Parkinson’s disease (PD) is a neuromotor disorder, primarily manifested by motor anomalies due to progressive loss of dopaminergic neurons. Although alterations in genetic factors have been linked with its etiology, exponential accumulation of environmental entities such as reactive oxygen species (ROS) initiate a cyclic chain reaction resulting in accumulation of cellular inclusions, dysfunctional mitochondria, and overwhelming of antioxidant machinery, thus accelerating disease pathogenesis. Involvement of oxidative stress in PD is further substantiated through ROS induced Parkinsonian models and elevated oxidative markers in clinical PD samples; thereby, making modulation of neuronal oxidative load as one of the major approaches in management of PD. Here we have found a potent antioxidant moiety Scopoletin (Sp), a common derivative in most of the nootropic herbs, with robust neuroprotective ability. Sp increased cellular resistance to ROS through efficient recycling of GSH to prevent oxidative damage. The Sp treated cells showed higher loads of reduced glutathione making them resistant to perturbation of antioxidant machinery or neurotoxin MPP⁺. Sp could restore the redox balance, mitochondrial function, and prevented oxidative damage, leading to recovery of dopaminergic neural networks and motion abilities in Drosophila genetic model of PD. Our data also suggest that Sp, in combination increases the therapeutic potency of L-DOPA by mitigating its chronic toxicity. Together, we highlight the possible ability of Sp in preventing oxidative stress mediated loss of dopaminergic neurons and at the same time enhance the efficacy of dopamine recharging regimens.

帕金森病 (PD) 是一种神经运动障碍，主要表现为由于多巴胺能神经元进行性丧失引起的运动异常。尽管遗传因素的改变与其病因有关，但诸如活性氧 (ROS) 等环境实体的指数积累会引发循环链反应，导致细胞内含物积累、线粒体功能障碍和抗氧化机制不堪重负，从而加速疾病的发病机制. 氧化应激在 PD 中的作用通过 ROS 诱导的帕金森模型和临床 PD 样本中升高的氧化标志物得到进一步证实；因此，使调节神经元氧化负荷成为治疗 PD 的主要方法之一。在这里，我们发现了一种有效的抗氧化成分东莨菪碱 (Sp)，大多数益智草药中的常见衍生物，具有强大的神经保护能力。Sp 通过有效回收 GSH 来防止氧化损伤，从而增加细胞对 ROS 的抵抗力。Sp 处理的细胞显示出更高的还原型谷胱甘肽负荷，使它们能够抵抗抗氧化机制或神经毒素 MPP 的扰动⁺。Sp 可以恢复氧化还原平衡、线粒体功能并防止氧化损伤，导致果蝇PD 遗传模型中多巴胺能神经网络和运动能力的恢复。我们的数据还表明，Sp 联合使用可通过减轻其慢性毒性来提高 L-DOPA 的治疗效力。我们一起强调了 Sp 在预防氧化应激介导的多巴胺能神经元丢失方面的可能能力，同时增强了多巴胺再充电方案的功效。