Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400, UPM Serdang, Selangor, Malaysia; Department of Biochemistry, Kaduna State University, Main Campus, PMB 2339, Kaduna, Nigeria.
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, UPM Serdang, Selangor, Malaysia.
Neurotoxicology. 2019 Dec;75:89-104. doi: 10.1016/j.neuro.2019.09.008. Epub 2019 Sep 12.
Neurodegenerative diseases (NDDs) are pathological conditions characterised by progressive damage of neuronal cells leading to eventual loss of structure and function of the cells. Due to implication of multi-systemic complexities of signalling pathways in NDDs, the causes and preventive mechanisms are not clearly delineated. The study was designed to investigate the potential signalling pathways involved in neuroprotective activities of purely isolated glucomoringin isothiocyanate (GMG-ITC) against HO-induced cytotoxicity in neuroblastoma (SH-SY5Y) cells. GMG-ITC was isolated from Moringa oleifera seeds, and confirmed with NMR and LC-MS based methods. Gene expression analysis of phase II detoxifying markers revealed significant increase in the expression of all the genes involved, due to GMG-ITC pre-treatment. GMG-ITC also caused significant decreased in the expression of NF-kB, BACE1, APP and increased the expressions of IkB and MAPT tau genes in the differentiated cells as confirmed by multiplex genetic system analysis. The effect was reflected on the expressed proteins in the differentiated cells, where GMG-ITC caused increased in expression level of Nrf2, SOD-1, NQO1, p52 and c-Rel of nuclear factor erythroid factor 2 (Nrf2) and nuclear factor kappa-B (NF-kB) pathways respectively. The findings revealed the potential of GMG-ITC to abrogate oxidative stress-induced neurodegeneration through Nrf2 and NF-kB signalling pathways.
神经退行性疾病（NDDs）是一种以神经元细胞进行性损伤为特征的病理状况，最终导致细胞结构和功能丧失。由于 NDDs 涉及多系统信号通路的复杂性，其病因和预防机制尚不清楚。本研究旨在探讨在神经母细胞瘤（SH-SY5Y）细胞中，纯分离的 glucomoringin 异硫氰酸酯（GMG-ITC）对 HO 诱导的细胞毒性的神经保护活性所涉及的潜在信号通路。GMG-ITC 从辣木种子中分离得到，并通过 NMR 和 LC-MS 方法进行了确认。II 相解毒标志物的基因表达分析显示，由于 GMG-ITC 的预处理，所有涉及的基因表达均显著增加。GMG-ITC 还导致 NF-kB、BACE1、APP 的表达显著降低，而在分化细胞中 MAPT tau 基因的表达增加，这通过多重基因系统分析得到了证实。这种效应反映在分化细胞中表达的蛋白质上，GMG-ITC 导致核因子红细胞 2（Nrf2）和核因子 kappa-B（NF-kB）途径中的 Nrf2、SOD-1、NQO1、p52 和 c-Rel 的表达水平增加。研究结果表明，GMG-ITC 具有通过 Nrf2 和 NF-kB 信号通路阻断氧化应激诱导的神经退行性变的潜力。
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