Clovamide and rosmarinic acid induce neuroprotective effects in in vitro models of neuronal death
Clovamide and rosmarinic acid induce neuroprotective effects in in vitro models of neuronal death
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DOI：
10.1111/j.1476-5381.2009.00213.x
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发表时间：
2009-07-01
影响因子：
7.3
通讯作者：
Lombardi, G.
中科院分区：
文献类型：
--
作者：
Fallarini, S.;Miglio, G.;Lombardi, G.
背景和目的：酚类化合物具有细胞保护作用，我们的目的是研究等排多酚化合物氯伐酰胺和迷迭香酸是否具有神经保护作用。实验方法：选择三种体外神经元死亡模型：（i）分化的SH-SY 5 Y人神经母细胞瘤细胞暴露于叔丁基过氧化氢（t-BOOH），用于氧化应激;（ii）分化的SK-N-BE（2）用L-谷氨酸处理的人神经母细胞瘤细胞，用于兴奋性毒性;和（iii）暴露于氧-葡萄糖剥夺/再氧合的分化的SH-SY 5 Y人神经母细胞瘤细胞，用于缺血-再灌注。通过测量细胞培养基中的乳酸脱氢酶来评价细胞死亡，同时通过测量以下效应的潜在机制：（i）t-BOOH诱导的谷胱甘肽消耗和脂质过氧化增加;和（ii）通过逆转录酶-PCR，L-谷氨酸诱导的细胞内Ca 2+过载（fura-2方法）和诱导型基因表达（c-fos，c-jun）。化合物调节核因子-κ B和过氧化物酶体增殖物激活受体-γ激活的能力通过Western印迹法在SH-SY 5 Y细胞中进行了评估，该细胞未暴露于有害的stimulation.Key结果：氯伐酰胺和迷迭香酸（10-100 μ mol.L-1）均以类似的效力和功效显著保护神经元免受损伤。EC 50值在低微摩尔范围内（0.9-3.7 μ mol.L-1），而在100 μ mol.L-1时，与未处理对照相比，最大效应范围为40%至-60%。这些作用是通过预防氧化应激、细胞内Ca 2+超载和c-fos表达介导的。此外，迷迭香酸抑制核因子-κ B易位和增加过氧化物酶体增殖物激活受体-G的表达在SH-SY 5 Y细胞不暴露于有害的stimulation.Conclusion和影响：氯伐胺和迷迭香酸是神经保护化合物的潜在用途在营养/药物界面。英国药理学杂志（2009）157，1072-1084; doi：10.1111/j.1476-5381.2009.00213.x; 2009年5月21日在线发表
Background and purpose: Phenolic compounds exert cytoprotective effects; our purpose was to investigate whether the isosteric polyphenolic compounds clovamide and rosmarinic acid are neuroprotective.Experimental approach: Three in vitro models of neuronal death were selected: (i) differentiated SH-SY5Y human neuroblastoma cells exposed to tert-butylhydroperoxide (t-BOOH), for oxidative stress; (ii) differentiated SK-N-BE(2) human neuroblastoma cells treated with L-glutamate, for excitotoxicity; and (iii) differentiated SH-SY5Y human neuroblastoma cells exposed to oxygen-glucose deprivation/reoxygenation, for ischaemia-reperfusion. Cell death was evaluated by lactate dehydrogenase measurements in the cell media, while the mechanisms underlying the effects by measuring: (i) t-BOOH-induced glutathione depletion and increase in lipoperoxidation; and (ii) L-glutamate-induced intracellular Ca2+ overload (fura-2 method) and inducible gene expression (c-fos, c-jun), by reverse transcriptase-PCR. The ability of compounds to modulate nuclear factor-kappa B and peroxisome proliferator-activated receptor-gamma activation was evaluated by Western blot in SH-SY5Y cells not exposed to harmful stimuli.Key results: Both clovamide and rosmarinic acid (10-100 mu mol.L-1) significantly protected neurons against insults with similar potencies and efficacies. The EC50 values were in the low micromolar range (0.9-3.7 mu mol.L-1), while the maximal effects ranged from 40% to -60% protection from cell death over untreated control at 100 mu mol.L-1. These effects are mediated by the prevention of oxidative stress, intracellular Ca2+ overload and c-fos expression. In addition, rosmarinic acids inhibited nuclear factor-kappa B translocation and increased peroxisome proliferator-activated receptor-g expression in SH-SY5Y cells not exposed to harmful stimuli.Conclusion and implications: Clovamide and rosmarinic acid are neuroprotective compounds of potential use at the nutritional/pharmaceutical interface. British Journal of Pharmacology (2009) 157, 1072-1084; doi:10.1111/j.1476-5381.2009.00213.x; published online 21 May 2009