Polydatin is the major active ingredient of Polygonum cuspidatum Sieb. Et Zucc. A recent study indicated that polydatin could protect against substantia nigra dopaminergic degeneration in rodent models associated with Parkinson's disease. However, mechanisms that underlie the neuroprotection of polydatin have not been fully elucidated. In the current study, the neuroprotective effects and detailed mechanisms of action of polydatin were investigated in Parkinson's disease-related cellular models. Polydatin dose- and time-dependently prevented neurotoxicity caused by 1-methyl-4-phenylpyridinium ion (MPP+) in primary cerebellar granule neurons. Moreover, we found that polydatin enhanced the activity of the transcription factor myocyte enhancer factor 2D (MEF2D) at both basal and pathological conditions using luciferase reporter gene assay. Additionally, western blot analysis revealed that polydatin could downregulate glycogen synthase kinase 3β (GSK3β), which is a negative regulator of MEF2D. Molecular docking simulations finally suggested an interaction between polydatin and a hydrophobic pocket within GSK3β. All these results suggest that polydatin prevents MPP+-induced neurotoxicity via enhancing MEF2D through the inhibition of GSK3β and that treatment with polydatin is worthy of further anti-Parkinson's disease study in future.

中文翻译：

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天然存在的虎杖甙通过激活转录因子 MEF2D 对 1-甲基-4-苯基吡啶鎓诱导的细胞毒性具有神经保护作用。

虎杖甙是虎杖的主要活性成分。等祖克。最近的一项研究表明，虎杖甙可以预防与帕金森病相关的啮齿动物模型中的黑质多巴胺能变性。然而，虎杖甙的神经保护机制尚未完全阐明。在当前的研究中，在帕金森病相关的细胞模型中研究了虎杖甙的神经保护作用和详细的作用机制。虎杖甙剂量和时间依赖性地预防初级小脑颗粒神经元中 1-甲基-4-苯基吡啶鎓离子 (MPP+) 引起的神经毒性。此外，我们通过荧光素酶报告基因检测发现，虎杖甙在基础和病理条件下均增强了转录因子肌细胞增强因子 2D (MEF2D) 的活性。此外，蛋白质印迹分析显示虎杖甙可以下调糖原合成酶激酶 3β (GSK3β)，这是 MEF2D 的负调节因子。分子对接模拟最终表明虎杖苷与 GSK3β 内的疏水口袋之间存在相互作用。所有这些结果表明，虎杖甙通过抑制GSK3β增强MEF2D来预防MPP+诱导的神经毒性，虎杖甙治疗值得未来进一步的抗帕金森病研究。