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

鼠尾草酸通过靶向启动和组装步骤来抑制 NLRP3 炎症小体的活化

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作者:Guoxin Lin, Nannan Li, Dan Li, Lu Chen, Huiyin Deng, Saiying Wang, Juan Tang, Wen Ouyang

Abstract

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-κB 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.

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