A pro-drug of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) prevents differentiated SH-SY5Y cells from toxicity induced by 6-hydroxydopamine
A pro-drug of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) prevents differentiated SH-SY5Y cells from toxicity induced by 6-hydroxydopamine
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DOI：
10.1016/j.neulet.2009.12.028
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发表时间：
2010-01-29
影响因子：
2.5
通讯作者：
Chang, Raymond Chuen-Chung
中科院分区：
文献类型：
--
作者：
Chao, Jianfei;Lau, Way Kwok-Wai;Chang, Raymond Chuen-Chung
经常饮用绿色茶有利于人们预防心血管疾病，肥胖症以及神经退行性疾病。表没食子儿茶素没食子酸酯（EGCG）被认为是绿色茶中最具生物活性的儿茶素。但是，EGCG的稳定性和生物利用度受到限制。本研究的目的是探讨前体药物，一个完全乙酰化的表没食子儿茶素没食子酸酯（pEGCG），是否可以更有效地在帕金森病模拟细胞模型的神经保护。用不同浓度的EGCG和pEGCG预处理视黄酸（RA）分化的神经母细胞瘤SH-SY 5 Y细胞30分钟，然后用25 μ M 6-羟基多巴胺（6-OHDA）孵育24小时。我们发现，一个广泛的剂量范围内的pEGCG（从0.1至10 μ M）可以显着减少乳酸脱氢酶的释放。同样地，10 μ M的pEGCG在降低半胱天冬酶-3活性方面是有效的，而在模型中测试的所有浓度的EGCG都不能减弱由6-OHDA诱导的半胱天冬酶-3活性。Western-blot分析表明Akt可能是pEGCG刺激的神经保护作用的特异性信号通路之一。结果表明，25 μ M的6-OHDA显著抑制Akt的磷酸化水平。与单独的6-OHDA相比，只有10 μ M的pEGCG显著增加其磷酸化水平。综上所述，由于pEGCG具有更高的稳定性和生物利用度，有待进一步研究，它可能是一种潜在的神经保护剂，我们目前的研究结果可能为优化其未来的应用提供一定的线索。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Regular consumption of green tea benefits people in prevention from cardiovascular disorders, obesity as well as neurodegenerative diseases. (-)-Epigallocatechin-3-gallate (EGCG) is regarded as the most biologically active catechin in green tea. However, the stability and bioavailability of EGCG are restricted. The purpose of the present study was to investigate whether a pro-drug, a fully acetylated EGCG (pEGCG), could be more effective in neuroprotection in Parkinsonism mimic cellular model. Retinoic acid (RA)differentiated neuroblastoma SH-SY5Y cells were pre-treated with different concentrations of EGCG and pEGCG for 30 min and followed by incubation of 25 mu M 6-hydroxydopamine (6-OHDA) for 24 h. We found that a broad dosage range of pEGCG (from 0.1 to 10 mu M) could significantly reduce lactate dehydrogenase release. Likewise, 10 mu M of pEGCG was effective in reducing caspase-3 activity, while EGCG at all concentrations tested in the model failed to attenuate caspase-3 activity induced by 6-OHDA. Furthermore, Western-blot analysis showed that Akt could be one of the specific signaling pathways stimulated by pEGCG in neuroprotection. It was demonstrated that 25 mu M of 6-OHDA significantly suppressed the phosphorylation level of Akt. Only pEGCG at 10 mu M markedly increased its phosphorylation level compared to 6-OHDA alone. Taken together, as pEGCG has higher stability and bioavailbility for further investigation, it could be a potential neuroprotective agent and our current findings may offer certain clues for optimizing its application in future. (C) 2009 Elsevier Ireland Ltd. All rights reserved.