Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the striatum, leading to dopamine (DA) deficiency in the striatum and typical motor symptoms. A small molecule as a dietary supplement for PD would be ideal for practical reasons. Hordenine (HOR) is a phenolic phytochemical marketed as a dietary supplement found in cereals and germinated barley, as well as in beer, a widely consumed beverage. This study was aimed to identify HOR as a dopamine D2 receptor (DRD2) agonist in living cells, and investigate the alleviative effect and mechanism of HOR on PD-like motor deficits in mice and nematodes. Our results firstly showed that HOR is an agonist of DRD2, but not DRD1, in living cells. Moreover, HOR could improve the locomotor dysfunction, gait, and postural imbalance in MPTP- or 6-OHDA-induced mice or Caenorhabditis elegans, and prevent α-synuclein accumulation via the DRD2 pathway in C. elegans. Our results suggested that HOR could activate DRD2 to attenuate the PD-like motor deficits, and provide scientific evidence for the safety and reliability of HOR as a dietary supplement.

中文翻译：

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大麦芽碱通过激活多巴胺 D2 受体介导的信号传导改善小鼠和线虫的帕金森样运动缺陷

帕金森病（PD）是一种慢性神经退行性疾病，其特征是黑质致密部（SNpc）和纹状体中的多巴胺能神经元选择性丧失，导致纹状体中多巴胺（DA）缺乏和典型的运动症状。出于实际原因，小分子作为帕金森病的膳食补充剂是理想的选择。大麦芽碱 (HOR) 是一种酚类植物化学物质，作为膳食补充剂销售，存在于谷物和发芽大麦以及啤酒（一种广泛消费的饮料）中。本研究旨在鉴定HOR作为活细胞中的多巴胺D2受体（DRD2）激动剂，并探讨HOR对小鼠和线虫类PD样运动缺陷的缓解作用和机制。我们的结果首先表明，在活细胞中，HOR 是 DRD2 的激动剂，但不是 DRD1 的激动剂。此外，HOR 可以改善 MPTP 或 6-OHDA 诱导的小鼠或秀丽隐杆线虫的运动功能障碍、步态和姿势不平衡，并通过秀丽隐杆线虫中的 DRD2 途径防止 α-突触核蛋白积累。我们的结果表明，HOR 可以激活 DRD2 以减轻 PD 样运动缺陷，并为 HOR 作为膳食补充剂的安全性和可靠性提供科学证据。