Pycnogenol®, French Maritime Pine Bark Extract, Augments Endothelium-Dependent Vasodilation in Humans


Pycnogenol®, an extract of bark from the French maritime pine, Pinus pinaster Ait., consists of a concentrate of water-soluble polyphenols. Pycnogenol® contains the bioflavonoids catechin and taxifolin as well as phenolcarbonic acids. Antioxidants, such as bioflavonoids, enhance endothelial nitric oxide (NO) synthase expression and subsequent NO release from endothelial cells. The purpose of this study was to determine Pycnogenol®'s effects on endothelium-dependent vasodilation in humans. This was a double-blind, randomized, placebo and active drug study. We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, in healthy young men before and after 2 weeks of daily oral administration of Pycnogenol® (180 mg/day) (n=8) or placebo (n=8). FBF was measured by using strain-gauge plethysmography. Neither the placebo nor Pycnogenol® altered forearm or systemic hemodynamics. Pycnogenol®, but not placebo, augmented FBF response to ACh, from 13.1±7.0 to 18.5±4.0 mL/min per 100 mL tissue (p<0.05). SNP-stimulated vasodilation was similar before and after 2 weeks of treatment in the control and Pycnogenol® groups. The administration of NG-monomethyl-L-arginine, an NO synthase inhibitor, completely abolished Pycnogenol®-induced augmentation of the FBF response to ACh. These findings suggest that Pycnogenol® augments endothelium-dependent vasodilation by increasing in NO production. Pycnogenol® would be useful for treating various diseases whose pathogeneses involve endothelial dysfunction.


  1. 1

    Renaud S, Lorgeril M : Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992; 339: 1523–1526.

    CAS  Article  Google Scholar 

  2. 2

    Tunstall-Pedoe H, Kuulasmaa K, Mahonen M, et al: Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA project population. Monitoring trends and determinants in cardiovascular disease. Lancet 1999; 353: 1547–1557.

    CAS  Article  Google Scholar 

  3. 3

    Kuulasmaa K, Tunstall-Pedoe H, Dobson A, et al: Estimation of contribution of changes in classic risk factor to trends in coronary-event rates across the WHO MONICA Project populations. Lancet 2000; 355: 675–687.

    CAS  Article  Google Scholar 

  4. 4

    Ross R : Atherosclerosis—an inflammatory disease. N Engl J Med 1999; 340: 115–126.

    CAS  Article  Google Scholar 

  5. 5

    Perticone F, Ceravolo R, Pujia A, et al: Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation 2001; 104: 191–196.

    CAS  Article  Google Scholar 

  6. 6

    Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR Jr, Lerman A : Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 2000; 101: 948–954.

    CAS  Article  Google Scholar 

  7. 7

    Schachinger V, Britten MB, Zeiher AM : Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000; 101: 1899–1906.

    CAS  Article  Google Scholar 

  8. 8

    Schäfer A, Chovanova Z, Muchova J, et al: Inhibitor of COX-1 and COX-2 activity by plasma of human volunteers ingestion of French maritime pine bark extract (Pycnogenol®). Biomed Pharmacother 2005; 60: 5–9.

    Article  Google Scholar 

  9. 9

    Rohodewald P : A review of the French maritime pink bark extract (Pycnogenol®), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther 2002; 40: 158–168.

    Article  Google Scholar 

  10. 10

    Williamson G, Manach C : Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am J Clin Nutr 2005; 81 ( 1 Suppl): 243S–255S.

    CAS  Article  Google Scholar 

  11. 11

    Liu X, Wei J, Tan F, Zhou S, Wurthwein G, Rohdewald P : Antidiabetic effect of Pycnogenol® French maritime pine bark extract in patients with diabetes type II. Life Sci 2004; 75: 2505–2513.

    CAS  Article  Google Scholar 

  12. 12

    Panza JA, Quyyumi AA, Buhler FR Jr, Epstein SE : Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 1990; 323: 22–27.

    CAS  Article  Google Scholar 

  13. 13

    Higashi Y, Sasaki S, Kurisu S, et al: Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide. Circulation 1999; 100: 1194–1202.

    CAS  Article  Google Scholar 

  14. 14

    Friedewald WT, Levy RI, Fredrickson DS : Estimation of low density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.

    CAS  PubMed  Google Scholar 

  15. 15

    Fitzpatrick DF, Bing B, Rohdewald P : Endothelium-dependent vascular effects of Pycnogenol. J Cardiovasc Pharmacol 1998; 32: 509–515.

    CAS  Article  Google Scholar 

  16. 16

    Ying CJ, Xu JW, Yamori Y, et al: Tea polyphenols regulate nicotinamide adenine dinucleotide phosphate oxidase subunit expression and ameliorate angiotensin II–induced hyperpermeability in endothelial cells. Hypertens Res 2003; 26: 823–828.

    CAS  Article  Google Scholar 

  17. 17

    Higashi Y, Sasaki S, Nakagawa K, Matsuura H, Oshima T, Chayama K : Endothelial function and oxidative stress in renovascular hypertension. N Engl J Med 2002; 346: 1954–1962.

    CAS  Article  Google Scholar 

  18. 18

    Broere A, Van Den Meiracker AH, Boomsma F, Derkx FH, Man Ina'T Veld, Schalekamp MADH : Human renal and systemic hemodynamics, natriuretic, and neurohumoral responses to different doses of L-NMMA. Am J Physiol 1998; 275: F870–F877.

    CAS  Article  Google Scholar 

  19. 19

    Neishi Y, Mochizuki S, Miyasaka T, et al: Evaluation of bioavailability of nitric oxide in coronary circulation by direct measurement of plasma nitric oxide concentration. Proc Natl Acad Sci U S A 2005; 102: 11456–11461.

    CAS  Article  Google Scholar 

  20. 20

    Imanishi T, Kobayashi K, Kuroi A, Mochizuki S, Goto M, Yoshida K, Akasaka T : Effects of angiotensin II on NO bioavailability evaluated using a catheter-type NO sensor. Hypertension 2006; 48: 1058–1065.

    CAS  Article  Google Scholar 

  21. 21

    Packer L, Rimbach G, Virgili F : Antioxidant activity and biologic properties of procynamidin-rich extract from pine bark, Pycnogenol. Free Radic Biol Med 1999; 27: 704–724.

    CAS  Article  Google Scholar 

  22. 22

    Devaraj S, Vega-Lopez S, Kaul N, Schonlau F, Rohdewald P, Jialal I : Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile. Lipids 2002; 37: 931–934.

    CAS  Article  Google Scholar 

  23. 23

    Grimm T, Schafer A, Hogger P : Antioxidant activity and inhibition of matrix metalloproteinases by metabolites of maritime pine bark extract (Pycnogenol®). Free Radic Biol Med 2004; 36: 811–822.

    CAS  Article  Google Scholar 

  24. 24

    Goto C, Higashi Y, Kimura M, et al: Effect of deferent intensities of exercise on endothelium-dependent vasodilation in human. Role of endothelium-dependent nitric oxide and oxidative stress. Circulation 2003; 108: 530–535.

    Article  Google Scholar 

  25. 25

    Jitsuiki D, Higashi Y, Goto C, et al: Effect of edaravone, a novel free radical scavenger, on endothelium-dependent vasodilation in smokers. Am J Cardiol 2004; 94: 1070–1073.

    CAS  Article  Google Scholar 

  26. 26

    Maeda K, Yasunari K, Watanabe T, Nakamura M : Oxidative stress by peripheral blood mononuclear cells is increased in hypertensives with an extreme-dipper pattern and/or morning surge in blood pressure. Hypertens Res 2005; 28: 755–761.

    CAS  Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Yukihito Higashi.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Nishioka, K., Hidaka, T., Nakamura, S. et al. Pycnogenol®, French Maritime Pine Bark Extract, Augments Endothelium-Dependent Vasodilation in Humans. Hypertens Res 30, 775–780 (2007).

Download citation


  • endothelial function
  • nitric oxide
  • oxidative stress
  • Pycnogenol®

Further reading