Flavonoid metabolites transport across a human BBB model

• Published in: Food chemistry 2014-04, Vol.149, p.190-196
• Main Authors: Faria, Ana, Meireles, Manuela, Fernandes, Iva, Santos-Buelga, Celestino, Gonzalez-Manzano, Susana, Dueñas, Montserrat, de Freitas, Victor, Mateus, Nuno, Calhau, Conceição
• Format: Article
• Language: English
• Subjects: Anthocyanins; Biological and medical sciences; Biological Transport; Blood-brain barrier; Blood-Brain Barrier - enzymology; Blood-Brain Barrier - metabolism; Cell Line; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Flavanoids; Flavonoids - pharmacokinetics; Flavonoids metabolites; Fundamental and applied biological sciences. Psychology; hCMEC/D3 cells; Humans; Kinetics; Models, Biological; Phosphoric Monoester Hydrolases - metabolism; Phosphorylation; Transport; Vertebrates: nervous system and sense organs
• ISSN: 0308-8146; 1873-7072
• DOI: 10.1016/j.foodchem.2013.10.095

•Flavonoid metabolites crossed the hBBB model in a higher rate than unconjugated compounds.•Anthocyanins and metabolites crossed hBBB cells in a lipophilicity-dependent way.•Quercetin transport appears to be modulated by phosphatase modulators.•No further biotransformation of the metabolites was found after cell incubation. This study aimed to evaluate the transmembrane transport of different flavonoids (flavan-3-ols, anthocyanins and flavonols) and some of their metabolites (methylated and conjugated with glucuronic acid) across hCMEC/D3 cells (a blood–brain barrier (BBB) model). Further metabolism of the tested compounds was assayed and their transport modulated in an attempt to elucidate the mechanisms behind this process. The transport across hCMEC/D3 cells was monitored in basolateral media at 1, 3 and 18h by HPLC-DAD/MS. All the flavonoids and their metabolites were transported across hCMEC/D3 cells in a time-dependent manner. In general, the metabolites showed higher transport efficiency than the native flavonoid. No further biotransformation of the metabolites was found as consequence of cellular metabolism. Anthocyanins and their metabolites crossed this BBB cell model in a lipophilicity-dependent way. Quercetin transport was influenced by phosphatase modulators, suggesting a phosphorylation/dephosphorylation regulation mechanism. Overall, this work suggests that flavonoids are capable of crossing the BBB and reaching the central nervous system.