Gallic acid is the major component of grape seed extract that inhibits amyloid fibril formation

Bioorg Med Chem Lett. 2013 Dec 1;23(23):6336-40. doi: 10.1016/j.bmcl.2013.09.071. Epub 2013 Oct 1.


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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / biosynthesis*
  • Animals
  • Gallic Acid / chemistry*
  • Gallic Acid / pharmacology*
  • Grape Seed Extract / analysis
  • Grape Seed Extract / chemistry*
  • Grape Seed Extract / pharmacology*
  • Mice
  • Protein Folding


  • Amyloid beta-Peptides
  • Grape Seed Extract
  • Gallic Acid