title: Oxidized epigallocatechin gallate inhibited lysozyme fibrillation more strongly than the native form.
abstract: 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.
authors.affiliation: Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: An
authors.affiliation: School of Chemical Engineering, Guizhou Institute of Technology, Guiyang 550003, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Feng
authors.affiliation: Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119, China. Electronic address: chengmingzeng@snnu.edu.cn.
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Zeng
mesh_terms: D058227:Amyloidogenic Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D001205:Ascorbic Acid / Q000737:chemistry; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry; D002645:Chickens; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D009113:Muramidase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D010084:Oxidation-Reduction; D012996:Solutions
chemical_list: D058227:Amyloidogenic Proteins; D000975:Antioxidants; D012996:Solutions; D002392:Catechin; C045651:epigallocatechin gallate; D009113:Muramidase; D001205:Ascorbic Acid
keywords: Amyloid fibrils; Anti-amyloidogenic activity; Cytotoxicity; Epigallocatechin gallate; Lysozyme; Oxidation