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Echinatin effectively protects against NLRP3 inflammasome–driven diseases by targeting HSP90

Aberrant activation of NLRP3 inflammasome has been implicated in a variety of human inflammatory diseases, but currently, no pharmacological NLRP3 inhibitor has been approved. In this study, we showed that echinatin, the ingredient of the traditional herbal medicine licorice, effectively suppresses...

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Autores principales: Xu, Guang, Fu, Shubin, Zhan, Xiaoyan, Wang, Zhilei, Zhang, Ping, Shi, Wei, Qin, Nan, Chen, Yuanyuan, Wang, Chunyu, Niu, Ming, Guo, Yuming, Wang, Jiabo, Bai, Zhaofang, Xiao, Xiaohe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934863/
https://www.ncbi.nlm.nih.gov/pubmed/33350984
http://dx.doi.org/10.1172/jci.insight.134601
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author Xu, Guang
Fu, Shubin
Zhan, Xiaoyan
Wang, Zhilei
Zhang, Ping
Shi, Wei
Qin, Nan
Chen, Yuanyuan
Wang, Chunyu
Niu, Ming
Guo, Yuming
Wang, Jiabo
Bai, Zhaofang
Xiao, Xiaohe
author_facet Xu, Guang
Fu, Shubin
Zhan, Xiaoyan
Wang, Zhilei
Zhang, Ping
Shi, Wei
Qin, Nan
Chen, Yuanyuan
Wang, Chunyu
Niu, Ming
Guo, Yuming
Wang, Jiabo
Bai, Zhaofang
Xiao, Xiaohe
author_sort Xu, Guang
collection PubMed
description Aberrant activation of NLRP3 inflammasome has been implicated in a variety of human inflammatory diseases, but currently, no pharmacological NLRP3 inhibitor has been approved. In this study, we showed that echinatin, the ingredient of the traditional herbal medicine licorice, effectively suppresses the activation of NLRP3 inflammasome in vitro and in vivo. Further investigation revealed that echinatin exerts its inhibitory effect on NLRP3 inflammasome by binding to heat-shock protein 90 (HSP90), inhibiting its ATPase activity and disrupting the association between the cochaperone SGT1 and HSP90-NLRP3. Importantly, in vivo experiments demonstrated that administration of echinatin obviously inhibits NLRP3 inflammasome activation and ameliorates LPS-induced septic shock and dextran sodium sulfate–induced (DSS-induced) colitis in mice. Moreover, echinatin exerted favorable pharmacological effects on liver inflammation and fibrosis in a mouse model of nonalcoholic steatohepatitis (NASH). Collectively, our study identifies echinatin as a potentially novel inhibitor of NLRP3 inflammasome, and its use may be developed as a therapeutic approach for the treatment of NLRP3-driven diseases.
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spelling pubmed-79348632021-03-09 Echinatin effectively protects against NLRP3 inflammasome–driven diseases by targeting HSP90 Xu, Guang Fu, Shubin Zhan, Xiaoyan Wang, Zhilei Zhang, Ping Shi, Wei Qin, Nan Chen, Yuanyuan Wang, Chunyu Niu, Ming Guo, Yuming Wang, Jiabo Bai, Zhaofang Xiao, Xiaohe JCI Insight Research Article Aberrant activation of NLRP3 inflammasome has been implicated in a variety of human inflammatory diseases, but currently, no pharmacological NLRP3 inhibitor has been approved. In this study, we showed that echinatin, the ingredient of the traditional herbal medicine licorice, effectively suppresses the activation of NLRP3 inflammasome in vitro and in vivo. Further investigation revealed that echinatin exerts its inhibitory effect on NLRP3 inflammasome by binding to heat-shock protein 90 (HSP90), inhibiting its ATPase activity and disrupting the association between the cochaperone SGT1 and HSP90-NLRP3. Importantly, in vivo experiments demonstrated that administration of echinatin obviously inhibits NLRP3 inflammasome activation and ameliorates LPS-induced septic shock and dextran sodium sulfate–induced (DSS-induced) colitis in mice. Moreover, echinatin exerted favorable pharmacological effects on liver inflammation and fibrosis in a mouse model of nonalcoholic steatohepatitis (NASH). Collectively, our study identifies echinatin as a potentially novel inhibitor of NLRP3 inflammasome, and its use may be developed as a therapeutic approach for the treatment of NLRP3-driven diseases. American Society for Clinical Investigation 2021-01-25 /pmc/articles/PMC7934863/ /pubmed/33350984 http://dx.doi.org/10.1172/jci.insight.134601 Text en © 2021 Xu et al. http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Xu, Guang
Fu, Shubin
Zhan, Xiaoyan
Wang, Zhilei
Zhang, Ping
Shi, Wei
Qin, Nan
Chen, Yuanyuan
Wang, Chunyu
Niu, Ming
Guo, Yuming
Wang, Jiabo
Bai, Zhaofang
Xiao, Xiaohe
Echinatin effectively protects against NLRP3 inflammasome–driven diseases by targeting HSP90
title Echinatin effectively protects against NLRP3 inflammasome–driven diseases by targeting HSP90
title_full Echinatin effectively protects against NLRP3 inflammasome–driven diseases by targeting HSP90
title_fullStr Echinatin effectively protects against NLRP3 inflammasome–driven diseases by targeting HSP90
title_full_unstemmed Echinatin effectively protects against NLRP3 inflammasome–driven diseases by targeting HSP90
title_short Echinatin effectively protects against NLRP3 inflammasome–driven diseases by targeting HSP90
title_sort echinatin effectively protects against nlrp3 inflammasome–driven diseases by targeting hsp90
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934863/
https://www.ncbi.nlm.nih.gov/pubmed/33350984
http://dx.doi.org/10.1172/jci.insight.134601
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