Ageing Biology Lab Microbial Technology & Nematology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, Lucknow, 226015, India.
Mol Neurobiol. 2021 Jan;58(1):65-77. doi: 10.1007/s12035-020-02080-4. Epub 2020 Sep 7.
Parkinsonism is an age-associated neurodegenerative disorder characterized by aggregation of α-synuclein (α-syn) protein in the substantia nigra region, degeneration of dopaminergic neurons, and deregulated lipid metabolism. Currently, only symptomatic relief has been provided by FDA-approved therapeutic approaches for Parkinson's disease (PD). The present study aims to evaluate the potential of wedelolactone (WDL), a natural occurring coumestan found in Eclipta alba to mitigate the parkinsonism in Caenorhabditis elegans disease model. In the present studies, supplementation with 37.5 μM WDL exhibited a reduction in the level of α-syn in an age-dependent manner (22% at day 5, p < 0.05; and 16% at day 10, p < 0.001, n = 30), along with improvement in neuronal health through basal movement, and elevated the dopamine levels evident through 1-nonanol repulsion results in wild-type and diseased worms. Moreover, WDL augmented the mitochondrial health in wild-type, PD-diseased, and mev-1 mutant worms that establish the inherent activity of WDL in the alleviation of oxidative stress. Furthermore, WDL supplementation significantly decreases the neutral lipid and triglyceride level and also alleviates protein carbonyl level in PD disease condition. The overall investigation will provide a pioneer to the future insights of PD research related to plant-based drugs. qPCR studies after WDL supplementation revealed alteration of genes involved in the regulation of various stress-responsive (sod-5, gst-4, skn-1), α-syn-suppressing (lrk-1, ymel-1, lagr-1, grk-1), and mitochondrial (pink-1) genes. All together, these findings support that the WDL is a promising candidate to combat age-related multi-factorial PD pathology associated with protein misfolding and accumulation. The results provide sufficient information in the development of therapeutic medicines from natural products for improving the health.
帕金森病是一种与年龄相关的神经退行性疾病，其特征是α-突触核蛋白（α-syn）在黑质区域聚集、多巴胺能神经元变性和脂质代谢失调。目前，美国食品和药物管理局批准的治疗帕金森病（PD）的方法仅提供了对症缓解。本研究旨在评估wedelolactone（WDL）的潜力，WDL 是一种天然存在的大波斯菊素，存在于 ecliptea alba 中，以减轻秀丽隐杆线虫帕金森病模型中的帕金森病。在本研究中，补充 37.5 μM WDL 表现出随年龄依赖性降低α-syn 水平（第 5 天 22%，p<0.05；第 10 天 16%，p<0.001，n=30），同时通过基础运动改善神经元健康，并通过 1-壬醇排斥结果提高多巴胺水平，在野生型和患病蠕虫中均如此。此外，WDL 增强了野生型、PD 患病型和 mev-1 突变型蠕虫的线粒体健康，这确立了 WDL 在缓解氧化应激中的固有活性。此外，WDL 补充剂可显著降低中性脂质和甘油三酯水平，并减轻 PD 疾病状态下的蛋白质羰基水平。总的来说，这项研究为植物类药物治疗 PD 的未来研究提供了一个新的视角。WDL 补充后的 qPCR 研究显示，参与各种应激反应（sod-5、gst-4、skn-1）、α-syn 抑制（lrk-1、ymel-1、lagr-1、grk-1）和线粒体（pink-1）基因调控的基因发生改变。所有这些发现都支持 WDL 是一种有前途的候选药物，可以对抗与蛋白质错误折叠和积累相关的与年龄相关的多因素 PD 病理学。这些结果为从天然产物中开发治疗药物以改善健康提供了充分的信息。
