The use of plant-derived
polyphenols for the management of diseases has been under debate in the last decades. Most studies have focused on the specific effects of
polyphenols on particular targets, while ignoring their pleiotropic character. The multitargeted character of
polyphenols, a plausible consequence of their molecular promiscuity, may suppose an opportunity to fight multifactorial diseases. Therefore, a wider perspective is urgently needed to elucidate whether their rational use as bioactive food components may be valid for the management of diseases. In this chapter, we discuss the most likely targets of
polyphenols that may account for their salutary effects from a global perspective. Among these targets, the modulation of signalling and energy-sensitive pathways, oxidative stress and
inflammation-related processes, mitochondrial functionality, epigenetic machinery,
histone acetylation and membrane-dependent processes play central roles in
polyphenols' mechanisms of action.Sufficient evidence on
polyphenols has accumulated for them to be considered a serious option for the management of
non-communicable diseases, such as
cancer and
obesity, as well as
infectious diseases. The remaining unresolved issues that must be seriously addressed are their bioavailability, metabolite detection, specific molecular targets, interactions and toxicity. The Xenohormesis hypothesis, which postulates that
polyphenols are the product of plant evolutive adaptation to stress and conferee their resistance to mammals, offers a reasonable explanation to justify the beneficial and non-toxic effects of plant mixtures, but do not fully meet expectations. Hence, future research must be supported by the use of complex polypharmacology approaches and synergic studies focused on the understanding of the pleiotropic effects of
polyphenols. Revisiting
polyphenol mechanisms of action with the help of these techniques may allow for the improvement of human health and wellness by using intelligent nutritional intervention.