Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTP-probenecid-induced parkinsonism mouse model by targeting α-synuclein abnormalities in the substantia nigra
Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTP-probenecid-induced parkinsonism mouse model by targeting α-synuclein abnormalities in the substantia nigra
复制标题
人参皂苷 Rg1 通过针对黑质中的 α-突触核蛋白异常减轻 MPTP 丙磺舒诱发的帕金森病小鼠模型中的运动障碍和神经炎症
DOI：
10.1016/j.toxlet.2015.12.005
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发表时间：
2016-01-22
影响因子：
3.5
通讯作者：
Chen, Nai-Hong
中科院分区：
文献类型：
--
作者：
Heng, Yang;Zhang, Qiu-Shuang;Chen, Nai-Hong
帕金森病（PD）的病理特征在于黑质丘脑部（SNpc）中多巴胺能神经元的进行性损失和特定中枢神经系统（CNS）区域中聚集的α-突触核蛋白的积累。疾病发展归因于α-突触核蛋白异常，特别是聚集和磷酸化。人参的活性成分Rg 1具有神经保护和抗炎作用。本研究首次观察了Rg 1对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）/丙磺舒（probenecid，MPTP/p）诱导的PD小鼠模型的上述作用，并阐明了Rg 1的作用机制。其他试验表明，Rg 1的保护作用可能是通过其抗神经炎症特性介导的。Rg 1调节MPTP诱导的反应性星形胶质细胞和小胶质细胞，并减少SNpc中肿瘤坏死因子-α（TNF-α）和白细胞介素-1 β（IL-1 β）等细胞因子的释放。Rg 1还减轻了SNpc中不寻常的MPTP诱导的寡聚、磷酸化和疾病相关的α-突触核蛋白的增加。总之，Rg 1保护多巴胺能神经元，最有可能是通过减少异常的α-突触核蛋白介导的神经炎症，并为PD治疗带来希望。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Parkinson's disease (PD) is pathologically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of aggregated alpha-synuclein in specific central nervous system (CNS) regions. Disease development is attributed to alpha-synuclein abnormalities, particularly aggregation and phosphorylation. The ginsenoside Rg1, an active component of ginseng, possesses neuroprotective and anti-inflammatory effects. The purpose of the present study was to evaluate these activities of Rg1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid (MPTP/p)-induced PD mouse model for the first time and to elucidate the underlying mechanisms.Oral treatment with Rg1 significantly attenuated the high MPTP-induced mortality, behavior defects, loss of dopamine neurons and abnormal ultrastructure changes in the SNpc. Other assays indicated that the protective effect of Rg1 may be mediated by its anti-neuroinflammatory properties. Rg1 regulated MPTP-induced reactive astrocytes and microglia and decreased the release of cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in the SNpc. Rg1 also alleviated the unusual MPTP-induced increase in oligomeric, phosphorylated and disease-related alpha-synuclein in the SNpc. In conclusion, Rg1 protects dopaminergic neurons, most likely by reducing aberrant alpha-synuclein-mediated neuroinflammation, and holds promise for PD therapeutics. (C) 2015 Elsevier Ireland Ltd. All rights reserved.