Emodin methyl ether protects the intestinal barrier and alleviates colitis through the microbiota-NAS-Nrf2 pathway

Current clinical treatments for inflammatory bowel disease (IBD) primarily rely on traditional anti-inflammatory therapies such as aminosalicylate drugs and biological agents, yet their therapeutic efficacy remains limited. Therefore, the development of natural drugs for the treatment of ulcerative colitis (UC) is of great significance. Physcion 1,8-dihydroxy-3-methoxy-6-methyl anthracene-9,10-dione (PY), a natural anthraquinone compound, has been confirmed to possess anti-tumor, anti-oxidant, and immunomodulatory activities; however, its anti-inflammatory effects in UC have not been thoroughly investigated.In this study, we found that PY significantly ameliorates disease phenotypes in dextran sulfate sodium (DSS)-induced UC model mice, including alleviating weight loss and intestinal inflammation, as well as reshaping the structure of the intestinal flora. Further verification via fecal microbiota transplantation experiments demonstrated that transplanting feces from colitis mice intervened with PY into recipient colitis mice could effectively reduce intestinal inflammation, suggesting that PY exerts a positive regulatory effect on intestinal flora imbalance under colitis conditions.Through sequencing and in-depth analysis of metabolites in mouse intestinal contents, it was revealed that PY significantly up-regulates the secretion level of N-acetyl-5-hydroxytryptamine (NAS). In vivo supplementation of NAS could notably mitigate intestinal inflammation and intestinal barrier damage.In conclusion, this study indicates that PY has potential application value in UC treatment, providing new experimental evidence for the development of natural drugs for UC.