Molecular Promiscuity of Plant Polyphenols in the Management of Age-Related Diseases: Far Beyond Their Antioxidant Properties

  • Enrique Barrajón-Catalán
  • María Herranz-López
  • Jorge Joven
  • Antonio Segura-Carretero
  • Carlos Alonso-Villaverde
  • Javier A. Menéndez
  • Vicente MicolEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 824)


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.


AMPK Cancer CCL2 Inflammation Obesity Polyphenols Synergy Xenohormesis 



Concepts expressed in this review have been discussed and approved by investigators from the Bioactive Food Component Platform which is currently being supported by competitive public grants from different Institutions (CD08/00283, SAF2009-11579, PI08/1381; PI08/1032, PI08/1175, PI011/130, P11-CTS-7625, GREIB.PT.2011.18, AGL2011-29857-C03-03, PROMETEO/2012/007, ACOMP/2013/093 CIBER CB12/03/30038).

Conflict of Interest Statement

The authors declare that there are no conflicts of interest.


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Enrique Barrajón-Catalán
    • 1
  • María Herranz-López
    • 1
  • Jorge Joven
    • 2
  • Antonio Segura-Carretero
    • 3
  • Carlos Alonso-Villaverde
    • 2
  • Javier A. Menéndez
    • 4
  • Vicente Micol
    • 1
    • 5
    Email author
  1. 1.Instituto de Biología Molecular y Celular (IBMC)Universidad Miguel HernándezElche, AlicanteSpain
  2. 2.Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i VirgiliReusSpain
  3. 3.Department of Analytical Chemistry, Faculty of SciencesUniversity of GranadaGranadaSpain
  4. 4.Head of the Traslation Research UnitCatalan Institute of Oncology and Biomedical Research InstituteGironaSpain
  5. 5.CIBER (CB12/03/30038, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III)Palma de MallorcaSpain

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