title: Gallic acid is the major component of grape seed extract that inhibits amyloid fibril formation.
abstract: Many protein misfolding diseases, for example, Alzheimer's, Parkinson's and Huntington's, are characterised by the accumulation of protein aggregates in an amyloid fibrillar form. Natural products which inhibit fibril formation are a promising avenue to explore as therapeutics for the treatment of these diseases. In this study we have shown, using in vitro thioflavin T assays and transmission electron microscopy, that grape seed extract inhibits fibril formation of kappa-casein (κ-CN), a milk protein which forms amyloid fibrils spontaneously under physiological conditions. Among the components of grape seed extract, gallic acid was the most active component at inhibiting κ-CN fibril formation, by stabilizing κ-CN to prevent its aggregation. Concomitantly, gallic acid significantly reduced the toxicity of κ-CN to pheochromocytoma12 cells. Furthermore, gallic acid effectively inhibited fibril formation by the amyloid-beta peptide, the putative causative agent in Alzheimer's disease. It is concluded that the gallate moiety has the fibril-inhibitory activity.
authors.affiliation: School of Chemistry and Physics, The University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Liu
authors.forename: Tara L
authors.initials: TL
authors.lastname: Pukala
authors.forename: Ian F
authors.initials: IF
authors.lastname: Musgrave
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Williams
authors.forename: Francis C
authors.initials: FC
authors.lastname: Dehle
authors.forename: John A
authors.initials: JA
authors.lastname: Carver
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D000818:Animals; D005707:Gallic Acid / Q000737:chemistry* / Q000494:pharmacology*; D056604:Grape Seed Extract / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D017510:Protein Folding
chemical_list: D016229:Amyloid beta-Peptides; D056604:Grape Seed Extract; D005707:Gallic Acid
keywords: 1,4-dithiothreitol; 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; AD; Alzheimer’s disease; Amyloid fibril; Amyloid-beta peptide; Aβ; DTT; EGCG; GA; GSE; Gallic acid; Grape seed extract; HD; Huntington’s disease; Kappa-casein; MTT; PC12; PD; Parkinson’s disease; Protein aggregation; RCM-κ-CN; TEM; ThT; Thioflavin T; amyloid-beta peptide; epigallocatechin-3-gallate; gallic acid; grape seed extract; pheochromocytoma12; reduced and carboxymethylated kappa-casein; transmission electron microscopy