Frontiers in Pharmacology (Oct 2021)
Dihydrotanshinone I Specifically Inhibits NLRP3 Inflammasome Activation and Protects Against Septic Shock In Vivo
- Ziying Wei,
- Ziying Wei,
- Xiaoyan Zhan,
- Xiaoyan Zhan,
- Kaixin Ding,
- Kaixin Ding,
- Guang Xu,
- Wei Shi,
- Lutong Ren,
- Lutong Ren,
- Zhie Fang,
- Tingting Liu,
- Xiaorong Hou,
- Jia Zhao,
- Hui Li,
- Hui Li,
- Jiayi Li,
- Jiayi Li,
- Zhiyong Li,
- Qiang Li,
- Li Lin,
- Yan Yang,
- Xiaohe Xiao,
- Xiaohe Xiao,
- Zhaofang Bai,
- Zhaofang Bai,
- Junling Cao,
- Junling Cao
Affiliations
- Ziying Wei
- School of Chinese Meteria Medica, Beijing University of Chinese Medicine, Beijing, China
- Ziying Wei
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Xiaoyan Zhan
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Xiaoyan Zhan
- China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Kaixin Ding
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Kaixin Ding
- China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Guang Xu
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Wei Shi
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Lutong Ren
- School of Chinese Meteria Medica, Beijing University of Chinese Medicine, Beijing, China
- Lutong Ren
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Zhie Fang
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Tingting Liu
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Xiaorong Hou
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Jia Zhao
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Hui Li
- School of Chinese Meteria Medica, Beijing University of Chinese Medicine, Beijing, China
- Hui Li
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Jiayi Li
- School of Chinese Meteria Medica, Beijing University of Chinese Medicine, Beijing, China
- Jiayi Li
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Zhiyong Li
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Qiang Li
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Li Lin
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Yan Yang
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Xiaohe Xiao
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Xiaohe Xiao
- China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Zhaofang Bai
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Bejjing, China
- Zhaofang Bai
- China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Junling Cao
- School of Chinese Meteria Medica, Beijing University of Chinese Medicine, Beijing, China
- Junling Cao
- Department of Pharmacy, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
- DOI
- https://doi.org/10.3389/fphar.2021.750815
- Journal volume & issue
-
Vol. 12
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.
Keywords
