Mechanistic Elucidation of the Antiulcer Activity of Cnidoscolus aconitifolius Leaf Extract in Experimental Gastric Ulcer Models with Cytoprotective and Acid-Suppressive Profiling

Peptic ulcer disease is prevalent across Nigeria, with dietary habits, Helicobacter pylori infection, and NSAID use being primary drivers. Cnidoscolus aconitifolius (tree spinach), known locally as iyana-ipaja in South West Nigeria, is consumed as a leafy vegetable and applied medicinally for gastric pain and ulcer conditions in Oyo and Ogun States. Despite recognised ethnomedicinal use, the mechanistic basis of its antiulcer activity has not been systematically investigated. This PhD research elucidates the antiulcer mechanisms of Cnidoscolus aconitifolius leaf extract through a multi-model approach combining cytoprotective, acid-suppressive, anti-H. pylori, and anti-secretory mechanistic studies. Gastric ulcer was experimentally induced by ethanol-HCl, indomethacin, cold restraint stress, and pylorus-ligation models in Wistar rats. Anti-H. pylori activity was evaluated in vitro by MIC determination and urease inhibition assay. Cytoprotective mechanisms were assessed by gastric mucus measurement, prostaglandin E2 determination, and gastric wall sulphydryl quantification. Acid suppression was characterised by measurement of gastric secretory volume, pH, and total acidity in the pylorus-ligation model. Oxidative mucosal protection was evaluated by MDA, SOD, and catalase assays in gastric mucosa homogenates. Cnidoscolus aconitifolius extract demonstrated significant ulcer protection in all four induction models, with cytoprotective mechanisms dominant over acid suppression. Prostaglandin E2 levels were significantly elevated in the extract-treated groups. Anti-H. pylori MIC was 0.78 mg/mL, with 81% urease inhibition at 2 mg/mL. Flavonoid-rich fractions were pharmacologically most active. Keywords: Cnidoscolus aconitifolius, antiulcer, cytoprotective, Helicobacter pylori, South West Nigeria