Elevation of oxidative free radicals in Alzheimer's disease models can be attenuated by Ginkgo biloba extract EGb 761
Elevation of oxidative free radicals in Alzheimer's disease models can be attenuated by Ginkgo biloba extract EGb 761
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DOI：
10.3233/jad-2003-5404
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发表时间：
2003-01-01
影响因子：
4
通讯作者：
Luo, Yuan
中科院分区：
文献类型：
--
作者：
Smith, Julie Vining;Luo, Yuan
淀粉样β肽（A β）在阿尔茨海默病（AD）神经毒性的自由基氧化应激模型中的作用近年来受到广泛关注。在这项研究中，我们采用了在体外和体内模型显示内源性A β的生产，研究A β对细胞内自由基水平的影响。我们采用了一个神经母细胞瘤细胞系稳定表达AD相关的双突变，表现出增加的分泌和细胞内积累的A β刺激时，以及转基因秀丽隐杆线虫组成型表达人类A β。与野生型对照相比，在体外和体内AD相关转基因模型中均观察到过氧化氢（H2O2）水平升高。处理细胞或C. Elegans与银杏叶提取物EGb 761显着减弱基础以及诱导水平的H2O2相关的活性氧（ROS）。在测试的单个EGb 761组分中，山奈酚和槲皮素在两种模型中均提供最大衰减。此外，在野生型C中观察到H2O2相关ROS的年龄依赖性增加。elegans，在AD相关的C. elegans突变体这些结果支持了A β和ROS参与AD的假设。
The role of amyloid beta-peptide (A beta) in the free-radical oxidative-stress model of neurotoxicity in Alzheimer's disease (AD) has received much attention recently. In this study, we have employed both in vitro and in vivo models displaying endogenous A beta production to study the effects of A beta on intracellular free radical levels. We employed a neuroblastoma cell line stably expressing an AD-associated double mutation, which exhibits both increased secretion and intracellular accumulation of A beta when stimulated, as well as transgenic Caenorhabditis elegans constitutively expressing human A beta. A rise in levels of hydrogen peroxide (H2O2) was observed in both in vitro and in vivo AD-associated transgenic models expressing the A beta peptide compared with the wild type controls. Treatment of the cells or C. elegans with Ginkgo biloba extract EGb 761 significantly attenuated the basal as well as the induced levels of H2O2-related reactive oxygen species (ROS). Among individual EGb 761 components tested, kaempferol and quercetin provided maximum attenuation in both models. Furthermore, an age-dependent increase in H2O2-related ROS was observed in wild type C. elegans, which is accelerated in the AD-associated C. elegans mutant. These results support the hypothesis of the involvement of A beta and ROS in association with AD.