Gastrodin protects apoptotic dopaminergic neurons in a toxin-induced Parkinson's disease model.

Gastrodin protects apoptotic dopaminergic neurons in a toxin-induced Parkinson's disease model.
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DOI:
10.1155/2013/514095
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发表时间:
2013
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Choi DK
Choi DK
中科院分区:
其他
文献类型:
--
作者:
Kumar H;Kim IS;More SV;Kim BW;Bahk YY;Choi DK

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天麻是东方国家最重要的传统植物之一,数百年来一直被用来改善各种条件。天麻素是天麻素中的活性成分。本研究旨在探讨天麻素对1-甲基-4-苯基吡啶(MPP+)/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-诱导人多巴胺能SH-SY5Y细胞和帕金森病小鼠模型的神经保护作用。天麻素通过调节自由基、Bax/Bcl-2mRNA、caspase-3和裂解多聚腺苷二磷酸核糖聚合酶(PARP),显著地和剂量依赖地保护多巴胺能神经元免受神经毒性。天麻素在亚慢性MPTP小鼠PD模型中也显示出神经保护作用,分别通过改善极杆和转杆试验中的运动迟缓和运动障碍。通过免疫组织化学和免疫印迹法对小鼠黑质和纹状体进行的研究表明,天麻素可预防MPTP引起的多巴胺耗竭和反应性星形胶质细胞增生症。此外,天麻素还通过减弱这些脑区的抗氧化和抗凋亡活性而有效地防止神经细胞凋亡。这些结果有力地表明天麻素对实验性帕金森病模型具有保护作用,可作为临床候选药物来改善帕金森病症状。
Gastrodia elata (GE) Blume is one of the most important traditional plants in Oriental countries and has been used for centuries to improve various conditions. The phenolic glucoside gastrodin is an active constituent of GE. The aim of this study was to investigate the neuroprotective role of gastrodin in 1-methyl-4-phenylpyridinium (MPP+)/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP) induced human dopaminergic SH-SY5Y cells and mouse model of Parkinson's disease (PD), respectively. Gastrodin significantly and dose dependently protected dopaminergic neurons against neurotoxicity through regulating free radicals, Bax/Bcl-2 mRNA, caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP) in SH-SY5Y cells stressed with MPP+. Gastrodin also showed neuroprotective effects in the subchronic MPTP mouse PD model by ameliorating bradykinesia and motor impairment in the pole and rotarod tests, respectively. Consistent with this finding, gastrodin prevented dopamine depletion and reduced reactive astrogliosis caused by MPTP as assessed by immunohistochemistry and immunoblotting in the substantiae nigrae and striatata of mice. Moreover, gastrodin was also effective in preventing neuronal apoptosis by attenuating antioxidant and antiapoptotic activities in these brain areas. These results strongly suggest that gastrodin has protective effects in experimental PD models and that it may be developed as a clinical candidate to ameliorate PD symptoms.
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