Licochalcone B specifically inhibits the NLRP3 inflammasome by disrupting NEK7-NLRP3 interaction

EMBO Rep. 2022 Feb 3;23(2):e53499. doi: 10.15252/embr.202153499. Epub 2021 Dec 9.

Abstract

The activation of the nucleotide oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is related to the pathogenesis of a wide range of inflammatory diseases, but drugs targeting the NLRP3 inflammasome are still scarce. In the present study, we demonstrated that Licochalcone B (LicoB), a main component of the traditional medicinal herb licorice, is a specific inhibitor of the NLRP3 inflammasome. LicoB inhibits the activation of the NLRP3 inflammasome in macrophages but has no effect on the activation of AIM2 or NLRC4 inflammasome. Mechanistically, LicoB directly binds to NEK7 and inhibits the interaction between NLRP3 and NEK7, thus suppressing NLRP3 inflammasome activation. Furthermore, LicoB exhibits protective effects in mouse models of NLRP3 inflammasome-mediated diseases, including lipopolysaccharide (LPS)-induced septic shock, MSU-induced peritonitis and non-alcoholic steatohepatitis (NASH). Our findings indicate that LicoB is a specific NLRP3 inhibitor and a promising candidate for treating NLRP3 inflammasome-related diseases.

Keywords: LPS-induced septic shock; Licochalcone B; MSU-induced peritonitis; NASH; NEK7; NLRP3 inflammasome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chalcones* / pharmacology
  • Inflammasomes* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NIMA-Related Kinases / genetics
  • NIMA-Related Kinases / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein

Substances

  • Chalcones
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • NIMA-Related Kinases
  • Nek7 protein, mouse
  • licochalcone B