Proanthocyanidins from Vitis vinifera inhibit oxidative stress-induced vascular impairment in pulmonary arteries from diabetic rats

Phytomedicine. 2017 Feb 15;25:39-44. doi: 10.1016/j.phymed.2016.12.015. Epub 2016 Dec 23.


Background: Vitis vinifera L. (grape seed extract) is a natural source of proanthocyanidins with antioxidant and free radical-scavenging activities.

Hypothesis: Grape seed extract supplementation may prevent vascular endothelium impairment associated with diabetes mellitus in rat pulmonary artery.

Study design: We evaluated endothelial function of rat pulmonary artery ex-vivo at the intermediate stage (4 weeks) of streptozotocin (STZ)-induced diabetes mellitus. We also evaluated the protective effect of grape seed extract administered daily, beginning the day after diabetes induction, or 15 days after diabetes induction, until the day of sacrifice. In addition, we compared the effect of grape seed extract supplementation with that of vitamin C.

Methods: Rats were made diabetic with streptozotocin (STZ, 65mg/kg i.v.). Thirty days later rats were sacrificed and pulmonary vessels reactivity and endothelial function compared to that of age-matched healthy animals.

Results: Concentration-response curves to ACh, NE, sodium nitroprusside (NO donor), but not to histamine and iloprost (prostacyclin analog), were significantly altered 4 weeks after STZ-injection. Antioxidant supplementation (3mg/kg/day) with either vitamin C or grape seed extract, starting the day after diabetes induction, significantly improved vasodilation to ACh and SNP. Norepinephrine-induced contractions were preserved by grape seed extract, but not vitamin C supplementation. Conversely, vitamin C but not grape seed extract showed beneficial effects contrasting the loss of body weight in diabetic animals. Abnormal vascular function was not reversed when antioxidant supplementations were postponed 15 days after the induction of diabetes.

Conclusions: This study provides scientific support for the therapeutic potential of an antioxidant therapy in endothelial impairment associated with diabetes. A daily supplementation of grape seed proanthocyanidins and/or vitamin C given at the earlier stage of disease may have a complementary role in the pharmacological therapy of diabetes and pulmonary vascular dysfunction.

Keywords: Antioxidant treatment; Diabetes; Oxidative stress; Proanthocyanidins; Pulmonary vascular impairment.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Ascorbic Acid / pharmacology
  • Diabetes Complications / drug therapy
  • Diabetes Complications / metabolism
  • Diabetes Complications / pathology*
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology*
  • Dietary Supplements
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Grape Seed Extract / pharmacology*
  • Grape Seed Extract / therapeutic use
  • Male
  • Nitric Oxide Donors / pharmacology
  • Nitroprusside / pharmacology
  • Oxidative Stress / drug effects*
  • Phytotherapy
  • Proanthocyanidins / pharmacology*
  • Proanthocyanidins / therapeutic use
  • Pulmonary Artery / drug effects*
  • Pulmonary Artery / metabolism
  • Pulmonary Artery / pathology
  • Rats, Sprague-Dawley
  • Vasodilation / drug effects
  • Vitis / chemistry*


  • Antioxidants
  • Grape Seed Extract
  • Grape Seed Proanthocyanidins
  • Nitric Oxide Donors
  • Proanthocyanidins
  • Nitroprusside
  • Ascorbic Acid