Protective effects of genipin on ethanol-induced acute gastric injury in mice by inhibiting NLRP3 inflammasome activation

Eur J Pharmacol. 2020 Jan 15:867:172800. doi: 10.1016/j.ejphar.2019.172800. Epub 2019 Dec 2.

Abstract

Genipin has been shown to exert anti-inflammatory effects, but its mechanism in protecting the ethanol-induced acute gastric injuries remains largely unclear. The present study aimed to investigate the effects of genipin on ethanol-induced acute gastric injuries in mice. After intragastrical administration of genipin for 7 consecutive days, acute gastric injuries were induced in the mice by ethanol treatment for 1 h. The expression levels of MDA, MPO, SOD, CAT, and NO in gastric tissues, and the levels of IL-6, TNF-α, MTL, SP, VIP and SS in serum samples were measured by ELISA. In addition, Western blotting was used to determine the expression levels of proteins involved in NLRP3 signaling pathway. The findings revealed that oral administration of genipin significantly ameliorated the pathological injury of gastric mucosa induced by ethanol, decreased the oxidative stress induced by ethanol and suppressed the expression levels of in-flammatory cytokines in gastric tissues and serum samples. In addition, it was observed that oral administration of genipin could remarkably inhibit the expression levels of related proteins in the NLRP3 signaling pathway. In conclusion, these results suggest that genipin may exhibit protective roles in ethanol-induced gastric mucosal injuries by activating antioxidant system and attenuating inflammatory reaction.

Keywords: Gastric ulcer; Genipin; Inflammasome; NLRP3; Oxidative stress.

MeSH terms

  • Acute Disease / therapy
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Disease Models, Animal
  • Ethanol / toxicity
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / immunology
  • Gastric Mucosa / pathology
  • Humans
  • Inflammasomes / antagonists & inhibitors
  • Inflammasomes / immunology
  • Inflammasomes / metabolism
  • Iridoids / administration & dosage*
  • Male
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Oxidative Stress / drug effects*
  • Oxidative Stress / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / drug therapy*
  • Stomach Ulcer / immunology
  • Stomach Ulcer / pathology

Substances

  • Anti-Inflammatory Agents
  • Inflammasomes
  • Iridoids
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Ethanol
  • genipin