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Maritime Pine Pycnogenol  is the super-antioxidant that has been tried and tested by over 30 years of research for many acute and chronic disorders. The Ojibwe knew about it almost 500 years ago.  Didn't call it that, though. White man took credit.

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1. Review article: discusses in details the biological activities of Maritime Pine Plus®, mainly focusing on its antioxidant and cardiovascular pharmacological profile in light of up to date available data on Maritime Pine Plus®.
Packer, L., Rimbach, G. and Virgili, F. (1999)
Antioxidant activity and biologic properties of a procyanidin-rich extract from the pine (Pinus maritima) bark, Pycnogenol.
Review Article In Free Radical Biology and Medicine, 27(5/6): 704-724.
 
2. Review article: describes cardiovascular pharmacologic profile of Maritime Pine Plus®, mainly high lighting its inhibitory effects on the smoking-induced platelet aggregation in humans.
Watson, R. (1999)
Reduction of cardiovascular disease risk factors by French Maritime Pine Bark Extract.
Cardiovascular Reviews and Reports XX (VI): 326-329.
 
3. Review article: describes efficacy and safety profile of Maritime Pine Plus® in venous disorders in humans. Mechanisms of reducing oedema are also discussed.
Gulati, O. P. (1999)
Maritime Pine Plus® in venous disorders: A review.
European Bulletin of Drug Research, 7 (2): 8-13.
 
4. Review article: discusses the history of ancient pine bark uses to the present day development of Maritime Pine Plus®.
Drehsen, G. (1999)
From ancient pine bark uses to Pycnogenol, ,In "Antioxidant Food Supplements in human health", ed. L. Packer, M. Hiramatsu and T. Yoshikawa, published by Academic Press, 1999, Chapter 20, pages 311-322.
 
5. Review article: describes in addition to the antioxidant activity of Maritime Pine Plus®, its effects on the immune system and modulation of nitrogen monoxide metabolism, the development of Maritime Pine Plus®.
Virgili F., Kobuchi, H., Noda, Y., Cossins, E. and Packer, L. (1999)
Procyanidins from Pinus maritima bark: Antioxidant activity, effects on the immune system and L. Packer, M. Hiramatsu and T. Yoshikawa, published by Academic Press, 1999. Chapter 21 pages 323-342.
 
6. Review article: Maritime Pine Plus® is a potent antioxidant. It provides cytoprotection, produces immuno-modulation and strengthens blood vessels. In addition, Maritime Pine Plus® improves circulation by inhibiting platelets aggregation and producing vaso-dilatation.
Rohdewald, P. (1998)
Maritime Pine Plus®.
In "Flavonoids in Health and Disease", ed. Catherine A. Rice-Evans and Lester Packer, Marcel Dekker Inc. NY, 1998, Chapter 17, pages 405-419.
 
7. Maritime Pine Plus® modulates the production of nitric oxide radicals in activated inflammatory cells. Maritime Pine Plus® produces beneficial effects in pathologies relating to oxidative stress and inflammatory conditions.
Virgili, F., Kobuchi, H. and Packer, L. (1998)
Nitrogen monoxide (NO) metabolism: antioxidant properties and modulation of inducible NO synthase activity in activated macrophages by Procyanidins extracted from Pinus maritima (Pycnogenol().
In Flavonoids in Health and Disease, ed. Catherine A. Rice-Evans and Lester Packer, Marcel Dekker Inc. NY, 1998.Chapter 18. Pages 421-436.
 
8. Maritime Pine Plus® shows free radical scavenging activity against reactive oxygen species. It inhibits the generation of pro-inflammatory mediators confirming the anti-inflammatory and immuno-modulatory profile of Maritime Pine Plus®.
Cho, K-J., Yun C-H., Yoon, D-Y., Cho, Y-S., Rimbach, G., Packer, L and Chung A-S. (2000)
Effect of bioflavonoids extracted from the bark of Pinus maritime on proinflammatory cytokine interleukin.1 production in lipopolysaccharide-stimulated raw 264.7.
Toxicology and applied pharmacology,1687: 64-71.
 
9. Maritime Pine Plus® produces cell protection by reducing the malonaldehyde (MDA) modified protein, a known biochemical marker of free radical related cell injury.
Kim, J., Chehade, J., Pinnas, J.L., and Mooradian, A.D. (2000)
Effect of select antioxidants on malondialdehyde modification of proteins
Nutrition, 16: 1079-1081.
 
10. Maritime Pine Plus® produces selective action on cell enzyme system relating to their binding capacity, explaining its specificity of action against oxidative stress.
Moini, H.,Guo, Q., and Packer, L. 2000)
Enzyme inhibition and protein binding action of Procyanidin -rich French maritime pine bark extract, Pycnogenol: effect on xanthine oxidase.
J. Agric. Food Chem. 48: 5630-5639.
 
11. Maritime Pine Plus® inhibits the formation of "dense cells" involved in sickle cell anemia in humans. Maritime Pine Plus® is more potent compared to other herbal-sourced nutritional supplements.
Ohnishi, S. T., Ohnishi, T. and Ogunmola, G.B. (2000)
Sickle cell anemia: A potential nutritional approach for a molecular disease.
Nutrition, 16: 330-338.
 
12. Maritime Pine Plus® by virtue of its relatively higher content of procyanidins is more potent antioxidant than other herbal-sourced antioxidants cotaining relatively higher content of regular flavon(ol)s. This fact is explained on structural and functional basis.
Bors, W., Michel C and Stettmaier, K (2000)
Electron paramagnetic resonance studies of radical species of proanthocyanidins and gallete esters.
Archives of Biochemistry and Biophysics 374 (2):347-355.
 
13. Maritime Pine Plus® produces significant reduction in vascular damage caused by beta-amyloid protein. beta-amyloidosis is one of the neuropathological hallmarks of Alzheimer's disease(AD). This explains the role of Maritime Pine Plus® in reducing the risk of AD.
Liu, F. Lau, B.H.S., Peng, Q and Shah, V. (2000)
Pycnogenol protects vascular endothelial cells from beta-amyloid-induced injury.
Biol. Pharm. Bull 23 (6): 735-737.
 
14. Maritime Pine Plus® and one of its components caffeic acid, modulate cellular response to oxidative stress, contributing to the mechanisms involved in their biological effects.
Nardini, M., Scaccini, C., Packer, L. and Virgili, F (2000)
In vitro inhibition of the activity of phosphorylase kinase, protein kinase C and protein kinase A by caffeic acid and a procyanidin-rich pine bark (Pinus maritima) extract.
Biochimica et Biophysica Acta, 1474:219-225
 
15. Maritime Pine Plus® in addition to its antioxidant activity, affects the regulation of nitric oxide metabolism and cell adhesion, contributing to its beneficial effects in inflammatory and degenerative conditions.
Packer, L. et al., (1999)
French Maritime Pine Bark Extract: Antioxidant activity and effects on regulation of nitric oxide metabolism and cell adhesion.
Experimental Biology 99 (FASEB) Washington D.C., April, 1999; (Abstract).
 
16. Maritime Pine Plus® protects retina of the eye against damage caused by oxidative stress. The effect is more pronounced when compared to other antioxidant bioflavonoids. Maritime Pine Plus® enhances the effects of other antioxidant like Coenzyme Q10 when combined together.
Chida, M., Suzuki, K., Nakanishi-Ueda, T., Ueda, T., Yasuhara, H., Koide, R. and Armstrong, D. (1999)
In vitro testing of antioxidants and biochemical end-points in bovine retinal tissue.
Ophthalmic Research 31: 407-415.
 
17. Maritime Pine Plus® is an efficient antioxidant due to the relative stability of its corresponding radical and its regeneration by vitamin C and vitamin E homologue Trolox.
Guo, Q. and Packer, L. (1999)
ESR studies of the procyanidin-rich French maritime pine bark extract free radical.
Oxygen Club of California (OCC) World Congress, March 1999; (abstract).
Guo, Q., Zhao, B. and Packer, L. (1999)
Electron spin resonance study of free radicals formed from a procyanidin-rich pine (Pinus maritime)
bark extract, Pycnogenol.
Free Radical Biology Medicine 27 (11-12): 1308-1312.
 
18. Maritime Pine Plus® significantly enhances the level of antioxidant defence against reactive nitrogen species in vitro cell (macrophage) model system.
Rimbach, G., Virgili, F., Park, Y.C. and Packer, L. (1999)
Effect of procyanidins from Pinus maritima on glutathione levels in endothelial cells challenged by 3-morpholinosydnomine and activated macrophages.
Oxygen Club of California (OCC) World Congress, March 1999; (presentation)
 
19. The beneficial effects of electron donating and protein binding properties of Maritime Pine Plus® with respect to SAR of different enzyme system have been demonstrated and discussed.
Packer, L., Bito, T., Cossins, E., Kobuchi, H., Moini, H., Noda, Y., Rimbach, G., Roy, S., Vaya, J. and Virgili, F. (1999)
Antioxidant activity and biological properties of a French Maritime Pine Bark extract.
Oxygen Club of California (OCC) World Congress, March 1999; (presentation).
 
20. Maritime Pine Plus® protects (-tocopherol in endothelial cells.
Virgili F., Kim, D. and Packer, L. (1998)
Procyanidins extracted from pine bark protect (-tocopherol in ECV 304 endothelial cells challenged by activated RAW 264.7 macrophages: role of nitric oxide peroxynitrite.
FEBS letters, 431:315-318.
 
21. Maritime Pine Plus® inhibits the effect of oxidative stress and minimises hydroxyl radical-induced DNA damage in vitro.
Nelson, A.B., Lau, B.H.S., Ide, N. and Rong, Y. (1998)
Pycnogenol inhibits macrophage oxidative burst, lipoprotein oxidation and hydroxyl radical-induced DNA damage.
Drug Development and Industrial Pharmacy, 24 (2): 139-144.
 
22. Maritime Pine Plus® modulates the production of nitric oxide radicals in activated inflammatory cells. Maritime Pine Plus® produces beneficial effects in pathologies relating to oxidative stress and inflammatory conditions.
Virgili, F., Kobuchi, H. and Packer, L. (1998)
Nitrogen monoxide (NO) metabolism: antioxidant properties and modulation of inducible NO synthase activity in activated macrophages by Procyanidins extracted from Pinus maritima (Pycnogenol().
In Flavonoids in Health and Disease, ed. Catherine A. Rice-Evans and Lester Packer, Marcel Dekker Inc. NY, 1998.Chapter 18. Pages 421-436.
Virgili, F., Kobuchi, H. and Packer, L. (1998)
Procyanidins extracted from Pinus maritima (Pycnogenol() scavengers of free radical species and modulators of nitrogen monoxide metabolism in activated murine raw 264.7 macrophages.
Free Radical Biology & Medicine 24 (7/8) 1120-1129.
 
23. Maritime Pine Plus® prolongs the lifetime of vitamin C more than other flavonoids.
Cossins, E., Lee, R. and Packer, L. (1998)
ESR studies of vitamin C regeneration, order of reactivity of natural source phytochemical preparations.
Biochem Mol. Biol. Int., 45 (3): 583-597.
 
24. Maritime Pine Plus® is shown to be the strongest hydroxyl and superoxide radical scavenger among other extracts tested. In addition, Maritime Pine Plus® is resistant to heat and ascorbate oxidase.
Noda, Y., Anzai, K., Mori, A., Kohno, M., Shinmei, M. and Packer, L. (1997)
Hydroxyl and superoxide anion radical scavenging activities of natural source antioxidants using the computerized JES-FR30 ESR spectrometer system.
Biochem. & Mol. Biol. Int., 42 (1): 35-44.
 
25. Maritime Pine Plus® protects the endothelial cells which line the blood vessels from free radicals damage. Damage to endothelial cells is considered a prime cause for atherosclerosis.
Rong Y., Li, L., Shah, V. and Lau, B.H.S. (1995)
Pycnogenol protects vascular endothelial cells from t-butyl hydroperoxide induced oxidant injury.
Biotechnology Therapeutics, 5 (3 & 4): 117-126.
 
26. Maritime Pine Plus® scavenges superoxide radicals in vitro and inhibits oedema in vivo. The anti-inflammatory and free radical scavenging activities are closely correlated.
Blazso, G., Gabor, M., Sibbel, R. and Rohdewald, P. (1994)
Anti-inflammatory and superoxide radical scavenging activities of procyanidins containing extract from the bark of Pinus pinaster sol. and its fractions.
Pharm. Parmacol. Lett., 3: 217-220.
 
27. Maritime Pine Plus® was proved to be an excellent radical scavenger of enzymatically produced hydroxyl and singlet oxygen free radicals, two of the most dangerous free radicals.
Elstner, E.F. and Kleber, E. (1990)
Radical scavenger properties of leucocyanidine.
In: Das NP, ed. Flavonoids in Biology & Medicine III: Current issues in Flavonoid Research: National University of Singapore Press (1990): 221-235.
 
28. Maritime Pine Plus® inhibits the formation of "dense cells" involved in sickle cell anemia in humans. Maritime Pine Plus® is more potent compared to other herbal-sourced nutritional supplements.
Ohnishi, S. T., Ohnishi, T. and Ogunmola, G.B. (2000)
Sickle cell anemia: A potential nutritional approach for a molecular disease.
Nutrition, 16: 330-338.
 
29. Maritime Pine Plus® inhibits smoking-induced increased levels of thromboxane B2, the noxious agent involved in the increased platelet reactivity/aggregation in smokers. These results explain the mechanism of anti-platelet aggregation activity of Maritime Pine Plus® observed in smokers.
Araghi-Nicknam, M., ., Hosseini, S., Larson D., Rohdewald, P. and Watson R.R. (1999)
Pine bark extract reduces platelet aggregation.
Integrative Medicine, 2 (2/3). 73-77.
 
30. Maritime Pine Plus® inhibits smoking induced platelet aggregation in dose-dependent manner in humans. The effect lasts for more than 6 days and unlike aspirin, it does not produce increase in bleeding time.
Pütter, M., Grotemeyer, K.H.M., Würthwein, G., Araghi-Nicknam, M., Watson R.R., Hosseini, S. and Rohdewald, P. (1999)
Inhibition of smoking-induced platelet aggregation by aspirin and Pycnogenol.
Thrombosis Research, 95: 155-161.
 
31. Maritime Pine Plus® helps to maintain a healthy circulation through vasodilatation, anti platelet aggregation, free radical scavenging and capillary sealing effects. The role of endothelial nitric oxide (NO) is also discussed.
Rohdewald, P. (1999)
Reducing the risk for stroke and heart infarction with Maritime Pine Plus®.
European Bulletin of Drug Research, 7 (2): 14-17.
 
32. Maritime Pine Plus® helps fighting against heart disease by inhibiting adhesion and aggregation of platelets and improving microcirculatory blood flow in human.
Wang, S., Tan, D. , Zhao, Y., Gao, G., Gao, X. and Hu, L. (1999)
The effect of Maritime Pine Plus® on the microcirculation, platelet function and ischemic myocardium in patients with coronary artery diseases.
European Bulletin of Drug Research. 7 (2): 19-25.
 
33. Maritime Pine Plus® counteracts the constriction of blood vessels due to stress. The vaso-relaxant activity of Maritime Pine Plus® is mediated through nitric oxide.
Fitzpatrick, D.F., Bing, B. and Rohdewald, P. (1998)
Endothelium-dependent vascular effects of Maritime Pine Plus®.
Journal Cardiovascular Pharmacology, 32: 509-515.
 
34. Maritime Pine Plus® inhibits the formation of "dense cells" involved in sickle cell anemia in humans. Maritime Pine Plus® is more potent compared to other herbal-sourced nutritional supplements.
Ohnishi, S. T., Ohnishi, T. and Ogunmola, G.B. (2000)
Sickle cell anemia: A potential nutritional approach for a molecular disease.
Nutrition, 16: 330-338.
 
35. Maritime Pine Plus® inhibits smoking-induced increased levels of thromboxane B2, the noxious agent involved in the increased platelet reactivity/aggregation in smokers. These results explain the mechanism of anti-platelet aggregation activity of Maritime Pine Plus® observed in smokers.
Araghi-Nicknam, M., ., Hosseini, S., Larson D., Rohdewald, P. and Watson R.R. (1999)
Pine bark extract reduces platelet aggregation.
Integrative Medicine, 2 (2/3). 73-77.
 
36. Maritime Pine Plus® inhibits smoking induced platelet aggregation in dose-dependent manner in humans. The effect lasts for more than 6 days and unlike aspirin, it does not produce increase in bleeding time.
Pütter, M., Grotemeyer, K.H.M., Würthwein, G., Araghi-Nicknam, M., Watson R.R., Hosseini, S. and Rohdewald, P. (1999)
Inhibition of smoking-induced platelet aggregation by aspirin and Pycnogenol.
Thrombosis Research, 95: 155-161.
 
37. Maritime Pine Plus® helps to maintain a healthy circulation through vasodilatation, anti platelet aggregation, free radical scavenging and capillary sealing effects. The role of endothelial nitric oxide (NO) is also discussed.
Rohdewald, P. (1999)
Reducing the risk for stroke and heart infarction with Maritime Pine Plus®.
European Bulletin of Drug Research, 7 (2): 14-17.
 
38. Maritime Pine Plus® helps fighting against heart disease by inhibiting adhesion and aggregation of platelets and improving microcirculatory blood flow in human.
Wang, S., Tan, D. , Zhao, Y., Gao, G., Gao, X. and Hu, L. (1999)
The effect of Maritime Pine Plus® on the microcirculation, platelet function and ischemic myocardium in patients with coronary artery diseases.
European Bulletin of Drug Research. 7 (2): 19-25.
 
39. Maritime Pine Plus® helps fighting against heart disease by inhibiting adhesion and aggregation of platelets and improving microcirculatory blood flow in human.
Wang, S., Tan, D. , Zhao, Y., Gao, G., Gao, X. and Hu, L. (1999)
The effect of Maritime Pine Plus® on the microcirculation, platelet function and ischemic myocardium in patients with coronary artery diseases.
European Bulletin of Drug Research. 7 (2): 19-25.
 
40. Maritime Pine Plus® slows down the process of decline in the activities of immune and blood generating systems related to ageing and restores their functions to normal.
Liu, F.J., Zhang, Y.X. and Lau B.H.S. (1998)
Maritime Pine Plus® enhances immune and haemopoietic function in senescence-accelerated mice.
CMLS, Cell. Mol. Life. Sci., 54: 1168-1172.
 
41. Maritime Pine Plus® counteracts the constriction of blood vessels due to stress. The vaso-relaxant activity of Maritime Pine Plus® is mediated through nitric oxide.
Fitzpatrick, D.F., Bing, B. and Rohdewald, P. (1998)
Endothelium-dependent vascular effects of Maritime Pine Plus®.
Journal Cardiovascular Pharmacology, 32: 509-515.
 
42. Maritime Pine Plus® inhibits the angiotensin II converting enzyme (ACE) and produces a moderate hypotensive effect in rats. This is not an anti-hypertensive effect, as that of Captopril(.
Blazso, G., Gaspar R., Gabor, M., Rüve H-J and Rohdewald, P. (1996)
ACE inhibition and hypotensive effect of procyanidinis containing extract from the bark of Pinus pinaster Sol.
Pharm. Pharmacol. Lett., 6(1): 8-11.
 
43. Maritime Pine Plus® protects the endothelial cells which line the blood vessels from free radicals damage. Damage to endothelial cells is considered a prime cause for atherosclerosis.
Rong Y., Li, L., Shah, V. and Lau, B.H.S. (1995)
Pycnogenol protects vascular endothelial cells from t-butyl hydroperoxide induced oxidant injury.
Biotechnology Therapeutics, 5 (3 & 4): 117-126.
 
44. Maritime Pine Plus® produces vaso-protective an effect at the level of capillaries as shown in clinical studies. Maritime Pine Plus® decreases oedema and haemorrhagic tendencies in conditions characterised by increased capillary permeability.
Becker, S.R. (1995)
Le pycnogénol: une substance douée de properiétés angioprotectrices
dans le traitement de l'insuffisance veineuse chronique.
Journal Suisse de médecine globale, 1/95 : 11-14 et 2/95 : 69-73.
 
45. The efficacy of Maritime Pine Plus® has been confirmed on the basis of objective and subjective signs and symptoms of static oedema in a double blind study in 40 patients suffering from chronic venous insufficiency. Maritime Pine Plus® is a safe veno- protector.
Schmidtke, I. and Schoop, W. (1995)
Le pycnogénol: Thérapeutique médicamenteuse de l'oedème statique.
Journal Suisse de médecine globale, 3/95 :114-115.
 
46. Maritime Pine Plus® increases the pathologically low capillary wall resistance. Maritime Pine Plus® is shown to be the most potent among other bioflavonoids tested. Maritime Pine Plus® provides strength to capillary walls and makes them less permeable and thus contributes to anti-oedema, anti-inflammatory effects.
Gabor, M., Engi, E. and Sonkodi, S. (1993)
Die Kapillarwandresistenz und ihre Beeinflussung durch wasserlösliche Flavonderivate bei spontan hypertonischen Ratten.
Phlebologie, 22: 178-182
 
47. Maritime Pine Plus® tested in a placebo-controlled, double-blind phase as well as in open phase clinical trial. It produced significant relief and disappearance of symptoms of chronic venous insufficiency. Safety was confirmed by lack of side effects, changes in blood biochemistry and haematological parameters.
Petrassi, C., Mastromarino, A. and Spartera, C. (2000)
Phytomedicine 7(5): 383-388
 
48. Maritime Pine Plus® tested in a placebo-controlled, double-blind clinical trial, has been shown to produce significant relief and disappearance of symptoms of chronic venous insufficiency.
Arcangeli, P. (2000)
Maritime Pine Plus® in chronic venous insufficiency.
Fitoterapia, 71:236-244
 
49. Maritime Pine Plus® helps fighting against heart disease by inhibiting adhesion and aggregation of platelets and improving microcirculatory blood flow in human.
Wang, S., Tan, D. , Zhao, Y., Gao, G., Gao, X. and Hu, L. (1999)
The effect of Maritime Pine Plus® on the microcirculation, platelet function and ischemic myocardium in patients with coronary artery diseases.
European Bulletin of Drug Research. 7 (2): 19-25.
 
50. Maritime Pine Plus® produces an anti-oedema effect. Topical application of Maritime Pine Plus® gel protects the skin against UV radiation.
Blazso, G., Gabor, M. and Rohdewald, P. (1997)
Antiinflammatory activities of procyanidin containing extracts from Pinus pinaster Ait. after oral and cutaneous application.
Pharmazie, 52 (5): 380-382.
 
51. Maritime Pine Plus® produces vaso-protective an effect at the level of capillaries as shown in clinical studies. Maritime Pine Plus® decreases oedema and haemorrhagic tendencies in conditions characterised by increased capillary permeability.
Becker, S.R. (1995)
Le pycnogénol: une substance douée de properiétés angioprotectrices
dans le traitement de l'insuffisance veineuse chronique.
Journal Suisse de médecine globale, 1/95 : 11-14 et 2/95 : 69-73.
 
52. The efficacy of Maritime Pine Plus® has been confirmed on the basis of objective and subjective signs and symptoms of static oedema in a double blind study in 40 patients suffering from chronic venous insufficiency. Maritime Pine Plus® is a safe veno- protector.
Schmidtke, I. and Schoop, W. (1995)
Le pycnogénol: Thérapeutique médicamenteuse de l'oedème statique.
Journal Suisse de médecine globale, 3/95 :114-115.
 
53. Maritime Pine Plus® increases the pathologically low capillary wall resistance. Maritime Pine Plus® is shown to be the most potent among other bioflavonoids tested. Maritime Pine Plus® provides strength to capillary walls and makes them less permeable and thus contributes to anti-oedema, anti-inflammatory effects.
Gabor, M., Engi, E. and Sonkodi, S. (1993)
Die Kapillarwandresistenz und ihre Beeinflussung durch wasserlösliche Flavonderivate bei spontan hypertonischen Ratten.
Phlebologie, 22: 178-182
 
54. Maritime Pine Plus® affects favourably the gene expression profile in human keratinocytes in vitro, thus having a great potential in psoriasis and dermatoses.
Rihn, B., Saliou, C., Bottin, MC., Keith, G. and Packer, L. (2001)
From ancient remedies to modern therapeutics. Pinebark uses in skin disorders revisited.
Phytotherapy Research, 15:76-78.
 
55. Maritime Pine Plus® inhibits Interferon -gamma (IFN-gamma)-induced ICAM-1 expression in human skin cells (keratinocytes). This effect is dose and time dependent indicating the therapeutic potential of Maritime Pine Plus® in inflammatory skin disorders.
Bito, T., Roy, S., Sen, C.K. and Packer, L. (2000)
Pine bark extract Pycnogenol downregulates IFN-gamma - induced adhesion of T cells to human keratinocytes by inhibiting inducible ICAM-1 expression.
Free Radical Biology Medicine 28 (2): 219-227.
 
56. Maritime Pine Plus® prevents solar ultraviolet (UV)-induced NF-kB dependent gene expression in human keratinocytes. This effect was concentration dependent indicating the beneficial effects of Maritime Pine Plus® in skin disorders induced by UVR.
Saliou, C., McLaughlin, L. and Packer, L. (1999)
French Pinus maritima bark extract prevents ultraviolet-induced NF-kB dependent gene expression in a human keratinocyte cell line.
Oxygen Club of California (OCC) World Congress, March 1999; (presentation)
 
57. Maritime Pine Plus® prolongs the lifetime of vitamin C more than other flavonoids.
Cossins, E., Lee, R. and Packer, L. (1998)
ESR studies of vitamin C regeneration, order of reactivity of natural source phytochemical preparations.
Biochem Mol. Biol. Int., 45 (3): 583-597.
 
58. Maritime Pine Plus® produces an anti-oedema effect. Topical application of Maritime Pine Plus® gel protects the skin against UV radiation.
Blazso, G., Gabor, M. and Rohdewald, P. (1997)
Antiinflammatory activities of procyanidin containing extracts from Pinus pinaster Ait. after oral and cutaneous application.
Pharmazie, 52 (5): 380-382.
 
59. Maritime Pine Plus® produces an anti-oedema effect. applied topically, Maritime Pine Plus® significantly reduces UVB radiation induced-erythema.
Blazso, G., Rohdewald, P., Sibbel, R. and Gabor, M. (1995)
Anti-inflammatory activities of procyanidin-containing extracts from Pinus pinaster sol.
Proceedings of the International Bioflavonoid Symposium, Vienna, Austria, ed. Antus, S., Gabor, M. and Vetschera, K. July 16-19, 1995, pages 231-238.
 
60. Maritime Pine Plus® protects the skin from ultraviolet-radiation-induced oxidative stress injury (lipid peroxidation and cytotoxicity). The protective effects were related to dose, with the highest concentration providing the greatest benefits.
Guochang, Z. (1993)
Ultraviolet radiation-induced oxidative stress in cultured human skin fibroblasts and antioxidant protection.
Ph.D. Thesis, University of Jyväskylä 33:1-86, Jyväskylä, Finland.
 
61. Maritime Pine Plus® shows beneficial effects in retinopathy
Spadea, L. and Balestrazzi, E. (2001)
Treatment of vascular retinopathies with Maritime Pine Plus®.
Phytother. Res., 15: 219-223.
 
62. Maritime Pine Plus® protects retina of the eye against damage caused by oxidative stress. The effect is more pronounced when compared to other antioxidant bioflavonoids. Maritime Pine Plus® enhances the effects of other antioxidant like Coenzyme Q10 when combined together.
Chida, M., Suzuki, K., Nakanishi-Ueda, T., Ueda, T., Yasuhara, H., Koide, R. and Armstrong, D. (1999)
In vitro testing of antioxidants and biochemical end-points in bovine retinal tissue.
Ophthalmic Research 31: 407-415.
 
63. Maritime Pine Plus® helps fighting against heart disease by inhibiting adhesion and aggregation of platelets and improving microcirculatory blood flow in human.
Wang, S., Tan, D. , Zhao, Y., Gao, G., Gao, X. and Hu, L. (1999)
The effect of Maritime Pine Plus® on the microcirculation, platelet function and ischemic myocardium in patients with coronary artery diseases.
European Bulletin of Drug Research. 7 (2): 19-25.
 
64. Maritime Pine Plus® protects the retina of the eye against free radicals damage.
Ueda, T., Ueda, T. and Armstrong D. (1996)
Preventive effect of natural and synthetic antioxidants on lipid peroxidation in the mammalian eye.
Ophthalmic Research, 28: 184-192.
 
65. Maritime Pine Plus® produces vaso-protective an effect at the level of capillaries as shown in clinical studies. Maritime Pine Plus® decreases oedema and haemorrhagic tendencies in conditions characterised by increased capillary permeability.
Becker, S.R. (1995)
Le pycnogénol: une substance douée de properiétés angioprotectrices
dans le traitement de l'insuffisance veineuse chronique.
Journal Suisse de médecine globale, 1/95 : 11-14 et 2/95 : 69-73.
 
66. Maritime Pine Plus® increases the pathologically low capillary wall resistance. Maritime Pine Plus® is shown to be the most potent among other bioflavonoids tested. Maritime Pine Plus® provides strength to capillary walls and makes them less permeable and thus contributes to anti-oedema, anti-inflammatory effects.
Gabor, M., Engi, E. and Sonkodi, S. (1993)
Die Kapillarwandresistenz und ihre Beeinflussung durch wasserlösliche Flavonderivate bei spontan hypertonischen Ratten.
Phlebologie, 22: 178-182
 
67. Maritime Pine Plus® produces significant reduction in vascular damage caused by beta-amyloid protein. beta-amyloidosis is one of the neuropathological hallmarks of Alzheimer's disease(AD). This explains the role of Maritime Pine Plus® in reducing the risk of AD.
Liu, F. Lau, B.H.S., Peng, Q and Shah, V. (2000)
Pycnogenol protects vascular endothelial cells from beta-amyloid-induced injury.
Biol. Pharm. Bull 23 (6): 735-737.
 
68. Maritime Pine Plus® protects nerve cells against glutamate-induced cell damage.
Kobayashi, M.S., Han, D., and Packer, L. (2000)
Antioxidants and herbal extracts protect HT-4 neuronal cells against glutamate-induced cytotoxicity
Free Rad. Res. 32:115-124.
 
69. Maritime Pine Plus® improves learning impairment and loss of memory, common symptoms of the ageing process.
Liu, F., Zhang, Y., and Lau, B.H.S. (1999)
Pycnogenol improves learning impairment and memory deficit in Senescence-accelerated mice.
Journal of Anti-aging Medicine, 2 (4): 349-355.
Lau B.H.S. Liu, F.J., Peng, Q.L. and Zhang, Y.X. (1999)
Maritime Pine Plus® improves learning impairment and memory deficit in senescence accelerated mice.
Experimental Biology 99 (FASEB) Washington D.C., April 1999; (Abstract.).
 
70. Maritime Pine Plus® slows down the process of decline in the activities of immune and blood generating systems related to ageing and restores their functions to normal.
Liu, F.J., Zhang, Y.X. and Lau B.H.S. (1998)
Maritime Pine Plus® enhances immune and haemopoietic function in senescence-accelerated mice.
CMLS, Cell. Mol. Life. Sci., 54: 1168-1172.
 
71. Maritime Pine Plus® enhances clearance of H2O2 and O2-. It increases the GSH-redox cycle and antioxidant enzymes (SOD & CAT) activities. These antioxidant mechanisms may contribute to the beneficial effects of Maritime Pine Plus® in cancer, atherosclerosis, diabetes, ischemia, inflammatory diseases and the aging process.
Wei, Z H., Peng Q.L. and Lau B.H.S. (1997)
Pycnogenol enhances endothelial cell antioxidant defences.
Redox Report, 3 (4): 219-224.
 
72. Maritime Pine Plus® increases the synthesis of important anti-oxidative enzymes in macrophages. Additionally, it inhibits the production of noxious peroxides the major mediators of inflammation thus confirming the anti-inflammatory profile of Maritime Pine Plus®.
Bayeta, E. and Lau, B.H.S. (2001)
Pycnogenol inhibits generation of inflammatory mediators in macrophages.
Nutrition Research, 20 (2): 249-259.
 
Maritime Pine Plus® shows free radical scavenging activity against reactive oxygen species. It inhibits the generation of pro-inflammatory mediators confirming the anti-inflammatory and immuno-modulatory profile of Maritime Pine Plus®.
Cho, K-J., Yun C-H., Yoon, D-Y., Cho, Y-S., Rimbach, G., Packer, L and Chung A-S.
Effect of bioflavonoids extracted from the bark of Pinus maritime on proinflammatory cytokine interleukin.1 production in lipopolysaccharide-stimulated raw 264.7.
Toxicology and applied pharmacology,1687: 64-71.
 
73. Maritime Pine Plus® inhibits Interferon -gamme (IFN-gamma)-induced ICAM-1 expression in human skin cells (keratinocytes). This effect is dose and time dependent indicating the therapeutic potential of Maritime Pine Plus® in inflammatory skin disorders.
Bito, T., Roy, S., Sen, C.K. and Packer, L. (2000)
Pine bark extract Pycnogenol downregulates IFN-gamma - induced adhesion of T cells to human keratinocytes by inhibiting inducible ICAM-1 expression.
Free Radical Biology Medicine 28 (2): 219-227.
 
74. Maritime Pine Plus® modulates the production of nitric oxide radicals in activated inflammatory cells. Maritime Pine Plus® produces beneficial effects in pathologies relating to oxidative stress and inflammatory conditions.
Virgili, F., Kobuchi, H. and Packer, L. (1998)
Nitrogen monoxide (NO) metabolism: antioxidant properties and modulation of inducible NO synthase activity in activated macrophages by Procyanidins extracted from Pinus maritima (Pycnogenol().
In Flavonoids in Health and Disease, ed. Catherine A. Rice-Evans and Lester Packer, Marcel Dekker Inc. NY, 1998.Chapter 18. Pages 421-436.
Virgili, F., Kobuchi, H. and Packer, L. (1998)
Procyanidins extracted from Pinus maritima (Pycnogenol() scavengers of free radical species and modulators of nitrogen monoxide metabolism in activated murine raw 264.7 macrophages.
Free Radical Biology & Medicine 24 (7/8) 1120-1129.
 
75. Maritime Pine Plus® enhances clearance of H2O2 and O2-. It increases the GSH-redox cycle and antioxidant enzymes (SOD & CAT) activities. These antioxidant mechanisms may contribute to the beneficial effects of Maritime Pine Plus® in cancer, atherosclerosis, diabetes, ischemia, inflammatory diseases and the aging process.
Wei, Z H., Peng Q.L. and Lau B.H.S. (1997)
Pycnogenol enhances endothelial cell antioxidant defences.
Redox Report, 3 (4): 219-224.
 
76. Maritime Pine Plus® scavenges superoxide radicals in vitro and inhibits oedema in vivo. The anti-inflammatory and free radical scavenging activities are closely correlated.
Blazso, G., Gabor, M., Sibbel, R. and Rohdewald, P. (1994)
Anti-inflammatory and superoxide radical scavenging activities of procyanidins containing extract from the bark of Pinus pinaster sol. and its fractions.
Pharm. Parmacol. Lett., 3: 217-220.
 
77. Maritime Pine Plus® increases the pathologically low capillary wall resistance. Maritime Pine Plus® is shown to be the most potent among other bioflavonoids tested. Maritime Pine Plus® provides strength to capillary walls and makes them less permeable and thus contributes to anti-oedema, anti-inflammatory effects.
Gabor, M., Engi, E. and Sonkodi, S. (1993)
Die Kapillarwandresistenz und ihre Beeinflussung durch wasserlösliche Flavonderivate bei spontan hypertonischen Ratten.
Phlebologie, 22: 178-182
 
78. Maritime Pine Plus® shows free radical scavenging activity against reactive oxygen species. It inhibits the generation of pro-inflammatory mediators confirming the anti-inflammatory and immuno-modulatory profile of Maritime Pine Plus®.
Cho, K-J., Yun C-H., Yoon, D-Y., Cho, Y-S., Rimbach, G., Packer, L and Chung A-s.
Effect of bioflavonoids extracted from the bark of Pinus maritime on proinflammatory cytokine interleukin.1 production in lipopolysaccharide-stimulated raw 264.7.
Toxicology and applied pharmacology,1687: 64-71.
 
79. Maritime Pine Plus® inhibits tumor necrosis factor-alpha(TNF-alpha)-induced nuclear factor kappa B activation, and adhesion molecule expression, the processes involved in the atherogenesis. TNF-alpha increases the release of superoxide anion and H2O2; Maritime Pine Plus® dose-dependently inhibits their release
Peng, Q., Wei, Z. and Lau B.H.S. (2000)
Maritime Pine Plus® inhibits tumor necrosis factor-alpha(TNF-alpha)-induced nuclear factor kappa B activation, and adhesion molecule expression in human vascular endothelial cells.
CMLS. Cell. Mol. Life Sci. 57:834-841.
 
80. Maritime Pine Plus® selectively kills cancerous human mammary cells (MCF-7), without affecting the normal mammary cells (MCF-10).
Huynh, H.T. and Teel R.W. (2000)
Selective induction of apoptosis in human mammary cancer cells (MCF-7) by Pycnogenol.
Anticancer Research, 20 (4): 2417-2420.
 
81. Maritime Pine Plus® increases TNF-alpha secretion in the macrophage system in a concentration and time dependent manner indicating that it acts as modulator of the immune response in macrophages.
Park, Y.C., Rimbach, G., Saliou, C., Valacchi, G. and Packer, L. (2000)
Activity of monomeric, dimeric, and trimeric flavonoids on NO production, TNF-alpha secretion, and NF-kappaB-dependent gene expression in RAW 264.7 macrophages.
FEBS Letters 2000, 14 (2-3): 93-97.
 
82. Maritime Pine Plus® is an efficient antioxidant due to the relative stability of its corresponding radical and its regeneration by vitamin C and vitamin E homologue Trolox.
Guo, Q. and Packer, L. (1999)
ESR studies of the procyanidin-rich French maritime pine bark extract free radical.
Oxygen Club of California (OCC) World Congress, March 1999; (abstract).
Guo, Q., Zhao, B. and Packer, L. (1999)
Electron spin resonance study of free radicals formed from a procyanidin-rich pine (Pinus maritime)
bark extract, Pycnogenol.
Free Radical Biology Medicine 27 (11-12): 1308-1312.
 
83. Maritime Pine Plus® significantly enhances the level of antioxidant defence against reactive nitrogen species in vitro cell (macrophage) model system.
Rimbach, G., Virgili, F., Park, Y.C. and Packer, L. (1999)
Effect of procyanidins from Pinus maritima on glutathione levels in endothelial cells challenged by 3-morpholinosydnomine and activated macrophages.
Oxygen Club of California (OCC) World Congress, March 1999; (presentation)
 
84. Maritime Pine Plus® slows down the process of decline in the activities of immune and blood generating systems related to ageing and restores their functions to normal.
Liu, F.J., Zhang, Y.X. and Lau B.H.S. (1998)
Maritime Pine Plus® enhances immune and haemopoietic function in senescence-accelerated mice.
CMLS, Cell. Mol. Life. Sci., 54: 1168-1172.
 
85. Maritime Pine Plus® inhibits the formation of reactive metabolites of the tobacco-specific nitroso compound and thus supports a chemo-preventive action against NNK induced lung cancer.
Huynh, H.T. and Teel, R.W. (1998)
Effects of Maritime Pine Plus® on the microsomal metabolism of the tobacco-specific nitrosamine NNK as a function of age.
Cancer letters, 132:135-139.
 
86. Maritime Pine Plus® inhibits the effect of oxidative stress and minimises hydroxyl radical-induced DNA damage in vitro.
Nelson, A.B., Lau, B.H.S., Ide, N. and Rong, Y. (1998)
Pycnogenol inhibits macrophage oxidative burst, lipoprotein oxidation and hydroxyl radical-induced DNA damage.
Drug Development and Industrial Pharmacy, 24 (2): 139-144.
 
87. Maritime Pine Plus® modulates the production of nitric oxide radicals in activated inflammatory cells. Maritime Pine Plus® produces beneficial effects in pathologies relating to oxidative stress and inflammatory conditions.
Virgili, F., Kobuchi, H. and Packer, L. (1998)
Nitrogen monoxide (NO) metabolism: antioxidant properties and modulation of inducible NO synthase activity in activated macrophages by Procyanidins extracted from Pinus maritima (Pycnogenol().
In Flavonoids in Health and Disease, ed. Catherine A. Rice-Evans and Lester Packer, Marcel Dekker Inc. NY, 1998.Chapter 18. Pages 421-436.
 
88. Virgili, F., Kobuchi, H. and Packer, L. (1998)
Procyanidins extracted from Pinus maritima (Pycnogenol() scavengers of free radical species and modulators of nitrogen monoxide metabolism in activated murine raw 264.7 macrophages.
Free Radical Biology & Medicine 24 (7/8) 1120-1129.
 
89. Maritime Pine Plus® prolongs the lifetime of vitamin C more than other flavonoids.
Cossins, E., Lee, R. and Packer, L. (1998)
ESR studies of vitamin C regeneration, order of reactivity of natural source phytochemical preparations.
Biochem Mol. Biol. Int., 45 (3): 583-597.
 
90. Maritime Pine Plus® enhances the activity of the immune system in mice infected with a leukemia- causing retrovirus. Maritime Pine Plus® increases the natural killer cell cytotoxicity.
Cheshier, J.E., Ardestani-Kaboudanian, S., Liang B., Araghinicknam, M., Chung, S., Lane, L., Castro, A. and Watson, R.R. (1996)
Immuno-modulation by Maritime Pine Plus® in retro-virus infected or ethanol-fed mice.
Life Sci., 58(5): 87-96.
 
92. Maritime Pine Plus® increases human endurance during exercise by 21% providing antioxidant reserves.
Pavlovic, P. (1999)
Improved endurance by use of antioxidants.
European Bulletin of Drug Research, 7 (2): 26-29.
 
93. Pavlovic, P., Swanson, D. and Tirado, D. (1998)
Human response to physical stress improved by antioxidants.
Proeedings Oxygen Society meeting on 20th November, 1998 (Abstract).
 
94. Maritime Pine Plus® helps in gynaecological disorders such as endometriosis and dysmenorrhea. It reduces menstrual cramps, abdominal pain and tenderness.
Kohama, T. and Suzuki, N. (1999)
The treatment of gynaecological disorders with Maritime Pine Plus®.
European Bulletin of Drug Research, 7 (2):30-32.
 
95. Maritime Pine Plus® inhibits the accumulation of fat droplets in the fatty tissue, which may contribute to preventing obesity and maintaining optimal health.
Hasegawa, N. (2000)
Inhibition of lipogenesis by Pycnogenol.
Phytotherapy Research, 14: 472-473.
 
96. Maritime Pine Plus® stimulates lipolysis which may contribute to preventing obesity and maintaining optimal health.
Hasegawa, N. (1999)
Stimulation of lipolysis by Pycnogenol.
Phytotherapy Research, 13: 619-620.
 
97. Maritime Pine Plus® improves the morphology of spermatozoa. The percentage of non-deformed sperms in sub-fertile men was increased by 99% after supplementation with Maritime Pine Plus® for three months.
Roseff, S and Gulati, R. (1999)
Improvement of sperm quality by Maritime Pine Plus®.
European Bulletin of Drug Research, 7 (2): 33-36.
Roseff, S., Kessler, K. and Gulati, R. (1998)
Oral administration of Maritime Pine Plus®, A novel antioxidant affects baseline human sperm morphology, but not sperm count , motility or functions.
Proc. 54th Ann. Meet. Am. Soc. Reprod. Med.October,1998 in San Francisco, USA.
Fertility & Sterility 70(3): S-265-266.
 
98. Maritime Pine Plus®, its components and metabolites are bio-available in human for more than 24 hours to produce their beneficial effects.
Grosse-Düweler, K. and Rohdewald, P. (2000)
Urinary metabolites of French maritime pine bark extract in humans.
Pharmazie 55:364-368.
 
Bio-kinetics (absorption, metabolism and excretion) of Maritime Pine Plus® in healthy human subjects has been demonstrated by studying the excretion pattern of ferulic acid (one of the components of Maritime Pine Plus®).
Virgili, F., Pagana, G. Bourne, L., Rimbach, G., Natella, F., Rice-Evance, C and Packer, L. (2000)
Ferulic acid excretion as a marker of consumption of a French maritime pine (Pinus maritima) bark extract.
Free Radical Biology & Medicine, 28 (8)1249-1256.
 
99. Maritime Pine Plus® is shown to be bioavailable based on its therapeutic effects in vivo:- the prevention of platelet aggregation and the capillary sealing effect. Valerolactones as sulphates or glucronides appear in the urine and they represent the active metabolites of Maritime Pine Plus®.
Rohdewald, P. (1999)
Bioavailabilty and metabolism of Maritime Pine Plus®.
European Bulletin of Drug Research, 7 (2): 5-7.

 

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