Qingre Xingyu recipe exerts inhibiting effects on ulcerative colitis development by inhibiting TNF alpha/NLRP3/Caspase-1/IL-1 beta pathway and macrophage M1 polarization

As a chronic inflammatory bowel disease, ulcerative colitis (UC) imposes a significant burden on public healthcare worldwide due to its increasing morbidity. Chinese medicines are regarded as potent therapeutic agents for UC treatment with minimal side effects. In the present study, we sought to determine the novel role of a traditional medicine Qingre Xingyu (QRXY) recipe in the development of UC and aimed to contribute to the currently available knowledge about UC by exploring the downstream mechanism of QRXY recipe in UC. Mouse models of UC were established by injections with dextran sulphate sodium (DSS), where the expression of tumor necrosis factor-alpha (TNF alpha), NLR family pyrin domain containing 3 (NLRP3), and interleukin-1 beta (IL-1 beta) was determined followed by an analysis of their interactions. The DSS-treated NLRP3 knockout ((-/-)) Caco-2 cell model was successfully constructed. The in vitro and in vivo effects of the QRXY recipe on UC were investigated with the determination of disease activity index (DAI), histopathological scores, transepithelial electrical resistance, FITC-dextran, as well as cell proliferation and apoptosis. In vivo and in vitro experiments indicated that the QRXY recipe reduced the degree of intestinal mucosal injury of UC mice and functional damage of DSS-induced Caco-2 cells by inhibition of the TNF alpha/NLRP3/caspase-1/IL-1 beta pathway and M1 polarization of macrophages, and TNF alpha overexpression or NLRP3 knockdown could counterweigh the therapeutic effects of QRXY recipe. To conclude, our study elicited that QRXY inhibited the expression of TNF alpha and inactivated the NLRP3/Caspase-1/IL-1 beta pathway, thereby alleviating intestinal mucosal injury and relieving UC in mice.