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

doi:10.1016/S1043-6618(03)00155-5

Pharmacological Research

Volume 48, Issue 3, September 2003, Pages 291-294

https://doi.org/10.1016/S1043-6618(03)00155-5 Get rights and content

Abstract

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 (mm²) 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 mm²) 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 μm in controls to 540 μm in oleanolic acid- (100 mg/kg) and 945 μm 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.

Introduction

Many native plants are used in Latin American traditional medicine to treat gastric ulcers and related symptomatologies. Despite of the high South American biodiversity and lore, little has been done on the search for antiulcer agents from its flora. The few existing data pointed out to promising lead compounds such as the clerodane diterpenes from Croton cajucara [1], labdane derivatives from Solidago chilensis [2], [3] and oleanolic acid [4].

Some triterpenes or their derivatives have been reported to display gastroprotective activity in different models of induced gastric lesions in animals [5], [6]. Oleanolic acid (OA) (Fig. 1), a triterpene widely distributed in the plant kingdom, 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 [4].

A key question when looking for potential antiulcer compounds is if whether the product displays curative effect in animal models. Since OA was effective in prevention models with low toxicity, an experiment was undertaken to assess the gastric ulcer healing properties of OA in the acetic acid-induced gastric ulcers in rats.

Section snippets

Animals

Fasted male Sprague–Dawley rats weighing 200–250 g bred at the Central Animal House of the Universidad de Talca were used. Animals were fed on certified Champion diet with free access to water under standard conditions of 12-h dark–light period, humidity and temperature. The protocols were approved by the Universidad de Talca Institutional Animal Care and Use Committee following the recommendations of the Canadian Council on Animal Care [7]. The number of animals used was determined on the basis

Results

OA was orally administered during 14 days to rats with acetic acid-induced gastric ulcers. Animals treated with OA at 50 and 100 mg/kg and ranitidine at 50 mg/kg were statistically different to the control group, with comparable efficacies for ranitidine at 50 mg/kg and OA at 100 mg/kg (Table 1). A dose-related response was observed for OA both in the reduction of the lesion area as well as in the curative ratio. Histological examinations of the stomach showed regeneration of the lesions. The

Discussion

Previous studies have shown that some terpenes or their derivatives isolated from higher plants present antiulcerogenic activity in vivo [2], [5], [6], [10]. The active compounds, comprising sesquiterpenes, diterpenes and triterpenes seem to exert their effect by different and complementary mechanisms, exhibiting as common feature an improvement of the mucosal defensive factors more than effects on the aggressive factors [5], [10], [11]. It is well known that antisecretory drugs such as

Acknowledgements

Financial support by FONDECYT, Grant No. 1990872 and the Programa de Productos Bioactivos, University of Talca are gratefully acknowledged.

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

Abstract

Introduction

Section snippets

Animals

Results

Discussion

Acknowledgements

J. Ethnopharmacol.

Phytomedicine

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Life Sci.

Phytomedicine

Pharmacol. Res.

Regul. Pept.

J. Physiol. Paris

Phytomedicine

J. Ethnopharmacol.

Antiulcerogenic activity of trans-dehydrocrotonin from Croton cajucara

Planta Med.

Gastroprotective activity of solidagenone on experimentally induced gastric lesions in rats

J. Pharm. Pharmacol.

Gastroprotective activity of oleanolic acid derivatives on experimentally induced gastric lesions in mice

J. Pharm. Pharmacol.