Piperlongumine Is an NLRP3 Inhibitor With Anti-inflammatory Activity

Jie Shi; Yang Xia; Huihong Wang; Zhongjie Yi; Ruoruo Zhang; Xiufeng Zhang

doi:10.3389/fphar.2021.818326

Piperlongumine Is an NLRP3 Inhibitor With Anti-inflammatory Activity

Front Pharmacol. 2022 Jan 12:12:818326. doi: 10.3389/fphar.2021.818326. eCollection 2021.

Authors

Jie Shi^{1

2}, Yang Xia¹, Huihong Wang¹, Zhongjie Yi³, Ruoruo Zhang⁴, Xiufeng Zhang¹

Affiliations

¹ Department of Respiratory Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, China.
² Department of General Surgery, The Third Xiangya Hospital of Central South University, Changsha, China.
³ Department of Plastic and Aesthetic (Burn) Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
⁴ Institute of Transplantation Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, China.

Abstract

Piperlongumine (PL) is an alkaloid from Piper longum L. with anti-inflammatory and antitumor properties. Numerous studies have focused on its antitumor effect. However, the underlying mechanisms of its anti-inflammation remain elusive. In this study, we have found that PL is a natural inhibitor of Nod-like receptor family pyrin domain-containing protein-3 (NLRP3) inflammasome, an intracellular multi-protein complex that orchestrates host immune responses to infections or sterile inflammations. PL blocks NLRP3 activity by disrupting the assembly of NLRP3 inflammasome including the association between NLRP3 and NEK7 and subsequent NLRP3 oligomerization. Furthermore, PL suppressed lipopolysaccharide-induced endotoxemia and MSU-induced peritonitis in vivo, which are NLRP3-dependent inflammation. Thus, our study identified PL as an inhibitor of NLRP3 inflammasome and indicated the potential application of PL in NLRP3-relevant diseases.

Keywords: NLRP3; Nek7; inflammasome assembly; inflammation; piperlongumine.