Institute of Anesthesia, Department of Anatomy, Baotou Medical College, Baotou, Inner Mongolia, China.
Department of Neurology, Baotou Central Hospital, Baotou, Inner Mongolia, China.
J Toxicol Environ Health A. 2019;82(19):1019-1026. doi: 10.1080/15287394.2019.1684007. Epub 2019 Nov 18.
The extract of Schisandrin a traditional Chinese medicine was postulated to be effective in prevention and treatment of Alzheimer's disease (AD). The aim of this study was to examine the underlying protective actions of Schizandrin using a human neuroblastoma cell line (SH-SY5Y). In particular Schizandrin-mediated effects on expression of glycogen synthase kinase (GSK)-3β, protein kinase B (Akt) and Tau protein, known to be altered in AD were determined. In preliminary assays, various concentrations of Schisandrin were incubated SH-SY5Y cells to establish effects on cell viability and potential toxicity in further experimentation. Amyloid-β (Aβ) peptide 10 μmol/L was used to induce AD model in SH-SY5Y. Exposure to Aβ significantly reduced cell viability. Treatment with Schisandrin to Aβ exposed cells increased cell viability compared to amyloid peptide; however only the 10 μmol/L Schisandrin concentration was effective in restoring cell viability to control. Western blot analysis demonstrated that Aβ produced a significant decrease in -Akt protein expression levels accompanied by marked elevation in -tau and -GSK-3β protein expression levels. Addition of 10 μmol/L Schisandrin to amyloid-treated SH-SY5Y cells was found to significantly increase protein expression levels of -Akt associated with reduction in expression levels of -tau and -GSK-3β protein. Treatment with 10 μmol/L Schisandrin of SH-SY5Y cells with the -Akt inhibitor LY294002 demonstrated that the herbal-induced rise in -Akt protein expression was diminished by this inhibitor indicating that signal transduction occurred in the observed cellular effects. Evidence indicates that Schisandrin inhibition of Aβ -mediated cellular damage in AD neurons may involve activation of the PI3K/Akt signaling pathway where up-regulation of -Akt activity consequently leads downstream to decreased activity of -GSK-3β phosphorylation accompanied by reduced tau protein. Consequently, restoration of neuronal cell viability was noted. Our findings suggest that the use of Schisandrin may be considered beneficial as a therapeutic agent in AD.
五味子提取物被认为对预防和治疗阿尔茨海默病（AD）有效。本研究旨在通过人神经母细胞瘤细胞系（SH-SY5Y）来检验五味子的潜在保护作用。特别是，研究了五味子对 AD 中改变的糖原合酶激酶（GSK）-3β、蛋白激酶 B（Akt）和 Tau 蛋白表达的影响。在初步实验中，将不同浓度的五味子孵育到 SH-SY5Y 细胞中，以确定其对细胞活力的影响及其在进一步实验中的潜在毒性。用 10 μmol/L 的淀粉样β（Aβ）肽诱导 SH-SY5Y 建立 AD 模型。暴露于 Aβ 显著降低细胞活力。与淀粉样肽相比，用五味子处理暴露于 Aβ 的细胞可增加细胞活力；然而，只有 10 μmol/L 的五味子才能有效恢复细胞活力至对照水平。Western blot 分析表明，Aβ 显著降低了 Akt 蛋白的表达水平，同时显著增加了 Tau 和 GSK-3β 蛋白的表达水平。在淀粉样肽处理的 SH-SY5Y 细胞中加入 10 μmol/L 的五味子，发现 Akt 蛋白的表达水平显著升高，同时 Tau 和 GSK-3β 蛋白的表达水平降低。用 Akt 抑制剂 LY294002 处理 SH-SY5Y 细胞，发现该抑制剂减弱了五味子诱导的 Akt 蛋白表达升高，表明观察到的细胞效应中存在信号转导。有证据表明，五味子抑制 AD 神经元中 Aβ 介导的细胞损伤可能涉及激活 PI3K/Akt 信号通路，其中 Akt 活性的上调导致下游 GSK-3β 磷酸化活性降低，Tau 蛋白减少。因此，神经元细胞活力得到恢复。我们的研究结果表明，五味子的使用可能被认为是 AD 治疗中的有益治疗剂。
