Ameliorative effects of flavonoids and polyketides on the rotenone induced Drosophila model of Parkinson's disease.

Parkinson's disease (PD) is a movement disorder associated with the progressive loss of dopaminergic neurons (DA). PD treatment remains unsatisfactory as the current synthetic drugs in clinical use relies on managing only motor symptoms. This study investigated antioxidant potentials of selected compounds namely, 5,6,7,4'-tetramethoxyflavone (1), 6-hydroxy-2,3,4,4'-tetramethoxychalcone (2), 6-methoxyhamiltone A (3), diosquinone (4) and toussantine D (5) against rotenone (6) induced PD in Drosophila melanogaster. Toxicity of these compounds was conducted by monitoring flies' survival for seven days and determining the lethal concentrations (LC50). Whereas compound 1 had LC50 value of 91.3 μM within three days, compounds 2, 3, 4, and 5 had LC50 values of 87.2, 58.0, 64.0 and > 1000 μM, respectively on the seventh day of the experiment. We exposed flies (1-4 days old) to 500 μM rotenone and co-treated with different doses of the test compounds in the diet for seven days at final concentrations of 11.0, 43.6 and 87.2 μM for compounds 2 and 3. The concentrations used for compound 4 were 8.0, 32.0 and 64.0 μM, while 250, 500 and 1000 μM were used for compound 5. Rotenone fed flies showed impaired climbing ability compared to control flies, the phenotype that was rescued by the treatment of tested phytochemicals. Rotenone toxicity also increased malondialdehyde levels assayed by lipid peroxidation in the brain tissues relative to control flies. This effect was reduced in flies exposed to rotenone and co-treated with the phytochemicals. Moreover, expression levels of mRNA of antioxidant enzymes; superoxide dismutase and catalase were elevated in flies exposed to rotenone and normalized in flies that were co-treated with tested compounds. Besides compound 1, this study provides overall evidence that the tested flavonoids and polyketides ameliorated the rotenone provoked neurotoxicity in D. melanogaster by battling the induced oxidative stress in brain cells including DA neurons and hence rescue the locomotor behaviour deficits.