Mitigative Effects Of Moringa Oleifera Against Liver Injury Induced By Artesunate-amodiaquine Antimalarial Combination In Wistar Rats

Abstract

Background: Artesunate-amodiaquine (AS-AQ) is an antimalarial drug. It is associated with improved cure rates, accelerated response to therapy and delayed development of resistance. However, liver damage, neurotoxicity and agranulocytosis have been reported as adverse effects whose origins have been linked to free radicals generated by the drug. According to native materia medica, Moringa oleifera (MO) has wide utility in ethnomedicine. However, there is paucity of information on the hepatoprotective efficacy of this plant. The present study evaluated the mitigative effects of MO leaf extracts against liver injury induced by AS-AQ combination in female Wistar rats. Methods: Dry leaf powder of MO was extracted with water and a 20:80 v/v mixture of water and methanol to give aqueous (AQ) and aqueous-methanol (AQ-ME) MO leaf extracts respectively. In vitro hydroxyl free radical scavenging activity of serial dilutions (10–100 μg/ml) of each of the extracts was then evaluated using an assay model where butylated hydroxytoluene (BHT) served as a reference standard. The extract with better free radical scavenging activity was then evaluated for hepatoprotective effects against AS-AQ intoxication in female Wistar rats based on the Acute Toxic Class method (OECD 2000). Serum asparate amino transferase (AST), alanine amino transferase (ALT), total bilirubin and histological examination of rat liver sections were used to evaluate the hepatoprotective activity of the selected MO leaf extract. Siliphos® (standard hepatoprotectant) was used for comparison. Results: There was a concentration dependent increase in the hydroxyl free radical scavenging activity of MO leaf extracts and standard (BHT) with values ranging from 46.36–66.36% for the AQ extract, 41.04–60.95% for the AQ-ME extract and 44.93–65.23% for BHT with corresponding IC50 values of 26.84 μg/ml, 51.88 μg/ml and 32.58 μg/ml respectively. A 1000 mg/kg dose of the AQ-ME MO leaf extract significantly (p < 0.05) lowered AST values of AS-AQ intoxicated rats to a level comparable to the standard hepatoprotectant; Siliphos® . Serum ALT and TB were also lowered but this was not statistically significant (p > 0.05). The 1000 mg/kg dose also reduced hepatocyte degeneration in rats treated with four times the clinical dose of AS-AQ. This study suggests that the hepatoprotective activity of the leaves of MO may have some relation to its free radical scavenging properties. These leaves may thus be useful in mitigating free radical initiated disease conditions. Conclusion: The aqueous-methanol Moringa oleifera leaf extract exhibits free radical scavenging and hepatoprotective properties. Further investigations on the structural identity of the phytoconstituents and their mechanisms of action should be performed to facilitate the development of a potent medicinal agent.