title: Metal chelation, radical scavenging and inhibition of Aβ₄₂ fibrillation by food constituents in relation to Alzheimer's disease.
abstract: Various food constituents have been proposed as disease-modifying agents for Alzheimer's disease (AD), due to epidemiological evidence of their beneficial effects, and for their ability to ameliorate factors linked to AD pathogenesis, namely by: chelating iron, copper and zinc; scavenging reactive oxygen species; and suppressing the fibrillation of amyloid-beta peptide (Aβ). In this study, nine different food constituents (l-ascorbic acid, caffeic acid, caffeine, curcumin, (-)-epigallocatechin gallate (EGCG), gallic acid, propyl gallate, resveratrol, and α-tocopherol) were investigated for their effects on the above factors, using metal chelation assays, antioxidant assays, and assays of Aβ42 fibrillation. An assay method was developed using 5-Br-PAPS to examine the complexation of Zn(II) and Cu(II). EGCG, gallic acid, and curcumin were identified as a multifunctional compounds, however their poor brain uptake might limit their therapeutic effects. The antioxidants l-ascorbic acid and α-tocopherol, with better brain uptake, deserve further investigation for specifically addressing oxidative stress within the AD brain.
authors.affiliation: The University of Queensland, School of Pharmacy, Brisbane, Queensland 4072, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Chan
authors.affiliation: The University of Queensland, School of Pharmacy, Brisbane, Queensland 4072, Australia.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Kantham
authors.affiliation: The University of Queensland, School of Pharmacy, Brisbane, Queensland 4072, Australia.
authors.forename: Venkatesan M
authors.initials: VM
authors.lastname: Rao
authors.affiliation: The University of Queensland, School of Pharmacy, Brisbane, Queensland 4072, Australia.
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Palanivelu
authors.affiliation: The University of Queensland, School of Pharmacy, Brisbane, Queensland 4072, Australia.
authors.forename: Hoang L
authors.initials: HL
authors.lastname: Pham
authors.affiliation: The University of Queensland, School of Pharmacy, Brisbane, Queensland 4072, Australia.
authors.forename: P Nicholas
authors.initials: PN
authors.lastname: Shaw
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, Queensland 4072, Australia.
authors.forename: Ross P
authors.initials: RP
authors.lastname: McGeary
authors.affiliation: The University of Queensland, School of Pharmacy, Brisbane, Queensland 4072, Australia. Electronic address: b.ross1@uq.edu.au.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Ross
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D001921:Brain / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005707:Gallic Acid / Q000494:pharmacology; D006801:Humans; D008670:Metals / Q000378:metabolism*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*
chemical_list: D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D016166:Free Radical Scavengers; D008670:Metals; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D005707:Gallic Acid; D002392:Catechin; C045651:epigallocatechin gallate; D003474:Curcumin
keywords: (−)-Epigallocatechin gallate (PubChem CID: 65064); Amyloid-beta peptide; Antioxidants; Caffeic acid (PubChem CID: 689043); Caffeine (PubChem CID: 2519); Curcumin (PubChem CID: 969516); Gallamide (PubChem CID: 69256); Gallic acid (PubChem CID: 370); Metal chelators; Polyphenols; Propyl gallate (PubChem CID: 4947); Resveratrol (PubChem CID: 445154); Vitamins; l-Ascorbic acid (PubChem CID: 54670067); α-Tocopherol (PubChem CID: 14985)