Prevention of Ischemic Neuronal Death by Intravenous Infusion of a Ginseng Saponin, Ginsenoside Rb1, That Upregulates Bcl-xL Expression
Prevention of Ischemic Neuronal Death by Intravenous Infusion of a Ginseng Saponin, Ginsenoside Rb1, That Upregulates Bcl-xL Expression
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DOI：
10.1038/sj.jcbfm.9600225
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发表时间：
2006-05
影响因子：
6.3
通讯作者：
Bo Zhang;R. Hata;Pengxiang Zhu;Kohji Sato;T. Wen;Lihua Yang;H. Fujita;N. Mitsuda;Junya Tanaka;K. Samukawa;N. Maeda;M. Sakanaka
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文献类型：
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作者：
Bo Zhang;R. Hata;Pengxiang Zhu;Kohji Sato;T. Wen;Lihua Yang;H. Fujita;N. Mitsuda;Junya Tanaka;K. Samukawa;N. Maeda;M. Sakanaka
几乎所有当施用到脑室中时表现出神经保护作用的药剂在输注到血流中时在拯救受损神经元方面是无效的或有效性低得多。寻找一种具有有效神经保护作用的静脉输注药物对于治疗数百万患有急性脑疾病的患者至关重要。在这里，我们报告了缺血后静脉输注人参皂苷，gRb 1（gRb 1），（C54H92O23，分子量1109.46）对永久性闭塞大脑中动脉远侧纹状体支的易卒中自发性高血压大鼠显著改善缺血诱导的定位导航障碍，并引起约50%的与赋形剂输注的缺血对照相比，皮质梗塞病变的体积减小。在随后的研究中，重点是gRb 1诱导的基因产物的表达负责神经元死亡或存活，我们表明，gRb 1刺激的表达的cardion相关的抗凋亡因子Bcl-xLin体外和体内。此外，我们发现，在bcl-x启动子的Stat 5响应元件变得活跃的gRb 1治疗的反应。人参皂苷Rb 1不仅可用于治疗脑卒中，而且可用于治疗其他涉及线粒体细胞死亡信号激活的疾病。
Almost all agents that exhibit neuroprotection when administered into the cerebral ventricles are ineffective or much less effective in rescuing damaged neurons when infused into the blood stream. Search for an intravenously infusible drug with a potent neuroprotective action is essential for the treatment of millions of patients suffering from acute brain diseases. Here, we report that postischemic intravenous infusion of a ginseng saponin, ginsenoside Rb1(gRb1) (C54H92O23, molecular weight 1109.46) to stroke-prone spontaneously hypertensive rats with permanent occlusion of the middle cerebral artery distal to the striate branches significantly ameliorated ischemia-induced place navigation disability and caused an approximately 50% decrease in the volume of the cortical infarct lesion in comparison with vehicle-infused ischemic controls. In subsequent studies that focused on gRb1-induced expression of gene products responsible for neuronal death or survival, we showed that gRb1stimulated the expression of the mitochondrion-associated antiapoptotic factor Bcl-xLin vitroandin vivo. Moreover, we revealed that a Stat5 responsive element in the bcl-x promoter became active in response to gRb1treatment. Ginsenoside Rb1appears to be a promising agent not only for the treatment of cerebral stroke, but also for the treatment of other diseases involving activation of mitochondrial cell death signaling.