Mechanism Through Which Antioxidant Polysaccharide from Tetrastigma hemsleyanum Protects Against DSS-Induced Ulcerative Colitis: Insights from Multi-Omics.

Tetrastigma hemsleyanum polysaccharide (TH-P) exhibited anti-inflammatory and intestinal protective activities, but its mechanism against ulcerative colitis (UC) remained unclear. This study used a multi-omics approach to elucidate the effects of TH-P in protecting against dextran sulfate sodium (DSS)-induced UC mice and the underlying mechanisms. In vitro, TH-P dose-dependently suppressed LPS-induced ROS production and pro-inflammatory cytokine release in RAW264.7 cells. In vivo, TH-P alleviated DSS-induced weight loss, disease activity index, colon shortening, edema, and mucosal damage. Transcriptomic analysis and Western blotting revealed that TH-P significantly reversed DSS-induced gene expression alterations, with particular enrichment of the PI3K/AKT signaling pathway. Serum metabolomics showed that TH-P restored metabolic disturbances in glycerophospholipid and arachidonic acid metabolism. The results of 16S rRNA sequencing indicated that TH-P increased microbial diversity, enriched beneficial Bacteroidota, and reduced opportunistic Actinomycetota and Pseudomonadota. Untargeted metabolomics further demonstrated elevated acetate, propionate, and butyrate levels. Collectively, TH-P alleviated UC through a multi-target mechanism involving antioxidant and anti-inflammatory activities, gut microbiota modulation, enhanced SCFA production, and activation of the PI3K/AKT signaling pathway.