Author:
Wei Ziying,Zhan Xiaoyan,Ding Kaixin,Xu Guang,Shi Wei,Ren Lutong,Fang Zhie,Liu Tingting,Hou Xiaorong,Zhao Jia,Li Hui,Li Jiayi,Li Zhiyong,Li Qiang,Lin Li,Yang Yan,Xiao Xiaohe,Bai Zhaofang,Cao Junling
Abstract
The abnormal activation of the NLRP3 inflammasome is closely related to the occurrence and development of many inflammatory diseases. Targeting the NLRP3 inflammasome has been considered an efficient therapy to treat infections. We found that dihydrotanshinone I (DHT) specifically blocked the canonical and non-canonical activation of the NLRP3 inflammasome. Nevertheless, DHT had no relation with the activation of AIM2 or the NLRC4 inflammasome. Further study demonstrated that DHT had no influences on potassium efflux, calcium flux, or the production of mitochondrial ROS. We also discovered that DHT suppressed ASC oligomerization induced by NLRP3 agonists, suggesting that DHT inhibited the assembly of the NLRP3 inflammasome. Importantly, DHT possessed a significant therapeutic effect on NLRP3 inflammasome–mediated sepsis in mice. Therefore, our results aimed to clarify DHT as a specific small-molecule inhibitor for the NLRP3 inflammasome and suggested that DHT can be used as a potential drug against NLRP3-mediated diseases.
Funder
Beijing Municipal Natural Science Foundation
Foundation for Innovative Research Groups of the National Natural Science Foundation of China
Beijing Nova Program
Subject
Pharmacology (medical),Pharmacology
Cited by
11 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献