The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Interaction between flavonoids and the blood–brain barrier: in vitro studies
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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“Rodent research indicated that the citrus flavonoids hesperetin and naringenin and their relevant metabolites had been shown in the brain after oral ingestion [52].”
From Flavonoid-rich orange juice intake and altered gut microbiome in young adults with depressive symptom: a randomized controlled study (2020) · cites this paper as [52]
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Cites
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Polyphenols: Food sources and bioavailability
Manach, C., Scalbert, A., Morand, C., Rémésy, C., & Jiménez, L. (2004) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/79.5.727 · Cited by 8,175
Halliwell, B., Rafter, J., & Jenner, A. (2005) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.1.268s · Cited by 711
Permeability Studies on In Vitro Blood–Brain Barrier Models: Physiology, Pathology, and Pharmacology
Deli, M. A., Ábrahám, C. S., Kataoka, Y., & Niwa, M. (2005) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-004-1377-8 · Cited by 666
Flavonoid permeability across an in situ model of the blood–brain barrier
Youdim, K. A., Qaiser, M. Z., Begley, D. J., Rice-Evans, C. A., & Abbott, N. J. (2003) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2003.11.023 · Cited by 605
Self-citationAnthocyanins in aged blueberry-fed rats are found centrally and may enhance memory
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Metadata
- 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)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2003-03-18
- Volume
- 85
- Issue
- 1
- Pages
- 180-192
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- 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
- 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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