Ascorbyl palmitate ameliorates inflammatory diseases by inhibition of NLRP3 inflammasome

Int Immunopharmacol. 2024 Apr 20:131:111915. doi: 10.1016/j.intimp.2024.111915. Epub 2024 Mar 23.

Abstract

The aberrant activation of NLRP3 inflammasome contributes to pathogenesis of multiple inflammation-driven human diseases. However, the medications targeting NLRP3 inflammasome are not approved for clinic use to date. Here, we show that ascorbyl palmitate (AP), a lipophilic derivative of ascorbic acid (AA) and a safe food additive, is a potent inhibitor of NLRP3 inflammasome. Compared with AA, AP inhibited the activation of NLRP3 inflammasome with increased potency and specificity. Mechanistically, AP directly scavenged mitochondrial reactive oxygen species (mitoROS) by its antioxidant activity and blocked NLRP3-NEK7 interaction and NLRP3 inflammasome assembly. Moreover, AP showed more significant preventive effects than AA in LPS-induced systemic inflammation, dextran sulfate sodium (DSS)-induced colitis and experimental autoimmune encephalomyelitis (EAE). Thus, our results suggest that AP is a potential therapeutic combating NLRP3-driven diseases.

MeSH terms

  • Animals
  • Ascorbic Acid / analogs & derivatives*
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use
  • Colitis* / chemically induced
  • Colitis* / drug therapy
  • Dextran Sulfate
  • Humans
  • Inflammasomes*
  • Inflammation / drug therapy
  • Mice
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • 6-O-palmitoylascorbic acid
  • Ascorbic Acid
  • Dextran Sulfate