Tea Polyphenol (-)-epigallocatechin-3-gallate: A new trapping agent of reactive dicarbonyl species
Tea Polyphenol (-)-epigallocatechin-3-gallate: A new trapping agent of reactive dicarbonyl species
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DOI：
10.1021/tx700190s
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发表时间：
2007-12-01
影响因子：
4.1
通讯作者：
Ho, Chi-Tang
中科院分区：
文献类型：
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作者：
Sang, Shengmin;Shao, Xi;Ho, Chi-Tang
先前的研究表明，活性二羰基化合物[如甲基乙二醛（MGO）和乙二醛（GO）]随着时间的推移，不可逆地渐进式修饰蛋白质，并产生晚期糖基化终产物（AGEs），这被认为是糖尿病及其后续并发症的发展因素之一。因此，降低MGO和GO的水平将是减少AGEs形成和糖尿病并发症发生的有效途径。在研究中，我们发现主要生物活性绿茶多酚表没食子儿茶素-3-没食子酸酯（EGCG）可以在生理条件下（pH 7.4, 37℃）有效地捕获活性二羰基化合物（MGO或GO）形成单、双MGO或GO加合物。采用LC/MS分析了EGCG和MGO（或GO）以不同比例组合形成的产物。我们还开发了一种不衍生提纯EGCG的两个主要单mgo加合物的方法，并根据它们的1D和2D NMR谱确定了它们的结构为EGCG的单mgo加合物的立体异构体。我们的LC/MS和NMR数据表明，EGCG a环的位置6和8是捕获活性二羰基化合物的主要活性位点。我们还发现EGCG在酸性条件下(pH
Previous studies have demonstrated that reactive dicarbonyl compounds [e.g., methylglyoxal (MGO) and glyoxal (GO)] irreversibly and progressively modify proteins over time and yield advanced glycation end products (AGEs), which are thought to contribute to the development of diabetes mellitus and its subsequent complications. Thus, decreasing the levels of MGO and GO will be an effective approach to reduce the formation of AGEs and the development of diabetic complications. In our studies to find nontoxic trapping agents of reactive dicarbonyl species from dietary sources, we found that epigallocatechin-3-gallate (EGCG), the major bioactive green tea polyphenol, could efficiently trap reactive dicarbonyl compounds (MGO or GO) to form mono- and di-MGO or GO adducts under physiological conditions (pH 7.4, 37 degrees C. The products formed from EGCG and MGO (or GO), combined at different ratios, were analyzed using LC/MS. We also developed a method to purify the two major mono-MGO adducts of EGCG without derivatization, and their structures were identified as stereoisomers of mono-MGO adducts of EGCG based on their 1D and 2D NMR spectra. Our LC/MS and NMR data showed that positions 6 and 8 of the EGCG A-ring were the major active sites for trapping reactive dicarbonyl compounds. We also found that EGCG lost its trapping efficacy under acidic conditions (pH