Anti-oxidant polydatin (piceid) protects against substantia nigral motor degeneration in multiple rodent models of Parkinson's disease.
Anti-oxidant polydatin (piceid) protects against substantia nigral motor degeneration in multiple rodent models of Parkinson's disease.
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DOI：
10.1186/1750-1326-10-4
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发表时间：
2015-03-02
影响因子：
15.1
通讯作者：
Xu JP
中科院分区：
文献类型：
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作者：
Chen Y;Zhang DQ;Liao Z;Wang B;Gong S;Wang C;Zhang MZ;Wang GH;Cai H;Liao FF;Xu JP
令人信服的证据表明，抑制复合物I的电子传递链和升高的氧化应激是帕金森病（PD）发病过程中最早的事件。因此，抗氧化剂，特别是来自天然来源的抗氧化剂，在治疗PD方面有很好的前景，这主要通过啮齿动物模型的研究来证明。在此，我们确定了白藜芦醇苷（白藜芦醇苷），一种天然多酚，是否可以发挥抗氧化活性，并在三种常用的啮齿动物模型的PD中减弱多巴胺能神经变性。雄性Sprague道利大鼠皮下注射鱼藤酮5周后，出现了PD的所有基本特征，包括从4周开始，僵硬症评分显著增加，运动协调活动减少。与海马和皮质相比，在纹状体区域发现氧化损伤的选择性增加，伴随着黑质（SNc）中多巴胺能神经元的大量变性。白藜芦醇苷口服联合给药能够以剂量依赖性方式减轻鱼藤酮诱导的运动缺陷，80 mg/kg剂量显示出甚至比L-左旋多巴（L-dopa）更好的效果。白藜芦醇苷处理显着阻止鱼藤酮引起的纹状体中谷胱甘肽、硫氧还蛋白、ATP、丙二醛（MDA）和锰超氧化物歧化酶（SOD）水平的变化。此外，白藜芦醇苷治疗挽救鱼藤酮诱导的多巴胺能神经元变性的SNc区域。在另外两种PD模型中也观察到类似的白藜芦醇苷保护作用，即小鼠MPTP和大鼠6-OHDA，显示出校正的运动功能、SOD和MDA活性以及p-Akt和活化的caspase-3水平。在三种啮齿动物模型的PD，白藜芦醇苷保留和纠正几个主要的抗氧化途径/参数选择性地在受影响的SNc区域。这意味着其有效的抗氧化活性是保护这些模型中脆弱的SNc神经变性的一个主要强调机制。总而言之，这些发现强烈表明白藜芦醇苷在治疗PD方面具有治疗潜力。本文的在线版本（doi：10.1186/1750-1326-10-4）包含补充材料，可供授权用户使用。
Compelling evidence suggests that inhibition of the complex I of the electron transport chain and elevated oxidative stress are the earliest events during the pathogenesis of Parkinson’s disease (PD). Therefore, anti-oxidants, especially those from natural sources, hold good promise in treating PD as demonstrated mostly by the studies in rodent models. Herein, we determined if polydatin (piceid), a natural polyphenol, could exert anti-oxidative activity and attenuate dopaminergic neurodegeneration in three commonly used rodent models of PD. Male Sprague Dawley rats given rotenone subcutaneously for 5 weeks developed all the essential features of PD, including a strong increase in catalepsy score and a decrease in motor coordination activity, starting at 4 weeks. Selective increase in oxidative damage was found in the striatal region as compared to the hippocampus and cortex, accompanied by massive degeneration of dopaminergic neurons in the substantia nigra (SNc). Co-administration of piceid orally was able to attenuate rotenone-induced motor defects in a dose dependent manner, with 80 mg/kg dosage showing even better effect than L-levodopa (L-dopa). Piceid treatment significantly prevented the rotenone-induced changes in the levels of glutathione, thioredoxin, ATP, malondialdehyde (MDA) and the manganese superoxide dismutases (SOD) in striatum. Furthermore, piceid treatment rescued rotenone-induced dopaminergic neurodegeneration in the SNc region. Similar protective effect of piceid was also observed in two additional models of PD, MPTP in mice and 6-OHDA in rats, showing corrected motor functions, SOD and MDA activities as well as p-Akt and activated caspase-3 levels. In three rodent models of PD, piceid preserves and corrects several major anti-oxidant pathways/parameters selectively in the affected SNc region. This implies its potent anti-oxidant activity as one major underscoring mechanism for protecting the vulnerable SNc neurodegeneration in these models. Taken together, these findings strongly suggest a therapeutic potential of piceid in treating PD. The online version of this article (doi:10.1186/1750-1326-10-4) contains supplementary material, which is available to authorized users.