Uptake and metabolism of (-)-epicatechin in endothelial cells.
Accumulating evidence suggest that diets rich in cocoa flavanols may have beneficial effects on cardiovascular health. The major cocoa flavanol monomer, (-)-epicatechin (EC), is readily absorbed and circulates primarily as glucuronidated, sulfated, and O-methylated metabolites in human plasma. However, cellular metabolism, for example in endothelial cells, is less well defined. In the present study we detail the uptake and cellular metabolism of EC and its major in vivo metabolites, (-)-epicatechin-3'-β-D-glucuronide (E3G), (-)-epicatechin-3'-sulfate (E3S), 3'-O-methyl-(-)-epicatechin-5-sulfate (3ME5S), and 3'-O-methyl-(-)-epicatechin-7-sulfate (3ME7S) in human endothelial (HUVEC), liver (HepG2) and intestinal epithelial cells (Caco-2 monolayer). Our results indicate that EC associates with HUVECs, leading to its intracellular metabolism to 3ME7G and 3ME7S. In contrast, none of the metabolites were taken up by the cells. The metabolic rate and pattern of metabolism in HUVECs was similar to that observed in HepG2 cells, whilst in Caco-2 cells EC was metabolized to E3G, 3ME5G, 3ME7G, 4ME5G, 4ME7G and 3ME7S. Our data support the notion that endothelial cells may contribute significantly to EC metabolism. However, major human circulating metabolites are not accounted for in these model systems underscoring that caution should be taken when drawing conclusions on in vivo flavanol metabolism from in vitro experiments.
Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Duesseldorf, D-40225 Dusseldorf, Germany; Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, RG2 6AP Reading, UK. Electronic address: ana.rodriguez-mateos@med.uni-duesseldorf.de.
Ana
A
Rodriguez-Mateos
Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, RG2 6AP Reading, UK; Department of Nutrition and Food Science-XaRTA, Faculty of Pharmacy, University of Barcelona, 08921 Barcelona, Spain.
Natalia
N
Toro-Funes
Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, RG2 6AP Reading, UK.
Tania
T
Cifuentes-Gomez
Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Duesseldorf, D-40225 Dusseldorf, Germany.
Miriam
M
Cortese-Krott
Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Duesseldorf, D-40225 Dusseldorf, Germany.
Christian
C
Heiss
Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, RG2 6AP Reading, UK.
Jeremy P E
JP
Spencer
D000042:Absorption; D001692:Biological Transport; D018938:Caco-2 Cells; D002392:Catechin / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans
D002392:Catechin
(−)-Epicatechin; Caco-2 monolayer; Endothelial cells; HUVEC; HepG2; Phase II metabolism; Uptake