Gallic acid is the major component of grape seed extract that inhibits amyloid fibril formation |
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Authors: | Yanqin Liu Tara L. Pukala Ian F. Musgrave Danielle M. Williams Francis C. Dehle John A. Carver |
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Affiliation: | 1. School of Chemistry and Physics, The University of Adelaide, Adelaide, SA 5005, Australia;2. Discipline of Pharmacology, The University of Adelaide, Adelaide, SA 5005, Australia;3. Research School of Chemistry, The Australian National University, Canberra, ACT 0200, Australia |
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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. |
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Keywords: | Amyloid fibril Grape seed extract Gallic acid Kappa-casein Amyloid-beta peptide Protein aggregation |
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