Cardamonin from a medicinal herb protects against LPS-induced septic shock by suppressing NLRP3 inflammasome.
10.1016/j.apsb.2019.02.003
- Author:
Zhilei WANG
1
;
Guang XU
2
;
Yuan GAO
3
;
Xiaoyan ZHAN
2
;
Nan QIN
2
;
Shubin FU
2
;
Ruisheng LI
4
;
Ming NIU
2
;
Jiabo WANG
2
;
Youping LIU
1
;
Xiaohe XIAO
5
;
Zhaofang BAI
2
Author Information
1. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
2. China Military Institute of Chinese Materia, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing 100039, China.
3. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
4. Research Center for Clinical and Translational Medicine, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing 100500, China.
5. Integrative Medical Center, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing 100039, China.
- Publication Type:Journal Article
- Keywords:
Cardamonin;
Caspase-1;
IL-1β;
NLRP3 inflammasome;
Septic shock
- From:
Acta Pharmaceutica Sinica B
2019;9(4):734-744
- CountryChina
- Language:English
-
Abstract:
Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin (CDN), the major active ingredient of the traditional Chinese medicinal herb , has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-B-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner. Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1 production induced by LPS , which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases.
