Excessive activation of NLRP3
inflammasome is associated with the pathogenesis of inflammatory diseases.
Pristimerin (Pri) is a quinonoid
triterpene derived from traditional Chinese medical herb Celastraceae and Hippocrateaceae. Pri has shown antifungal, antibacterial,
antioxidant, and anticancer activities. In this study we investigated whether NLRP3
inflammasome was associated with the anti-inflammatory activity of Pri. We showed that Pri (0.1-0.4 μM) dose-dependently blocked caspase-1 activation and IL-1β maturation in LPS-primed mouse bone-marrow-derived macrophages (BMDMs). Pri specifically inhibited NLRP3
inflammasome activation, had no visible effects on NLRC4 and AIM2
inflammasome activation. Furthermore, we demonstrated that Pri blocked the assembly of the NLRP3
inflammasome via disturbing the interaction between NEK7 and NLRP3; the α, β-unsaturated carbonyl moiety of Pri was essential for NLRP3
inflammasome inactivation. In LPS-induced systemic
inflammation mouse model and MSU-induced mouse
peritonitis model, preinjection of Pri (500 μg/kg, ip) produced remarkable
therapeutic effects via inhibition of NLRP3
inflammasome in vivo. In HFD-induced diabetic mouse model, administration of Pri (100 μg· kg-1 ·d-1, ip, for 6 weeks) reversed HFD-induced metabolic disorders via suppression of NLRP3
inflammasome activation. Taken together, our results demonstrate that Pri acts as a NLRP3 inhibitor, suggesting that Pri might be useful for the treatment of NLRP3-associated diseases.