Erianin: A Direct NLRP3 Inhibitor With Remarkable Anti-Inflammatory Activity

Xinyong Zhang; Lei Hu; Shilei Xu; Chao Ye; Aidong Chen

doi:10.3389/fimmu.2021.739953

Erianin: A Direct NLRP3 Inhibitor With Remarkable Anti-Inflammatory Activity

Front Immunol. 2021 Oct 20:12:739953. doi: 10.3389/fimmu.2021.739953. eCollection 2021.

Authors

Xinyong Zhang^{1

2}, Lei Hu³, Shilei Xu⁴, Chao Ye², Aidong Chen²

Affiliations

¹ Department of Neurology, Huaian Hospital Affiliated to Xuzhou Medical University, Huaian, China.
² The Key Laboratory of Targeted Intervention of Clinical Disease, Collaborative Innovation Center of Translational Medicine for Clinical Disease, Nanjing Medical University, Nanjing, China.
³ Guiyang Women and Children's Hospital, Guizhou Medical University, Guiyang, China.
⁴ Department of General Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

Abstract

Erianin (Eri) is the extract of Dendrobium chrysotoxum Lindl. The NLRP3 inflammasome is a multiprotein complex that plays key roles in a wide variety of chronic inflammation-driven human diseases. Nevertheless, little is known about the protection of Eri against NLRP3 inflammasome-related diseases. In this study, we demonstrated that Eri inhibited NLRP3 inflammasome activation in vitro and in vivo. Mechanistically, Eri directly interacted with NLRP3, leading to inhibition of NLRP3 inflammasome assembly. Eri associated with the Walker A motif in the NACHT domain and suppressed NLRP3 ATPase activity. In mouse models, Eri had therapeutic effects on peritonitis, gouty arthritis and type 2 diabetes, via NLRP3. More importantly, Eri was active ex vivo for synovial fluid cells and monocytes from patients with IAV infection and gout. Eri may serve as a potential novel therapeutic compound against NLRP3-driven diseases.

Keywords: NLRP3; erianin; inflammasome; inflammatory disorders; traditional Chinese medicine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / pharmacology*
Arthritis, Gouty / drug therapy*
Arthritis, Gouty / genetics
Arthritis, Gouty / metabolism
Bibenzyls / pharmacology*
Diabetes Mellitus, Type 2 / drug therapy*
Diabetes Mellitus, Type 2 / genetics
Diabetes Mellitus, Type 2 / metabolism
Disease Models, Animal
Dogs
HEK293 Cells
Humans
Inflammasomes / antagonists & inhibitors*
Inflammasomes / genetics
Inflammasomes / metabolism
Madin Darby Canine Kidney Cells
Mice
Mice, Inbred C57BL
Mice, Knockout
NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors*
NLR Family, Pyrin Domain-Containing 3 Protein / genetics
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Peritonitis / drug therapy*
Peritonitis / genetics
Peritonitis / metabolism
Phenol / pharmacology*
Protein Interaction Domains and Motifs
THP-1 Cells

Substances

Anti-Inflammatory Agents
Bibenzyls
Erianin
Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3 protein, human
Nlrp3 protein, mouse
Phenol