Curcumin ameliorates hyperuricemia and gout-induced damage via modulating the ROS-dependent NEK7-NLRP3 inflammasome activation

Abstract

Curcumin, a bioactive compound extracted from Curcuma longa. L., demonstrates significant therapeutic potential in inflammatory diseases. This study aims to explore the effects of curcumin on hyperuricemia with acute gout and associated renal dysfunction in a mouse model. The results show that curcumin treatment alleviates ankle joint swelling, reduces inflammatory cytokines IL-1β and TNF-α, and lowers serum uric acid concentrations. High-dose curcumin notably inhibits xanthine oxidase (XOD) activity, a key enzyme in uric acid production, while it enhances the renal expression of the urate transporter ABCG2, thereby promoting uric acid excretion. Furthermore, curcumin effectively mitigates renal injury as evidenced by reduced serum creatinineand blood urea nitrogen levels and suppresses renal inflammation. At the molecular level, curcumin exerts potent antioxidant effects by lowering reactive oxygen species (ROS) levels in both cultured HK-2 human renal tubular epithelial cells and RAW264.7 mouse macrophages. The curcumin-mediated effects are associated with the disruption of NEK7-NLRP3 complex formation, leading to the suppression of the ROS/NEK7-NLRP3 inflammasome pathway. This, in turn, inhibits pyroptosis and the subsequent release of mature IL-1β. These findings suggest that curcumin not only reduces uric acid production but also modulates inflammation through ROS-scavenging properties and its ability to inhibit the NLRP3 inflammasome.

Keywords

gout / hyperuricemia / NLRP3 inflammasome / pyroptosis

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