Chrysanthemum indicum extract inhibits NLRP3 and AIM2 inflammasome activation via regulating ASC phosphorylation

J Ethnopharmacol. 2019 Jul 15:239:111917. doi: 10.1016/j.jep.2019.111917. Epub 2019 Apr 25.

Abstract

Ethnopharmacological relevance: Chrysanthemum indicum (C. indicum), a perennial plant, has long been used to treat inflammation-related disorders, such as pneumonia, hypertension, gastritis, and gastroenteritis.

Aim of the study: The inhibitory effect of C. indicum extract (C.I) on inflammasome activation was investigated to validate its potential in treating inflammation related disorders.

Materials and methods: LPS-primed bone marrow-derived macrophages (BMDMs) were used to confirm the inhibitory effect of C.I on selective inflammasome activation in vitro. A monosodium urate (MSU)-induced murine peritonitis model was employed to study the effect of C.I in vivo.

Results: C.I inhibited activation of NLRP3 and AIM2 inflammasomes, leading to suppression of interleukin-1β secretion in vitro. Further, C.I regulates the phosphorylation of apoptosis-associated speck-like protein containing a CARD (ASC), which could be the main contribution to attenuate these inflammasomes activation. C.I also suppressed secretion of pro-inflammatory cytokines and neutrophils recruitment in MSU-induced murine peritonitis model.

Conclusions: This study provides scientific evidence substantiating the traditional use of C. indicum in the treatment of inflammatory diseases, including gout, which is induced by physiologically analogous cause to MSU-induced peritonitis.

Keywords: ASC phosphorylation; Chrysanthemum indicum; Inflammasome; MSU-Induced peritonitis; NLRP3.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • CARD Signaling Adaptor Proteins / metabolism*
  • Chrysanthemum*
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gout / drug therapy
  • Gout / metabolism
  • Gout Suppressants / pharmacology
  • Gout Suppressants / therapeutic use
  • Inflammasomes / metabolism*
  • MAP Kinase Kinase 4 / metabolism
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Peritonitis / chemically induced
  • Peritonitis / drug therapy
  • Peritonitis / metabolism*
  • Phosphorylation / drug effects
  • Plant Components, Aerial
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Uric Acid

Substances

  • Aim2 protein, mouse
  • Anti-Inflammatory Agents
  • CARD Signaling Adaptor Proteins
  • DNA-Binding Proteins
  • Gout Suppressants
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Plant Extracts
  • Pycard protein, mouse
  • Uric Acid
  • MAP Kinase Kinase 4