Cited by 579Barrier Structure and Function StudiesFlavonoids in Medical ResearchPhytochemicals and Antioxidant Activities

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Interaction between flavonoids and the blood–brain barrier: in vitro studies

Youdim, Kuresh A., Dobbie, Michael S., Kuhnle, Gunter, Proteggente, Anna R., Abbott, N. Joan, Rice‐Evans, Catherine·2003·Journal of Neurochemistry

DOI 10.1046/j.1471-4159.2003.01652.x

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Abstract

There is considerable current interest in the neuroprotective effects of flavonoids. This study focuses on the potential for dietary flavonoids, and their known physiologically relevant metabolites, to enter the brain endothelium and cross the blood-brain barrier (BBB) using well-established in vitro models (brain endothelial cell lines and ECV304 monolayers co-cultured with C6 glioma cells). We report that the citrus flavonoids, hesperetin, naringenin and their relevant in vivo metabolites, as well as the dietary anthocyanins and in vivo forms, cyanidin-3-rutinoside and pelargonidin-3-glucoside, are taken up by two brain endothelial cell lines from mouse (b.END5) and rat (RBE4). In both cell types, uptake of hesperetin and naringenin was greatest, increasing significantly with time and as a function of concentration. In support of these observations we report for the first time high apparent permeability (Papp) of the citrus flavonoids, hesperetin and naringenin, across the in vitro BBB model (apical to basolateral) relative to their more polar glucuronidated conjugates, as well as those of epicatechin and its in vivo metabolites, the dietary anthocyanins and to specific phenolic acids derived from colonic biotransformation of flavonoids. The results demonstrate that flavonoids and some metabolites are able to traverse the BBB, and that the potential for permeation is consistent with compound lipophilicity.

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Authors: Youdim, K. A., Dobbie, M. S., Kuhnle, G., Proteggente, A. R., Abbott, N. J., & Rice‐Evans, C.
Affiliations: King's College London (GB)
Wolfson Medical Center (IL)
ORCID: Youdim, Kuresh A.
Dobbie, Michael S.
Kuhnle, Gunter
Abbott, N. Joan
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2003-03-18
Volume: 85
Issue: 1
Pages: 180-192
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1046/j.1471-4159.2003.01652.x
OpenAlex: W1824652155
Cited by: 578
References: 48
Citations by year: 2026: 26 · 2025: 29 · 2024: 30 · 2023: 44 · 2022: 32 · 2021: 32 · 2020: 34 · 2019: 37 · 2018: 20 · 2017: 29 · 2016: 33 · 2015: 41 · 2014: 26 · 2013: 27 · 2012: 21
FWCI: 7.78
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Research Portal (King's College London) (submittedVersion)
Funders: Wellcome Trust
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Pharmacology (medical) › Flavonoids in Medical Research
Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
Keywords: flavonoids, blood-brain barrier, brain endothelial cells, hesperetin, naringenin, citrus flavonoids, anthocyanins, cyanidin-3-rutinoside, pelargonidin-3-glucoside, flavonoid metabolites, apparent permeability, epicatechin, neuroprotection, lipophilicity, RBE4 cells
MeSH terms: Animals, Anthocyanins, Blood-Brain Barrier, Brain, Cell Line, Chromatography, High Pressure Liquid, Endothelium, Vascular, Flavonoids, Glioma, Hesperidin, Microcirculation, Mass Spectrometry, Coculture Techniques, Glucuronides, Flavanones, Mice, Rats

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Interaction between flavonoids and the blood–brain barrier: in vitro studies

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