Curcumin suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock

Scope: The NLRP3 inflammasome responds to various pathogen-derived factors and danger-associated molecules, mediating IL-1 beta maturation, therefore is involved in multiple inflammatory diseases. Curcumin has been shown to possess strong anti-inflammatory activity, but the underlying mechanism is not fully understood. Here, we sought to investigate the role and mechanism of curcumin on the inhibition of mature IL-1 beta production via the regulation of NLRP3 inflammasome. Methods and results: Curcumin dramatically inhibited the production of mature IL-1 beta in LPS-primed macrophages triggered by multiple NLRP3 inflammasome activators, and also reduced the level of cleaved caspase-1 as measured by western blot and ELISA. Curcumin prevented K+ efflux, the common trigger for NLRP3 inflammasome activation, and attenuated lysosomes disruption and intracellular ROS formation as well. The inhibition of NLRP3 inflammasome by curcumin was in part mediated via the suppression of extracellular regulated protein kinases phosphorylation. Furthermore, administration of curcumin significantly reduced peritoneal IL-1 beta and HMGB-1 concentration induced by LPS and improved the survival of mice suffering from lethal endotoxic shock. Conclusion: Curcumin potently inhibits the activation of NLRP3 inflammasome which may contribute to its anti-inflammatory activity. Our finding offers a mechanistic basis for the therapeutic potential of curcumin in septic shock and other NLRP3 inflammasome-driven diseases.