An Ting-Ting, Feng Shuang, Zeng Cheng-Ming
Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119, China.
School of Chemical Engineering, Guizhou Institute of Technology, Guiyang 550003, China.
Redox Biol. 2017 Apr;11:315-321. doi: 10.1016/j.redox.2016.12.016. Epub 2016 Dec 21.
Epigallocatechin gallate (EGCG), the most abundant flavanoid in green tea, is currently being evaluated in the clinic due to its benefits in the treatment of amyloid disorders. Its anti-amyloidogenic effect has been attributed to direct interaction of the intact molecule with misfolded polypeptides. In addition, antioxidant activity is also involved in the anti-amyloidogenic role. The detailed molecular mechanism is still unclear and requires further investigation. In the present study, the kinetics of EGCG oxidation and the anti-amyloidogenic effect of the resultant oxidation substances have been examined. The results indicate that EGCG degrades in a medium at pH 8.0 with a half-life less than 2h. By utilizing lysozyme as an in vitro model, the oxidized EGCG demonstrates a more potent anti-amyloidogenic capacity than the intact molecule, as shown by ThT and ANS fluorescence, TEM determination, and hemolytic assay. The oxidized EGCG also has a stronger disruptive effect on preformed fibrils than the native form. Ascorbic acid eliminates the disruptive role of native EGCG on the fibrils, suggesting that oxidation is a prerequisite in fibril disruption. The results of this work demonstrate that oxidized EGCG plays a more important role than the intact molecule in anti-amyloidogenic activity. These insights into the action of EGCG may provide a novel route to understand the anti-amyloidogenic activity of natural polyphenols.
表没食子儿茶素没食子酸酯（EGCG）是绿茶中含量最丰富的类黄酮，由于其在治疗淀粉样变性疾病方面的益处，目前正在临床评估中。其抗淀粉样蛋白生成作用归因于完整分子与错误折叠多肽的直接相互作用。此外，抗氧化活性也参与了抗淀粉样蛋白生成作用。详细的分子机制仍不清楚，需要进一步研究。在本研究中，研究了EGCG氧化的动力学以及所得氧化产物的抗淀粉样蛋白生成作用。结果表明，EGCG在pH 8.0的介质中降解，半衰期小于2小时。通过使用溶菌酶作为体外模型，如ThT和ANS荧光、TEM测定和溶血试验所示，氧化的EGCG比完整分子表现出更强的抗淀粉样蛋白生成能力。氧化的EGCG对预先形成的纤维也比天然形式具有更强的破坏作用。抗坏血酸消除了天然EGCG对纤维的破坏作用，表明氧化是纤维破坏的先决条件。这项工作的结果表明，氧化的EGCG在抗淀粉样蛋白生成活性中比完整分子发挥更重要的作用。这些对EGCG作用的见解可能为理解天然多酚的抗淀粉样蛋白生成活性提供一条新途径。
