posted on 2021-03-15, 20:15authored byMohammad Ramezani, Maryam Dehghan Hesami, Yasin Rafiei, Ebrahim Rostampour Ghareghozloo, Ali Akbar Meratan, Nasser Nikfarjam
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.