Neuroprotective effects of Asiaticoside.
Neuroprotective effects of Asiaticoside.
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DOI：
10.4103/1673-5374.137574
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发表时间：
2014-07-01
影响因子：
6.1
通讯作者：
An JZ
中科院分区：
文献类型：
--
作者：
Qi FY;Yang L;Tian Z;Zhao MG;Liu SB;An JZ
在中枢神经系统，积雪草皂苷已被证明可以减轻暴露于β-淀粉样蛋白引起的体外神经元损伤。体内实验表明，积雪草总苷能减轻短暂性局灶性大脑中动脉闭塞动物的神经行为学、神经化学和组织学改变。此外，积雪草总苷对急性和慢性应激动物均有抗焦虑作用。然而，其在谷氨酸诱导的兴奋性毒性中的潜在神经保护作用尚未得到充分研究。我们研究了积雪草苷对n -甲基- d -天冬氨酸引起谷氨酸诱导的兴奋性毒性小鼠皮质神经元的神经保护作用。积雪草苷预处理以浓度依赖的方式减少神经元细胞损失，恢复凋亡相关蛋白Bcl-2和Bax的表达变化。积雪草苷预处理还能减弱n -甲基- d -天冬氨酸受体亚基NR2B的表达上调，但不影响NR2A亚基的表达。此外，在培养的神经元中，积雪草苷显著抑制n -甲基- d -天冬氨酸诱导的Ca2+内流。这些实验结果初步证明，在n -甲基- d -天冬氨酸暴露诱导的皮质神经元兴奋性毒性过程中，积雪草苷的神经保护作用是通过抑制钙内流介导的。除抗氧化活性外，下调含n-甲基- d -天冬氨酸受体nr2b可能是积雪草苷神经保护的潜在机制之一。
In the central nervous system, Asiaticoside has been shown to attenuate in vitro neuronal damage caused by exposure to β-amyloid. In vivo studies demonstrated that Asiaticoside could attenuate neurobehavioral, neurochemical and histological changes in transient focal middle cerebral artery occlusion animals. In addition, Asiaticoside showed anxiolytic effects in acute and chronic stress animals. However, its potential neuroprotective properties in glutamate-induced excitotoxicity have not been fully studied. We investigated the neuroprotective effects of Asiaticoside in primary cultured mouse cortical neurons exposed to glutamate-induced excitotoxicity invoked by N-methyl-D-aspartate. Pretreatment with Asiaticoside decreased neuronal cell loss in a concentration-dependent manner and restored changes in expression of apoptotic-related proteins Bcl-2 and Bax. Asiaticoside pretreatment also attenuated the upregulation of NR2B expression, a subunit of N-methyl-D-aspartate receptors, but did not affect expression of NR2A subunits. Additionally, in cultured neurons, Asiaticoside significantly inhibited Ca2+ influx induced by N-methyl-D-aspartate. These experimental findings provide preliminary evidence that during excitotoxicity induced by N-methyl-D-aspartate exposure in cultured cortical neurons, the neuroprotective effects of Asiaticoside are mediated through inhibition of calcium influx. Aside from its anti-oxidant activity, down-regulation of NR2B-containing N-methyl-D-aspartate receptors may be one of the underlying mechanisms in Asiaticoside neuroprotection.