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.
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.
Arch Biochem Biophys. 2014 Oct 1;559:17-23. doi: 10.1016/j.abb.2014.03.014. Epub 2014 Apr 6.
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.
越来越多的证据表明，富含可可黄烷醇的饮食可能对心血管健康有益。可可黄烷醇的主要单体（-）-表儿茶素（EC）易被吸收，并主要以葡糖醛酸化、硫酸化和 O-甲基化代谢物的形式循环存在于人血浆中。然而，细胞代谢，例如在内皮细胞中的代谢，定义得还不够清楚。在本研究中，我们详细描述了 EC 及其主要体内代谢物（-）-表儿茶素-3'-β-D-葡萄糖醛酸（E3G）、（-）-表儿茶素-3'-硫酸盐（E3S）、3'-O-甲基-（-）-表儿茶素-5-硫酸盐（3ME5S）和 3'-O-甲基-（-）-表儿茶素-7-硫酸盐（3ME7S）在人内皮细胞（HUVEC）、肝（HepG2）和肠上皮细胞（Caco-2 单层）中的摄取和细胞内代谢。我们的结果表明，EC 与 HUVEC 结合，导致其细胞内代谢为 3ME7G 和 3ME7S。相比之下，没有一种代谢物被细胞摄取。HUVEC 中代谢的速率和模式与在 HepG2 细胞中观察到的相似，而在 Caco-2 细胞中，EC 代谢为 E3G、3ME5G、3ME7G、4ME5G、4ME7G 和 3ME7S。我们的数据支持内皮细胞可能对 EC 代谢有重要贡献的观点。然而，这些模型系统中并未考虑到主要的人循环代谢物，这突出表明，从体外实验得出关于黄烷醇体内代谢的结论时应谨慎。
