Effects of Flavonoid Compounds on β-amyloid-peptide-induced Neuronal Death in Cultured Mouse Cortical Neurons.
Effects of Flavonoid Compounds on β-amyloid-peptide-induced Neuronal Death in Cultured Mouse Cortical Neurons.
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DOI：
10.4068/cmj.2014.50.2.45
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Kim JK
中科院分区：
文献类型：
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作者：
Choi SM;Kim BC;Cho YH;Choi KH;Chang J;Park MS;Kim MK;Cho KH;Kim JK
β-淀粉样肽（Aβ）的过度积累是导致阿尔茨海默病神经元死亡的主要机制之一。黄酮类化合物，主要是抗氧化剂，是一组在植物细胞中合成的多酚化合物。本研究旨在通过检测不同黄酮类化合物对Aβ片段25-35（Aβ25-35）神经毒性的影响，鉴定能够抑制Aβ诱导的神经元死亡的黄酮类化合物。Aβ25-35可诱导浓度和时间依赖性神经元死亡。Trolox或抗坏血酸处理可显著抑制20 µM Aβ25-35诱导的神经元死亡。在10种黄酮类化合物中[芹菜素、黄芩素、儿茶素、表儿茶素、表没食子儿茶素没食子酸酯（EGCG）、山奈酚、毛地黄黄酮、杨梅素、槲皮素和芦丁]，除芹菜素外，所有化合物在无细胞条件下均表现出强的1，1-二苯基-2-吡喃肼基（DPPH）清除活性。在暴露24小时结束时，除30 µM芹菜素外，黄酮类化合物也显著抑制20 µM Aβ25-35诱导的神经元死亡。表儿茶素，表没食子儿茶素没食子儿茶素，毛地黄黄酮，和杨梅素表现出更有力和持久的神经保护作用比其他化合物。这些结果表明氧化应激参与了Aβ诱导的神经元死亡，抗氧化黄酮类化合物，尤其是表儿茶素、EGCG、木犀草素和杨梅素，可以抑制神经元死亡。这些发现表明，这四种化合物可能被开发为抗阿尔茨海默病的神经保护剂。
Excessive accumulation of β-amyloid peptide (Aβ) is one of the major mechanisms responsible for neuronal death in Alzheimer's disease. Flavonoids, primarily antioxidants, are a group of polyphenolic compounds synthesized in plant cells. The present study aimed to identify flavonoid compounds that could inhibit Aβ-induced neuronal death by examining the effects of various flavonoids on the neurotoxicity of Aβ fragment 25-35 (Aβ25-35) in mouse cortical cultures. Aβ25-35 induced concentration- and exposure-time-dependent neuronal death. Neuronal death induced by 20 µM Aβ25-35 was significantly inhibited by treatment with either Trolox or ascorbic acid. Among 10 flavonoid compounds tested [apigenin, baicalein, catechin, epicatechin, epigallocatechin gallate (EGCG), kaempferol, luteolin, myricetin, quercetin, and rutin], all except apigenin showed strong 1,1-diphenyl-2-pycrylhydrazyl (DPPH) scavenging activity under cell-free conditions. The flavonoid compounds except apigenin at a concentration of 30 µM also significantly inhibited neuronal death induced by 20 µM Aβ25-35 at the end of 24 hours of exposure. Epicatechin, EGCG, luteolin, and myricetin showed more potent and persistent neuroprotective action than did the other compounds. These results demonstrated that oxidative stress was involved in Aβ-induced neuronal death, and antioxidative flavonoid compounds, especially epicatechin, EGCG, luteolin, and myricetin, could inhibit neuronal death. These findings suggest that these four compounds may be developed as neuroprotective agents against Alzheimer's disease.