title: In vitro protective effects of colon-available extract of Camellia sinensis (tea) against hydrogen peroxide and beta-amyloid (Aβ((1-42))) induced cytotoxicity in differentiated PC12 cells.
abstract: There is mounting evidence that the deposition and aggregation of β-amyloid peptides (Aβ) in the brain play a significant role in the development and pathogenesis of Alzheimer's disease. There is further evidence that free radical species such as hydrogen peroxide (H(2)O(2)) mediate Aβ induced toxicity. Previous studies have demonstrated that green tea polyphenols possess neuroprotective properties through their ability to ameliorate oxidative stress induced by free radical species. Green tea polyphenols have also been shown to enhance cognition in various animal models of induced cognitive impairment. Upon ingestion, green tea polyphenols are metabolised and undergo bio-transformation which affects their bioavailability and therefore efficacy. In this study, a green tea extract was subjected to a simulated gastrointestinal digestion and a 'colon-available' extract (CAGTE) prepared and assessed for its potential protective effects against H(2)O(2) and Aβ((1-42)) induced cytotoxicity using differentiated PC12 cells (dPC12) as a model for neuronal cells. CAGTE represents green tea phytochemicals potentially available after upper gastrointestinal digestion. CAGTE which was depleted in flavan-3-ols, as shown by LC-MS analysis, protected dPC12 cells at concentration ranges of 0.3-10 μg/ml and 0.03-0.125 μg/ml for H(2)O(2) and Aβ((1-42)), induced cytotoxicity, respectively. At high concentrations, CAGTE exhibited direct anti-proliferative effects, in line with the reputed anti-cancer properties of green tea polyphenols. These results demonstrate that potentially bioavailable green tea metabolites are able to ameliorate both H(2)O(2) and Aβ((1-42)) induced cytotoxicity.
authors.affiliation: School of Agriculture, Food and Rural Development, Newcastle University, Newcastle upon Tyne, United Kingdom. e.j.okello@ncl.ac.uk
authors.forename: E J
authors.initials: EJ
authors.lastname: Okello
authors.forename: G J
authors.initials: GJ
authors.lastname: McDougall
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: C J
authors.initials: CJ
authors.lastname: Seal
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D028241:Camellia sinensis / Q000737:chemistry*; D005419:Flavonoids / Q000378:metabolism / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D010636:Phenols / Q000378:metabolism / Q000494:pharmacology; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D005419:Flavonoids; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; C075222:amyloid beta-protein (1-42); D006861:Hydrogen Peroxide