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Interaction between flavonoids and the blood–brain barrier: in vitro studies
Author(s) -
Youdim Kuresh A.,
Dobbie Michael S.,
Kuhnle Gunter,
Proteggente Anna R.,
Abbott N. Joan,
RiceEvans Catherine
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01652.x
Subject(s) - hesperetin , naringenin , blood–brain barrier , chemistry , in vivo , lipophilicity , biochemistry , in vitro , pharmacology , flavonoid , proanthocyanidin , biology , antioxidant , polyphenol , microbiology and biotechnology , neuroscience , central nervous system
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 ( P app ) 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.