Neuroprotective effects of Polygonum multiflorum extract against glutamate-induced oxidative toxicity in HT22 hippocampal cells
Neuroprotective effects of Polygonum multiflorum extract against glutamate-induced oxidative toxicity in HT22 hippocampal cells
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DOI：
10.1016/j.jep.2013.08.014
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发表时间：
2013-10-28
影响因子：
5.4
通讯作者：
Choi, Byung Tae
中科院分区：
文献类型：
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作者：
Kim, Ha Neui;Kim, Yu Ri;Choi, Byung Tae
民族药理学相关性：何首乌的干燥根传统上被用于延缓衰老过程中，在东亚国家和其提取物表现出抗氧化activity.Materials和方法：从何首乌乙酸乙酯提取物（EEPM）的神经保护作用进行了研究，对谷氨酸诱导的氧化性细胞死亡在HT 22海马细胞。细胞活力，细胞毒性，形态学，流式细胞仪，和Western印迹分析进行，以观察神经细胞存活或死亡相关pathways.Results的改变：EEPM预处理导致谷氨酸诱导的神经毒性显着降低，也导致大幅抑制谷氨酸诱导的神经元凋亡和坏死性死亡。为了阐明EEPM神经保护的可能途径，我们探讨了丝裂原活化蛋白激酶（MAPKs），磷脂酰肌醇-3-激酶和cAMP反应元件结合蛋白（CREB）的激活。单独用谷氨酸处理导致细胞外调节激酶（ERK），Jun N-末端激酶和p38在谷氨酸暴露后的后期激活，但用EEPM预处理导致这些蛋白质的激活显着减弱。用EEPM预处理导致CREB激活增加。ERK和p38的特异性抑制剂PD 98059和SB 203580可消除EEPM的神经保护作用。当我们评估钙蛋白酶I和纹状体富集蛋白酪氨酸磷酸酶（STEP）时，谷氨酸暴露后活性形式的钙蛋白酶I显著增加，并且沿着此，活性形式的STEP显示出减少。用EEPM预处理导致谷氨酸引起的前钙蛋白酶I和活性形式的STEP的显著恢复。钙蛋白酶抑制剂ALLN和EEPM的共同治疗对神经元死亡具有协同作用，并有助于阻断ERK和p38的激活，同时增加CREB的激活。这些结果表明，何首乌提取物可能通过减轻ERK和p38激活以及增加CREB在氧化应激下的激活而具有神经保护作用，并且具有作为治疗干预的潜力。氧化性神经元死亡(C)2013爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: Dried roots of Polygonum multiflorum have traditionally been used in the retarding of aging process in East Asian countries and its extracts exhibit anti-oxidative activities.Materials and methods: Neuroprotective effects of ethyl acetate extract from Polygonum multiflorum (EEPM) were investigated against glutamate-induced oxidative cell death in HT22 hippocampal cells. Cell viability, cytotoxicity, morphological, flow cytometty, and Western blot assays were performed in order to observe alterations of neuronal cell survival or death related pathways.Results: Pretreatment with EEPM resulted in significantly decreased glutamate-induced neurotoxicity and also resulted in drastically inhibited glutamate-induced apoptotic and necrotic neuronal death. To elucidate possible pathways of neuroprotection by EEPM, we explored the activation of mitogen activated protein kinases (MAPKs), phosphatidylinositol-3-kinase, and cAMP responsive element binding protein (CREB). Treatment with glutamate alone led to activation of extracellular regulated kinase (ERK), Jun N-terminal kinase, and p38 during the late phase after glutamate exposure, but pretreatment with EEPM resulted in significantly attenuated activation of these proteins. Pretreatment with EEPM resulted in increased activation of CREB. The specific inhibitors of ERK and p38, PD98059 and SB203580, abrogated the neuroprotective effects of EEPM. When we evaluated calpain I and striatal-enriched protein tyrosine phosphatase (STEP), active form of calpain I was significantly increased after glutamate exposure, and, along with this, active form of STEP showed a decrease. Pretreatment with EEPM resulted in significant recovery of pro-calpain I and active form of STEP caused by glutamate. Co-treatment with calpain inhibitor ALLN and EEPM had a synergistic effect on neuronal death and contributed to blockade of activation of both ERK and p38 with increased activation of CREB.Conclusions: These results suggest that Polygonum multiflorum extract may have neuroprotective effects through both alleviation of ERK and p38 activation with increased activation of CREB under oxidative stress and has potential as a therapeutic intervention for treatment of oxidative neuronal death. (C) 2013 Elsevier Ireland Ltd. All rights reserved.