摘要
作为阿尔茨海默氏症的特点之一,β--淀粉样蛋白(Aβ)聚合引发复杂的神经毒性。证据表明,潜在的神经毒性机制包括谷氨酸受体亚型,即n -甲基- d -天门冬氨酸(NMDA)受体增加了细胞内钙(( II))离子加载并且提高了氧化应激。本项目,在中草药的35个化学成分(CHMs)中筛查了β-淀粉样蛋白聚合物抑制剂,其中四种,即白芍内酯苷、芦荟泻素、新橙皮苷和大黄素甲醚,首次被发现对β-淀粉样蛋白1-40和β-淀粉样蛋白1-42聚合物具有抑制作用的证据。MTT试验、活性氧含量测定和细胞内钙(II)离子浓度测定证实它们对海马神经元细胞具有神经保护功能。一个有趣的发现是:大黄素甲醚时对神经细胞有一定毒性,而白芍内酯苷、芦荟泻素和新橙皮苷能减少毒性和被β--淀粉样蛋白单体和低聚物诱导的氧化活性。此外, 白芍内酯苷表现在维持细胞内钙离子浓度的作用方面尤为显著。
关键词: 淀粉样蛋白聚合物;钙流入;草本植物;抑制剂;神经保护作用;活性氧
Current Alzheimer Research
Title:Inhibition of β-Amyloid Aggregation by Albiflorin, Aloeemodin and Neohesperidin and their Neuroprotective Effect on Primary Hippocampal Cells Against β-Amyloid Induced Toxicity
Volume: 12 Issue: 5
Author(s): See-Lok Ho, Chung-Yan Poon, Chengyuan Lin, Ting Yan, Daniel Wai-Jing Kwong and Ken Kin-Lam Yung, Man S. Wong, Zhaoxiang Bian and Hung-Wing Li
Affiliation:
关键词: 淀粉样蛋白聚合物;钙流入;草本植物;抑制剂;神经保护作用;活性氧
摘要: Being one of the hallmarks of Alzheimer’s disease, β-amyloid (Aβ) aggregates induce complicated neurotoxicity. Evidences show that the underlying mechanism of neurotoxicity involves a glutamate receptor subtype, N-methyl-D-aspartate (NMDA) receptor, an increase in intracellular calcium( II) ion loading as well as an elevation in oxidation stress. In this work, among the 35 chemical components of Chinese herbal medicines (CHMs) being screened for inhibitors of Aβ aggregation, four of them, namely albiflorin, aloeemodin, neohesperidin and physcion, were found for the first time to exhibit a potent inhibitory effect on Aβ1-40 and Aβ1-42 aggregation. Their neuroprotective capability on primary hippocampal neuronal cells was also investigated by MTT assay, ROS assay and intracellular calcium(II) ion concentration measurement. It was interesting to find that physcion was rather toxic to neuronal cells while albiflorin, aloeemodin and neohesperidin reduced the toxicity and ROS induced by both monomeric and oligomeric Aβ species. In addition, albiflorin was particularly powerful in maintaining the intracellular Ca2+ concentration.
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See-Lok Ho, Chung-Yan Poon, Chengyuan Lin, Ting Yan, Daniel Wai-Jing Kwong and Ken Kin-Lam Yung, Man S. Wong, Zhaoxiang Bian and Hung-Wing Li , Inhibition of β-Amyloid Aggregation by Albiflorin, Aloeemodin and Neohesperidin and their Neuroprotective Effect on Primary Hippocampal Cells Against β-Amyloid Induced Toxicity, Current Alzheimer Research 2015; 12 (5) . https://dx.doi.org/10.2174/1567205012666150504144919
DOI https://dx.doi.org/10.2174/1567205012666150504144919 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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