Division of Pharmaceutical Sciences, Arnold and Marie Schwartz college of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA.
J Parkinsons Dis. 2012;2(4):287-302. doi: 10.3233/JPD-012110.
Parkinson's disease (PD) is characterized by excessive deposition of neuritic plaques known as Lewy bodies of which α-synuclein is the major contributor to neuronal death. Both oxidative stress and cytokines signaling have been proposed to play an important role in α-synuclein-induced neuronal death in MPTP and PD-related neuronal cell death. Fisetin, a natural polyphenol, possesses antioxidant, anti-inflammatory, and anti-apoptotic properties. However, the molecular neuroprotective mechanisms of fisetin against MPTP-induced cytotoxicity are still unknown.
The present study investigated the inhibitory effect of fisetin on MPTP/MPP+-induced neurotoxicity in PC12 cells.
Cells were pretreated with varying concentrations of fisetin prior exposure to MPTP/MPP+. Cell viability and apoptosis were investigated using MTT assay and DNA fragmentation. The expression and release of transcription factor, pro-inflammatory cytokines, and apoptotic mediators were assessed using western blot analysis and ELISA.
Results showed that a pre-treatment with fisetin before exposure to MPTP/MPP+ significantly decreased MPTP/MPP+-induced cytotoxicity and cell death probably by decreasing α-synuclein expression. Mechanisms study showed that fisetin has the potential to inhibit several apoptotic and inflammatory pathways, which play important roles in the initiation and progression of PD.
Altogether, these observations indicate that fisetin is capable of attenuating α-synuclein levels and promoting neuroprotective effects, meanwhile also present some insights into the potential signaling pathways that are involved. Thus, these findings support the role of natural polyphenols in preventive and/or complementary therapies for neurodegenerative diseases.
帕金森病（PD）的特征是神经纤维缠结的过度沉积，即众所周知的路易体，其中α-突触核蛋白是神经元死亡的主要贡献者。氧化应激和细胞因子信号转导都被认为在 MPTP 和 PD 相关神经元死亡中发挥了重要作用。漆黄素是一种天然多酚，具有抗氧化、抗炎和抗凋亡作用。然而，漆黄素对 MPTP 诱导的细胞毒性的分子神经保护机制尚不清楚。
本研究探讨了漆黄素对 PC12 细胞中 MPTP/MPP+诱导的神经毒性的抑制作用。
细胞先用不同浓度的漆黄素预处理，然后暴露于 MPTP/MPP+中。使用 MTT 法和 DNA 片段化检测细胞活力和细胞凋亡。采用 Western blot 分析和 ELISA 检测转录因子、促炎细胞因子和凋亡介质的表达和释放。
结果表明，在暴露于 MPTP/MPP+之前用漆黄素预处理可显著降低 MPTP/MPP+诱导的细胞毒性和细胞死亡，可能是通过降低α-突触核蛋白的表达。机制研究表明，漆黄素具有抑制几种凋亡和炎症途径的潜力，这些途径在 PD 的发生和发展中起重要作用。
总之，这些观察结果表明，漆黄素能够降低α-突触核蛋白水平并促进神经保护作用，同时也为潜在的信号通路提供了一些见解。因此，这些发现支持天然多酚在预防和/或补充治疗神经退行性疾病中的作用。
