BackgroundRecently, the use of traditional Chinese medicine (TCM) has become more generally accepted, including by the Food and Drug Administration. To expand the use of TCM worldwide, it is important to study the molecular mechanisms by which TCM and its active ingredients produce effects. Gastrodin is an active ingredient from Gastrodia elata Blume. It is reported that gastrodin has neuroprotective function in Parkinson’s disease. But its mechanisms of neuroprotection remain not clear in PD. Here, we build two C. elegans PD model using 6-OHDA and transgenic animal to observe the changes of PD worms treated with or without gastrodin to confirm the function of gastrodin, then utilize mutant worms to investigate DAF-2/DAF-16 signaling pathway, and finally verify the mechanism of gastrodin in PD.ResultsGastrodin attenuates the accumulation of α-synuclein and the injury of dopaminergic neurons, improves chemotaxis behavior in Parkinson’s disease models, then recovers chemotaxis behavior by insulin-like pathway. DAF-2/DAF-16 is required for neuroprotective effect of dopamine neuron in PD.ConclusionsOur study demonstrated that gastrodin rescued dopaminergic neurons and reduced accumulation of α-synuclein protein, and the activity of gastrodin against Parkinson’s disease depended on the insulin-like DAF-2/DAF-16 signaling pathway. Our findings revealed that this insulin-like pathway mediates neuroprotection of gastrodin in a Parkinson’s disease model.

中文翻译：

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天麻素通过帕金森病模型中的胰岛素样通路保护多巴胺能神经元

背景近来，中药（TCM）的使用已得到更广泛的接受，包括食品和药物管理局。为了在全球范围内扩大中药的使用，研究中药及其活性成分产生作用的分子机制非常重要。天麻素是一种来自天麻的活性成分。据报道，天麻素在帕金森病中具有神经保护作用。但其在 PD 中的神经保护机制尚不清楚。在这里，我们使用 6-OHDA 和转基因动物建立了两个秀丽隐杆线虫 PD 模型，观察用或不用天麻素处理的 PD 蠕虫的变化，以确认天麻素的功能，然后利用突变蠕虫研究 DAF-2/DAF-16 信号传导途径，最终验证天麻素在PD中的作用机制。结果天麻素减轻α-突触核蛋白的积累和多巴胺能神经元的损伤，改善帕金森病模型的趋化行为，然后通过类胰岛素途径恢复趋化行为。DAF-2/DAF-16 是 PD 中多巴胺神经元的神经保护作用所必需的。 结论我们的研究表明，天麻素拯救了多巴胺能神经元并减少了 α-突触核蛋白的积累，天麻素对帕金森病的活性依赖于胰岛素样 DAF -2/DAF-16 信号通路。我们的研究结果表明，这种胰岛素样途径介导了帕金森病模型中天麻素的神经保护作用。DAF-2/DAF-16 是 PD 中多巴胺神经元的神经保护作用所必需的。 结论我们的研究表明，天麻素拯救了多巴胺能神经元并减少了 α-突触核蛋白的积累，天麻素对帕金森病的活性依赖于胰岛素样 DAF -2/DAF-16 信号通路。我们的研究结果表明，这种胰岛素样途径介导了帕金森病模型中天麻素的神经保护作用。DAF-2/DAF-16 是 PD 中多巴胺神经元的神经保护作用所必需的。 结论我们的研究表明，天麻素拯救了多巴胺能神经元并减少了 α-突触核蛋白的积累，天麻素对帕金森病的活性依赖于胰岛素样 DAF -2/DAF-16 信号通路。我们的研究结果表明，这种胰岛素样途径介导了帕金森病模型中天麻素的神经保护作用。