Targeting NF‐κB/COX‐2 signaling by soyasaponin I alleviates diclofenac‐induced gastric ulceration in male albino rats

Abstract

Gastric ulceration is a prevalent worldwide clinical presentation due to altered gastric defense mechanisms. Nonsteroidal anti‐inflammatory drugs are one of the common causes of gastric ulcers mediated by the release of inflammatory mediators. The study aimed to investigate the potential protective effect of soyasaponin I (soya) against diclofenac (DIC)‐induced gastric ulcer in rats and to highlight the underlying mechanisms. The experiment was conducted on 40 male Wistar albino rats, equally distributed into five groups: control, DIC‐induced ulcer (9 mg/kg/d, orally, twice daily for 3 days), ulcer/soya‐, ulcer/ranitidine‐, and ulcer/soya/selective nuclear factor kappa B inhibitor (JSH‐23)‐treated groups. The doses of soya, ranitidine, and JSH were 20, 25, and 5 mg/kg/d, respectively, given orally. Gastric specimens were prepared for gene and histological study and for biochemical analysis of gastric prostaglandin E2 (PGE2), oxidative markers, and inflammatory cytokines. The gastric samples were formalin‐fixed, paraffin‐embedded, and subjected to hematoxylin and eosin (H&E), PAS staining, and immunohistochemical assay for identification of nuclear factor kappa B (NF‐κB), cyclooxygenase‐2 (COX‐2), and proliferation marker (Ki67) expressions. The findings revealed decreased gastric PGE2 and altered inflammatory and oxidative markers in the ulcer model group. The H&E staining showed mucosal injury characterized by mucosal surface defects and inflammatory cell infiltrations. The polymerase chain reaction (PCR) and immunohistochemistry demonstrated an upregulation of NF‐κB and COX‐2 expression at gene/protein levels; meanwhile, Ki67 downregulation. The soya‐treated group showed maintained biochemical, histological, and PCR findings comparable to the ranitidine‐treated group. The JSH‐23‐treated group still showed partial gastric protection with biochemical and immunohistochemical changes. Soyasaponin I ameliorated DIC‐induced gastric ulcers by targeting the COX‐2 activity through modulation of NF‐κB signaling.