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Original Research Communication |
1 From the Vascular Biology Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston.
Background: Flavonoids may exert their health benefit in cardiovascular disease by modulating monocyte adhesion in the inflammatory process of atherosclerosis. Most in vitro studies used forms of flavonoids present in food rather than forms that appear in plasma after ingestion.
Objectives: We tested the effects of plasma metabolites of (+)-catechin and quercetin on the modulation of monocyte adhesion to human aortic endothelial cells (HAEC) and on the production of reactive oxygen species (ROS).
Design: Plasma extracts of flavonoid metabolites were prepared after intragastric administration of pure compounds to rats. The plasma preparations contained sulfate or glucuronide conjugates or both and methylated forms. We measured adhesion of U937 monocytic cells to HAEC and the production of ROS in HAEC when cells were pretreated with either pure compounds or plasma extracts from control or treated rats. Adhesion assays were performed with HAEC stimulated with interleukin (IL)-1ß or U937 cells activated with phorbol myristyl acetate; ROS were measured after challenging HAEC with IL-1ß or hydrogen peroxide.
Results: Pretreatment of HAEC with (+)-catechin metabolites inhibited U937 cell adhesion to IL-1ßstimulated cells, whereas pretreatment with intact (+)-catechin had no effect. Generation of ROS in hydrogen peroxidestimulated HAEC was inhibited by (+)-catechin, its metabolites, and control plasma extract, whereas ROS generation in IL-1ßstimulated HAEC was inhibited by (+)-catechin metabolites only. In contrast, quercetin inhibited U937 cell adhesion to IL-1ßstimulated HAEC, whereas its metabolites were not effective.
Conclusions: Metabolic conversion of flavonoids such as (+)-catechin and quercetin modifies the flavonoids' biological activity. Metabolites of flavonoids, rather than their intact forms, may contribute to the reported effects of flavonoids on reducing the risk of cardiovascular disease.
Key Words: Flavonoid metabolites monocyte endothelium endothelial cell reactive oxygen species rats cardiovascular disease
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