EMBO reports · 2021
Licochalcone B specifically inhibits the NLRP3 inflammasome by disrupting NEK7-NLRP3 interaction.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Li Qiang, Feng Hui, Wang Hongbo, Wang Yinghao, Mou Wenqing, Xu Guang, Zhang Ping, Li Ruisheng, Shi Wei, Wang Zhilei, Fang Zhie, Ren Lutong, Wang Yan, Lin Li, Hou Xiaorong, Dai Wenzhang, Li Zhiyong, Wei Ziying, Liu Tingting, Wang Jiabo, Guo Yuming, Li Pengyan, Zhao Xu, Zhan Xiaoyan, Xiao Xiaohe, Bai Zhaofang
Аннотация
The activation of the nucleotide oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is related to the pathogenesis of a wide range of inflammatory diseases, but drugs targeting the NLRP3 inflammasome are still scarce. In the present study, we demonstrated that Licochalcone B (LicoB), a main component of the traditional medicinal herb licorice, is a specific inhibitor of the NLRP3 inflammasome. LicoB inhibits the activation of the NLRP3 inflammasome in macrophages but has no effect on the activation of AIM2 or NLRC4 inflammasome. Mechanistically, LicoB directly binds to NEK7 and inhibits the interaction between NLRP3 and NEK7, thus suppressing NLRP3 inflammasome activation. Furthermore, LicoB exhibits protective effects in mouse models of NLRP3 inflammasome-mediated diseases, including lipopolysaccharide (LPS)-induced septic shock, MSU-induced peritonitis and non-alcoholic steatohepatitis (NASH). Our findings indicate that LicoB is a specific NLRP3 inhibitor and a promising candidate for treating NLRP3 inflammasome-related diseases.