Oleanolic acid promotes healing of chronic gastric lesions acetic acid-induced in rats

Purpose: Previous work demonstrates that oleanolic acid (OA), a triterpene widely distributed in plants, shows gastroprotective effect in the ethanol, aspirin and pilorous ligature-induced gastric ulcer in rats as well as in the ethanol/hydrochloric acid-induced ulcer in mice. The aim of this work was to assess the healing effect of OA in the acetic acid-induced chronic gastric ulcer model in rats. Methods: Chronic gastric lesions were induced in male Sprague-Dawley rats with acetic acid. OA was administered orally during 14 days at 25, 50 and 100 mg/kg per day. Ranitidine (50 mg/kg) and the vehicle were used as controls. The ulcer area (mm(2)) and the curative ratio (%) were determined. Histological preparations were carried out for comparative purposes. Results: The effect of OA was significantly different as compared to the control reducing the lesion area (in mm(2)) from 39 +/- 7 in controls to 17.8 +/- 1.9 and 9.4 +/- 1.1 at the doses of 50 and 100 mg/kg, respectively. The curative ratio was 54.5 and 76% for the compound at 50 and 100 mg/kg, while ranitidine at 50 mg/kg reduced the lesion area to 6.9 +/- 0.8 with a curative ratio of 84%. Mucosal thickness increased from 342 mum in controls to 540 mum in oleanolic acid- (100 mg/kg) and 945 mum in ranitidine-treated animals. Histological examination of the stomach showed regeneration of the lesions. Conclusions: OA improves healing of chronic gastric lesions in rats. The low toxicity and widespread occurrence of OA in plants suggest a potential for the development of the triterpene or their derivatives as a new antiulcer drug. (C) 2003 Elsevier Science Ltd. All rights reserved.