EVALUATION OF THE GASTROPROTECTIVE AND SUB-CHRONIC TOXICITY OF METHANOL STEM BARK EXTRACT OF XIMENIA AMERICANA LINN (OLACACEAE) IN MALE WISTAR RATS
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Abstract
Ximenia americana is a plant used traditionally in northern parts of Nigeria for treatment of leprotic ulcers and mouth ulcers in addition to other medicinal uses. It contains flavanoids, saponins, tannins among others that has been reported to possess gastroprotective potentials. . The aim of this study is to evaluate the gastro-protective effects and establish the toxicity profile of the methanol stem back extract of Ximenia americana. The oral median lethal dose of the extract was estimated in mice and rats using Lorke‟s method of acute toxicity test, while the composite constituents of the extract were determined using established standard preliminary phytochemical screening procedures of colour changes in test-tube chemical reactions. The antiulcer effect of the extract was evaluated using two ulcerogenic models of indomethacin and ethanol induced ulcers in rats at extract doses of 250, 500 and 1000 mg/kg body weight. Subchronic toxicities of the extract on some organs, haematological and biochemical parameters were also investigated following 28 days daily pretreatment in rats. Alkaloids, anthraquinones, carbohydrates, flavonoids, saponins, steroidal glycosides, tannins and terpenoids were found to be present in the methanol stem back extract of Ximenia americana. The extract caused no death in mice and rats at doses of up to 5,000 mg/kg oral administration and no observable behavioural changes were seen in both animal species (mice and rats) within 24 hours. The indomethacineinduced ulcer lesions were reduced in the extract pretreated groups of rats and in a dose dependent manner that was significant (p<0.05) for the two higher doses of the extract (500 and 1000 mg/kg) when compared to the control group. The extract significantly (p≤0.05) and dosedependently reduced the mean ulcer spots in a similar manner as the standard agents cimetidine and misoprostol. The reduction was significant for only the two higher extract doses (500 and 1000 mg/kg). However, the ulcer lesions were more prevented in the rat groups of the standard drugs. A mean of only 3 severe ulcer spots for each of the two lower extract dose pre-treated rat groups against 9 severe ulcer spots for the normal saline control group occurred with the vii indomethacin ulcerogen. However, no severe ulcer spots were found in both the cimetidine and 1000 mg/kg extract pretreated rat groups. There were no severe ulcers (≥ 3mm spots) found with the ethanol-ulcerogen in any of the groups including the normal saline control group. In conclusion the extract did not cause changes in the organ sizes in relation to the control experiment. The body weights of the extract-treated rats did also not change. However, histological examinations showed vascular congestion with polymorphonuclear cells in the kidney at the extract dose of 1000 mg/kg; consolidated areas of polymorphs infiltration at the alveoli and terminal bronchioles of the lungs; and distorted germinal centres in spleen. No remarkable changes were observed of the heart, liver, stomach and brain. Amongst the evaluated electrolytes, only Na+ , Cland Ca2+ showed consistent but slight increases in their concentrations across the various doses of the extract, while changes in K+ and HCO3 - levels were neither significant nor of a consistent pattern. The liver enzymes including the aminotransferases and alkaline phosphatase were not altered. A dose dependent increase in total protein that was significant (p<0.05) only at 1000 mg/kg; and a reduction in albumin level that was significant at the two higher extract doses (500 and 1000 mg/kg) were observed. The changes in the urea level were inconsistent and insignificant, while the dose dependent reduction in creatinine level seen in this study was not significant at any of the doses. In conclusion, the methanol stem back extract of Ximenia americana possess gastro-mucosal protective properties that prevented ulceration and / or promoted ulcer healing and is also relatively systemically non-toxic.
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