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. 2010 Feb 8;15(2):234–241. doi: 10.2478/s11658-010-0006-4

Flavonoid transport across RBE4 cells: A blood-brain barrier model

Ana Faria 1,2,✉, Diogo Pestana 1, Diana Teixeira 1, Joana Azevedo 2, Victor De Freitas 2, Nuno Mateus 2, Conceição Calhau 1
PMCID: PMC6275689  PMID: 20140760

Abstract

There is a growing interest in dietary therapeutic strategies to combat oxidative stress-induced damage to the Central Nervous System (CNS), which is associated with a number of pathophysiological processes, including Alzheimer’s and Parkinson’s diseases and cerebrovascular diseases. Identifying the mechanisms associated with phenolic neuroprotection has been delayed by the lack of information concerning the ability of these compounds to enter the CNS. The aim of this study was to evaluate the transmembrane transport of flavonoids across RBE-4 cells (an immortalized cell line of rat cerebral capillary endothelial cells) and the effect of ethanol on this transport. The detection and quantification of all of the phenolic compounds in the studied samples (basolateral media) was performed using a HPLC-DAD (Diode Array Detector). All of the tested flavonoids (catechin, quercetin and cyanidin-3-glucoside) passed across the RBE-4 cells in a time-dependent manner. This transport was not influenced by the presence of 0.1% ethanol. In conclusion, the tested flavonoids were capable of crossing this blood-brain barrier model.

Key words: Anthocyanin, Blood-brain barrier, Flavonol, 3-flavanol, RBE4, Transport

Full Text

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Abbreviations used

BBB

blood-brain barrier

CNS

central nervous system

GLUT1

facilitative glucose transporter

RBE4

rat brain endothelial cell

References

  • 1.Hollman P.C., Katan M.B. Dietary flavonoids: intake, health effects and bioavailability. Food Chem. Toxicol. 1999;37:937–942. doi: 10.1016/s0278-6915(99)00079-4. [DOI] [PubMed] [Google Scholar]
  • 2.Van Duyn M.A., Pivonka E. Overview of the health benefits of fruit and vegetable consumption for the dietetics professional: selected literature. J. Am. Diet. Assoc. 2000;100:1511–1521. doi: 10.1016/S0002-8223(00)00420-X. [DOI] [PubMed] [Google Scholar]
  • 3.Hu J.P., Calomme M., Lasure A., De Bruyne T., Pieters L., Vlietinck A., Vanden Berghe D.A. Structure-activity relationship of flavonoids with superoxide scavenging activity. Biol. Trace Elem. Res. 1995;47:327–331. doi: 10.1007/BF02790134. [DOI] [PubMed] [Google Scholar]
  • 4.Rice-Evans C.A., Miller N.J., Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic. Biol. Med. 1996;20:933–956. doi: 10.1016/0891-5849(95)02227-9. [DOI] [PubMed] [Google Scholar]
  • 5.Aquilano K., Baldelli S., Rotilio G., Ciriolo M.R. Role of nitric oxide synthases in Parkinson’s disease: a review on the antioxidant and anti-inflammatory activity of polyphenols. Neurochem. Res. 2008;33:2416–2426. doi: 10.1007/s11064-008-9697-6. [DOI] [PubMed] [Google Scholar]
  • 6.Singh M., Arseneault M., Sanderson T., Murthy V., Ramassamy C. Challenges for research on polyphenols from foods in Alzheimer’s disease: bioavailability, metabolism, and cellular and molecular mechanisms. J. Agric. Food Chem. 2008;56:4855–4873. doi: 10.1021/jf0735073. [DOI] [PubMed] [Google Scholar]
  • 7.Hertog M.G., Hollman P.C., Katan M.B., Kromhout D. Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. Nutr. Cancer. 1993;20:21–29. doi: 10.1080/01635589309514267. [DOI] [PubMed] [Google Scholar]
  • 8.Hertog M.G.L., Hollman P.C.H., Katan M.B. Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in The Netherlands. J. Agric. Food Chem. 1992;40:2379–2383. [Google Scholar]
  • 9.Lee M.J., Wang Z.Y., Li H., Chen L., Sun Y., Gobbo S., Balentine D.A., Yang C.S. Analysis of plasma and urinary tea polyphenols in human subjects. Cancer Epidemiol. Biomarkers Prev. 1995;4:393–399. [PubMed] [Google Scholar]
  • 10.Yang G.Y., Liu Z., Seril D.N., Liao J., Ding W., Kim S., Bondoc F., Yang C.S. Black tea constituents, theaflavins, inhibit 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. Carcinogenesis. 1997;18:2361–2365. doi: 10.1093/carcin/18.12.2361. [DOI] [PubMed] [Google Scholar]
  • 11.Frankel E.N., Waterhouse A.L., Teissedre P.L. Principal phenolic phytochemicals in selected California wines and their antioxidant activity in inhibiting oxidation of human low-density lipoproteins. J. Agric. Food Chem. 1995;43:890–894. [Google Scholar]
  • 12.Arts I.C.W., Hollman P.C.H., Kromhout D. Chocolate as a source of tea flavonoids. Lancet. 1999;354:488–488. doi: 10.1016/S0140-6736(99)02267-9. [DOI] [PubMed] [Google Scholar]
  • 13.Oliveira J., de Freitas V., Silva A.M.S., Mateus N. Reaction between hydroxycinnamic acids and anthocyanin-pyruvic acid adducts yielding new portisins. J. Agric. Food Chem. 2007;55:6349–6356. doi: 10.1021/jf070968f. [DOI] [PubMed] [Google Scholar]
  • 14.Sousa C., Mateus N., Silva A.M.S., Gonzalez-Paramas A.M., Santos-Buelga C., de Freitas V. Structural and chromatic characterization of a new malvidin 3-glucoside-vanillyl-catechin pigment. Food Chem. 2007;102:1344–1351. [Google Scholar]
  • 15.Yi W., Akoh C.C., Fischer J., Krewer G. Absorption of anthocyanins from blueberry extracts by caco-2 human intestinal cell monolayers. J. Agric. Food Chem. 2006;54:5651–5658. doi: 10.1021/jf0531959. [DOI] [PubMed] [Google Scholar]
  • 16.Lau F.C., Shukitt-Hale B., Joseph J.A. Oxidative stress and age-related neurodegeneration. Boca Raton: Crc Press-Taylor & Francis Group; 2006. Age-related neuronal and behavioral deficits are improved by polyphenol-rich blueberry supplementation; pp. 373–393. [Google Scholar]
  • 17.Davalos A., Castilla P., Gomez-Cordoves C., Bartolome B. Quercetin is bioavailable from a single ingestion of grape juice. Int. J. Food Sci. Nutr. 2006;57:391–398. doi: 10.1080/09637480600858662. [DOI] [PubMed] [Google Scholar]
  • 18.Manach C., Williamson G., Morand C., Scalbert A., Remesy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am. J. Clin. Nutr. 2005;81:230S–242S. doi: 10.1093/ajcn/81.1.230S. [DOI] [PubMed] [Google Scholar]
  • 19.Mullen W., Edwards C.A., Crozier A. Absorption, excretion and metabolite profiling of methyl-, glucuronyl-, glucosyl- and sulphoconjugates of quercetin in human plasma and urine after ingestion of onions. Br. J. Nutr. 2006;96:107–116. doi: 10.1079/bjn20061809. [DOI] [PubMed] [Google Scholar]
  • 20.Mazza G., Kay C.D., Cottrell T., Holub B.J. Absorption of anthocyanins from blueberries and serum antioxidant status in human subjects. J. Agric. Food Chem. 2002;50:7731–7737. doi: 10.1021/jf020690l. [DOI] [PubMed] [Google Scholar]
  • 21.Youdim K.A., Dobbie M.S., Kuhnle G., Proteggente A.R., Abbott N.J., Rice-Evans C. Interaction between flavonoids and the blood-brain barrier: in vitro studies. J. Neurochem. 2003;85:180–192. doi: 10.1046/j.1471-4159.2003.01652.x. [DOI] [PubMed] [Google Scholar]
  • 22.Regina A., Roux F., Revest P.A. Glucose transport in immortalized rat brain capillary endothelial cells in vitro: transport activity and GLUT1 expression. Biochim. Biophys. Acta. 1997;1335:135–143. doi: 10.1016/s0304-4165(96)00131-6. [DOI] [PubMed] [Google Scholar]
  • 23.Faria A., Pestana D., Azevedo J., Martel F., de Freitas V., Azevedo I., Mateus N., Calhau C. Absorption of anthocyanins through intestinal epithelial cells - Putative involvement of GLUT2. Mol. Nutr. Food Res. 2009;53:1–8. doi: 10.1002/mnfr.200900007. [DOI] [PubMed] [Google Scholar]
  • 24.Youdim K.A., Hale B.S., Joseph J.A. Flavonoids and the brain: interactions at the blood-brain barrier and their physiological effects on the central nervous system. Free Radic. Biol. Med. 2004;37:1683–1693. doi: 10.1016/j.freeradbiomed.2004.08.002. [DOI] [PubMed] [Google Scholar]
  • 25.Dragoni S., Gee J., Bennett R., Valoti M., Sgaragli G. Red wine alcohol promotes quercetin absorption and directs its metabolism towards isorhamnetin and tamarixetin in rat intestine in vitro. Br. J. Pharmacol. 2006;147:765–771. doi: 10.1038/sj.bjp.0706662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Assuncao M., Santos-Marques M.J., de Freitas V., Carvalho F., Andrade J.P., Lukoyanov N.V., Paula-Barbosa M.M. Red wine antioxidants protect hippocampal neurons against ethanol-induced damage: a biochemical, morphological and behavioral study. Neuroscience. 2007;146:1581–1592. doi: 10.1016/j.neuroscience.2007.03.040. [DOI] [PubMed] [Google Scholar]
  • 27.Papandreou M.A., Dimakopoulou A., Linardaki Z.I., Cordopatis P., Klimis-Zacas D., Margarity M., Lamari F.N. Effect of a polyphenolrich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity. Behav. Brain Res. 2009;198:352–358. doi: 10.1016/j.bbr.2008.11.013. [DOI] [PubMed] [Google Scholar]

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