Polyphenols protect mitochondrial membrane against permeabilization induced by HEWL oligomers: Possible mechanism of action

Increasing body of evidence suggests that polyphenols frequently interacting with amyloid aggregates and/or interfering with aggregate species to bind biomembranes may serve as a therapeutic approach for the treatment of amyloid-related diseases. Hence, in the present study, the possible effects of three naturally occurring polyphenols including Curcumin, Quercetin, and Resveratrol on mitochondrial membrane permeabilization induced by Hen Egg White Lysozyme (HEWL) oligomers were investigated. Our results indicated that pre-incubation of mitochondrial homogenate with polyphenols considerably inhibit membrane permeabilization in a concentration dependent manner. In parallel, HEWL oligomers, which were co-incubated with the polyphenols, showed less effectiveness on membrane permeabilization, suggesting that toxicity of oligomers was hindered. Using a range of techniques including fluorescence quenching, Nile red binding assay, zeta potential and size measurements, CD (far- and near-UV) spectroscopy, and molecular docking, we found that the polyphenols, structure-dependently, interact with and induce conformational changes in HEWL oligomers, thereby inhibit their toxicity. We proposed a mechanism by which selected polyphenols induce their protective effects through binding to mitochondria and interfering with HEWL oligomer-membrane interactions and/or by direct interaction with HEWL oligomers, induction of conformational changes, and generating far less toxic species. However, additional studies are needed to elucidate the detailed mechanisms involved.