Echinatin effectively protects against NLRP3 inflammasome–driven diseases by targeting HSP90
Guang Xu, Shubin Fu, Xiaoyan Zhan, Zhilei Wang, Ping Zhang, Wei Shi, Nan Qin, Yuanyuan Chen, Chunyu Wang, Ming Niu, Yuming Guo, Jiabo Wang, Zhaofang Bai, Xiaohe Xiao
Guang Xu, Shubin Fu, Xiaoyan Zhan, Zhilei Wang, Ping Zhang, Wei Shi, Nan Qin, Yuanyuan Chen, Chunyu Wang, Ming Niu, Yuming Guo, Jiabo Wang, Zhaofang Bai, Xiaohe Xiao
View: Text | PDF
Research Article Immunology Inflammation

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

Abstract

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.

Authors

Guang Xu, Shubin Fu, Xiaoyan Zhan, Zhilei Wang, Ping Zhang, Wei Shi, Nan Qin, Yuanyuan Chen, Chunyu Wang, Ming Niu, Yuming Guo, Jiabo Wang, Zhaofang Bai, Xiaohe Xiao

×

Figure 7

Echinatin exhibits therapeutic effect in nonalcoholic steatohepatitis (NASH) model.

Options: View larger image (or click on image) Download as PowerPoint
Echinatin exhibits therapeutic effect in nonalcoholic steatohepatitis (N...
(A) Representative liver images, H&E-stained, and Masson-stained liver sections are shown from the mice fed MCD or MCS diets in the presence or absence of echinatin (Echi; 40 mg/kg), MCC950 (40 mg/kg), or Echi plus MCC950. Scale bar: 1 cm (top row), 200 μm (bottom 2 rows). (B) The activity of plasma ALT and AST were measured as described in A (n=6 for each group). (C) Representative IB analysis of active caspase-1 level in liver tissues described in A. (D–G) Hepatic α-Sma (D), Col1a1 (E), Il-1β (F), and Tnf-α (G) mRNA were measured from the mice described in A (n=6 for each group). Data are expressed as mean ± SD. One-way ANOVA, followed by LSD post hoc test, was used to assess the differences of multiple groups (B and D–G). ***P < 0.001.