Integrated Microbiome and Metabolomic to Explore the Mechanism of Coptisine in Alleviating Ulcerative Colitis

Coptisine (COP), a naturally occurring alkaloid, is known for its diverse pharmacological effects and its supportive role in intestinal health. Despite this, the detailed mechanisms behind its therapeutic benefits are not yet fully understood. The objective of this study is to investigate the therapeutic potential of COP for the treatment of Ulcerative Colitis (UC) and to delineate the critical pathways by which it exerts its therapeutic effects. To assess COP's therapeutic effectiveness, mice were administered COP and monitored for clinical symptoms, activity, and disease activity index (DAI) changes. Intestinal histopathology, mucosal barrier function, and gut microbiota structure were evaluated, along with metabolic profiling, focusing on Prenol lipids in the colon to identify COP-induced metabolic shifts. Mice treated with COP exhibited significant relief from diarrhea and bleeding, along with increased activity and a marked reduction in DAI scores. Histopathological evaluation revealed a reduction in intestinal inflammation, and the intestinal mucosal barrier function was notably enhanced. The gut microbiota composition in COP-treated mice showed improvements. Additionally, the levels of Prenol lipids in the colon were elevated by COP treatment, which is crucial for the recovery of intestinal function. Our study demonstrates that COP effectively ameliorates colitis symptoms by modulating colon Prenol lipids metabolism, particularly under the influence of key bacterial species. The findings of this study provide novel insights into the therapeutic mechanisms of COP in the treatment of UC.