The Evaluation of Efficacy of Pycnogenol® Fractions on Endothelial Dysfunction

S. Jankyova 1 , L. Hlavackova 2 , E. Kralova 1 , J. Slazneva 1 , V. Drobna 1 , P. Zuzik 1 , F. Drafi 1 , P. Mucaji 3 , and Eva Racanska 1
  • 1 Comenius University in Bratislava, Faculty of Pharmacy, Department of Pharmacology and Toxicology
  • 2 Comenius University in Bratislava, Faculty of Medicine, Institute of Pathological Anatomy
  • 3 Comenius University in Bratislava, Faculty of Pharmacy, Department of Pharmacognosy and Botany

The present study evaluates antihyperglycemic activity of fractionated Pycnogenol® and its ability to improve endothelial dysfunction in diabetic animals. The aim of this study was to isolate from Pycnogenol® mixture its active compounds and compare their efficacy on observed parameters. Pycnogenol® mixture was fractioned by re-extracting with petroleum ether, chloroform, ethyl acetate and butanol, subsequently. Pycnogenol® mixture and fractions (butanolic, water, ethyl acetate) were administered during 6 weeks to diabetic rats. Blood glucose levels were assessed from the arterio-venous blood at the beginning of experiment and at the end of experiment. Endothelial dysfunction was evaluated as the contractile responses to phenylephrine and acetylcholine. The amount of collagen I and III was assessed from thoracic aorta after picrosirius red staining. For the confirmation of the changes on molecular level, we determinated endothelial NO synthase (eNOS) and heat shock protein 90 (Hsp90) expression from left ventricle. Overall, the result suggest, that fractions are not so effective on observed parameters as Pycnogenol® mixture itself, indicating synergistic effect of the plant constituents.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • [1] Belcaro G et al. Investigation of Pycnogenol® in combination with coenzymeQ10 in heart failure patients (NYHA II/III). Panminerva Med. 2010;52(2 Suppl 1):21-5.

  • [2] Bozdag-Dundar O et al. Synthesis of hypoglycemic activity of some new flavone derivatives. 4th communications: 6 flavonyl- 2,4-thiazolidinediones. Arzneimittelforschung. 2001;51:623- 627.

  • [3] Bucala R, Tracey K., Cerami A. Advanced glycosylation products quench nitric oxide and mediate defective endotheliumdependent vasodilation in experimental diabetes. J Clin Invest. 1991;87:432-438.

  • [4] Cai H, Harrison, DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000;87(10):840-4.

  • [5] Cesarone MR et al. Improvement of diabetic microangiopathy with pycnogenol: A prospective, controlled study. Angiology. 2006;57(4):431-6.

  • [6] Cosentino F, Lüscher TF. Endothelial function in coronary artery disease. Cardiologia. 1997;42(12):1221-7.

  • [7] Chang KS, Stevens WC. Endothelium-dependent increase in vascular sensitivity to phenylephrine in long-term streptozotocin diabetic rat aorta. Br J Pharmacol. 1992;107(4):983–990.

  • [8] Chatterjeea A, Catravas JD. Endothelial nitric oxide (NO) and its pathophysiologic regulation. Vascular Pharmacology. 2008; 49(4-6):134-140.

  • [9] Cheynier V et al. Size separation of condensed tannins by normal phase high performance liquid chromatography. Methods Enzymol. 1998;299:178–184.

  • [10] Choudhary SK et al. Comprehensive Evaluation of Anti-hyperglycemic Activity of Fractionated Momordica charantia Seed Extract in Alloxan-Induced Diabetic Rats. Evid Based Complement Alternat Med. 2012; doi:10.1155/2012/293650

  • [11] Cosentino F et al. High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation. 1997;96:25.

  • [12] Davis BJ et al. Activation of the AMP-Activated Kinase by Antidiabetes Drug Metformin Stimulates Nitric Oxide Synthesis In Vivo by Promoting the Association of Heat Shock Protein 90 and Endothelial Nitric Oxide Synthase. Diabetes. 2006;55:496-505.

  • [13] Elrod JW et al. Cardiomyocyte-Specific Overexpression of NO Synthase- 3 Protects Against Myocardial Ischemia-Reperfusion Injury. Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1517- 1523.

  • [14] Fitzpatrick DF et al. Endothelium dependent vascular effects of Pycnogenol. Journal of cardiovascular pharmacology. 1998; 32:509–515.

  • [15] Hamden K et al. Combined vitamins (C and E) and insulin improve oxidative stress and pancreatic and hepatic injury in alloxan diabetic rats. Biomed Pharmacother. 2009;63(2):95-9.

  • [16] Hlavačková L et al. The Effect of Indapamide on Development of Myocardial Hypertrophy and Fibrosis in L-NAME-Induced Hypertension in Rat. Physiol. Res. 2011;60:845-852.

  • [17] Jankyova S et al. Glucose and blood pressure lowering effects of Pycnogenol® are inefficient to prevent prolongation of QT interval in experimental diabetic cardiomyopathy. Pathol Res Pract. 2012;208(8):452-7.

  • [18] Jankyova S et al. Pycnogenol efficiency on glycaemia, motor nerve conduction velocity and markers of oxidative stress in mild type diabetes in rats. Phytother Res. 2009;23(8):1169-74.

  • [19] Jay D, Hitomi H, Griendling KK. Oxidative stress and diabetic cardiovascular complications. Free radical Biology &Medicine. 2006;40:183-192.

  • [20] Kasiviswanath R, Ramesh A, Kumar KE. Hypoglycemic and antihyperglycemic effect of Gmelina asiatica LINN. in normal and in alloxan induced diabetic rats. Biol Pharm Bull. 2005;28(4):729-32.

  • [21] Klimas J et al. Pycnogenol improves left ventricular function in streptozotocin-induced diabetic cardiomyopathy in rats. Phytother Res. 2010;24(7):969-74.

  • [22] Kolacek M et al. Effect of natural polyphenols, pycnogenol® on superoxide dismutase and nitric oxide synthase in diabetic rats. Prague Med Rep. 2010;111(4):279-88.

  • [23] Krenek P et al. Increased expression of endothelial nitric oxide synthase and caveolin-1 in the aorta of rats with isoproterenol- induced cardiac hypertrophy. Can J Physiol Pharmacol. 2006;84(12):1245-50.

  • [24] Lin KY et al. Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation. 2002;106:987.

  • [25] Lin LY et al. Up-regulation of the association between heat shock protein 90 and endothelial nitric oxide synthase prevents high glucose-induced apoptosis in human endothelial cells. J Cell Biochem. 2005;94:194–201.

  • [26] Liu X, Zhou HJ, Rohdewald P. French Maritime Pine Bark Extract Pycnogenol Dose-Dependently Lowers Glucose in Type 2 diabetic Patients. Diabetes Care. 2004;27:893-896.

  • [27] Maiti R, Das UK, Ghosh D. Attenuation of hyperlycemia and hyperlipidemia in streptozotocin induced diabetic rats by aqueous extract of seed of Tarmarindus indica. Biol Pharm Bull. 2005;28:1172-1176.

  • [28] Maritim A, Sanders RA, Watkins JBIII. Oxidative stress and diabetic complications: A review. J Biochem Mol Toxicol. 2003;17:24-48.

  • [29] Packer L et al. Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, pycnogenol. Free radical biology & medicine. 1999;27:704-724.

  • [30] Parveen K et al. Protective effects of Pycnogenol on hyperglycemia- induced oxidative damage in the liver of type 2 diabetic rats. Chem Biol Interact. 2010;186(2):219-27.

  • [31] Pieper GM et al. Reversal by L-arginine of a dysfunctional arginine/ nitric oxide pathway in the endothelium of the genetic diabetic BB rat. Diabetologia. 1997;40:910.

  • [32] Rosei EA, Rizzoni D. Small artery remodelling in diabetes. J Cell Mol Med. 2010;14(5):1030-6.

  • [33] Ryan EA, Pick ME, Marceau C. Use of alternative medicines in diabetes mellitus. Diabetic Medicine. 2001;18(3):242–245.

  • [34] Schäfer A, Högger P. Oligomeric procyanidins of French maritime pine bark extract (Pycnogenol) effectively inhibit alpha-glucosidase. Diabetes Res Clin Pract. 2007;77(1):41-6.

  • [35] Sekar, D, Sivagnanam K, Subramanian S. Antidiabetic activity of Momordica charantia seeds on streptozotocin induced diabetic rats. Pharmazie. 2004;60:383–387.

  • [36] Srinivasan S et al. Hyperglycaemia-induced superoxide production decreases eNOS expression via AP-1 activation in aortic endothelial cells. Diabetologia. 2004;47:1727.

  • [37] Stuard S. et al. Kidney function in metabolic syndrome may be improved with Pycnogenol®. Panminerva Med. 2010;52(2 Suppl 1):27-32.

  • [38] Virgili F, Kim D, Packer L. Procyanidins extracted from pine bark protect α-tocopherol in ECV 304 endothelial cells challenged by activated RAW 264.7 macrophages: role of nitric oxide and peroxynitrite. FEBS letters. 1998; 431(3):315-318.

  • [39] Wang Y, Marsden PA. Nitric oxide synthases: gene structure and regulation. Adv. Pharmacol. 1995;34:71–90.

  • [40] Zibadi S et al. Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation. Nutrition Research. 2008; 28(5): 315-320.


Journal + Issues