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

Abstract

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.

Pomegranate seed polyphenol-based nanosheets as an efficient inhibitor of amyloid fibril assembly and cytotoxicity of HEWL

“…The assigned peak sequences at 690–900 cm −1 are for “out of plane”’ (oop) bending, indicating aromatic ring substitutes. 29 Upon undergoing nanonization, the spectrum pattern was changed due to the fusion of polyphenolic molecules and the production of a new structure. As shown in Fig.…”

“…PFPS nanosheets were prepared using direct oxidative pyrolysis, as previously reported with slight modifications. 29 Briefly, one gram of the PFPS powder was added into a 10 mL beaker and heated to 200 °C for 2.5 min. A color change from brown to dark brown indicates successful pyrolysis and nanosheet formation.…”

“…The samples were dried in a vacuum oven at 60 °C and thermal gravimetric analysis (TGA) was performed as described. 29 The surface zeta potential of PFPS nanosheets (20 μg mL −1 ) in a range of pH (from 2 to 12) was recorded using a zeta potential analyzer (Brookhaven Instrument, Holtsville, NY 11742-1896, USA). Finally, the microscopic features of PFPS nanosheets were analyzed using electron and atomic force microscopies.…”

“…The hemolytic activity of bulk/nano forms of PFPS (0–400 μg mL −1 ), or HEWL amyloid fibrils (0–50 μM) was evaluated as described previously. 29 To evaluate the protective effects of bulk/nano forms of PFPS against permeabilization induced by HEWL amyloid fibrils, the cell suspensions (1% hematocrit) were incubated alone or with various concentrations of incubated samples for 3 h at 37 °C while being gently stirred. The samples were then centrifuged at 1000 g for 10 min, followed by measuring the absorbance of supernatants at 540 nm.…”

Can Propolis Be a Useful Adjuvant in Brain and Neurological Disorders and Injuries? A Systematic Scoping Review of the Latest Experimental Evidence

“…In the neurological and neurodegenerative disease models, namely Alzheimer’s disease, Parkinson’s disease, and epilepsy, propolis also showed potential therapeutic benefits. Propolis was demonstrated to reduce amyloid fibrillation and reduce the impact of amyloid accumulation [ 39 , 42 ]. In addition, propolis inhibited the activity of both acetylcholinesterase and butyrylcholinesterase in a dose-dependent manner [ 40 , 41 , 42 , 43 ].…”