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Peptic ulcer disease (PUD) is a sore in the lining of the stomach or duodenal mucosa. The search for an ideal antiulcer drug continues and has also been extended to medicinal plants. Bridelia ferruginea Benth (Euphorbiaceae) is a plant used in traditional medical practice in South West Nigeria. This study was aimed at evaluating the antiulcer activity and mechanisms of the extract of the stem bark and to isolate the bioactive constituents responsible for the antiulcer activity. Methanol extract (ME) was obtained by cold maceration and concentration in vacuo. ME was partitioned in chloroform-methanol-water (2:2:1) mixture to obtain the chloroform (CF) and aqueous methanol (AMF) fractions. The extract and fractions were subjected to biological activity-guided screening using indomethacin-induced ulcer as activity-guide. Based on higher ulcer protection given by CF, it was fractionated in a silica gel and eluted with gradient mixtures of n-hexane-ethyl acetate to obtain six broad fractions (I – VI). Fractions III and VI offered the highest protection on screening for biological activity. Purification of fractions III and VI in a sephadex LH-20 column with methanol as eluent gave compounds I (BF1) and II (BF2) respectively. The antiulcer activity of BF1 and BF2 was done using the activity-guide and the structural identities established using nuclear magnetic resonance (1H-NMR, 13C-NMR) and electron impact mass (EIM) spectroscopies. The extract was subjected to phytochemical analysis using conventional methods. The oral acute toxicity of ME was determined in mice. The antiulcer activity of ME, bioactive column fractions and isolated compounds was investigated using indomethacin, ethanol, cold-restraint stress and pyloric ligation-induced ulcers in rats. The mechanisms of antiulcer activity were studied using gastric acid secretion induced by pyloric ligation in rats, proton pump inhibition using inhibition of H+ K+ ATPase activity in vitro, determination of the roles of endogenous nitric oxide and sulfhydryl compounds using the effects of L-NAME (L-nitroarginine methylester) and NEM (N-ethylmaleimide) respectively on ulcer indices in ethanol-induced ulcer and antioxidant activity using DPPH radical scavenging activity. The results showed that ME tested positive to saponins, reducing sugars, tannins, carbohydrates, flavonoids, glycosides, alkaloids, steroids, proteins and terpenoids. No lethality was observed in the mice on oral administration of doses up to 5000 mg/kg. There were no obvious signs of abnormal behavioural changes in the mice. The extract, fractions and isolated compounds produced significant (p < 0.05) dose-related inhibition of indomethacin, ethanol, cold restraint stress and pyloric ligation-induced ulcers. The isolated compounds, BF1 and BF2, significantly (p < 0.05) decreased the total acid and volume of gastric secretion and elevated the pH. The fractions and isolated compounds significantly (p < 0.05) inhibited the activity of H+ K+ ATPase in a dose-dependent manner. The isolated compounds, BF1 and BF2 did not increase gastric lesion indices in L-NAME pre-treated rats but they significantly (p < 0.05) increased ulcer indices in the NEM pre-treated rats. The extract, fractions and isolated compounds scavenged DPPH radical in a dose-dependent manner. Comparison of the spectral data of BF1 and BF2 with the published libraries of isolated compounds revealed their identities to be β-sitosterol and β-sitosterol-3-O-βD-glucopyranoside respectively.