related signaling pathways, including the NF-κB pathway and NLRP3 inflammasome activation, leading to decreased production of pro-inflammatory mediators such as TNF-α, IL-6, and lipopolysaccharide. In addition, P-CPPs modulated gut microbiota composition and metabolic activity, as reflected by increased microbial diversity and elevated levels of short-chain fatty acids. Collectively, these findings indicate that phosphorylation enhances the immunomodulatory and gut-regulatory effects of Cyclocarya paliurus polysaccharides. This study provides new insight into the structure-function relationship of modified polysaccharides and highlights the potential of P-CPPs as functional biomacromolecules for regulating colitis-associated intestinal immune responses.