Parthenolide targets NLRP3 to treat inflammasome-related diseases

Int Immunopharmacol. 2023 Jun:119:110229. doi: 10.1016/j.intimp.2023.110229. Epub 2023 May 9.

Abstract

Natural products have attracted extensive attention from researchers in medical fields due to their abundant biological activities. Parthenolide (PTL) is a sesquiterpene lactone originally purified from herb Feverfew (Tanacetum parthenium), recent studies have showed its potential activities of anti-cancer and anti-inflammatory. Acting as the most studied inflammasome, NLRP3 inflammasome played an important role in human diseases including type-2 diabetes (T2D), Alzheimer's disease (AD) and cryopyrin-associated periodic syndromes (CAPS). In this article, we show that PTL specially inhibits the activation of NLRP3 inflammation by block the upstream signal and prevent the assembly of NLRP3 inflammasome complex. Furthermore, we showed the treatment of PTL significantly attenuates the symptoms of lipopolysaccharide (LPS)-induced systemic inflammation and dextran sulfate sodium (DSS)-induced colitis in mice models. Thus, our results demonstrate that PTL alleviates inflammation by targeting NLRP3 inflammasome, which indicate that PTL acting as a promising natural product for the treatment of NLRP3 inflammasome-related diseases.

Keywords: IL-1β release; Inflammatory diseases; NLRP3 inflammasome; Natural products; Parthenolide; Pyroptosis.

MeSH terms

  • Animals
  • Dextran Sulfate
  • Humans
  • Inflammasomes*
  • Inflammation
  • Mice
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Sesquiterpenes* / pharmacology
  • Sesquiterpenes* / therapeutic use

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • feverfew extract
  • parthenolide
  • Sesquiterpenes
  • Dextran Sulfate
  • Nlrp3 protein, mouse