Gastroprotective and Ulcer-Healing Activities of Protea madiensis Oliv. (Proteaceae) Stem Bark Methanol Extract and Its Solvent Fractions in Wistar Albino Rats

Background: Protea madiensis stem bark is used traditionally for gastric ailments, but experimental evidence of its gastroprotective and ulcer-healing effects is limited. Aims: To evaluate the acute oral toxicity, phytochemical profile and antiulcer activity of the methanol stem bark extract of Protea madiensis and its solvent fractions, and explore the mechanism of the most active fraction. Study Design: A controlled experimental study in rodents. Place and Duration of Study: Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Nigeria, between July 2024 and June 2025. Methodology: The methanol extract (ME) was fractionated by vacuum liquid chromatography into n-hexane (HF), ethyl acetate (EF) and methanol (MF) fractions. Phytochemicals were screened qualitatively and quantitatively, and acute oral toxicity was assessed in mice by Lorke’s method. Antiulcer activity was tested in Wistar albino rats (n = 5 per group) in ethanol- and indomethacin-induced gastric lesion models and the acetic acid-induced chronic ulcer model (ME 100–400 mg/kg; fractions 100 and 400 mg/kg, orally), with omeprazole (20 mg/kg) as the reference treatment. MF (200 and 400 mg/kg) was further evaluated for its effects on gastric prostaglandin E2 (PGE2) and pH in indomethacin-treated rats and on gastric secretion volume in pylorus-ligated rats. Data (mean ± SEM) were analysed by one-way ANOVA followed by Dunnett’s test. Results: Phenolics were the most abundant constituent class in ME. No deaths or signs of toxicity occurred at oral doses up to 5000 mg/kg. All test materials significantly reduced lesion severity compared with vehicle (n = 5 per group; P < .05). MF at 400 mg/kg gave the greatest inhibition in the indomethacin (92.2%) and acetic acid (97.5%) models and 93.7% inhibition against ethanol, values comparable in magnitude with those of omeprazole (76.0–95.2%); ME at 400 mg/kg gave 97.0% inhibition against ethanol. MF increased gastric PGE2 from 352 to 781–811 pg/mL and gastric pH to 5.7–6.6 (P < .001), and reduced gastric secretion volume in pylorus-ligated rats by 81.0–88.8% (P < .001). Conclusion: P. madiensis stem bark has low acute oral toxicity (single oral doses up to 5000 mg/kg) and dose-related gastroprotective and ulcer-healing activity in rats, which supports its folk use for peptic ulcer; these preliminary findings do not establish long-term safety or clinical efficacy. The methanol fraction is the most active, and its effect is associated with preservation of gastric PGE2 and reduced gastric secretion, and its flavonoids, tannins, saponins and phenolics are candidate active constituents.