Dietary 5-demethylnobiletin attenuated dextran sulfate sodium-induced colitis in mice by inhibiting immune response and regulating gut microbiota

This study investigated the preventive effect of 5-demethylnobiletin (5DN), a natural polymethoxyflavone found mainly in citrus fruits, on dextran sulfate sodium (DSS)-induced colitis in mice and explored its potential mechanisms. Our results indicated that dietary 5DN (0.05% w/w in diet) could alleviate colitis symptoms in DSS-treated mice by preventing body weight loss, reducing the disease activity index, decreasing the colon weight to colon length ratio, and lessening colon tissue damage. Additionally, 5DN inhibited the inflammatory response in colitis mice through decreasing the production of inflammatory cytokines. Immunohistochemical analysis revealed that 5DN could reverse the DSS-induced decrease in the expression of claudin-1 and ZO-1 to improve the intestinal barrier function. Furthermore, 5DN altered gut microbiota dysbiosis in DSS-treated mice via up-regulating the level of probiotics (Roseburia) and down-regulating the level of pathogenic bacteria (Clostridium, Parabacteroides, and Sutterella). Taken together, these data provided a solid scientific basis for utilizing 5DN as a therapeutic candidate in colitis and related diseases.