MECHANISM OF ANTI-GASTRIC ULCER EFFECT OF BETULINIC ACID IN MALE ALBINO RATS

Abstract

Betulinic acid (BA) is a lupane-type triterpene that has been identified and isolated from different plant species used in ethnomedicine worldwide. It is known to possess anti-ulcer, anti-tumor and anti-microbial properties. However, the mechanism underlying the anti-ulcer property of BA has not been well investigated. The effect of BA on indomethacin-induced peptic ulcer, gastric mucus secretion (GMS), gastric mucus cell count (GMCC), basal and histamine induced gastric acid secretion (GAS), and malondialdehyde (MDA) concentration level were studied as means of elucidating the mechanism. Thirty-two rats divided into four groups of eight rats each were used for each study. Group I (Control) was pretreated orally with dimethyl sulfoxide (DMSO) in normal saline for seven days. Groups II, III and IV were pretreated orally with BA (0.5 mg/kg, 1.5 mg/kg, and 3.0 mg/kg) dissolved in DMSO respectively for seven days. Gastric ulceration was induced using indomethacin and scored by ulcer scoring technique. Measurement of GMS was performed using spectrophotometric method, while GMCC was done by using calibrated microscopy. Continuous perfusion technique was used to assess GAS and its acidity determined by titration. Histological study of the stomach mucosa was also carried out. MDA levels were determined by measuring thiobarbituric acid reactive substances produced. Data were expressed as Mean ± SEM. Student’s t-test and one way ANOVA were used to determine levels of significance at p<0.05. There was a dose - dependent reduction in ulcer scores in the BA treated animals. This reduction was significant at doses of 1.5mg/kg (0.75  0.10) and 3.0mg/kg (0.25  0.09) compared to the control (7.0  0.27). GMS (mg/g tissue x 10-2) significantly increased in the 1.5 mg/kg (4.9 ± 0.22) and 3.0 mg/kg (5.2 ± 0.09) pretreated groups compared to the control (4.4 ± 0.20) group. There was also a dose-dependent significant increase in the GMCC/mm2 of rats treated with 0.5 mg/kg (44.4 ± 0.84); 1.5 mg/kg (45.9 ± 0.79); 3.0 mg/kg (54.1± 0.71)] compared with the control group (41.4 ± 0.71). The histamine-induced GAS was significantly higher than the basal GAS. However, there was a significant decrease in GAS of BA treated groups compared with the control. Histological study showed significant hyperplasia of mucus cells in BA treated groups compared to the control group. There was a significant decrease in MDA (μmol/L x 10-6) levels in groups II, III and IV (1.86± 0.076, 1.83 ± 0.069 and 1.10 ± 0.056) compared to the control (2.60 ± 0.110) group. The results of the study suggest that betulinic acid produces anti-ulcer effect by increasing gastric mucus secretion, gastric mucus cell count and decreasing malonialdehyde concentration. It decreases gastric acid secretion via the blocking of H2-receptors.