Mechanism of koumine in treating ulcerative colitis by targeting TSPO to regulate energy metabolism.

The pathogenesis of ulcerative colitis (UC) remains incompletely understood, and impairment of intestinal barrier function represents its most significant pathological alteration. All cellular functions require an energy supply for maintenance, and UC has been proposed as a potential energy deficiency disease. Translocator protein 18 kDa (TSPO) contributes to energy metabolism and is significantly related to the function of the intestinal barrier. Koumine, a high-affinity TSPO ligand, has well-documented anti-inflammatory activity. However, its effectiveness in treating UC hasn't been examined. The aim of our study was to examine the therapeutic effect of koumine on UC and clarify its mechanisms. First, a UC mouse model was induced with dextran sulfate sodium to investigate the effects of koumine on acute and chronic UC. Next, the effect of koumine on the function of the intestinal barrier was analysed. In addition, TSPO-knockout mice were used to assess whether the therapeutic effect of koumine on UC depends on TSPO. Widely targeted energy metabolomics was ultimately employed to examine the effect of koumine on energy metabolism in UC. The results showed that in both acute and chronic UC models, koumine was therapeutically effective and helped mitigate damage to intestinal barrier function. Moreover, the therapeutic effect of koumine on UC was almost completely eliminated by TSPO knockout. Metabolomics analysis revealed that koumine elevated the levels of DL-glyceric acid while reducing the levels of acetyl-CoA and 3-phenyllactic acid. In conclusion, koumine exerts its therapeutic effect against UC by targeting TSPO to regulate energy metabolism, thereby protecting intestinal barrier function.