Cryptotanshinone specifically suppresses NLRP3 inflammasome activation and protects against inflammasome-mediated diseases

Pharmacol Res. 2021 Feb:164:105384. doi: 10.1016/j.phrs.2020.105384. Epub 2020 Dec 19.

Abstract

NLRP3 inflammasome activation is implicated in the pathogenesis of a wide range of inflammatory diseases, but medications targeting the NLRP3 inflammasome are not available for clinical use. Here, we demonstrate that cryptotanshinone (CTS), a major component derived from the traditional medicinal herb Salvia miltiorrhiza Bunge, is a specific inhibitor for the NLRP3 inflammasome. Cryptotanshinone inhibits NLRP3 inflammasome activation in macrophages, but has no effects on AIM2 or NLRC4 inflammasome activation. Mechanistically, cryptotanshinone blocks Ca2+ signaling and the induction of mitochondrial reactive oxygen species (mtROS), which are important upstream signals of NLRP3 inflammasome activation. In vivo, cryptotanshinone attenuates caspase-1 activation and IL-1β secretion in mouse models of NLRP3 inflammasome-mediated diseases such as endotoxemia syndrome and methionine- and choline-deficient-diet-induced nonalcoholic steatohepatitis (NASH). Our findings suggest that cryptotanshinone may be a promising therapeutic agent for the treatment of NLRP3 inflammasome-mediated diseases.

Keywords: Cryptotanshinone; Cryptotanshinone (PubChem CID: 160254); Endotoxemia; NASH; NLRP3 inflammasome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Female
  • Inflammasomes / immunology*
  • Interleukin-1beta / immunology
  • Lipopolysaccharides
  • Liver / drug effects
  • Liver / immunology
  • Liver / pathology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / immunology*
  • Non-alcoholic Fatty Liver Disease / drug therapy
  • Non-alcoholic Fatty Liver Disease / immunology
  • Non-alcoholic Fatty Liver Disease / pathology
  • Phenanthrenes / pharmacology*
  • Phenanthrenes / therapeutic use
  • Reactive Oxygen Species / metabolism
  • Shock, Septic / drug therapy
  • Shock, Septic / immunology
  • T-Lymphocytes, Regulatory / drug effects
  • Th17 Cells / drug effects
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • IL1B protein, mouse
  • Inflammasomes
  • Interleukin-1beta
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Phenanthrenes
  • Reactive Oxygen Species
  • Tnf protein, mouse
  • Tumor Necrosis Factor-alpha
  • cryptotanshinone