Flavonoids are secondary plant metabolites that exert many physiological benefits against various
cellular dysfunction mechanisms. Although flavonoids have poor bioavailability, it is known that
they are able to improve endothelial health and thus reduce cardiac events. This conundrum has
been called the “flavonoid paradox”. In the present proposal, the mode of action of flavonoids
towards endothelial dysfunction, will be studied in order to unravel the flavonoid paradox. The
main hypothesis is that the pool of signaling molecules surrounding the endothelial cells, under
healthy and diseased conditions, will determine the bioactivity of the flavonoid. To demonstrate
this mechanism, a novel triple cell co-culture model will be developed in-house, which will be
validated by performing flavonoid bioactivity studies on tissue level. This project has the aim to
generate scientific evidence concerning the cause-effect relationship of flavonoid consumption
and improvement of endothelial health. This will have an enormous impact on the functional food
industry and will be a big support in EFSA health claim applications of flavonoid-rich products