Neuroprotective effects of ginsenoside-Rg1 in primary nigral neurons against rotenone toxicity
Neuroprotective effects of ginsenoside-Rg1 in primary nigral neurons against rotenone toxicity
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DOI：
10.1016/j.neuropharm.2006.10.001
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发表时间：
2007-03-01
影响因子：
4.7
通讯作者：
Wong, R. N. S.
中科院分区：
文献类型：
--
作者：
Leung, K. W.;Yung, K. K. L.;Wong, R. N. S.
人参皂苷rg1是人参中分离的药理活性成分，对原代培养的大鼠神经神经元具有抗鱼藤酮毒性的神经保护作用。鱼藤酮是一种常见的家用农药，以其特异性和不可逆的线粒体复合体I抑制作用而闻名，已被认为是通过诱导实质黑质细胞变性而导致帕金森病（PD）的病因。本研究表明，鱼藤酮与Rg1共处理可使鱼藤酮诱导的细胞死亡减少58% （SEM = +/- 5.60; N = 3）。Rg1恢复鱼藤酮诱导的线粒体膜电位（MMP, Delta Psi m）耗损，并使其至少提高38% （SEM = +/- 2.15; N = 3）。此外，Rg1通过激活PI3K/Akt通路，阻止细胞色素c从线粒体膜释放，增加对促凋亡蛋白Bad的磷酸化抑制。Rg1的保护作用被糖皮质激素受体拮抗剂RU486阻断，表明Rg1的作用是通过糖皮质激素受体（GR）介导的。综上所述，Rg1抑制线粒体凋亡通路，增加原代培养的黑质神经元对鱼藤酮毒性的存活率。因此，Rg1及其相关化合物可能被开发为线粒体毒素诱导的神经退行性疾病的保护剂。(c) 2006 Elsevier Ltd.版权所有。
Ginsenoside-Rg1, the pharmacologically active component isolated from ginseng, demonstrated neuroprotective effects on primary cultured rat nigral neurons against rotenone toxicity. Rotenone, a common household pesticide known for its specific and irreversible mitochondria complex I inhibition, has been suggested to be the causal agent of Parkinson's disease (PD) by inducing degeneration of cells in the substantial nigra. The present study demonstrated that co-treatruent of rotenone and Rg1 could reduce rotenone-induced cell death by 58% (SEM = +/- 5.60; N = 3). Rotenone-induced mitochondria membrane potential (MMP, Delta Psi m) depletion was restored and elevated by at least 38% (SEM = +/- 2.15; N = 3) by Rg1. In addition, Rg1 prevented cytochrome c release from the rnitochrondrial membrane and increased the phosphorylation inhibition of the pro-apoptotic protein Bad through activation of the PI3K/Akt pathway. The protective effects of Rg1 was blocked by glucocorticoid receptor antagonist RU486, indicating that the action of Rg1 is mediated through glucocorticoid receptor (GR). In conclusion, Rg1 inhibits the mitochondrial apoptotic pathway and increases the survival chance of the primary cultured nigral neurons against rotenone toxicity. Thus, Rg1 and its related compounds may be developed as protective agents against neuroclegenerative diseases induced by mitochondrial toxins. (c) 2006 Elsevier Ltd. All rights reserved.