Flavonoids: structure-function and mechanisms of action and opportunities for drug development.

Flavonoids are polyphenolic phytochemicals produced in fruits, nuts and vegetables and dietary consumption of these structurally diverse compounds is associated with multiple health benefits including increased lifespan, decreased cardiovascular problems and low rates of metabolic diseases. Preclinical studies with individual flavonoids demonstrate that these compounds exhibit anti-inflammatory and anticancer activities and they enhance the immune system. Their effectiveness in both chemoprevention and chemotherapy is associated with their targeting of multiple genes/pathways including nuclear receptors, the aryl hydrocarbon receptor (AhR), kinases, receptor tyrosine kinases and G protein-coupled receptors. However, despite the remarkable preclinical activities of flavonoids, their clinical applications have been limited and this is due, in part, to problems in drug delivery and poor bioavailability and these problems are being addressed. Further improvements that will expand clinical applications of flavonoids include mechanism-based precision medicine approaches which will identify critical mechanisms of action of individual flavonoids with optimal activities that can be used in combination therapies.