Department of Medical Elementology and Toxicology (Fund for the Improvement of Science and Technology Sponsored by DST and Special Assistance Programme Sponsored by UGC), Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India.
Mol Cell Biochem. 2012 Oct;369(1-2):55-65. doi: 10.1007/s11010-012-1368-x. Epub 2012 Jul 1.
Beta-amyloid (Aβ) peptides are considered to play a major role in the pathogenesis of Alzheimer's disease (AD) and compounds that can prevent pathways of Aβ-induced neurotoxicity may be potential therapeutic agents for treatment of AD. This study examined the hypothesis that thymoquinone (TQ) would reduce oxidative stress and mitochondrial dysfunction in differentiated pheochromocytoma (PC 12) cells exposed to Aβ fragment 25-35 (Aβ(25-35)). To test this hypothesis, Aβ was used to induce an in vitro model of AD in differentiated PC 12 cell line of rat. After 24 h of exposure with Aβ(25-35), a significant reduction in cell viability and mitochondrial membrane potential (MMP) was observed. In addition, a significant elevation in the TBARS content and nitric oxide (NO) and activity of acetylcholine esterase (AChE) was observed which was restored significantly by TQ pretreatment. Furthermore, TQ also ameliorated glutathione and its dependent enzymes (glutathione peroxidase, glutathione reductase) which were depleted by Aβ(25-35) in PC 12 cells. These results were supported by the immunocytochemical finding that has shown protection of cells by TQ from noxious effects of Aβ(25-35). These results indicate that TQ holds potential for neuroprotection and may be a promising approach for the treatment of neurodegenerative disorders including AD.
β-淀粉样肽（Aβ）被认为在阿尔茨海默病（AD）的发病机制中起主要作用，能够预防 Aβ 诱导的神经毒性途径的化合物可能是治疗 AD 的潜在治疗剂。本研究检验了这样一个假设，即百里醌（TQ）可降低暴露于 Aβ 片段 25-35（Aβ（25-35））的分化嗜铬细胞瘤（PC12）细胞中的氧化应激和线粒体功能障碍。为了验证这一假设，用 Aβ 诱导大鼠分化 PC12 细胞系的体外 AD 模型。在暴露于 Aβ（25-35）24 小时后，观察到细胞活力和线粒体膜电位（MMP）显着降低。此外，还观察到 TBARS 含量和一氧化氮（NO）和乙酰胆碱酯酶（AChE）活性显着升高，而 TQ 预处理可显着恢复。此外，TQ 还改善了谷胱甘肽及其依赖的酶（谷胱甘肽过氧化物酶，谷胱甘肽还原酶），Aβ（25-35）耗尽了 PC12 细胞中的谷胱甘肽及其依赖的酶（谷胱甘肽过氧化物酶，谷胱甘肽还原酶）。这些结果得到免疫细胞化学发现的支持，该发现表明 TQ 可保护细胞免受 Aβ（25-35）的有害影响。这些结果表明，TQ 具有神经保护作用，可能是治疗包括 AD 在内的神经退行性疾病的有前途的方法。
