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Life Extension Magazine August 2012

Pycnogenol®: Multi-Modal Defense Against Aging

By Janet Sarto


1. Packer L, Rimbach G, Virgili F. Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, Pycnogenol®. Free Radic Biol Med. 1999 Sep;27(5-6):704-24.

2. Rohdewald P. A review of the French maritime pine bark extract (Pycnogenol®), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther. 2002 Apr;40(4):158-68.

3. D’Andrea G. Pycnogenol®: a blend of procyanidins with multifaceted therapeutic applications? Fitoterapia. 2010 Oct;81(7):724-36.

4. Sivonova M, Waczulikova I, Kilanczyk E, et al. The effect of Pycnogenol® on the erythrocyte membrane fluidity. Gen Physiol Biophys. 2004 Mar;23(1):39-51.

5. Krizková L, Chovanová Z, Duracková Z, Krajcovic J. Antimutagenic in vitro activity of plant polyphenols: Pycnogenol® and Ginkgo biloba extract (EGb 761). Phytother Res. 2008 Mar;22(3):384-8.

6. Zibadi S, Rohdewald PJ, Park D, Watson RR. Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol® supplementation. Nutr Res. 2008 May;28(5):315-20.

7. Liu FJ, Zhang YX, Lau BH. Pycnogenol® enhances immune and haemopoietic functions in senescence-accelerated mice. Cell Mol Life Sci. 1998 Oct; 54(10):1168-72.

8. Sime S, Reeve VE. Protection from inflammation, immunosuppression and carcinogenesis induced by UV radiation in mice by topical Pycnogenol®. Photochem Photobiol. 2004 Feb;79(2):193-8.

9. Saliou C, Rimbach G, Moini H, et al. Solar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract. Free Radic Biol Med. 2001 Jan 15;30(2):154-60.

10. Rona C, Vailati F, Berardesca E. The cosmetic treatment of wrinkles. J Cosmet Dermatol. 2004 Jan;3(1):26-34.

11. Marini A, Grether-Beck S, Jaenicke T, et al. Pycnogenol® effects on skin elasticity and hydration coincide with increased gene expressions of collagen type I and hyaluronic acid synthase in women. Skin Pharmacol Physiol. 2012;25(2):86-92.

12. Tixier JM, Godeau G, Robert AM, Hornebeck W. Evidence by in vivo and in vitro studies that binding of Pycnogenol® to elastin affects its rate of degradation by elastases. Biochem Pharmacol. 1984 Dec 15;33(24):3933-9.

13. Cho HS, Lee MH, Lee JW, et al. Anti-wrinkling effects of the mixture of vitamin C, vitamin E, Pycnogenol® and evening primrose oil, and molecular mechanisms on hairless mouse skin caused by chronic ultraviolet B irradiation. Photodermatol Photoimmunol Photomed. 2007 Oct;23(5):155-62.

14. Segger D, Schonlau F. Supplementation with Evelle improves skin smoothness and elasticity in a double-blind, placebo-controlled study with 62 women. J Dermatolog Treat. 2004 Jul;15(4):222-6.

15. Ni Z, Mu Y, Gulati O. Treatment of melasma with Pycnogenol®. Phytother Res. 2002 Sep;16(6):567-71.

16. Cesarone MR, Belcaro G, Rohdewald P, et al. Rapid relief of signs/symptoms in chronic venous microangiopathy with Pycnogenol®: a prospective, controlled study. Angiology. 2006 Oct-Nov;57(5):569-76.

17. Cesarone MR, Belcaro G, Rohdewald P, et al. Comparison of Pycnogenol® and Daflon in treating chronic venous insufficiency: a prospective, controlled study. Clin Appl Thromb Hemost. 2006 Apr;12(2):205-12.

18. Available at: Accessed April 20, 2012.

19. Liu F, Lau BH, Peng Q, Shah V. Pycnogenol® protects vascular endothelial cells from beta-amyloid-induced injury. Biol Pharm Bull. 2000 Jun;23(6):735-7.

20. Spadea L, Balestrazzi E. Treatment of vascular retinopathies with Pycnogenol®. Phytother Res. 2001 May;15(3):219-23.

21. Liu X, Wei J, Tan F, Zhou S, Wurthwein G, Rohdewald P. Pycnogenol®, French maritime pine bark extract, improves endothelial function of hypertensive patients. Life Sci. 2004 Jan 2;74(7):855-62.

22. Belcaro G, Cesarone MR, Ricci A, et al. Control of edema in hypertensive subjects treated with calcium antagonist (nifedipine) or angiotensin-converting enzyme inhibitors with Pycnogenol®. Clin Appl Thromb Hemost. 2006 Oct;12(4):440-4.

23. Nishioka K, Hidaka T, Nakamura S, et al. Pycnogenol®, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans. Hypertens Res. 2007 Sep;30(9):775-80.

24. Enseleit F, Sudano I, Periat D, et al. Effects of Pycnogenol® on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. Eur Heart J. 2012 Jan 11.

25. Stanislavov R, Nikolova V, Rohdewald P. Improvement of erectile function with Prelox: a randomized, double-blind, placebo-controlled, crossover trial. Int J Impot Res. 2008 Mar-Apr;20(2):173-80.

26. Neves MF, Kasal DA, Cunha AR, Medeiros F. Vascular dysfunction as target organ damage in animal models of hypertension. Int J Hypertens. 2012. Epub 2012 Feb 14. 27. Nishioka K, Hidaka T, Nakamura S, et al. Pycnogenol®, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans. Hypertens Res. 2007 Sep;30(9):775-80.

28. Fitzpatrick DF, Bing B, Rohdewald P. Endothelium-dependent vascular effects of Pycnogenol®. J Cardiovasc Pharmacol. 1998 Oct;32(4):509-15.

29. Rezzani R, Porteri E, De Ciuceis C, et al. Effects of melatonin and Pycnogenol® on small artery structure and function in spontaneously hypertensive rats. Hypertension. 2010 Jun;55(6):1373-80.

30. Zibadi S, Yu Q, Rohdewald PJ, Larson DF, Watson RR. Impact of Pycnogenol® on cardiac extracellular matrix remodeling induced by L-NAME administration to old mice. Cardiovasc Toxicol. 2007;7(1):10-8.

31. Klimas J, Kmecova J, Jankyova S, et al. Pycnogenol® improves left ventricular function in streptozotocin-induced diabetic cardiomyopathy in rats. Phytother Res. 2010 Jul;24(7):969-74.

32. Araghi-Niknam M, Hosseini S, Larson D, Rohdewald P, Watson RR. Pine bark extract reduces platelet aggregation. Integr Med. 2000 Mar 21;2(2):73-7.

33. Nocun M, Ulicna O, Muchova J, Durackova Z, Watala C. French maritime pine bark extract Pycnogenol® reduces thromboxane generation in blood from diabetic male rats. Biomed Pharmacother. 2008 Mar;62(3):168-72.

34. Belcaro G, Cesarone MR, Rohdewald P, et al. Prevention of venous thrombosis and thrombophlebitis in long-haul flights with Pycnogenol®. Clin Appl Thromb Hemost. 2004 Oct;10(4):373-7.

35. Liu X, Zhou HJ, Rohdewald P. French maritime pine bark extract Pycnogenol® dose-dependently lowers glucose in type 2 diabetic patients. Diabetes Care. 2004 Mar;27(3):839.

36. Jankyova S, Kucera P, Goldenberg Z, et al. Pycnogenol® efficiency on glycaemia, motor nerve conduction velocity and markers of oxidative stress in mild type diabetes in rats. Phytother Res. 2009 Aug;23(8):1169-74.

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

38. Lee HH, Kim KJ, Lee OH, Lee BY. Effect of Pycnogenol® on glucose transport in mature 3T3-L1 adipocytes. Phytother Res. 2010 Aug;24(8):1242-9.

39. Iravani S, Zolfaghari B. Pharmaceutical and nutraceutical effects of Pinus pinaster bark extract. Res Pharm Sci. 2011 Jan;6(1):1-11.

40. Schonlau F, Rohdewald P. Pycnogenol® for diabetic retinopathy. A review. Int Ophthalmol. 2001;24(3):161-71.

41. Steigerwalt R, Belcaro G, Cesarone MR, et al. Pycnogenol® improves microcirculation, retinal edema, and visual acuity in early diabetic retinopathy. J Ocul Pharmacol Ther. 2009 Dec;25(6):537-40.

42. Belcaro G, Cesarone MR, Errichi BM, et al. Diabetic ulcers: microcirculatory improvement and faster healing with Pycnogenol®. Clin Appl Thromb Hemost. 2006 Jul;12(3):318-23.

43. Cesarone MR, Belcaro G, Rohdewald P, et al. Improvement of diabetic microangiopathy with Pycnogenol®: A prospective, controlled study. Angiology. 2006 Aug-Sep;57(4):431-6.

44. Ansari MA, Keller JN, Scheff SW. Protective effect of Pycnogenol® in human neuroblastoma SH-SY5Y cells following acrolein-induced cytotoxicity. Free Radic Biol Med. 2008 Dec 1;45(11):1510-9.

45. Peng QL, Buz’Zard AR, Lau BH. Pycnogenol® protects neurons from amyloid-beta peptide-induced apoptosis. Brain Res Mol Brain Res. 2002 Jul 15;104(1):55-65.

46. Ishrat T, Parveen K, Hoda MN, et al. Effects of Pycnogenol® and vitamin E on cognitive deficits and oxidative damage induced by intracerebroventricular streptozotocin in rats. Behav Pharmacol. 2009 Oct;20(7):567-75.

47. Ryan J, Croft K, Mori T, et al. An examination of the effects of the antioxidant Pycnogenol® on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population. J Psychopharmacol. 2008 Jul;22(5):553-62.

48. Hasegawa N, Mochizuki M. Improved effect of Pycnogenol® on impaired spatial memory function in partial androgen deficiency rat model. Phytother Res. 2009 Jun;23(6):840-3.

49. Errichi S, Bottari A, Belcaro G, et al. Supplementation with Pycnogenol® improves signs and symptoms of menopausal transition. Panminerva Med. 2011 Sep;53(3 Suppl 1):65-70.

50. Luzzi R, Belcaro G, Zulli C, et al. Pycnogenol® supplementation improves cognitive function, attention and mental performance in students. Panminerva Med. 2011 Sep;53(3 Suppl 1):75-82.

51. Available at: Accessed April 20, 2012.

52. Belcaro G, Cesarone MR, Errichi S, et al. Treatment of osteoarthritis with Pycnogenol®. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects. Phytother Res. 2008 Apr;22(4):518-23.

53. Cisar P, Jany R, Waczulikova I, et al. Effect of pine bark extract (Pycnogenol®) on symptoms of knee osteoarthritis. Phytother Res. 2008 Aug;22(8):1087-92.

54. Peng YJ, Lee CH, Wang CC, Salter DM, Lee HS. Pycnogenol® attenuates the inflammatory and nitrosative stress on joint inflammation induced by urate crystals. Free Radic Biol Med. 2012 Feb 15;52(4):765-74.

55. Belcaro G, Cesarone MR, Errichi S, et al. Variations in C-reactive protein, plasma free radicals and fibrinogen values in patients with osteoarthritis treated with Pycnogenol®. Redox Rep. 2008;13(6):271-6.

56. 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 Oct;37(10):931-4.

57. Dvorakova M, Sivonova M, Trebaticka J, et al. The effect of polyphenolic extract from pine bark, Pycnogenol® on the level of glutathione in children suffering from attention deficit hyperactivity disorder (ADHD). Redox Rep. 2006;11(4):163-72.

58. Nelson AB, Lau BH, Ide N, Rong Y. Pycnogenol® inhibits macrophage oxidative burst, lipoprotein oxidation, and hydroxyl radical-induced DNA damage. Drug Dev Ind Pharm. 1998 Feb;24(2):139-44.

59. Arhima MH, Gulati OP, Sharma SC. The effect of Pycnogenol® on fluoride induced rat kidney lysosomal damage in vitro. Phytother Res. 2004 Mar;18(3):244-6.

60. Chovanova Z, Muchova J, Sivonova M, et al. Effect of polyphenolic extract, Pycnogenol®, on the level of 8-oxoguanine in children suffering from attention deficit/hyperactivity disorder. Free Radic Res. 2006 Sep;40(9):1003-10.

61. Rohdewald P. Pycnogenol® protects DNA against oxidative damage in vivo. Phytother Res. 2005 Mar;19(3):262.

62. Grimm T, Chovanova Z, Muchova J, et al. Inhibition of NF-kappaB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol®). J Inflamm (Lond). 2006;3:1.

63. Ince I, Yesil-Celiktas O, Karabay-Yavasoglu NU, Elgin G. Effects of Pinus brutia bark extract and Pycnogenol® in a rat model of carrageenan induced inflammation. Phytomedicine. 2009 Dec;16(12):1101-4.

64. Kim YJ, Kim YA, Yokozawa T. Pycnogenol® modulates apoptosis by suppressing oxidative stress and inflammation in high glucose-treated renal tubular cells. Food Chem Toxicol. 2011 Sep;49(9):2196-201.

65. 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 Oct 8;75(21):2505-13.

66. Parveen K, Khan MR, Mujeeb M, Siddiqui WA. Protective effects of Pycnogenol® on hyperglycemia-induced oxidative damage in the liver of type 2 diabetic rats. Chem Biol Interact. 2010 Jul 30;186(2):219-27.

67. Available at: Accessed May 15, 2012.