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Carnosic acid inhibits NLRP3 inflammasome activation by targeting both priming and assembly steps

Lin, G;Li, N;Li, D;Chen, L;Deng, H;Wang, S;Tang, J;Ouyang, W;

Carnosic acid (CA) is a polyphenolic diterpene from rosemary extract with anti-tumor and anti-inflammatory activities. Numerous reports have focused on its anti-tumor ability, while the exact mechanisms underlying its anti-inflammation remains unclear. Here, we have identified that CA is a potent inhibitor of NLRP3 inflammasome in vitro and in vivo. CA not only reduces NLRP3 expression by blocking NF-?B activation, but also inhibits NLRP3 inflammasome assembly and activation by suppressing mitochondrial ROS production and interrupting NLRP3-NEK7 interaction. Furthermore, in mouse models, CA alleviates lipopolysaccharide-induced acute systemic inflammation and MSU-induced peritonitis via NLRP3. Taken together, our data demonstrated the inhibitory effect of CA on NLRP3 inflammasome and pointed out the potential application of CA in the treatment of NLRP3-driven diseases.