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Ginkgo (Ginkgo biloba)

Synonyms / Common Names / Related Terms
Adiantifolia, AKL1, arbre aux quarante écus, ArginMax®, bai guo ye, baiguo, BioGinkgo®, Blackmores Ginkgo Brahmi (Bacopa monniera), BN-52063, duck foot tree, EGb, EGb 761, Elefantenohr, Eun-haeng, facherblattbaum, Fossil tree, GBE, GBE 24, GBX, ginan, Gincosan®, Ginexin Remind®, gingko, Gingopret®, Ginkai®, ginkgo balm, Ginkgo biloba blätter, Ginkgo biloba exocarp polysaccharides (GBEP), Ginkgo folium, Ginkgo Go®, Ginkgo Phytosome®, Ginkgo Powder®, Ginkgoaceae (family), ginkgoblätter, ginkgogink, Ginkgold®, ginkgopower, Ginkopur®, ginkyo, gin-nan, Herbal vX®, icho, ityo, Japanbaum, Japanese silver apricot, kew tree, kung sun shu, LI 1370, maidenhair tree, noyer du Japon, oriental plum tree, pei kuo, pei-wen, Pterophyllus, Pterophyllus salisburiensis, Rokan, Rö Kan®, salisburia, Salisburia adiantifolia, Salisburia macrophylla, Seredin, silver apricot, sophium, Tanakan, tanakene, tebofortan, tebonin, tempeltrae, temple balm, tramisal, valverde, vasan, vital, ya chio, yin-guo, yin-hsing.

Mechanism of Action
  • Constituents: Flavonoids (glycosides) and terpenoids (ginkgolide, bilobalide) are considered to be Ginkgo's primary active components.14,15,16,17,18,19 Other constituents include 6-hydroxykynurenic acid.20 Most studies have been conducted with the standardized Ginkgo preparation EGb 761 (24% ginkgo flavone glycosides, 6% terpenoids), or LI 1370 (25% ginkgo flavone glycosides, 6% terpenoids).
  • The pharmcaceutical quality of different Ginkgo biloba brands has been investigated.21 It was determined that many available brands do not have levels of certain constituents equivalent to those stated in the German Commission E Ginkgo monograph (for example, flavone glycosides, terpenlactones, and ginkgolides).
  • Antioxidant/Anti-inflammatory effects: Ginkgo significantly decreased platelet MDA-thiobarbituric acid reacting substances, in supplemented humans.22 Flavonoids serve as free-radical scavengers and have been shown to reduce oxidative stress in human models.23,24,25,26,1,27,2,28,29 This mechanism is hypothesized to reduce oxidative cellular damage in Alzheimer's disease and has prompted theories that Ginkgo may have favorable effects on reperfusion injury.30,31,32,33,34,35,36 Ginkgolides inhibit receptor binding of platelet activating factor (PAF), which may mediate beneficial clinical effects.37,38,39,40,41,42,43,44,45,46,47,48,49 PAF is pro-inflammatory, induces platelet aggregation, and contracts bronchial smooth muscle.50 Ginkgo has been found to increase corticosteroid secretion in rats.51
  • Coagulation effects: Ginkgo biloba extract decreased plasma D-dimer concentration, a marker of intravascular coagulation, in chronic peritoneal dialysis patients.52 Blood levels of fibrinogen, von Willebrand factor, hs-CRP, albumin and liver enzyme levels were not significantly changed. No bleeding episode was reported. These results suggested that Ginkgo biloba extract was effective in partially reversing the thrombogenic coagulation profile without increasing the risk of bleeding. A controlled clinical trial found that dry extract of Ginkgo biloba reduced blood viscosity more than Allium sativum (garlic).5 In a study in male subjects, Ginkgo use had no effect on international normalized ratio of prothrombin time or platelet aggregation.53 In combination with warfarin, Ginkgo at recommended doses did not significantly affect clotting status, or the pharmacokinetics, or pharmacodynamics of warfarin in healthy subjects.
  • CYP450 effects: Based on an open-label study, significant decreases in midazolam concentrations following Ginkgo biloba extract (GBE) administration suggested that GBE may induce CYP3A metabolism.10 Lopinavir, ritonavir, and fexofenadine exposures were not significantly affected by GBE administration.
  • MAOI effects: Monoamine oxidase (MAO) inhibition by Ginkgo has been reported in animals6 but has not been confirmed by subsequent animal research.7 One human study did not demonstrate significant changes in human brain MAO A or B, measured by positron emission tomography after one month of 120mg Ginkgo daily in a small human sample.8
  • Neurotransmitter effects: Neuroprotective properties have been attributed to inhibition of age-related decline of adrenergic and cholinergic receptors.54,55,56,57 Ginkgo has been found to increase serotonin levels, increase muscarinic binding sites, and increase serum levels of acetylcholine and norepinephrine.58
  • Ocular effects: Although improved vision was observed in a case report3, no effect of Ginkgo on ocular blood flow was observed in clinical study.59
  • Platelet inhibitory effects: Ginkgo supplementation inhibited platelet aggregation in healthy volunteers.60 In vitro, Ginkgo inhibited platelet aggregation.60
  • Vascular effects: Ginkgo has been found to have vasodilatory effects, which have been attributed to stimulation of endothelium-derived relaxing factor (EDRF) and prostacyclin release. Studies have suggested that Ginkgo inhibits nitric oxide, causing vascular relaxation.4,11,12,13 In a controlled single-blind study of 10 healthy human subjects61, and a controlled crossover study of patients with known claudication62, Ginkgo was shown to significantly increase blood capillary flow and decrease erythrocyte aggregation.
  • Other: An in vitro study has demonstrated Ginkgo to promote proliferation of human skin fibroblasts.9 Ginkgo biloba extract promotes EPC proliferative, migratory, adhesive, and in vitro vasculogenesis capacity, therefore, promoting EPC augmentation and enhancing its functional activity.63

  • Oral bioavailability of the terpene lactones ginkgolide A, ginkgolide B, and bilobalide are 98-100%, 79-93%, and 70%, respectively. Absorption has been found to occur principally via the small intestine. Half-life of ginkgolides A and B, and bilobalide have been found to be 4.5, 10.6, and 3.2 hours, respectively, with peak plasma levels at 2-3 hours. Approximately 70% of ginkgolide A, 50% of ginkgolide B, and 30% of bilobalide are excreted unchanged in urine, with seven other metabolites detectable in the urine but undetectable in serum. Toxicity is low, with an oral LD50 in mice of 7,725mg.64,65 Duration of action has been reported as seven hours. One study showed that after the oral administration of GBE (160mg) to healthy volunteers, the plasma concentrations of ginkgolides A and B and bilobalide were 41.8, 5.6 and 37.6ng/mL, respectively.18
  • Ten adult volunteers with an average age of 28 years were given a single oral dose of six tablets of Ginkgo biloba extract. Quercetin and kaempferol in human urine were determined by using RP-HPLC.66,67 The results showed that the elimination rate constant k and the absorption rate constant ka of quercetin were slightly more than that of kaempferol, and the absorption half-life (t1/2a), the elimination half-life (t1/2), and tmax of quercetin were less than that of kaempferol; the differences were, however, not statistically significant. The mean values of ka were 0.61 h(-1) and 0.55 h(-1), t1/2a 1.51 h and 1.56 h, k 0.37 h(-1) and 0.30 h(-1), t1/2 2.17 h and 2.76 h, tmax 2.30 h and 2.68 h for quercetin and kaempferol, respectively; mean absorption and elimination of quercetin and kaempferol are 0.17% and 0.22%, respectively. Quercetin and kaempferol are excreted in human urine mainly as glucuronides.

  1. Droy-Lefaix MT. Effect of the antioxidant action of ginkgo biloba extract (EGb 761) on aging and oxidative stress. Age 1997;20:141-149.
  2. Marcocci, L., Packer, L., Droy-Lefaix, M. T., Sekaki, A., and Gardes-Albert, M. Antioxidant action of Ginkgo biloba extract EGb 761. Methods Enzymol 1994;234:462-475. 7808320
  3. Dorairaj, S., Ritch, R., and Liebmann, J. M. Visual improvement in a patient taking ginkgo biloba extract: a case study. Explore (NY) 2007;3(4):391-395. 17681260
  4. Chen, X., Salwinski, S., and Lee, T. J. Extracts of Ginkgo biloba and ginsenosides exert cerebral vasorelaxation via a nitric oxide pathway. Clin Exp Pharmacol Physiol 1997;24(12):958-959. 9406663
  5. Galduroz, J. C., Antunes, H. K., and Santos, R. F. Gender- and age-related variations in blood viscosity in normal volunteers: a study of the effects of extract of Allium sativum and Ginkgo biloba. Phytomedicine 2007;14(7-8):447-451. 17618098
  6. White, H. L., Scates, P. W., and Cooper, B. R. Extracts of Ginkgo biloba leaves inhibit monoamine oxidase. Life Sci 1996;58(16):1315-1321. 8614288
  7. Porsolt, R. D., Roux, S., and Drieu, K. Evaluation of a ginkgo biloba extract (EGb 761) in functional tests for monoamine oxidase inhibition. Arzneimittelforschung 2000;50(3):232-235. 10758773
  8. Fowler JS and et al. Evidence that Gingko biloba extract does not inhibit MAO A and B in living human brain. Life Sci 2000;66:141-146.
  9. Kim, Y. S., Pyo, M. K., Park, K. M., Park, P. H., Hahn, B. S., Wu, S. J., and Yun-Choi, H. S. Antiplatelet and antithrombotic effects of a combination of ticlopidine and ginkgo biloba ext (EGb 761). Thromb Res 7-1-1998;91(1):33-38. 9700851
  10. Robertson, S. M., Davey, R. T., Voell, J., Formentini, E., Alfaro, R. M., and Penzak, S. R. Effect of Ginkgo biloba extract on lopinavir, midazolam and fexofenadine pharmacokinetics in healthy subjects. Curr Med Res Opin 2008;24(2):591-599. 18205997
  11. Cheung, F., Siow, Y. L., Chen, W. Z., and O K. Inhibitory effect of Ginkgo biloba extract on the expression of inducible nitric oxide synthase in endothelial cells. Biochem Pharmacol 11-15-1999;58(10):1665-1673. 10535759
  12. Kudolo GB and Blodgett J. Effect of Ginkgo biloba ingestion on arachidonic acid metabolism in the platelets of type 2 diabetic subjects [abstract]. International Scientific Conference on Complementary, Alternative and Integrative Medicine Research, April 12-14 2002;
  13. Satoh, H. and Nishida, S. Electropharmacological actions of Ginkgo biloba extract on vascular smooth and heart muscles. Clin Chim Acta 2004;342(1-2):13-22. 15026263
  14. Biber, A. Pharmacokinetics of Ginkgo biloba extracts. Pharmacopsychiatry 2003;36 Suppl 1:S32-S37. 13130386
  15. Deng, F. and Zito, S. W. Development and validation of a gas chromatographic-mass spectrometric method for simultaneous identification and quantification of marker compounds including bilobalide, ginkgolides and flavonoids in Ginkgo biloba L. extract and pharmaceutical preparations. J Chromatogr A 1-31-2003;986(1):121-127. 12585329
  16. Diamond, B. J., Shiflett, S. C., Feiwel, N., Matheis, R. J., Noskin, O., Richards, J. A., and Schoenberger, N. E. Ginkgo biloba extract: mechanisms and clinical indications. Arch Phys Med Rehabil 2000;81(5):668-678. 10807109
  17. Sticher, O. Quality of Ginkgo preparations. Planta Med 1993;59(1):2-11. 8441775
  18. Satoh, H. Comparative Electropharmacological Actions of Some Constituents from Ginkgo biloba Extract in Guinea-pig Ventricular Cardiomyocytes. Evid Based Complement Alternat Med 2004;1(3):277-284. 15841261
  19. Victoire C, Haag-Berrurier M, Lobstein-Guth A, and et al. Isolation of flavonoid glycosides from Ginkgo biloba leaves. Planta Med 1988;54:245-247.
  20. Schennen, A. and Holzl, J. [6-Hydroxykynurenic Acid, the First N-Containing Compound from the Ginkgo biloba Leaf.]. Planta Med 1986;52(3):235-236. 17345251
  21. Kressmann, S., Muller, W. E., and Blume, H. H. Pharmaceutical quality of different Ginkgo biloba brands. J Pharm Pharmacol 2002;54(5):661-669. 12005361
  22. Kudolo, G. B., Delaney, D., and Blodgett, J. Short-term oral ingestion of Ginkgo biloba extract (EGb 761) reduces malondialdehyde levels in washed platelets of type 2 diabetic subjects. Diabetes Res Clin Pract 2005;68(1):29-38. 15811563
  23. Pietri S, Seguin JR, D'Arbigny P, and et al. Ginkgo biloba extract (EGb 761) pretreatment limits free radical-induced oxidative stress in patients undergoing coronary bypass surgery. Cardiovasc Drugs Ther 1997;11(2):121-131.
  24. Pietri, S., Maurelli, E., Drieu, K., and Culcasi, M. Cardioprotective and anti-oxidant effects of the terpenoid constituents of Ginkgo biloba extract (EGb 761). J Mol Cell Cardiol 1997;29(2):733-742. 9140830
  25. Artmann GM and Schikarski C. Ginkgo biloba extract (EGb 761) protects red blood cells from oxidative damage. Clin Hemorheol 1993;13(4):529-539.
  26. Akiba, S., Kawauchi, T., Oka, T., Hashizume, T., and Sato, T. Inhibitory effect of the leaf extract of Ginkgo biloba L. on oxidative stress-induced platelet aggregation. Biochem Mol Biol Int 1998;46(6):1243-1248. 9891858
  27. Dumont, E., Petit, E., Tarrade, T., and Nouvelot, A. UV-C irradiation-induced peroxidative degradation of microsomal fatty acids and proteins: protection by an extract of Ginkgo biloba (EGb 761). Free Radic Biol Med 1992;13(3):197-203. 1505777
  28. Marcocci, L., Maguire, J. J., Droy-Lefaix, M. T., and Packer, L. The nitric oxide-scavenging properties of Ginkgo biloba extract EGb 761. Biochem Biophys Res Commun 6-15-1994;201(2):748-755. 8003011
  29. Pincemail, J., Dupuis, M., Nasr, C., Hans, P., Haag-Berrurier, M., Anton, R., and Deby, C. Superoxide anion scavenging effect and superoxide dismutase activity of Ginkgo biloba extract. Experientia 8-15-1989;45(8):708-712. 2547645
  30. Szabo, M. E., Droy-Lefaix, M. T., and Doly, M. Direct measurement of free radicals in ischemic/reperfused diabetic rat retina. Clin Neurosci 1997;4(5):240-245. 9292250
  31. Janssens, D., Michiels, C., Delaive, E., Eliaers, F., Drieu, K., and Remacle, J. Protection of hypoxia-induced ATP decrease in endothelial cells by ginkgo biloba extract and bilobalide. Biochem Pharmacol 9-28-1995;50(7):991-999. 7575684
  32. Koltringer P, Langsteger W, and Eber O. Dose-dependent hemorheological effects and microcirculatory modifications following intravenous administration of ginkgo biloba special extract EGb 761. Clin Hemorheol 1995;15(4):649-656.
  33. Kose, K. and Dogan, P. Lipoperoxidation induced by hydrogen peroxide in human erythrocyte membranes. 1. Protective effect of Ginkgo biloba extract (EGb 761). J Int Med Res 1995;23(1):1-8. 7774754
  34. Oberpichler, H., Beck, T., Abdel-Rahman, M. M., Bielenberg, G. W., and Krieglstein, J. Effects of Ginkgo biloba constituents related to protection against brain damage caused by hypoxia. Pharmacol Res Commun 1988;20(5):349-368. 3420139
  35. Szabo, M. E., Droy-Lefaix, M. T., Doly, M., and Braquet, P. Free radical-mediated effects in reperfusion injury: a histologic study with superoxide dismutase and EGB 761 in rat retina. Ophthalmic Res 1991;23(4):225-234. 1945294
  36. Szabo, M. E., Droy-Lefaix, M. T., and Doly, M. EGb 761 and the recovery of ion imbalance in ischemic reperfused diabetic rat retina. Ophthalmic Res 1995;27(2):102-109. 8538982
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