Procyanidine resists the fibril formation of human islet amyloid polypeptide

Human islet amyloid polypeptide (hIAPP) is widely studied due to its close correlation with the pathogenic mechanism of type II diabetes mellitus (T2DM). Bioflavonoids have been used in the neurodegeneration and diabetes studies. However, the structure-activity relationship remains unclear in many of these compounds. In this work, we performed diverse biophysical and biochemical methods to explore the inhibition of procyanidine on hIAPP and compared with that on amyloid-beta (A beta) protein which is linked to Alzheimer's disease (AD). The procyanidine effectively inhibited the aggregation of hIAPP and A beta through hydrophobic and hydrogen bonding interactions, it dissolved the aged fibrils into nanoscale particles. The compound also ameliorated the cytotoxicity and the membrane leakage by reducing the peptide oligomerization. The procyanidine showed better binding affinity and inhibitory effects on peptide aggregation and upregulated the cell viability to hIAPP than to A beta, which could be a prospective inhibitor against hIAPP. This work also offered a possible strategy for T2DM and AD treatments. (c) 2021 Published by Elsevier B.V.

Automated summary

This study investigated the inhibition of procyanidine on hIAPP and A beta aggregation through diverse biophysical and biochemical methods. Procyanidine effectively inhibited the aggregation of both peptides through hydrophobic and hydrogen bonding interactions, dissolved aged fibrils into nanoscale particles, and ameliorated cytotoxicity and membrane leakage. The compound showed better binding affinity and inhibitory effects on hIAPP, suggesting its potential as a prospective inhibitor against hIAPP, offering a possible strategy for T2DM and AD treatments.