Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bengaluru, India.
Can J Physiol Pharmacol. 2012 May;90(5):595-606. doi: 10.1139/y2012-030. Epub 2012 Apr 4.
The present investigation was designed to determine the efficacy of Bacopa monnieri (Brahmi; BM) to offset 3-nitropropionic acid (3-NPA) induced oxidative stress and mitochondrial dysfunction in dopaminergic (N27) cells and prepubertal mouse brain. Pretreatment of N27 cells with BM ethanolic extract (BME) significantly attenuated 3-NPA-induced cytotoxicity. Further, we determined the degree of oxidative stress induction, redox status, enzymic antioxidants, and protein oxidation in the striatal mitochondria of mice given BME prophylaxis followed by 3-NPA challenge. While 3-NPA-induced marked oxidative stress in the mitochondria of the striatum, BME prophylaxis markedly prevented 3-NPA-induced oxidative dysfunctions and depletion of reduced glutathione and thiol levels. The activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase, thioredoxin reductase), Na(+),K(+)-ATPase, and citric acid cycle enzymes in the striatum discernible among 3-NPA mice were significantly restored with BME prophylaxis. Interestingly, BME offered protection against 3-NPA-induced mitochondrial dysfunctions as evidenced by the restoration of the activities of ETC enzymes (NADH:ubiquinone oxidoreductase, NADH:cytochrome c reductase, succinate-ubiquinone oxidoreductase, and cytochrome c oxidase) and mitochondrial viability. We hypothesize that the neuroprotective effects of BME may be wholly or in part related to its propensity to scavenge free radicals, maintain redox status, and upregulate antioxidant machinery in striatal mitochondria.
本研究旨在确定益智（Brahmi；BM）对 3-硝基丙酸（3-NPA）诱导的多巴胺能（N27）细胞和幼鼠大脑中线粒体氧化应激和功能障碍的疗效。用 BM 乙醇提取物（BME）预处理 N27 细胞可显著减轻 3-NPA 诱导的细胞毒性。此外，我们还确定了在给予 BME 预防后再给予 3-NPA 挑战的小鼠纹状体线粒体中诱导氧化应激的程度、氧化还原状态、酶抗氧化剂和蛋白质氧化。虽然 3-NPA 可在纹状体的线粒体中引起明显的氧化应激，但 BME 预防可显著防止 3-NPA 诱导的氧化功能障碍和还原型谷胱甘肽和巯基水平的耗竭。在 3-NPA 小鼠中，纹状体中的抗氧化酶（超氧化物歧化酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、硫氧还蛋白还原酶）、Na(+)、K(+)-ATP 酶和柠檬酸循环酶的活性可被 BME 预防明显恢复。有趣的是，BME 可提供针对 3-NPA 诱导的线粒体功能障碍的保护，这可从 ETC 酶（NADH：泛醌氧化还原酶、NADH：细胞色素 c 还原酶、琥珀酸-泛醌氧化还原酶和细胞色素 c 氧化酶）和线粒体活力的恢复中得到证明。我们假设 BME 的神经保护作用可能完全或部分与其清除自由基、维持氧化还原状态和上调纹状体线粒体中的抗氧化机制有关。
