Dr. Willmar Schwabe III, a German physician-pharmacist, introduced Ginkgo biloba leaf extracts into medical practice in 1965. The earliest publications concerning the therapeutic use of these extracts dealt with their actions on cerebral and peripheral disturbances of blood flow. These extracts led to the development of the extract named EGb 761® (definition see editorial). Clinical studies conducted during the past 25 years have revealed that EGb 761® is useful in treating a wide range of symptoms associated with both early cognitive decline and more severe types of senile dementia of primary degenerative, vascular and mixed origin, as well as peripheral arterial occlusive diseases and various neurosensory disturbances. Laboratory experiments conducted during the past two decades have revealed that several effects of EGb 761® - vasoregulatory, antioxidant, neuroprotective, and anti-stress effects, as well as effects on learning and memory and on gene-regulation - caused by various active constituents of the extract (or their metabolites) act in a complementary manner in producing health-related benefits.
References
-
1
Ahlemeyer B, Junker V, Huhne R, Krieglstein J.
Neuroprotective effects of NV-31, a bilobalide-derived compound: Evidence for an antioxidative mechanism.
Brain Res.
2001;
890
338-342
-
2
Aldridge W N, Street B W, Skilleter D N.
Oxidative phosphorylation. Halide-dependent and halide-independent effects of triorganotin and trioganolead compounds on mitochondrial functions.
Biochem J.
1977;
168
353-364
-
3
Amri H, Ogwuegbu S O, Boujrad N, Drieu K, Papadopoulos V.
In vivo regulation of the peripheral-type benzodiazepine receptor and glucocorticoid synthesis by the Ginkgo biloba extract EGb 761® and isolated ginkgolides.
Endocrinology.
1996;
137
5707-5718
-
4
Anadere I, Chmiel H, Witte S.
Hemorheological findings in patients with completed stroke and the influence of a Ginkgo biloba extract.
Clin Hemorheol.
1985;
5
411-420
-
5
Artmann G A, Schikarski C.
Ginkgo biloba extract (EGb 761®) protects red blood cells from oxidative damage.
Clin Hemorheol.
1993;
13
529-539
-
6
Attella M J, Hoffman S W, Stasio M J, Stein D J.
Ginkgo biloba extract facilitates recovery from penetrating brain injury in adult male rats.
Exp Neurol.
1989;
105
62-71
-
7
Auguet M, DeFeudis F V, Clostre F.
Effects of Ginkgo biloba on arterial smooth muscle responses to vasoactive stimuli.
Gen Pharmacol.
1982;
13
169-171
-
8 Auguet M, Delaflotte S, Chabrier P E, Braquet P. Ginkgo biloba extract (EGb 761®) and the regulation of vascular tone. In: Clostre F., DeFeudis FV, editors Advances in Ginkgo biloba extract research, vol. 3. Cardiovascular effects of Ginkgo biloba extract (EGb 761®). Paris; Elsevier 1994: pp. 19-26
-
9
Backhauß C, Karkoutly C, Welsch M, Krieglstein J.
A mouse model of focal cerebral ischemia for screening neuroprotective drug effects.
J Pharmacol Meth.
1992;
27
27-32
-
10
Barkats M, Venault P, Christen Y, Cohen-Salmon C.
Effect of long-term treatment with EGb 761® on age-dependent structural changes in the hippocampi of three inbred mouse strains.
Life Sci.
1995;
56
213-222
-
11
Blume J, Kieser U, Hölscher U.
Placebo-kontrollierte Doppelblindstudie zur Wirksamkeit von Ginko-biloba-Spezialextrakt EGb 761® bei austrainierten Patienten mit Claudicatio intermittens.
VASA.
1996;
25
265-274
-
12
Chandrasekaran K, Mehrabian Z, Spinnewyn B, Drieu K, Fiskum G.
Neuroprotective effects of bilobalide, a component of the Ginkgo biloba extract (EGb 761®), in gerbil global brain ischemia.
Brain Res.
2001;
922
282-292
-
13 Chatterjee S S. Effects of Ginkgo biloba extract on cerebral metabolic processes. In: Agnoli A, Rapin JR, Scapagnini V, Weitbrecht WV, editors Effects of Ginkgo biloba on organic cerebral impairment. London; John Libbey 1985: pp. 5-14
-
14 Chatterjee S S, Gabard B L, Jaggy H EW. Pharmaceutical compositions containing bilobalid for the treatment of neuropathies. U. S. Patent No. 4,571,407 (Feb. 18, 1986).
-
15
Chatterjee S S, Nöldner M.
Behavioural observations demonstrating influences of the extract of Ginkgo biloba (EGb 761®) on some specific central cholinergic systems.
Naunyn-Schmiedeberg’s Arch Pharmacol.
1989;
339 (Suppl.)
Abstr. 425
-
16
Chermat R, Brochet D, DeFeudis F V, Drieu K.
Interactions of Ginkgo biloba extract (EGb 761®), diazepam and ethyl β-carboline-3-carboxylate on social behavior of the rat.
Pharmacol Biochem Behav.
1997;
56
333-339
-
17 Continella G, Drago F. Behavioral effects of Ginkgo-biloba extract. In: Agnoli A, Rapin JR, Scapagnini V, Weitbrecht WV, editors Effects of Ginkgo biloba on organic cerebral impairment. London; John Libbey 1985: pp. 35-42
-
18 DeFeudis F V. Ginkgo biloba extract (EGb 761®): Pharmacological activities and clinical applications. Paris; Elsevier 1991
-
19 DeFeudis F V. Ginkgo biloba extract (EGb 761®): From chemistry to the clinic. Wiesbaden; Ullstein-Mosby 1998
-
20
Delaflotte S, Auguet M, DeFeudis F V, Baranes J, Clostre F, Drieu K.
Endothelium-dependent relaxation of rabbit isolated aorta produced by carbachol and by Ginkgo biloba extract.
Biomed Biochim Acta.
1984;
43 (Suppl.)
212-216
-
21
Del Tredici P.
Ginkgos and people: A thousand years of interaction.
Arnoldia.
1991;
51
2-15
-
22
Ernst E.
Ginkgo biloba in the treatment of intermittent claudication. A systematic search based on controlled studies in the literature [In German].
Fortschr Med.
1996;
114
85-87
-
23
Ernst E, Pittler M H.
Ginkgo biloba and dementia: A systematic review of double-blind, placebo-controlled trials.
Clin Drug Invest.
1999;
17
301-308
-
24
Fitzpatrick D F, Bing B, Rohdewald P.
Endothelium-dependent vascular effects of pycnogenol.
J Cardiovasc Pharmacol.
1998;
32
509-515
-
25
Gohil K, Moy R K, Farzin S, Maguire J J, Packer L.
mRNA expression profile of a human cancer cell line in response to Ginkgo biloba extract: Induction of antioxidant response and the Golgi system.
Free Radic Res.
2000;
33
831-849
-
26
Hellegouarch A, Baranes J, Clostre F, Drieu K, Braquet P, DeFeudis F V.
Comparison of the contractile effects of an extract of Ginkgo biloba and some neurotransmitters on rabbit isolated vena cava.
Gen Pharmacol.
1985;
16
129-132
-
27
Hofferberth B.
The efficacy of EGb 761® in patients with senile dementia of the Alzheimer type, a double-blind, placebo-controlled study on different levels of investigation.
Human Psychopharmacol.
1994;
9
215-222
-
28
Itil T, Martorano D.
Natural substances in psychiatry (Ginkgo biloba in dementia).
Psychopharmacol Bull.
1995;
31
147-158
-
29
Jaggy H, Koch E.
Chemistry and biology of alkylphenols from Ginkgo biloba L.
Pharmazie.
1997;
52
735-738
-
30
Janssens D, Michiels C, Delaive E, Eliaers F, Drieu K, Remacle J.
Protection of hypoxia-induced ATP decrease in endothelial cells by Ginkgo biloba extract and bilobalide.
Biochem Pharmacol.
1995;
50
991-999
-
31
Kanowski S, Herrmann W M, Stephan K, Wierich W, Hörr R.
Proof of efficacy of the Ginkgo biloba special extract EGb 761® in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia.
Pharmacopsychiat.
1996;
29
47-56
-
32
Kleijnen J, Knipschild P.
Ginkgo biloba.
Lancet.
1992;
340
1136-1139
-
33
Kleijnen J, Knipschild P.
Ginkgo biloba for cerebral insufficiency.
Br J Clin Pharmacol.
1992;
34
352-358
-
34
Larsen R G, Dupeyron J P, Boulu R G.
Experimental models of cerebral ischemia in the rat using microspheres: Study of the effects of two extracts of Ginkgo biloba and naftidrofuryl.
[In French] Thérapie.
1978;
33
651-660
-
35
Le Bars P L, Katz M M, Berman N, Itil T M, Freedman A M, Schatzberg A F.
A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia.
JAMA.
1997;
278
1327-1332
-
36
Letzel H, Haan J, Feil W B.
Nootropics: Efficacy and tolerability of products from three active substance classes.
J Drug Dev Clin Pract.
1996;
8
77-94
-
37
Letzel H, Schoop W.
Ginkgo biloba extract EGb 761® and pentoxifylline in intermittent claudication: Secondary analysis of clinical studies.
[In German] VASA.
1992;
21
403-410
-
38
Mizuno M, Packer L.
Ginkgo biloba extract EGb 761® is a suppressor of AP-1 transcription factor stimulated by PMA.
Biochem Molec Biol Int.
1996;
39
395-401
-
39
Monte M, Davel L E, de Lustig E S.
Inhibition of lymphocyte-induced angiogenesis by free radical scavengers.
Free Radic Biol Med.
1994;
17
259-266
-
40
Oken B S, Storzbach D M, Kaye J A.
The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease.
Arch Neurol.
1998;
55
1409-1415
-
41
Papadopoulos V, Kapsis A, Li H, Amri H, Hardwick M, Culty M ,. et al .
Drug-induced inhibition of the peripheral-type benzodiazepine receptor expression and cell proliferation in human breast cancer cells.
Anticancer Res.
2000;
20
2835-2847
-
42
Pietri S, Maurelli E, Drieu K, Culcasi M.
Cardioprotective and antioxidant effects of the terpenoid constituents of Ginkgo biloba extract (EGb 761®).
J Mol Cell Cardiol.
1997;
29
733-742
-
43
Pincemail J, Dupuis M, Nasr C, Hans P, Haag-Berrurier M, Anton R ,. et al .
Superoxide anion scavenging effect and superoxide dismutase activity of Ginkgo biloba extract.
Experientia.
1989;
45
708-712
-
44
Pittler M H, Ernst E.
Ginkgo biloba extract for the treatment of intermittent claudication: A meta-analysis of randomized trials.
Am J Med.
2000;
108
276-281
-
45
Porsolt R D, Martin P, Lenègre A, Fromage S, Drieu K.
Effects of an extract of Ginkgo biloba (EGb 761®) on ”learned helplessness” and other models of stress in rodents.
Pharmacol Biochem Behav.
1990;
36
963-971
-
46
Prehn J HM, Krieglstein J.
Platelet-activating factor antagonists reduce excitotoxic damage in cultured neurons from embryonic chick telencephalon and protect the rat hippocampus and neocortex from ischemic injury in vivo.
J Neurosci Res.
1993;
34
179-188
-
47
Rapin J R, Lamproglou I, Drieu K, DeFeudis F V.
Demonstration of the ”anti-stress” activity of an extract of Ginkgo biloba (EGb 761®) using a discrimination learning task.
Gen Pharmacol.
1994;
25
1009-1016
-
48
Sancesario G, Kreutzberg G W.
Stimulation of astrocytes affects cytotoxic brain edema.
Acta Neuropath.
1986;
72
3-14
-
49
Schindowski K, Leutner S, Kressmann S, Eckert A, Muller W E.
Age-related increase of oxidative stress-induced apoptosis in mice: Prevention by Ginkgo biloba extract (EGb 761®).
J Neural Transm.
2001;
108
969-978
-
50
Schneider B.
Ginkgo biloba extract in peripheral arterial occlusive disease. Meta-Analysis of controlled clinical studies.
[In German] Arzneimittelforscg.
1992;
42
428-436
-
51
Spinnewyn B, Blavet N, Clostre F.
Effet de l’extrait de Ginkgo biloba sur un modèle d’ischémie cérébrale chez la gerbille.
Press Méd.
1986;
15
1511-1515
-
52
Watanabe C M, Wolffram S, Ader P, Rimbach G, Packer L, Maguire J J,. et al .
The in vivo neuromodulatory effects of the herbal medicine Ginkgo biloba.
Proc Natl Acad Sci USA.
2001;
98
6577-6580
-
53 Weiss H. Summary of a biometric evaluation of clinical trials intended to provide evidence for the clinical efficacy of Ginkgo biloba extract (EGb 761®). Part I: Indication ”disturbance of cerebral function”. Internal Report, Dr. Willmar Schwabe GmbH & Co Karlsruhe; 1988
-
54
Weiss H, Kallischnigg G.
Ginkgo biloba extract (EGb 761®): Meta-analysis of studies of the effects in peripheral arterial occlusive disease.
[In German] Münch Med Wschr.
1991;
133
138-142
-
55
Weitbrecht W U, Jansen W.
Primary degenerative dementia: Therapy with Ginkgo biloba extract. Placebo-controlled double-blind and comparative study.
[Article in German] Fortschr Med.
1986;
104
199-202
-
56
Winter E.
Effects of an extract of Ginkgo biloba on learning and memory in mice.
Pharmacol Biochem Behav.
1991;
38
109-114
Dr. Francis V. DeFeudis
Institute for BioScience
153 West Main Street
Westboro, MA 01581
U.S.A
Phone: +1 (508) 898-2689
Fax: +1 (508) 898-2689
Email: defeudis@gis.net
