Amyloid-β-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans
Amyloid-β-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans
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DOI：
10.1523/jneurosci.3448-06.2006
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发表时间：
2006-12-13
影响因子：
5.3
通讯作者：
Luo, Yuan
中科院分区：
文献类型：
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作者：
Wu, Yanjue;Wu, Zhixin;Luo, Yuan
淀粉样蛋白（A β）毒性被认为是阿尔茨海默病（AD）中出现的突触丧失和随后的神经元变性的开始。我们之前证明了标准银杏叶提取物EGb 761，通常用于增强记忆和阿尔茨海默病患者的痴呆症，抑制A β诱导的神经母细胞瘤细胞凋亡。在这项研究中，我们利用egb761及其单一成分，在一种模式生物秀丽隐杆线虫（Caenorhabditis elegans）中，将A β物种与A β诱导的病理行为联系起来。我们报道了egb761及其成分之一银杏内酯A在转基因秀丽隐杆线虫中减轻A β诱导的病理行为，包括瘫痪，减少趋化行为和5-羟色胺过敏。我们还发现EGb 761抑制了A - β寡聚和A - β在线虫体内的沉积。此外，减少氧化应激并不是EGb 761和银杏内酯A抑制A β诱导的瘫痪的机制，因为抗氧化剂l -抗坏血酸与EGb 761相同程度地降低了细胞内过氧化氢的水平，但在抑制转基因秀丽隐杆线虫的瘫痪方面却没有EGb 761那么有效。这些发现表明：(1)EGb761抑制A β相关的病理行为；(2)EGb761对A β毒性的保护主要是通过调节A β寡聚物来介导的；(3)银杏内酯A具有预防和治疗AD的治疗潜力。
Amyloid-beta (A beta) toxicity has been postulated to initiate synaptic loss and subsequent neuronal degeneration seen in Alzheimer's disease (AD). We previously demonstrated that the standardized Ginkgo biloba extract EGb 761, commonly used to enhance memory and by AD patients for dementia, inhibits A beta-induced apoptosis in neuroblastoma cells. In this study, we use EGb 761 and its single constituents to associate A beta species with A beta-induced pathological behaviors in a model organism, Caenorhabditis elegans. We report that EGb 761 and one of its components, ginkgolide A, alleviates A beta-induced pathological behaviors, including paralysis, and reduces chemotaxis behavior and 5-HT hypersensitivity in a transgenic C. elegans. We also show that EGb 761 inhibits A beta oligomerization and A beta deposits in the worms. Moreover, reducing oxidative stress is not the mechanism by which EGb 761 and ginkgolide A suppress A beta-induced paralysis because the antioxidant L-ascorbic acid reduced intracellular levels of hydrogen peroxide to the same extent as EGb 761, but was not nearly as effective in suppressing paralysis in the transgenic C. elegans. These findings suggest that (1) EGb 761 suppresses A beta-related pathological behaviors, (2) the protection against A beta toxicity by EGb761 is mediated primarily by modulating A beta oligomeric species, and (3) ginkgolide A has therapeutic potential for prevention and treatment of AD.