A new acid isolated from V. negundo L. inhibits NLRP3 inflammasome activation and protects against inflammatory diseases

Qianqian Di; Xibao Zhao; Jing Lin; Xunwei Li; Xiaoli Li; Haimei Tang; Ruihan Zhang; Weilie Xiao; Weilin Chen

doi:10.3389/fimmu.2023.1174463

A new acid isolated from V. negundo L. inhibits NLRP3 inflammasome activation and protects against inflammatory diseases

Front Immunol. 2023 Apr 20:14:1174463. doi: 10.3389/fimmu.2023.1174463. eCollection 2023.

Authors

Qianqian Di¹, Xibao Zhao¹, Jing Lin², Xunwei Li¹, Xiaoli Li², Haimei Tang¹, Ruihan Zhang², Weilie Xiao², Weilin Chen¹

Affiliations

¹ Guangdong Provincial Key Laboratory for Regional Immunity and Diseases, Institute of Biological Therapy, Department of Immunology, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, China.
² Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, Kunming, China.

Abstract

The NLRP3 inflammasome plays a critical role in the innate immune response, and its excessive activation will cause pyroptotic cell death and be associated with the onset of inflammatory diseases. However, NLRP3 inflammasome targeting therapies are still to be implemented in the clinic setting. Here, we first isolated, purified and characterized a novel Vitenegu acid from V. negundo L. herb that specifically inhibits NLRP3 inflammasome activation, without affecting NLRC4 or AIM2 inflammasomes. Vitenegu acid blocks the oligomerization of NLRP3, thus inhibiting NLRP3 inflammasome assembly and activation. In vivo data show that Vitenegu acid exerts therapeutic effects on NLRP3 inflammasome-dependent inflammation. Taken together, our results suggest that Vitenegu acid is a candidate therapeutic agent for treating NLRP3 inflammasome related diseases.

Keywords: NLRP3; Vitenegu acid; inflammasome; peritonitis; sepsis.

Publication types

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

MeSH terms

Humans
Inflammasomes* / metabolism
Inflammation
NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism

Substances

Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (No. 32000668, U1801283, 81903541), the Shenzhen Science and Innovation Commission grant (JCYJ20210324094611031, JCYJ20210324094405014, JCYJ20220531102005011), Joint project from Yunnan Science and Technology Office and Yunnan University (No.2018FY001-001), and Medical Science and Technology Research Foundation of Guangdong Province (No. A2023209).