Ulcerative colitis (UC) is a highly prevalent chronic non-specific intestinal inflammatory disorder for which effective therapeutic options are urgently needed. The active component cimigenoside (CIM) possesses promising anti-inflammatory bioactivity; however, its therapeutic efficacy and underlying molecular mechanism against UC remain to be fully elucidated. The present study aimed to investigate the effects and possible mechanisms of CIM on dextran sodium sulfate (DSS)-induced UC. Mice received drinking water containing 2.5% DSS to induce a UC model, and were then treated with different dosages of CIM for 10 consecutive days. The results found that CIM restored the colonic length, alleviated pathological damage to the colon, preserved intestinal mucosal barrier integrity, and inhibited colonic oxidative stress and inflammatory responses in DSS-induced mice. Additionally, DSS induction reduced the expression of sirtuin 3 (SIRT3) protein in the colonic tissues of mice; however, this was improved by treatment with CIM. Notably, the above protective roles of CIM on DSS-induced UC were unavailable in SIRT3-knockout (SIRT3-KO) mice. Notably, the docking score of CIM binding to SIRT3 is −11.3 kcal/mol, suggesting that CIM could directly bind to SIRT3. Collectively, CIM directly binds to SIRT3 and upregulates its protein expression, which in turn inhibits colonic inflammation and oxidative stress, thereby exerting anti-UC effects.
Chang et al. (Sat,) studied this question.