A-type dimeric epigallocatechin-3-gallate (EGCG) is a more potent inhibitor against the formation of insulin amyloid fibril than EGCG monomer

• Published in: Biochimie Vol. 125; pp. 204 - 212
• Main Authors: Nie, Rong-zu, Zhu, Wei, Peng, Jin-ming, Ge, Zhen-zhen, Li, Chun-mei
• Format: Journal Article
• Language: English
• Published: France Elsevier B.V 01-06-2016
• Subjects: A-type EGCG dimer; Amyloid; Amyloid - chemistry; Amyloid - metabolism; Animals; Catechin - analogs & derivatives; Catechin - pharmacology; Cattle; EGCG; Fibril; Inhibition; Insulin - chemistry; Insulin - metabolism; Protein Aggregation, Pathological - drug therapy; Protein Aggregation, Pathological - metabolism; Amyloid; Inhibition; EGCG; A-type EGCG dimer; Fibril
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2016.03.011

Because fibrillary protein aggregates is regarded to be closely associated with many diseases such as Alzheimer's disease, diabetes, and Parkinson's disease, growing interest and researches have been focused on finding potential fibrillation inhibitors. In the present study, the inhibitory effects of epigallocatechin-3-gallate (EGCG) and A-type dimeric epigallocatechin-3-gallate (A-type EGCG dimer) on the formation of insulin fibrillation were compared by multi-dimensional approaches including thioflavin-T (ThT) fluorescence assay, 1-anilinonaphthalene-8-sulfonic (ANS) fluorescence assay, dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and circular dichroism (CD) spectroscopy. Our results confirmed that A-type EGCG dimer is a more potent inhibitor against the formation of bovine insulin amyloid fibril than EGCG. In addition, A-type EGCG dimer could not only inhibit insulin amyloid fibril formation, but also change the aggregation pathway and induce bovine insulin into amorphous aggregates. The results of the present study may provide a new guide on finding novel anti-amyloidogenic agents.
•Effects of EGCG and A-type EGCG dimer on insulin fibril formation were studied.•The structure changes were prevented by high concentration of A-type EGCG dimer.•Amorphous aggregates were found in the presence of A-type EGCG dimer.•A-type EGCG dimer is a more potent amyloid inhibitor than EGCG.