Trichosanthes kirilowii Maxim. polysaccharides mitigate DSS-induced ulcerative colitis in mice via inflammation inhibition and gut microbiota modulation

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with complex pathogenesis, involving inflammatory imbalance, oxidative stress, intestinal microecological disorder and metabolic abnormalities. This study aimed to explore the therapeutic effect and potential mechanism of TKP-1 on UC. The UC mice were treated with different doses of TKP-1 or the positive drug sulfasalazine (SASP). The therapeutic effect was evaluated by detecting disease activity index (DAI), body weight, food intake, water intake and defecation status. Inflammatory factors, antioxidant indicators, colonic tissue morphology, intestinal flora and serum metabolomics were detected to clarify the intervention mechanism. The results showed that TKP-1 alleviated UC symptoms in a dose-dependent manner, reducing DAI scores, improving weight loss and nutrient intake, and alleviating diarrhea and hematochezia. It regulated inflammatory balance (downregulating TNF-α, IL-6; upregulating IL-10), enhanced antioxidant capacity (increasing SOD, GSH-Px; decreasing MDA), repaired colonic tissue damage and restored intestinal mucosal barrier function. Moreover, TKP-1 remodeled intestinal flora homeostasis, adjusted flora composition and improved microbial network stability, and reversed metabolic disorders by regulating amino acid and short-chain fatty acid metabolism. In conclusion, TKP-1 exerts anti-UC effects through multi-pathway regulation, providing experimental evidence for its clinical application as a potential UC therapeutic agent.