Eriodictyol Attenuates β-Amyloid 25-35 Peptide-Induced Oxidative Cell Death in Primary Cultured Neurons by Activation of Nrf2
Eriodictyol Attenuates β-Amyloid 25-35 Peptide-Induced Oxidative Cell Death in Primary Cultured Neurons by Activation of Nrf2
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DOI：
10.1007/s11064-015-1616-z
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发表时间：
2015-07-01
影响因子：
4.4
通讯作者：
Lou, Haiyan
中科院分区：
文献类型：
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作者：
Jing, Xu;Shi, Huanying;Lou, Haiyan
氧化应激在神经退行性疾病，包括阿尔茨海默病（AD）的发病机制中起着重要作用。Eriodictyol是一种从中国草药青兰中分离出来的黄酮类化合物，长期以来一直被认为是一种抗氧化剂。本研究旨在观察圣草酚对β-淀粉样蛋白25-35肽（A beta（25-35））诱导的原代神经元氧化性细胞死亡的影响，并探讨核因子红细胞2相关因子2/抗氧化反应元件（Nrf 2/ARE）通路在此过程中的作用。为此目的，将皮质神经元的原代培养物在不存在或存在圣草酚（20、40和80 μ M）的情况下暴露于15 μ M A β（25-35）。结果表明，圣草酚预处理可有效地减弱A β（25-35）诱导的细胞毒性和细胞凋亡特征，如JNK/p38凋亡信号通路的激活。圣草酚处理还导致原代培养的神经元中Nrf 2蛋白水平的增加和随后的ARE途径基因的激活。通过RNA干扰介导的Nrf 2表达的敲低减弱圣草酚的保护作用。综上所述，这些结果清楚地表明，圣草酚保护神经元免受A β（25-35）诱导的细胞死亡，部分通过Nrf 2/ARE信号通路，这进一步支持圣草酚可能是一种有前途的新型AD治疗剂。
Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Eriodictyol, a flavonoid isolated from the Chinese herb Dracocephalum rupestre, has long been established as an antioxidant. The present study was designed to investigate the effect of eriodictyol on beta-amyloid 25-35 peptide (A beta(25-35))-induced oxidative cell death in primary neurons and to explore the role of the nuclear factor erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in this process. For this purpose, primary cultures of cortical neurons were exposed to 15 mu M A beta(25-35) in the absence or presence of eriodictyol (20, 40 and 80 mu M). The results revealed that A beta(25-35)-induced cytotoxicity and apoptotic characteristics such as activation of JNK/p38 apoptotic signaling pathway were effectively attenuated by eriodictyol pretreatment. Eriodictyol treatment also resulted in an increase in Nrf2 protein levels and subsequent activation of ARE pathway genes in primary cultured neurons. The protective effects of eriodictyol were attenuated by RNA interference-mediated knockdown of Nrf2 expression. Taken together, these results clearly demonstrate that eriodictyol protects neurons against A beta(25-35)-induced cell death partially through Nrf2/ARE signaling pathway, which further supports that eriodictyol might be a promising novel therapeutic agent for AD.