Gastroprotective effect of an active ingredients group of Lindera reflexa Hemsl. On Ethanol-Induced gastric ulcers in Rats: Involvement of VEGFR2/ERK and TLR-2/Myd88 signaling pathway

Int Immunopharmacol. 2022 Jun:107:108673. doi: 10.1016/j.intimp.2022.108673. Epub 2022 Mar 5.

Abstract

Lindera reflexa Hemsl. (LR) has been used for the treatment of gastrointestinal disorders. The present study was carried out to investigate the gastroprotective effect of an active ingredients group of Lindera reflexa Hemsl. (LRG) on ethanol-induced gastric ulcer in rats and its possible mechanisms. The ulcer area was measured, and samples of gastric tissue were taken for histochemical, pathological, and biochemical analyses. Pretreatment with LRG protected the gastric mucosa as seen by reduction the GUI and gastric juice volume, regulated gastric acid secretion. LRG counteracted the ethanol-induced oxidative stress by increasing the levels of depleted SOD and CAT as well as significantly attenuating the lipid peroxidation by reducing the levels of MDA and MPO. LRG also reduced release of inflammatory mediator TNF-α, increased the content of PGE2 and inhibited MTL secretion. Immunofluorescence and Western blot analyses confirmed that the co-localization of TLR-2 and MyD88 protein in the gastric mucosa of LRG-treated rats was significantly lower than that of rats with gastric ulcers. Furthermore, LRG also modulated the expression of Ki-67 antigens. LRG markedly increased the expression of phosphorylated form of extracellular signal-regulated kinaseVEGFR2, ERK1/2, AKT and p38, thereby protecting the gastric mucosa. These findings indicated that the gastroprotective effect of LRG is attributable to its antioxidant, anti-inflammatory, and antisecretory properties. In addition, LRG can ameliorate ethanol-induced gastric ulcers in rats by regulating the VEGFR2/ERK and TLR-2/MyD88 signaling pathways.

Keywords: Active ingredients group; Ethanol; Gastric ulcer; Lindera reflexa Hemsl.; VEGFR2/ERK signaling pathway.

MeSH terms

  • Animals
  • Anti-Ulcer Agents* / pharmacology
  • Anti-Ulcer Agents* / therapeutic use
  • Ethanol / metabolism
  • Ethanol / toxicity
  • Gastric Mucosa
  • Lindera* / metabolism
  • Myeloid Differentiation Factor 88 / metabolism
  • Rats
  • Signal Transduction
  • Stomach Ulcer* / chemically induced
  • Stomach Ulcer* / drug therapy
  • Stomach Ulcer* / pathology
  • Toll-Like Receptor 2 / metabolism

Substances

  • Anti-Ulcer Agents
  • Myd88 protein, rat
  • Myeloid Differentiation Factor 88
  • Toll-Like Receptor 2
  • Ethanol