Efficient Amyloid Fibrillation Inhibition and Remodeling of Preformed Fibrils of Bovine Insulin by Propolis Polyphenols-Based Nanosheets

Among common strategies for amyloid fibrillation inhibition, the use of naturally occurring polyphenols as an efficient therapeutic approach has attracted a growing body of attention. However, the poor water solubility and low bioavailability of these compounds have greatly restricted their clinical application in amyloid-related diseases. Thus, different types of formulations have been developed to overcome these limitations; among them, nanonization appears to be one of the most notable approaches. Herein, we show that the polyphenolic fraction of propolis (PFP), in the nanosheet form (PFP nanosheet), exhibits an improved capacity for amyloid fibrillation inhibition as well as clearance of preformed fibrils of bovine insulin. This increased efficiency is suggested to be related to the aqueous solubility and surface area enhancement as well as surface modifications upon undergoing the nanonization process, which can lead to strong binding with and trapping of protein at the surface of the nanosheets. On the basis of thioflavin T results, it is suggested that although PFP may modulate the fibrillation process via shortening of the lag phase, prolongation of the nucleation phase through interaction with and stabilizing monomeric species is the mechanism of action of PFP nanosheets. We propose that nanonization of natural small molecules can be considered as a powerful approach to improve their anti-amyloidogenic properties and overcome obstacles originating from poor water solubility and low bioavailability of drug candidates relating to neurodegenerative diseases. Taken together, the obtained results may suggest PFP nanosheets as a potential candidate for use against neurological disorders.

Automated summary

Using naturally occurring polyphenols as a therapeutic approach for amyloid fibrillation inhibition has attracted attention, but their limited water solubility and bioavailability hinder their clinical applications. Nanonization of polyphenolic fraction of propolis (PFP) enhances its capability in inhibiting amyloid fibrillation and clearing preformed fibrils, likely due to improved aqueous solubility, surface area enhancement, and surface modifications. This suggests that nanonization of natural small molecules could be a powerful approach to enhance their anti-amyloidogenic properties and overcome limitations related to neurodegenerative diseases.