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Ginkgo biloba (EGb 761) in arteriosclerosis prophylaxis

Arteriosklerose-Prophylaxe mit Ginkgo biloba (EGb 761)

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Zusammenfassung

Die Vorbeugung oder Verzögerung der Arterioskleroseentstehung ist eine der bedeutsamsten Anti-Aging-Maßnahmen, da dies eine Möglichkeit zur Vermeidung von Myokardinfarkt und Schlaganfall ist. Der Erreichung dieses prophylaktischen Zieles kann möglicherweise eine phytochemische Behandlung dienen, die der Peroxidation von Blutlipiden aufgrund ihrer Radikalfängereigenschaften für reaktive Sauerstoffspecies (ROS) entgegenwirkt. So sind zum Beispiel oxidierte LDL-Partikel hochatherogen. Auf diesem Hintergrund erforschten wir in einer Pilotstudie die Wirkung von Ginkgo biloba (EGb 761, Rökan®novo), dessen Fängereigenschaften freier Sauerstoffradikale ausführlich dokumentiert sind, auf die arteriosklerotische Nanoplaquebildung bei kardiovaskulären Hochrisikopatienten. Bei acht Patienten, die sich einer aortokoronaren Bypass-Operation unterziehen mussten, betrug die Reduktion der arteriosklerotischen Nanoplaquebildung nach einer 2-monatigen Therapie mit Ginkgo biloba-Spezialextrakt (EGb 761, 2 × 120 mg täglich, Rökan®novo, Spitzner Arzneimittel, Ettlingen, Deutschland) im Mittel 11,9 ± 2,5 % (p < 0,0078) und der Nanoplaquegröße 24,4 ± 8,1 % (p < 0,0234). Zusätzlich war die Superoxiddismutase (SOD)-Aktivität um 15,7 ± 7,0 % (p < 0,0391) aufreguliert, der Quotient oxLDL/LDL um 17,0 ± 5,5 % (p < 0,0234) erniedrigt und die Lipoprotein(a)-Konzentration um 23,4 ± 7,9 % (p < 0,0234) im Patientenblut nach der 2-monatigen Ginkgo-Einnahme vermindert. Die Konzentration der gefäßerweiternden Substanzen cAMP und cGMP war um 37,5 ± 9,1 % (p < 0,0078) bzw. um 27,7 ± 8,3 % (p < 0,0156) erhöht. Eine multimodale Regressions analyse ergab die Basis für eine mechanistische Erklärung der Nanoplaquereduktion unter Ginkgo-Behandlung. Der Arteriosklerose-hemmende Effekt ist der Aktivitätserhöhung der körpereigenen Radikalfängerenzyme zuzuschreiben sowie einer Beeinträchtigung der Risikofaktoren oxLDL/LDL und Lp(a). Weiterhin wurde das Offenhalten des Bypasses durch die signifikante Erhöhung der gefäßerweiternden cAMP- und cGMP-Konzentrationen kräftig unterstützt.

Summary

The prevention or deceleration of atherogenesis is one of the most significant anti-aging objectives since this is a matter of avoidance of myocardial infarction and stroke. To approach this prophylactic aim, phytochemical nutrition counteracting peroxidation of blood lipids based on their scavenger qualities for reactive oxygen species (ROS) can possibly serve. For example, oxidized LDL particles are highly atherogenic. Against this background, we investigated in a pilot study the effect of Ginkgo biloba (EGb 761: Rökan®novo), the free oxygen radical scavenging properties of which are well-documented, on the atherosclerotic nanoplaque formation in cardiovascular high-risk patients. In eight patients who had undergone an aortocoronary bypass operation, the reduction of atherosclerotic nanoplaque formation amounted to 11.9 ± 2.5% (p < 0.0078) and of nanoplaque size to 24.4 ± 8.1% (p < 0.0234), respectively, after a 2-month therapy with Ginkgo biloba extract (EGb 761, 2 × 120 mg daily, Rökan®novo, Spitzner Arzneimittel, Ettlingen, Germany). Additionally, superoxide dismutase (SOD) activity was upregulated by 15.7 ± 7.0% (p < 0.0391), the quotient oxLDL/LDL lowered by 17.0 ± 5.5% (p < 0.0234) and lipoprotein(a) concentration decreased by 23.4 ± 7.9% (p < 0.0234) in the patients' blood after the 2-month medication regimen. The concentration of the vasodilating substances cAMP and cGMP was augmented by 37.5 ± 9.1% (p < 0.0078) and 27.7 ± 8.3% (p < 0.0156), respectively. A multimodal regression analysis reveals a basis for a mechanistic explanation of nanoplaque reduction under ginkgo treatment. The atherosclerosis inhibiting effect is due to an upregulation in the body's own radical scavenging enzymes and an attenuation of the risk factors oxLDL/LDL and Lp(a). Furthermore, the significant increase in the vasodilator cAMP and cGMP concentration powerfully supports the maintenance of an open bypass.

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References

  • Siegel G, Malmsten M (2005) Molecular model for athero/arteriosclerosis, patent EP 0 946 876

  • Siegel G, Malmsten M, Klüßendorf D, Walter A, Schmidt A (1997) Chemistry, recognition and function of a natural shear stress biosensor. ACS Polym Mater Sci Eng 76: 573–575

    CAS  Google Scholar 

  • Siegel G, Malmsten M, Klüßendorf D, Michel F (2001) A receptor-based biosensor for lipoprotein docking at the endothelial surface and vascular matrix. Biosensors & Bioelectronics 16: 895–904

    Article  CAS  Google Scholar 

  • Siegel G, Abletshauser C, Malmsten M, Schmidt A, Winkler K (2003) Reduction of arteriosclerotic nanoplaque formation and size by fluvastatin in a receptor-based biosensor model. Cardiovasc Res 58: 696–705

    Article  PubMed  CAS  Google Scholar 

  • Malmsten M, Claesson P, Siegel G (1994) Forces between proteoheparan sulfate layers adsorbed at hydrophobic surfaces. Langmuir 10: 1274–1280

    Article  CAS  Google Scholar 

  • Siegel G, Malmsten M, Klüßendorf D, Leonhardt W (1999) Physicochemical binding properties of the proteoglycan receptor for serum lipoproteins. Atherosclerosis 144: 59–67

    Article  PubMed  CAS  Google Scholar 

  • Siegel G, Abletshauser C, Malmsten M, Klüßendorf D (2002) The acute effect of fluvastatin on lipoprotein deposition in a model substrate for ellipsometry studies at an endothelial membrane equivalent. Desalination 148: 407–414

    Article  CAS  Google Scholar 

  • Malmsten M, Siegel G, Wood WG (2000) Ellipsometry studies of lipoprotein adsorption. J Colloid Interface Sci 224: 338–346

    Article  PubMed  CAS  Google Scholar 

  • Holgado Madruga M, De Castro S, Macías-Núñez JF (1995) Effects of Ginkgo biloba extract (EGb 761) on brain aging and oxygen free-radical metabolism in the rat. In: Christen Y et al (eds) Advances in Gingko biloba Extract Research, vol 4 Effects of Ginkgo biloba Extract (EGb 761) on Aging and Age-Related Disorders. Elsevier, Paris, pp 71–76

    Google Scholar 

  • Delaflotte S, Auguet M, DeFeudis FV, Baranes J, Clostre F, Drieu K, Braquet P (1984) Endothelium-dependent relaxation of rabbit isolated aorta produced by carbachol and by Ginkgo biloba extract. Biomed Biochim Acta 43: 212–216

    CAS  Google Scholar 

  • Ozkur MK, Bozkurt MS, Balabanli B, Aricioglu A, Ilter N, Gürer MA, Inalöz HS (2002) The effects of EGb 761 on lipid peroxide levels and superoxide dismutase activity in sunburn. Photodermatol Photoimmunol Photomed 18: 117–120

    Article  PubMed  CAS  Google Scholar 

  • Lotito SB, Actis-Goretta L, Renart ML, Caligiuri M, Rein D, Schmitz HH, Steinberg FM, Keen CL, Fraga CG (2000) Influence of oligomer chain length on the antioxidant activity of procyanidins. Biochem Biophys Res Commun 276: 945–951

    Article  PubMed  CAS  Google Scholar 

  • Mao GD, Thomas PD, Lopaschuk GD, Poznansky MJ (1993) Superoxide dismutase (SOD)-catalase conjugates. Role of hydrogen peroxide and the Fenton reaction in SOD toxicity. J Biol Chem 268: 416–420

    PubMed  CAS  Google Scholar 

  • Worthley S, Osende J, Helft G, Badimon J, Fuster V (2001) Coronary artery disease: Pathogenesis and acute coronary syndromes. Mt Sinai J Med 68: 167–181

    PubMed  CAS  Google Scholar 

  • Sasaki S, Kuwahara N, Kunitomo K, Harada S, Yamada T, Azuma A, Takeda K, Nakagawa M (2002) Effects of atorvastatin on oxidized low-density lipoprotein, low-density lipoprotein subfraction distribution, and remnant lipoprotein in patients with mixed hyperlipoproteinemia. Am J Cardiol 89: 386–389

    Article  PubMed  CAS  Google Scholar 

  • Scholz M, Kraft HG, Lingenhel A, Delport R, Vorster E, Bickeböller H, Utermann G (1999) Genetic control of lipoprotein(a) concentrations is different in Africans and Caucasians. Eur J Hum Genet 7: 169–178

    Article  PubMed  CAS  Google Scholar 

  • Tsimikas S, Lau HK, Han K-R, Shortal B, Miller ER, Segev A, Curtiss LK, Witztum JL, Strauss BH (2004) Percutaneous coronary intervention results in acute increases in oxidized phospholipids and lipoprotein(a): Shortterm and long-term immunologic responses to oxidized low-density lipoprotein. Circulation 109: 3164–3170

    Article  PubMed  CAS  Google Scholar 

  • Silaste M-L, Rantala M, Alfthan G, Aro A, Witztum JL, Kesäniemi YA, Hörkkö S (2004) Changes in dietary fat intake alter plasma levels of oxidized low-density lipoprotein and lipoprotein(a). Arterioscler Thromb Vasc Biol 24: 498–503

    Article  PubMed  CAS  Google Scholar 

  • Dangas G, Ambrose J, D'Agate D, Shao J, Chockalingham S, Levine D, Smith D (1999) Correlation of serum lipoprotein(a) with the angiographic and clinical presentation of coronary artery disease. Am J Cardiol 83: 583–585

    Article  PubMed  CAS  Google Scholar 

  • Manning GS (1969) Limiting laws and counterion condensation in polyelectrolyte solutions. I. Colligative properties. J Chem Phys 51: 924–933

    Article  CAS  Google Scholar 

  • Manning GS (1969) Limiting laws and counterion condensation in polyelectrolyte solutions. II. Self-diffusion of the small ions. J Chem Phys 51: 934–938

    Article  Google Scholar 

  • Koch E, Chatterjee SS (1993) Experimentelle Grundlagen für die therapeutische Anwendung von Ginkgoextrakt EGb 761. Hämostaseologie 13: 11–27

    CAS  Google Scholar 

  • Ren DC, Du G-H, Zhang JT (2002) Protective effect of Ginkgo biloba extract on endothelial cell against damage induced by oxidative stress. J Cardiovasc Pharmacol 40: 809–814

    Article  PubMed  CAS  Google Scholar 

  • Broadus AE, Northcutt RC, Hardman JG, Sutherland EW, Liddle GW (1970) Effects of glucagon on adenosine 3'-5'-monophosphate and guanosine 3'-5'-monophosphate in human plasma and urine. J Clin Invest 49: 2237–2245

    Article  PubMed  CAS  Google Scholar 

  • Nimpf J, Gries A, Wurm H, Kostner GM (1985) Influence of beta 2-glycoprotein-I upon the content of cAMP and cGMP in human blood platelets. Thromb Haemost 54: 824–827

    PubMed  CAS  Google Scholar 

  • Baumann R, Blass C, Gotz R, Dragon S (1999) Ontogeny of catecholamine and adenosine receptor-mediated cAMP signaling of embryonic red blood cells: role of cGMP-inhibited phosphodiesterase 3 and hemoglobin. Blood 94: 4314–4320

    PubMed  CAS  Google Scholar 

  • Ahloulay M, Déchaux M, Laborde K, Bankir L (1995) Influence of glucagon on GFR and on urea and electrolyte excretion: direct and indirect effects. Am J Physiol 269: F225–F235

    PubMed  CAS  Google Scholar 

  • Quinlan MC, O'Donnell MJ (1998) Anti-diuresis in the blood-feeding insect Rhodnius prolixus Stål: antagonistic actions of cAMP and cGMP and the role of organic acid transport. J Insect Physiol 44: 561–568

    Article  PubMed  CAS  Google Scholar 

  • Abletshauser C, Klüßendorf D, Schmidt A, Winkler K, März W, Buddecke E, Malmsten M, Siegel G (2002) Biosensing of arteriosclerotic nanoplaque formation and interaction with an HMG-CoA reductase inhibitor. Acta Physiol Scand 176: 131–145

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurophysiology, Charité – Universitätsmedizin Berlin, Berlin, Germany

    Günter Siegel & Petra Schäfer

  2. Institute of Clinical Chemistry, University Clinic Freiburg, Freiburg, Germany

    Karl Winkler

  3. Institute of Pharmacy, Department of Physical Chemistry, Uppsala University, Uppsala, Sweden

    Martin Malmsten

Authors
  1. Günter Siegel
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  2. Petra Schäfer
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  3. Karl Winkler
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  4. Martin Malmsten
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Correspondence to Günter Siegel.

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Siegel, G., Schäfer, P., Winkler, K. et al. Ginkgo biloba (EGb 761) in arteriosclerosis prophylaxis. Wien Med Wochenschr 157, 288–294 (2007). https://doi.org/10.1007/s10354-007-0426-6

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  • DOI: https://doi.org/10.1007/s10354-007-0426-6

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