Laboratory of Cellular and Molecular Neurobiology, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India, 110067.
Midnapore Medical College and Hospital, West Medinipur, Kolkata, West Bengal, India.
Mol Neurobiol. 2023 Aug;60(8):4693-4715. doi: 10.1007/s12035-023-03358-z. Epub 2023 May 5.
Parkinson's disease (PD) is a progressive neurodegenerative condition. The pathogenesis of PD is still unknown, and drugs available for PD treatment either have side effects or have suboptimal efficacy. Flavonoids are potent antioxidants having little toxicity with extended use, suggesting they might hold promising therapeutic potential against PD. Vanillin (Van) is a phenolic compound that has exhibited neuroprotective properties in various neurological disorders, including PD. However, the neuroprotective role of Van in PD and its underlying mechanisms are scarce and therefore need more exploration. Here, we evaluated the neuroprotective potential of Van and its associated mechanisms against MPP/MPTP-induced neuronal loss in differentiated human neuroblastoma (SH-SY5Y) cells and the mouse model of PD. In the present study, Van treatment significantly enhanced the cell viability and alleviated oxidative stress, mitochondrial membrane potential, and apoptosis in MPP-intoxicated SH-SY5Y cells. Moreover, Van significantly ameliorated the MPP-induced dysregulations in protein expression of tyrosine hydroxylase (TH) and mRNA expressions of GSK-3β, PARP1, p53, Bcl-2, Bax, and Caspase-3 genes in SH-SY5Y cells. Similar to our in vitro results, Van significantly alleviated MPTP-induced neurobehavioral dysregulations, oxidative stress, aberrant TH protein expressions, and immunoreactivity in SNpc of mice brains. Treatment of Van also prevented MPTP-mediated loss of TH-positive intrinsic dopaminergic neurons to SNpc and TH-fibers projecting to the striatum of mice. Thus, Van exhibited promising neuroprotective properties in the current study against MPP/MPTP-intoxicated SH-SY5Y cells and mice, indicating its potential therapeutic properties against PD pathology.
帕金森病（PD）是一种进行性神经退行性疾病。PD 的发病机制尚不清楚，目前可用的 PD 治疗药物要么有副作用，要么疗效不佳。类黄酮是一种有效的抗氧化剂，长期使用毒性较小，这表明它们可能具有治疗 PD 的潜在治疗价值。香草醛（Van）是一种酚类化合物，在包括 PD 在内的各种神经疾病中表现出神经保护特性。然而，Van 在 PD 中的神经保护作用及其潜在机制尚不清楚，因此需要进一步探索。在这里，我们评估了 Van 对 MPP/MPTP 诱导的分化人神经母细胞瘤（SH-SY5Y）细胞和 PD 小鼠模型中神经元丢失的神经保护潜力及其相关机制。在本研究中，Van 处理显著提高了 MPP 中毒的 SH-SY5Y 细胞的细胞活力，减轻了氧化应激、线粒体膜电位和细胞凋亡。此外，Van 显著改善了 MPP 诱导的 SH-SY5Y 细胞中酪氨酸羟化酶（TH）蛋白表达和 GSK-3β、PARP1、p53、Bcl-2、Bax 和 Caspase-3 基因的 mRNA 表达的失调。与我们的体外结果相似，Van 显著减轻了 MPTP 诱导的神经行为失调、氧化应激、TH 蛋白表达异常以及小鼠大脑 SNpc 中的免疫反应。Van 处理还防止了 MPTP 介导的 TH 阳性内在多巴胺能神经元对 SNpc 和投射到纹状体的 TH 纤维的丢失。因此，Van 在本研究中对 MPP/MPTP 中毒的 SH-SY5Y 细胞和小鼠表现出有希望的神经保护特性，表明其对 PD 病理学具有潜在的治疗特性。
