Curcumin alleviates DSS-induced colitis via inhibiting NLRP3 inflammsome activation and IL-1β production

Abstract Background NLRP3 inflammasomemediates IL-1β maturation, therefore plays a vital role in the development of IBD. Curcuminis known for possessing strong anti-inflammatory property. Objective The present study was to investigate the protective effects of curcuminon dextran sulfate sodium (DSS)-induced colitisthrough inhibiting NLRP3 inflammasomeactivation and IL-1β production. Methods LPS-primed macrophages were treated with curcuminprior to DSS triggering NLRP3 inflammasomeactivation, IL-1β secretion and ASC oligomerization were observed. The mechanisms of curcuminin the inhibition of DSS-induced inflammasomeactivation were explored. Curcuminor caspase-1/NLRP3 inhibitor was administrated respectively in DSS-induced colitismouse model. The changes of body weight, disease activity index, colon length were measured. Additionally, mature IL-1β and other inflammatory cytokines, MPO activity and histopathological damage were analyzed for the evaluation of colitisseverity. Results NLRP3 inflammasomeactivation was dramatically inhibited by curcuminin DSS-stimulated macrophages, as evidenced by decreased IL-1β secretion, less caspase-1activation and ASC specks. Mechanistically, curcuminprevented DSS-induced K + efflux, intracellular ROS formation and cathepsin Brelease, three major cellular events mediating NLRP3 inflammasomeactivation. In DSS-induced colitis, curcuminadministration significantly ameliorated colitissymptoms by reducing weight loss, DAI and colon length shortening. Meanwhile, curcuminsignificantly decreased the expression of multiple inflammatory cytokines (including mature IL-1β, IL-6, MCP-1), MPO activity, caspase-1activity as well as histopathological damage. Furthermore, blockage of NLRP3 inflammasomeactivation in vivo with specific NLRP3 inhibitor abrogated the further inhibitory effect of curcuminon DSS-induced colitis. Conclusion Curcumincould strongly suppress DSS-induced NLRP3 inflammsome activation and alleviate DSS-induced colitisin mice, thus it may be a promising candidate drug in clinical application for IBD therapy.