AFZELIA AFICANA ATTENUATES ROTENONE INDUCED NEUROBEHAVIOURAL, HAEMATOLOGICAL AND NEURONDEGENERATIVE CHANGES IN RODENTS

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurones, motor dysfunction and accumulation of misfolded alpha-synuclein protein in the brains of affected individuals. There is currently no cure for this disorder which is prevalent in African and Hispanic men. Drugs currently in use only alleviate symptoms but do not reverse underlying neurodegeneration, thus the need for novel therapies cannot be over emphasized. Afzelia africana, a plant used in Ethnomedicine for a host of diseases is credited with neuroprotective properties. This study evaluated the effect of the ethanol extract of Afzelia africana stem bark in neurobehaviour, haemotological indices and the presence of misfolded alpha synuclein protein in rotenoneinduced PD in Wistar rats. Phytochemical screening was conducted to determine the bioactive constituents present in the extract. Acute toxicity (LD50) was assessed in mice using the modified Lorke’s method, while the neurobehaviour was evaluated in rats using the beam walking and catalepsy tests. Thirty male rats randomly distributed into five groups were used for the second phase of this study. There were either untreated (control), treated with the vehicle only, 250 or 500 mg/kg A. Africana daily for 10 days (Groups 1-5). Animals in groups 3-5 received 1 mg/kg of rotenone on days 1, 4, 7 and 10. All animals were subjected to the beam walking assay and catalepsy tests on days 0,5 and 10. On the 11th day, animals were sacrificed with ketamine, the brains and blood of test animals were collected and used for assay of misfolded alpha synuclein and haematological analysis respectively. The phytochemical analysis revealed the presence of saponins, glycosides, reducing sugars, terpenoids, alkaloids, tannins and cardiac glycosides while steroids were absent. Acute toxicity studies showed no mortality at doses up to 5000 mg/kg, indicating a high safety margin. Treatment with both doses of A. africana significantly (p<0.05) increased time spent in the beam walking assay and reduced the cataleptic score following treatment with rotenone. Haematological indices were also significantly increased at both doses while only the low dose caused a decrease in the expression of misfolded alpha synuclein post treatment with rotenone. The ethanol extract of Afzelia africana exhibited a favourable safety profile, reduced neurological deficits, improved haematological indices and reduced expression of misfolded alpha synuclein protein, and thus may be a candidate in the search for agents useful in the amelioration of PD