Epiberberine ameliorates MNNG-induced chronic atrophic gastritis by acting on the EGFR-IL33 axis

Int Immunopharmacol. 2025 Jan 3:145:113718. doi: 10.1016/j.intimp.2024.113718. Epub 2024 Dec 6.

Abstract

Chronic atrophic gastritis (CAG) is a prevalent form of chronic gastritis that presents with chronic inflammation of the gastric mucosa, localised gastric mucosal glandular atrophy and intestinal metaplasia. Despite the existence of diagnostic criteria, effective therapeutic strategies for this condition remain to be developed. The objective of this study was to examine the potential therapeutic benefits of epiberberine in mitigating MNNG-induced CAG and to elucidate the underlying mechanisms. MNNG was employed to establish a CAG mouse model and a GES-1 cell model, and EPI was observed to be efficacious in ameliorating the gastric mucosal injury and inflammatory infiltration induced by MNNG in the CAG model mice, a finding that was subsequently validated in the GES-1 model cells. Bioinformatics analysis indicated that EPI may exert a direct effect on EGFR, thereby regulating the expression of IL-33 and thereby achieving the therapeutic effect of CAG. This hypothesis was also validated by molecular docking prediction, CETSA, and overexpression of EGFR in GES-1 model cells, using EGFR agonists and inhibitors to further demonstrate that EPI may act as an antagonist supplement to EGFR for the treatment of CAG.

Keywords: Chronic atrophic gastritis; EGFR; Epiberberine; IL33.

MeSH terms

  • Animals
  • Cell Line
  • Chronic Disease
  • Disease Models, Animal
  • ErbB Receptors* / metabolism
  • Gastric Mucosa* / drug effects
  • Gastric Mucosa* / pathology
  • Gastritis, Atrophic* / drug therapy
  • Gastritis, Atrophic* / pathology
  • Humans
  • Interleukin-33* / genetics
  • Interleukin-33* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Docking Simulation
  • Signal Transduction / drug effects

Substances

  • ErbB Receptors
  • EGFR protein, mouse
  • Interleukin-33
  • Il33 protein, mouse