NEUROPROTECTIVE ACTIVITY OF Antiaris Africana (FALSE IROKO TREE) LEAF EXTARCT AND FRACTIONS AGAINST MITOCHONDRIAL TOXICANTS

Abstract

Antiaris africana, popularly known as false Iroko tree is used in African ethnomedicine to treat several disorders, such as mental illness, neurodegenerative diseases, stomach disorder, respiratory disorders etc. The plant have array of documented pharmacological properties including antioxidant, antibacterial and anticancer properties, but the neuroprotective activity of A. africana against mitochondrial toxicants in the brain, a major causes of mitochondrial dysfunction has not been investigated. Hence, in the present study, the effect of A. africana leaf extract and fractions in rat brain subjected to rotenone, sodium azide and potassium cyanide was evaluated. Hexane, methanol and dichloromethane fractions were obtained by solvent partitioning. Cerebellum and cerebral cortex mitochondrial suspensions were obtained by differential centrifugation. The researchwas divided into three groups: un-induced (control), un-treated (toxicant) and treated (50-1000μg/ml of the extract). Mitochondrial damage was induced under in-vitro condition by incubating the brain homogenate withrotenone, potassium cyanide, and sodium azide under a temperature controlled water bath at 37oC for one hour. Mitochondrial integrity was accessed via inhibition of mitochondrial electron transport system, protein carbonyl, reduced glutathione, monoamine oxidase and lipid peroxidation levels evaluation.The results revealed that rotenone has the highest neurotoxicity (0.050±0.001)among the toxicants used to inhibit electron transport system, and all the fractions of A. africana tested were able to offer protection against the different neurotoxicants model used, with varying degree of neuroprotection. Hexane fraction has the highest activity of electron transport system in both cerebellum and cortex (0.89±0.021 -5.01±0.014) when compare with other fractions. However, methanol fraction has the highest elevated level of glutathione in all the toxicants (rotenone;3.76±0.012; potassium cyanide:4.07±0.002; sodium azide: 4.05±0.05).A. africana fractions treatment in vitro leads to significant reduction in the level of Lipid peroxidation, Protein carbonyl and Monoamine oxidase activity in both the cerebellum and cortex regions of the brain. Hexane and dichloromethane fractions have the best activity against lipid peroxidation (1.03±0.027), monoamine oxide activity (1.12±0.016) and protein carbonyl formation (6.23±0.01).The results suggest that the neuroprotective effect of A. africana is dependent on its constituent antioxidant phytochemicals and mitochondrial integrity was improved via scavenging of free reactive oxygen species.