Red wine extract protects against oxidative-stress-induced endothelial senescence

Clin Sci (Lond). 2012 Oct;123(8):499-507. doi: 10.1042/CS20110679.


Red wine polyphenols may preserve endothelial function during aging. Endothelial cell senescence enhances age-related endothelial dysfunction. We investigated whether RWE (red wine extract) prevents oxidative-stress-induced senescence in HUVECs (human umbilical-vein endothelial cells). Senescence was induced by exposing HUVECs to tBHP (t-butylhydroperoxide), and quantified by senescence-associated β-galactosidase staining. RWE (0-50 μg/ml) concentration dependently decreased senescence by maximally 33±7.1%. RWE prevented the senescence-associated increase in p21 protein expression, inhibited tBHP-induced DNA damage of endothelial cells and induced relaxation of PCAs (porcine coronary arteries). Inhibition of SIRT1 (sirtuin 1) by sirtinol partially reversed the effect of RWE on tBHP-induced senescence, whereas both the NOS (nitric oxide synthase) inhibitor L-NMMA (NG-monomethyl-L-arginine) and the COX (cyclo-oxygenase) inhibitor indomethacin fully inhibited it. Furthermore, incubation of HUVECs with RWE increased eNOS (endothelial NOS) and COX-2 mRNA levels as well as phosphorylation of eNOS at Ser1177. RWE protects endothelial cells from tBHP-induced senescence. NO and COX-2, in addition to activation of SIRT1, play a critical role in the inhibition of senescence induction in human endothelial cells by RWE.

MeSH terms

  • Antioxidants / pharmacology
  • Cells, Cultured
  • Cellular Senescence / drug effects*
  • Cellular Senescence / physiology
  • DNA Damage / drug effects
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Plant Extracts / pharmacology
  • Polyphenols / pharmacology
  • Prostaglandins / metabolism
  • Resveratrol
  • Sirtuin 1 / physiology
  • Stilbenes / pharmacology
  • Wine / analysis*
  • beta-Galactosidase / metabolism
  • tert-Butylhydroperoxide / pharmacology


  • Antioxidants
  • Plant Extracts
  • Polyphenols
  • Prostaglandins
  • Stilbenes
  • tert-Butylhydroperoxide
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • beta-Galactosidase
  • SIRT1 protein, human
  • Sirtuin 1
  • Resveratrol