title: Potential for brain accessibility and analysis of stability of selected flavonoids in relation to neuroprotection in vitro.
abstract: Natural food sources constitute a promising source of new compounds with neuroprotective properties, once they have the ability to reach the brain. Our aim was to evaluate the brain accessibility of quercetin, epigallocatechin gallate (EGCG) and cyanidin-3-glucoside (C3G) in relation to their neuroprotective capability. Primary cortical neuron cultures were exposed to oxidative insult in the absence and presence of the selected compounds, and neuroprotection was assessed through evaluation of apoptotic-like and necrotic-like cell death. The brain accessibility of selected compounds was assessed using an optimised human blood-brain barrier model. The blood-brain barrier model was crossed rapidly by EGCG and more slowly by C3G, but not by quercetin. EGCG protected against oxidation-induced neuronal necrotic-like cell death by ~40%, and apoptosis by ~30%. Both quercetin and C3G were less effective, since only the lowest quercetin concentration was protective, and C3G only prevented necrosis by ~37%. Quercetin, EGCG and C3G effectively inhibited α-synuclein fibrillation over the relevant timescale applied here. Overall, EGCG seems to be the most promising neuroprotective compound. Thus, inclusion of this polyphenol in the diet might provide an affordable means to reduce the impact of neurodegenerative diseases.
authors.affiliation: Department of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia. Electronic address: lea.pogacnik@bf.uni-lj.si.
authors.forename: Lea
authors.initials: L
authors.lastname: Pogačnik
authors.affiliation: Department of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Katja
authors.initials: K
authors.lastname: Pirc
authors.affiliation: Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; Department of Biochemistry and Human Biology (DBBH), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Palmela
authors.affiliation: Department of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Skrt
authors.affiliation: Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: Kwang S
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; Department of Biochemistry and Human Biology (DBBH), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Dora
authors.initials: D
authors.lastname: Brites
authors.affiliation: Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; Department of Biochemistry and Human Biology (DBBH), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Maria Alexandra
authors.initials: MA
authors.lastname: Brito
authors.affiliation: Department of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia; Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, CipKeBiP, Ljubljana, Slovenia.
authors.forename: Nataša Poklar
authors.initials: NP
authors.lastname: Ulrih
authors.affiliation: Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal; Department of Biochemistry and Human Biology (DBBH), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Rui F M
authors.initials: RF
authors.lastname: Silva
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000493:pharmacokinetics / Q000494:pharmacology; D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005960:Glucosides / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D009336:Necrosis / Q000188:drug therapy / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D055503:Protein Multimerization / Q000187:drug effects; D011794:Quercetin / Q000493:pharmacokinetics / Q000494:pharmacology; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D000975:Antioxidants; D005419:Flavonoids; D005960:Glucosides; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; C497604:SNCA protein, human; D051844:alpha-Synuclein; C462279:cyanidin-3-O-beta-glucopyranoside; D002392:Catechin; D011794:Quercetin; C045651:epigallocatechin gallate
keywords: Apoptosis; Blood–brain barrier; Flavonoids; Necrosis; Neuroprotection; α-synuclein fibrillation