British Journal of Nutrition

Review Article

Molecular mechanisms of the cardiovascular protective effects of polyphenols

Ramaroson Andriantsitohainaa1, Cyril Augera2, Thierry Chataigneaua2, Nelly Étienne-Sellouma2, Huige Lia3, M. Carmen Martíneza1, Valérie B. Schini-Kertha2 and Ismail Lahera4 c1

a1 LUNAM Université d'Angers, INSERM, U1063, Université d'Angers, Angers, France

a2 Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, UMR 7213 CNRS, Université de Strasbourg, Illkirch, France

a3 Department of Pharmacology, University Medical Center, Johannes Gutenberg University, D-55131 Mainz, Germany

a4 Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3


Epidemiological studies have reported a greater reduction in cardiovascular risk and metabolic disorders associated with diets rich in polyphenols. The antioxidant effects of polyphenols are attributed to the regulation of redox enzymes by reducing reactive oxygen species production from mitochondria, NADPH oxidases and uncoupled endothelial NO synthase in addition to also up-regulating multiple antioxidant enzymes. Although data supporting the effects of polyphenols in reducing oxidative stress are promising, several studies have suggested additional mechanisms in the health benefits of polyphenols. Polyphenols from red wine increase endothelial NO production leading to endothelium-dependent relaxation in conditions such as hypertension, stroke or the metabolic syndrome. Numerous molecules contained in fruits and vegetables can activate sirtuins to increase lifespan and silence metabolic and physiological disturbances associated with endothelial NO dysfunction. Although intracellular pathways involved in the endothelial effects of polyphenols are partially described, the molecular targets of these polyphenols are not completely elucidated. We review the novel aspects of polyphenols on several targets that could trigger the health benefits of polyphenols in conditions such as metabolic and cardiovascular disturbances.

(Received January 17 2012)

(Revised July 06 2012)

(Accepted July 06 2012)

(Online publication August 31 2012)

Key Words:

  • Polyphenols;
  • Cardiovascular system;
  • Nitric oxide;
  • Endothelium;
  • Free radicals;
  • Antioxidants


c1 Corresponding author: I. Laher, email


  Abbreviations: ACE, angiotensin-converting enzyme; AMPK, AMP-activated protein kinase; BH4, tetrahydrobiopterin; COX, cyclo-oxygenase; EDHF, endothelium-derived hyperpolarising factor; eNOS, endothelial NO synthase; ER, oestrogen receptor; GPx, glutathione peroxidase; HUVEC, human umbilical vein endothelial cells; KO, knockout; NOX, NADPH oxidase; Nrf2, nuclear factor E2-related factor-2; PGC, PPARγ coactivator; ROS, reactive oxygen species; SHR, spontaneously hypertensive rats; siRNA, small-interfering RNA; SIRT1, sirtuin 1; SOD, superoxide dismutase