Comparison of disaggregative effect of A-type EGCG dimer and EGCG monomer on the preformed bovine insulin amyloid fibrils

•The effects of A-type EGCG dimer on preformed amyloid fibrils were studied by biophysical methods.•A-type EGCG dimer decreased the surface hydrophobicity of amyloid fibrils.•The amyloid fibrils were disaggregated into amorphous aggregates and soluble species by A-type EGCG dimer.•A-type EGCG dimer might be used as an important lead structure for the design of anti-amyloid drugs.

In the present study, the disruptive effects of epigallocatechin-3-gallate (EGCG) and A-type dimeric epigallocatechin-3-gallate (A-type EGCG dimer) on the preformed bovine insulin amyloid fibrils were studied by several biophysical methods including thioflavin-T (ThT) fluorescence assay, 1-anilinonaphthalene-8-sulfonic (ANS) fluorescence assay, Congo red (CR) binding assay, dynamic light scattering (DLS), transmission electron microscopy (TEM), Gel electrophoresis (SDS-PAGE) and Bradford assay. Our results demonstrated that A-type EGCG dimer showed significantly more potential disaggregative effects on the bovine insulin amyloid fibrils than EGCG. A-type EGCG dimer could not only dramatically promote the disaggregation of the preformed bovine insulin amyloid fibrils, but also restructure the amyloid fibrils into amorphous aggregates. While, EGCG could only shorten and thin the fibrils, but induce no small amorphous aggregates. Our present results provided additional evidence for the more potent disaggregation effects of dimeric polyphenols than monomeric polyphenols and suggested that A-type EGCG dimer seems to have potential application as an excellent anti-amyloidogenic agent.

Graphical abstractDownload high-res image (264KB)Download full-size image