title: Inhibition of amyloid fibrillation and cytotoxicity of lysozyme fibrillation products by polyphenols.
abstract: An increasing number of studies conducted under in vitro and in vivo conditions, have concluded that polyphenols, compounds frequently occurring in many herbs with antioxidant properties, prevent and reverse amyloid fibril formation. However, the mechanisms by which these natural products modulate the protein aggregation process are poorly understood. Herein, a range of techniques including thioflavin T (ThT) and ANS fluorescence assays, electron microscopy and circular dichroism have been employed to determine the efficacy of rosmarinic acid (RA) and resveratrol (Res) on the inhibition/reversion of fibrillogenesis and hindering cytotoxicity induced by protofibrils and amyloid fibrils of hen egg white lysozyme (HEWL). Results demonstrated that both polyphenols effectively inhibit fibrillogenesis and destabilize preformed fibrils of HEWL in a concentration-dependent manner. Cytotoxicity protection on PC12 cells was also observed using the MTT assay, ROS production assay, and phase-contrast microscopy. It is suggested that the mechanism underlying the inhibitory effects of RA and Res is to prevent hydrophobic interactions between HEWL amyloidogenic prefibrillar species, although additional studies is needed to elucidate the detailed mechanisms involved. A combination of antioxidative and anti-amyloidogenic properties of these molecules may provide them with the described neuroprotective capacities.
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, P.O. Box 13145-1384, 1417614411 Tehran, Iran.
authors.forename: Sajad
authors.initials: S
authors.lastname: Shariatizi
authors.affiliation: Department of Biotechnology, Ramin University of Agricultural and Natural Resources, Khouzestan, Iran. Electronic address: a.meratan@gmail.com.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Meratan
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, P.O. Box 13145-1384, 1417614411 Tehran, Iran.
authors.forename: Atiyeh
authors.initials: A
authors.lastname: Ghasemi
authors.affiliation: Stanford Genome Technology Center, Stanford University, Palo Alto, CA, USA. Electronic address: mohsenn@stanford.edu.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Nemat-Gorgani
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival; D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D053630:Depsides / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D009113:Muramidase / Q000737:chemistry; D016716:PC12 Cells; D066263:Protein Aggregation, Pathological / Q000517:prevention & control*; D055550:Protein Stability; D017433:Protein Structure, Secondary; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D000097123:Rosmarinic Acid
chemical_list: D000682:Amyloid; D000975:Antioxidants; D002934:Cinnamates; D053630:Depsides; D009113:Muramidase; D000077185:Resveratrol; D013267:Stilbenes; D000097123:Rosmarinic Acid
keywords: Anti-amyloidogenic; Fibrillation products cytotoxicity; Polyphenol