Tambe Mitali A, de Rus Jacquet Aurélie, Strathearn Katherine E, Hensel Jennifer A, Colón Bryce D, Chandran Aswathy, Yousef Gad G, Grace Mary H, Ferruzzi Mario G, Wu Qingli, Simon James E, Lila Mary Ann, Rochet Jean-Christophe
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 207 S. Martin Jischke Dr., West Lafayette, IN 47907, USA.
Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN 47907, USA.
Antioxidants (Basel). 2023 Jul 20;12(7):1463. doi: 10.3390/antiox12071463.
Parkinson's disease (PD) is a neurodegenerative disorder involving motor symptoms caused by a loss of dopaminergic neurons in the substantia nigra region of the brain. Epidemiological evidence suggests that anthocyanin (ANC) intake is associated with a low risk of PD. Previously, we reported that extracts enriched with ANC and proanthocyanidins (PAC) suppressed dopaminergic neuron death elicited by the PD-related toxin rotenone in a primary midbrain culture model. Here, we characterized botanical extracts enriched with a mixed profile of polyphenols, as well as a set of purified polyphenolic standards, in terms of their ability to mitigate dopaminergic cell death in midbrain cultures exposed to another PD-related toxicant, paraquat (PQ), and we examined underlying neuroprotective mechanisms. Extracts prepared from blueberries, black currants, grape seeds, grape skin, mulberries, and plums, as well as several ANC, were found to rescue dopaminergic neuron loss in PQ-treated cultures. Comparison of a subset of ANC-rich extracts for the ability to mitigate neurotoxicity elicited by PQ versus rotenone revealed that a hibiscus or plum extract was only neuroprotective in cultures exposed to rotenone or PQ, respectively. Several extracts or compounds with the ability to protect against PQ neurotoxicity increased the activity of the antioxidant transcription factor Nrf2 in cultured astrocytes, and PQ-induced dopaminergic cell death was attenuated in Nrf2-expressing midbrain cultures. In other studies, we found that extracts prepared from hibiscus, grape skin, or purple basil (but not plums) rescued defects in O consumption in neuronal cells treated with rotenone. Collectively, these findings suggest that extracts enriched with certain combinations of ANC, PAC, stilbenes, and other polyphenols could potentially slow neurodegeneration in the brains of individuals exposed to PQ or rotenone by activating cellular antioxidant mechanisms and/or alleviating mitochondrial dysfunction.
帕金森病（PD）是一种神经退行性疾病，涉及由大脑黑质区域多巴胺能神经元丧失引起的运动症状。流行病学证据表明，花青素（ANC）摄入与患PD的低风险相关。此前，我们报道富含ANC和原花青素（PAC）的提取物在原代中脑培养模型中可抑制由PD相关毒素鱼藤酮引发的多巴胺能神经元死亡。在此，我们对富含多种多酚的植物提取物以及一组纯化的多酚标准品进行了表征，考察它们在减轻暴露于另一种PD相关毒物百草枯（PQ）的中脑培养物中多巴胺能细胞死亡方面的能力，并研究了潜在的神经保护机制。发现从蓝莓、黑加仑、葡萄籽、葡萄皮、桑葚和李子中制备的提取物以及几种ANC可挽救PQ处理培养物中的多巴胺能神经元损失。对一部分富含ANC的提取物减轻PQ与鱼藤酮引发的神经毒性的能力进行比较发现，芙蓉提取物或李子提取物分别仅在暴露于鱼藤酮或PQ的培养物中具有神经保护作用。几种具有防止PQ神经毒性能力的提取物或化合物可增加培养的星形胶质细胞中抗氧化转录因子Nrf2的活性，并且在表达Nrf2的中脑培养物中PQ诱导的多巴胺能细胞死亡得到减轻。在其他研究中，我们发现从芙蓉、葡萄皮或紫罗勒（但不是李子）中制备的提取物可挽救用鱼藤酮处理的神经元细胞中氧消耗的缺陷。总体而言，这些发现表明，富含ANC、PAC、芪类和其他多酚特定组合的提取物可能通过激活细胞抗氧化机制和/或减轻线粒体功能障碍，潜在地减缓暴露于PQ或鱼藤酮的个体大脑中的神经退行性变。
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