Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
Department of Human Sciences and Quality of Life Promotion, San Raffaele University, 00166 Rome, Italy.
Int J Mol Sci. 2022 Mar 13;23(6):3110. doi: 10.3390/ijms23063110.
Parkinson's disease (PD) is second-most common disabling neurological disorder worldwide, and unfortunately, there is not yet a definitive way to prevent it. Polyphenols have been widely shown protective efficacy against various PD symptoms. However, data on their effect on physio-pathological mechanisms underlying this disease are still lacking. In the present work, we evaluated the activity of a mixture of polyphenols and micronutrients, named A5, in the murine neuroblastoma cell line N1E115 treated with 6-Hydroxydopamine (6-OHDA), an established neurotoxic stimulus used to induce an in vitro PD model. We demonstrate that a pretreatment of these cells with A5 causes significant reduction of inflammation, resulting in a decrease in pro-inflammatory cytokines (IFN-γ, IL-6, TNF-α, and CXCL1), a reduction in ROS production and activation of extracellular signal-regulated kinases (ERK)1/2, and a decrease in apoptotic mechanisms with the related increase in cell viability. Intriguingly, A5 treatment promoted cellular differentiation into dopaminergic neurons, as evident by the enhancement in the expression of tyrosine hydroxylase, a well-established dopaminergic neuronal marker. Overall, these results demonstrate the synergic and innovative efficacy of A5 mixture against PD cellular pathological processes, although further studies are needed to clarify the mechanisms underlying its beneficial effect.
帕金森病（PD）是全球第二大常见的致残性神经障碍疾病，但不幸的是，目前尚无明确的预防方法。多酚已被广泛证明对各种 PD 症状具有保护作用。然而，关于它们对这种疾病潜在生理病理机制的影响的数据仍然缺乏。在本研究中，我们评估了一种名为 A5 的多酚和微量营养素混合物在 N1E115 小鼠神经母细胞瘤细胞系中 6-羟多巴胺（6-OHDA）处理后的活性，6-OHDA 是一种已建立的神经毒性刺激物，用于诱导体外 PD 模型。我们证明，这些细胞用 A5 预处理会导致炎症明显减少，从而导致促炎细胞因子（IFN-γ、IL-6、TNF-α 和 CXCL1）减少、ROS 产生减少和细胞外信号调节激酶（ERK）1/2 激活减少，并减少与细胞活力增加相关的凋亡机制。有趣的是，A5 处理促进了多巴胺能神经元的细胞分化，这表现为酪氨酸羟化酶的表达增强，酪氨酸羟化酶是一种公认的多巴胺能神经元标志物。总之，这些结果表明 A5 混合物对 PD 细胞病理过程具有协同和创新的疗效，但需要进一步研究来阐明其有益作用的机制。
