Effect of plasma metabolites of (+)-catechin and quercetin on monocyte adhesion to human aortic endothelial cells

Background: Flavonoids may exert their health benefit in cardiovascular dis ease by modulating monocyte adhesion in the inflammatory process of atheros clerosis. Most in vitro studies used forms of flavonoids present in food ra ther 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 endotheli al cells (HAEC) and on the production of reactive oxygen species (ROS). Design: Plasma extracts of flavonoid metabolites were prepared after intrag astric administration of pure compounds to rats. The plasma preparations co ntained 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 ex tracts from control or treated rats. Adhesion assays were performed with HA EC stimulated with interleukin (IL)-1 beta or U937 cells activated with pho rbol myristyl acetate; ROS were measured after challenging HAEC with IL-1 b eta or hydrogen peroxide. Results: Pretreatment of HAEC with (+)-catechin metabolites inhibited U937 cell adhesion to IL-1 beta -stimulated cells, whereas pretreatment with int act (+)-catechin had no effect. Generation of ROS in hydrogen peroxide-stim ulated HAEC was inhibited by (+)-catechin, its metabolites, and control pla sma extract, whereas ROS generation in ll,-1 beta -stimulated HAEC was inhi bited by (+)-catechin metabolites only. In contrast, quercetin inhibited U9 37 cell adhesion to IL-1 beta -stimulated HAEC, whereas its metabolites wer e not effective. Conclusions: Metabolic conversion of flavonoids such as (+)catechin and que rcetin modifies the flavonoids' biological activity. Metabolites of flavono ids, rather than their intact forms, may contribute to the reported effects of flavonoids on reducing the risk of cardiovascular disease.