Flavonoids are dietary components involved in decreasing oxidative stress in the vascular endothelium and thus the risk of endothelial dysfunction. However, their very low concentrations in plasma place this role in doubt. Thus, a relationship between the effective intracellular concentration of
flavonoids and their bioactivity needs to be assessed. This study examined the uptake of physiological concentrations of
cyanidin 3-glucoside, a widespread dietary
flavonoid, into human vascular endothelial cells. Furthermore, the involvement of the
membrane transporter bilitranslocase (TC No. 2.A.65.1.1) as the key underlying molecular mechanism for membrane transport was investigated by using purified anti-sequence
antibodies binding at the extracellular domain of the
protein. The experimental observations were carried out in isolated plasma membrane vesicles and intact endothelial cells from human endothelial cells (EA.hy926) and on an
ischemia-reperfusion model in isolated rat hearts.
Cyanidin 3-glucoside was transported via
bilitranslocase into endothelial cells, where it acted as a powerful intracellular
antioxidant and a
cardioprotective agent in the reperfusion phase after
ischemia. These findings suggest that dietary
flavonoids, despite their limited oral bioavailability and very low postabsorption plasma concentrations, may provide protection against oxidative stress-based
cardiovascular diseases.
Bilitranslocase, by mediating the cellular uptake of some
flavonoids, is thus a key factor in their protective activity on endothelial function.