Gintonin Alleviates HCl/Ethanol- and Indomethacin-Induced Gastric Ulcers in Mice

Int J Mol Sci. 2023 Nov 24;24(23):16721. doi: 10.3390/ijms242316721.

Abstract

Gintonin, newly extracted from ginseng, is a glycoprotein that acts as an exogenous lysophosphatidic acid (LPA) receptor ligand. This study aimed to demonstrate the in vivo preventive effects of gintonin on gastric damage. ICR mice were randomly assigned to five groups: a normal group (received saline, 0.1 mL/10 g, p.o.); a control group (administered 0.3 M HCl/ethanol, 0.1 mL/10 g, p.o.) or indomethacin (30 mg/kg, p.o.); gintonin at two different doses (50 mg/kg or 100 mg/kg, p.o.) with either 0.3 M HCl/ethanol or indomethacin; and a positive control (Ranitidine, 40 mg/kg, p.o.). After gastric ulcer induction, the gastric tissue was examined to calculate the ulcer index. The expression of gastric damage markers, such as tumor necrosis factor (TNF)-α, cyclooxygenase 2 (COX-2), and LPA2 and LPA5 receptors, were measured by Western blotting. Interleukin-6 (IL-6) and prostaglandin E2 (PGE2) levels were measured by enzyme-linked immunosorbent assay. The platelet endothelial cell adhesion molecule (PECAM-1), Evans blue, and occludin levels in gastric tissues were measured using immunofluorescence analysis. Both HCl/ethanol- and indomethacin-induced gastric ulcers showed increased TNF-α, IL-6, Evans blue permeation, and PECAM-1, and decreased COX-2, PGE2, occludin, and LPA5 receptor expression levels. However, oral administration of gintonin alleviated the gastric ulcer index induced by HCl/ethanol and indomethacin in a dose-dependent manner. Gintonin suppressed TNF-α and IL-6 expression, but increased COX-2 expression and PGE2 levels in mouse gastric tissues. Gintonin intake also increased LPA5 receptor expression in mouse gastric tissues. These results indicate that gintonin can play a role in gastric protection against gastric damage induced by HCl/ethanol or indomethacin.

Keywords: LPA5; anti-inflammation; gastric ulcer; gintonin; prostaglandin E2.

MeSH terms

  • Animals
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • Ethanol / pharmacology
  • Evans Blue / metabolism
  • Gastric Mucosa / metabolism
  • Indomethacin* / pharmacology
  • Interleukin-6 / metabolism
  • Mice
  • Mice, Inbred ICR
  • Occludin / metabolism
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Stomach Ulcer* / chemically induced
  • Stomach Ulcer* / drug therapy
  • Stomach Ulcer* / pathology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Indomethacin
  • gintonin
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Cyclooxygenase 2
  • Tumor Necrosis Factor-alpha
  • Ethanol
  • Interleukin-6
  • Dinoprostone
  • Evans Blue
  • Occludin