Furthermore, our study strongly suggested that hesperidin, its major flavonoid, is causally linked to the observed beneficial effect of orange juice. These vascular protective effects of orange juice and the possible specific role of hesperidin in mediating these effects are in agreement with a Rapamycin 53123-88-9 recent prospective study that showed convincing results for an association between the dietary intake of flavanones and flavanone-rich foods and reduced risks of coronary heart diseases. Other clinical studies in healthy subjects have also shown that orange juice consumption reduced oxidative DNA damage and may prevent meal-induced oxidative and inflammatory stress in circulating blood mononuclear cells. The reduction of reactive oxygen species generation and NF-kB binding following orange juice intake could possibly be due to its flavonoid content, as suggested by in vitro results. In fact, these changes occurred when mononuclear cells were incubated with hesperetin, while fructose or ascorbic acid did not cause any change. Nevertheless, much remains to be done to advance the understanding of the mechanisms by which the orange juice and some of its constituents could exert protective health effects. Nevertheless, much work remains in order to advance our understanding of the mechanisms by which orange juice and some of its constituents could exert protective health effects. For some foods rich in flavonoids, such as tea or cocoa, the role of these bioactive compounds in vascular protection has been demonstrated in clinical trials, studies on animal models of atherosclerosis and in in vitro studies using vascular cells. Some of these studies have suggested that flavonoids could mediate vascular cell function through the modulation of gene expression and intracellular signaling pathways. In addition, recent findings from animal studies suggest that the actions of flavonoids are related to their capacity to interact with the cellular signaling cascades that regulate transcription factors and as a consequence, expression of genes and proteins. More recently, transcriptome analysis of aortas from mice fed naringin revealed that the anti-atherogenic effect of this grapefruit flavonoid might be linked to changes in gene expression that play a role in the preservation of the vascular wall. Few human studies have shown the potential use of gene expression profiling in blood leukocytes to study the effects of diet on gene expression modulation. It has been proposed that modulation of gene expression in these cells might be related to the various clinical and biochemical changes that occur during cardiovascular disease development. Nevertheless, the nutrigenomic impact of dietary flavonoids has not been extensively investigated. To our knowledge, only one recent study has examined the effect of quercetin supplementation on the human monocyte gene expression profile. In our study, cDNA microarrays were used to identify gene expression changes in the white blood cells of healthy human volunteers after chronic consumption of either orange juice or purified hesperidin.