title: Bioactive polyphenols and cardiovascular disease: chemical antagonists, pharmacological agents or xenobiotics that drive an adaptive response?
abstract: Polyphenols are widely regarded to have a wide range of health-promoting qualities, including beneficial effects on cardiovascular disease. Historically, the benefits have been linked to their well-recognized powerful antioxidant activity. However, the concept that the beneficial effects are attributable to direct antioxidant activity in vivo does not pay sufficient heed to the fact that polyphenols degrade rapidly, are poorly absorbed and rapidly metabolized, resulting in very low bioavailability. This review explores alternative mechanisms by which polyphenols, or their metabolites, exert biological activity via mechanisms that can be activated by physiologically relevant concentrations. Evidence is presented to support the action of phenolic derivatives on receptors and signalling pathways to induce adaptive responses that drive changes in endogenous antioxidant, antiplatelet, vasodilatory and anti-inflammatory effects. The implications are that in vitro antioxidant measures as predictors of polyphenol protective activity in vivo hold little relevance and that closer attention needs to be paid to bioavailable metabolites to understand the mode of action of these diet-derived components.
  
  
  
  This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.
authors.affiliation: Department of Diabetes and Cardiovascular Science, University of the Highlands and Islands, Centre for Health Science, Inverness, UK.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Goszcz
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK.
authors.forename: Garry G
authors.initials: GG
authors.lastname: Duthie
authors.affiliation: The James Hutton Institute, Dundee, UK.|School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Stewart
authors.affiliation: Department of Diabetes and Cardiovascular Science, University of the Highlands and Islands, Centre for Health Science, Inverness, UK.|Cardiology Unit, Raigmore Hospital, Inverness, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Leslie
authors.affiliation: Department of Diabetes and Cardiovascular Science, University of the Highlands and Islands, Centre for Health Science, Inverness, UK.
authors.forename: Ian L
authors.initials: IL
authors.lastname: Megson
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D004032:Diet; D019587:Dietary Supplements; D006801:Humans; D059808:Polyphenols / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D059808:Polyphenols