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.

帕金森病 (PD) 是一种与多巴胺能神经元 (DA) 进行性丧失相关的运动障碍。PD 治疗仍然不能令人满意，因为目前临床使用的合成药物仅依赖于控制运动症状。本研究调查了所选化合物的抗氧化潜力，即 5,6,7,4'-四甲氧基黄酮 ( 1 )、6-羟基-2,3,4,4'-四甲氧基查尔酮 ( 2 )、6-甲氧基哈密酮A ( 3 )、 diosquinone ( 4 ) 和 toussantine D ( 5 ) 对抗鱼藤酮 ( 6 ) 诱导的果蝇PD 。这些化合物的毒性是通过监测果蝇存活 7 天并确定致死浓度 (LC ₅₀）。而化合物1具有LC ₅₀三天内91.3μM的值，化合物2，3，4，和5具有LC _50个87.2，58.0，64.0和值> 1000μM，分别在实验的第七天。我们将果蝇（1-4 天大）暴露于 500 μM 鱼藤酮，并在饮食中以 11.0、43.6 和 87.2 μM 的终浓度对化合物2和3用不同剂量的测试化合物共同处理 7 天。用于化合物4的浓度为8.0、32.0 和 64.0 μM，而用于化合物5 的浓度为 250、500 和 1000 μM. 与对照果蝇相比，鱼藤酮喂养的果蝇表现出攀爬能力受损，这种表型通过测试植物化学物质的处理得以挽救。相对于对照果蝇，鱼藤酮毒性还增加了通过脑组织中脂质过氧化测定的丙二醛水平。在暴露于鱼藤酮并与植物化学物质共同处理的果蝇中，这种影响会降低。此外，抗氧化酶mRNA的表达水平；暴露于鱼藤酮的果蝇中超氧化物歧化酶和过氧化氢酶升高，并在与测试化合物共同处理的果蝇中正常化。除了化合物1 之外，这项研究还提供了总体证据，即所测试的黄酮类化合物和聚酮化合物改善了黑腹果蝇中鱼藤酮引起的神经毒性。 通过对抗包括 DA 神经元在内的脑细胞中诱导的氧化应激，从而挽救运动行为缺陷。