A-type EGCG dimer, a new proanthocyanidins dimer from persimmon fruits, interacts with the amino acid residues of Aβ40 which possessed high aggregation-propensity and strongly inhibits its amyloid fibrils formation.

Graphical abstract Highlights • A-type EGCG dimer was a potent inhibitor of Aβ 40 peptide aggregation. • A-type EGCG dimer prominently inhibited the oligomerization of Aβ 40. • A-type EGCG dimer predominantly interacted with Aβ 40 peptide with 1:2. • A-type EGCG dimer interacted with amino acids possessed high aggregation-propensity. Abstract A-type EGCG dimer is a new proanthocyanidins dimer from persimmon fruits. In the present study, we firstly examined the effects of EGCG and A-type EGCG dimer on Aβ 40 -fibrillization, and then the detailed mechanisms behind the inhibitory effects of polyphenols on Aβ 40 amyloid fibrils formation were investigated by PICUP assay, ESI-MS, NMR and molecular docking. Our results confirmed that A-type EGCG dimer exhibited stronger inhibitory effect on the formation of Aβ 40 amyloid fibrils. We found that A-type EGCG dimer possessed more binding sites on Aβ 40 peptide than EGCG. Notably, compared with EGCG, A-type EGCG dimer could interact with more amino acid residues which possessed obvious aggregation-propensity. And our results also suggested that the hydrophobic interaction was the principal driving force to inhibit the formation of Aβ 40 amyloid fibrils by A-type EGCG dimer. We believed that our study could provide useful insights for the design of low-molecular weight inhibitors of Aβ aggregation. [ABSTRACT FROM AUTHOR]