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葛根素对小鼠 1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的帕金森病模型的神经保护作用。

Neuroprotective effects of puerarin on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced Parkinson's disease model in mice.

机构信息

Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Traditional Chinese Medicine, Hefei, 230038, China; Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, 91766, USA.

出版信息

Phytother Res. 2014 Feb;28(2):179-86. doi: 10.1002/ptr.4975. Epub 2013 Mar 20.

Abstract

Puerarin, an active component of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep is well-known for its anti-oxidative and neuroprotective activities. Although anti-Parkinson's disease activity of puerarin was reported in both of in vivo and in vitro model, detailed mechanisms are not clarified. In this study, we addressed that puerarin attenuated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral deficits, dopaminergic neuronal degeneration and dopamine depletion. Puerarin administration enhanced glutathione (GSH) activity, glial cell line-derived neurotrophic factor (GDNF) expression and PI3K/Akt pathway activation, which might ameliorate MPTP injection-induced progressive elevation of reactive oxygen species (ROS) formation in mice. In addition to the effect on ROS, puerarin ameliorated MPTP-reduced lysosome-associated membrane protein type 2A (Lamp 2A) expression. Taken together, our data demonstrate that puerarin attenuates MPTP-induced dopaminergic neuronal degeneration via modulating GDNF expression, PI3K/Akt pathway and GSH activation, which subsequently ameliorate MPTP-induced ROS formation and decrease of Lamp 2A expression.

摘要

葛根素是野葛(Willd.)三叶葛的一种活性成分,以其抗氧化和神经保护活性而闻名。虽然葛根素在体内和体外模型中都有抗帕金森病的活性,但详细的机制尚不清楚。在这项研究中,我们研究了葛根素对 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的行为缺陷、多巴胺能神经元变性和多巴胺耗竭的抑制作用。葛根素给药增强了谷胱甘肽(GSH)活性、胶质细胞源性神经营养因子(GDNF)表达和 PI3K/Akt 通路的激活,这可能改善了 MPTP 注射诱导的小鼠活性氧(ROS)形成的进行性升高。除了对 ROS 的作用外,葛根素还改善了 MPTP 降低的溶酶体相关膜蛋白 2A(Lamp 2A)表达。综上所述,我们的数据表明,葛根素通过调节 GDNF 表达、PI3K/Akt 通路和 GSH 激活来减轻 MPTP 诱导的多巴胺能神经元变性,从而改善 MPTP 诱导的 ROS 形成和 Lamp 2A 表达的降低。

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