Date palm (Phoenix dactylifera L.) fruit's polyphenols as potential inhibitors for human amylin fibril formation and toxicity in type 2 diabetes

Background: beta-Cell death is the key feature of type 2 diabetes mellitus (T2DM). The misfolding of human Islet Amyloid Polypeptide (hIAPP) is regarded as one of the causative factors of T2DM. Recent studies suggested that a diet based on date fruits presents various health benefits, as these fruits are naturally enriched in plant polyphenols. Method: In this study, we used a broad biophysical approach, using cell biology techniques and bioinformatic tools, to demonstrate that various polyphenols fromdate palm(Phoenix dactylifera L.) fruit significantly inhibited hIAPP aggregation and cytotoxicity. Result: Our results suggest that all of the polyphenols showed inhibitory effects, albeit varied, on the formation of toxic hIAPP amyloids. Correlation between cell viability assay, permeabilization of synthetic phospholipid vesicles tests, and ANS florescence measurements, revealed that both classes of polyphenols protected INS-1E cells from the toxicity of amylin aggregates. Docking results showed that the used polyphenols physically interacted with both hIAPP amyloidogenic region (residues Ser20-Ser29) and the non-amyloidogenic regions via hydrophobic and hydrogen interactions, thus reducing aggregation levels. Conclusion: These findings highlight the benefits of consuming dates and the great potential of its polyphenols as a potential therapy for the prevention and treatment of T2DMaswell as for many other amyloid-related diseases. (C) 2020 Elsevier B.V. All rights reserved.