Agnoli A.

Clinical and psychometric aspects of the therapeutic effects of GBE.

In: Effects of GBE and Organic Cerebral Impairment, Paris, London, John Lilley, 1985.

Allain H Raoul P Lieury A LeCoz F Gandon JM d'Arbigny P

Effect of two doses of ginkgo biloba extract (EGb 761) on the dual- coding test in elderly subjects.

In: Clin Ther (1993 May-Jun) 15(3):549-58

The subjects of this double-blind study were 18 elderly men and women (mean age, 69.3 years) with slight age-related memory impairment. In a crossover-study design, each subject received placebo or an extract of Ginkgo biloba (EGb 761) (320 mg or 600 mg) 1 hour before performing a dual-coding test that measures the speed of information processing; the test consists of several coding series of drawings and words presented at decreasing times of 1920, 960, 480, 240, and 120 ms. The dual-coding phenomenon (a break point between coding verbal material and images) was demonstrated in all the tests. After placebo, the break point was observed at 960 ms and dual coding beginning at 1920 ms. After each dose of the ginkgo extract, the break point (at 480 ms) and dual coding (at 960 ms) were significantly shifted toward a shorter presentation time, indicating an improvement in the speed of information processing.

Allard M

Treatment of the disorders of aging with Ginkgo biloba extract. From pharmacology to clinical medicine

In: PRESSE MED 1986 Sep 25; 15(31):1540-5 (Published in FRENCH)

Ginkgo biloba extract is prescribed in psychic and behavioural disorders of the elderly, in peripheral vascular deficiency and in functional disorders of ischaemic origin in the E.N.T. and eye areas. Numerous controlled clinical trials justify these prescriptions and are in agreement with the pharmacological data currently available. Experimentally, Ginkgo biloba extract has proved active on the circulatory and rheological functions, on neuronal metabolism threatened by ischaemia or hypoxia, on neurotransmission and on membrane lesions caused by free oxygenated radicals. Concerning Alzheimer's disease and dementia, no firm conclusion can be drawn for the time being due to the lack of animal model. However, experimental data suggest that the product may act on a number of major elements of these diseases. From what is already known about Ginkgo biloba extract, it appears that it fulfills the conditions laid down by the W.H.O. concerning the development of drugs effective against cerebral ageing.

Apaydin C Oguz Y Agar A Yargicoglu P Demir N Aksu G

Visual evoked potentials and optic nerve histopathology in normal and diabetic rats and effect of ginkgo biloba extract.

In: Acta Ophthalmol (Copenh) (1993 Oct) 71(5):623-8

The purpose of this study was to test the possible therapeutic role of ginkgo biloba extract on the impairment of visual function and pathological histology of the optic nerve caused by early diabetes. Ginkgo biloba extract entraps oxygenated free radicals and is also a strong inhibitor of the platelet activation factor (PAF). For this purpose, VEP recordings and optic nerve histopathology were studied on alloxan diabetic and normal Swiss albino rats in four experimental groups. The VEP recordings showed no statistical significance between diabetic and normal rats. However, the amplitudes were significantly increased in diabetic animals with ginkgo biloba extract compared with the diabetics, supposing an impression of axonal protection. But the amplitude values were decreased in normal rats treated with the same extract compared with normal animals, assuming a toxic activity. Optic nerve ultrastructural findings also confirmed these VEP changes. It was concluded that this extract could be encouraging for human clinical trials of diabetes.

Atzori C Bruno A Chichino G Bombardelli E Scaglia M Ghione M

Activity of bilobalide, a sesquiterpene from Ginkgo biloba, on Pneumocystis carinii.

In: Antimicrob Agents Chemother (1993 Jul) 37(7):1492-6

The sesquiterpene bilobalide, extracted from Ginkgo biloba leaves, was tested in vitro and in vivo for the ability to inhibit Pneumocystis carinii growth. Bilobalide was inhibitory to trophozoites cultured on human embryonic lung fibroblasts (HEL 299) at approximately the same concentration as trimethoprim plus sulfamethoxazole (lowest effective concentration, 50 micrograms of bilobalide per ml versus 9/45 microgram of trimethoprim- sulfamethoxazole per ml), inducing microscopically detectable morphological changes in the cytoplasm of the parasite. In pharmacologically immunosuppressed Sprague-Dawley rats transtracheally infected with a suspension of about 5 x 10(6) P. carinii trophozoites per ml, the daily intraperitoneal administration of bilobalide (10 mg/kg of body weight for 8 days) lowered the number of organisms by approximately 2 logs (that is, about 99%). There was no apparent toxicity either in uninfected HEL 299 feeder cells or in infected and uninfected animals. These studies suggest that the sesquiterpene bilobalide might be useful for therapy of and prophylaxis against P. carinii infections in humans.

Bauer U.,

Six months double-blind randomised clinical trial of Ginkgo biloba extract versus placebo in two parallel groups in patients suffering from peripheral arterial insufficiency.

In: Arzneimittel - ForsehlDru: Res, 1984, 34, 716-720.

Boismare F.:

Etude de l'action hemodynamique de l'extrait concentre de Ginkgo biloba comparee a celle du gaz carbonique chez le sujet jeune et chez le sujet senile.

In: Ouesl Medical, 1976, 29, 747-749.

Bono Y., Mouren P.:

L'insuffisance circulatoire cerebrale et son traitement par l'extrait de Ginkgo biloba.

In: Med. Med., 1975, 3, 59-62.

Boudouresques G., Vigouroux R., Boudouresques J.:

Interet et place de l'extrait de Ginkgo biloba en pathologie vasculaire cerebrale.

In: Medecine Pralicienne, 1975, 59:, 75-78.

Bourgain RH Maes L Andries R Braquet P

Thrombus induction by endogenic paf-acether and its inhibition by Ginkgo Biloba extracts in the guinea pig.

In: PROSTAGLANDINS (1986 Jul) 32(1):142-4

The anti-thrombotic effects of specific paf-acether antagonist BN 52021 were compared to the effects of Ginkgo Biloba extracts A, B, (A+ B), and C. Local superfusion of BN 52021 over an experimentally injured arterial segment embolizes an existent paf-acether induced platelet thrombus. When applied before paf-acether, BN 52021 prevents local thromboformation in this model. Applied intravenously, BN 52021 reduces local thromboformation in a significant way. As compared to this BN 52021 standard, only Ginkgo Biloba B and the (A + B)-mixture present major thromboreductive activity.

Braquet P

Cedemin, a Ginkgo biloba extract, should not be considered as a PAF antagonist [letter; comment]

In: Am J Gastroenterol (1993 Dec) 88(12):2138

Chabrier PE Roubert P

[Effect of Ginkgo biloba extract on the hemato-encephalic barrier]

Effet de l'extrait de Ginkgo biloba sur la barriere hemo-encephalique.

In: Presse Med (1986 Sep 25) 15(31):1498-501

The different methods used to explore the blood-brain barrier (made up of cerebral capillary vessels), and notably, at molecular level, isolated microvessel preparations, have greatly improved our knowledge in this particular field. Some of these methods could be used to evaluate the protective effects of therapeutic substances, such as Ginkgo biloba extract, on the blood-brain barrier.

Chaterjee G.:

Effects of Ginkgo biloba extract on cerebral metabolic processes.

In: Effects of GBE and Organic Cerebral Impairment, Paris, London, John Lilley, 1985.

Clostre F

[From the body to the cell membrane: the different levels of pharmacological action of Ginkgo biloba extract]

In: PRESSE MED 1986 Sep 25; 15(31):1529-38 (Published in FRENCH)

The pharmacological study of Ginkgo biloba extract has required numerous experiments over several years: diffe rent pathological models of cerebral ischaemia to evaluate its effects, and experiments at both cellular and molecular levels to determine its mechanisms of action. In experimental models of ischaemia, oedema and hypoxia, Ginkgo biloba extract reduced vascular, tissular and metabolic disturbances as well as their neurological and behavioural consequences. The pharmacological effects of Ginkgo biloba extract concern vascular, rheological and metabolic processes. Several membrane mechanisms seem to be involved: protection of the membrane ultrastructure against free radicals, modulation of some enzymatic systems and ionic pumps. The originality of the pharmacological properties of Ginkgo biloba extract lies in preferential focusing of its effects on ischaemic areas.

Creutzig A

[Is Ginkgo biloba extract EGb 761 clinically effective in intermittent claudication? (letter)]

In: Vasa (1993) 22(2):189-90 (Published in German)

Diwok M Kuklinski B Ernst B

[Superoxide dismutase activity of Ginkgo biloba extract]

In: Z Gesamte Inn Med (1992 Jul) 47(7):308-11 (Published in German)

The Ginkgo biloba extract is obtained from green leaves of the Ginkgo biloba tree. Preparations with this active substance are among others used for the treatment of disturbances of the cerebral function and arteriosclerotic diseases. In in-vitro and in-vivo studies antagonistic effects of radical scavenger and PAF (platelet activating factor) were described. In this study a concentration- depending superoxide dismutase activity of the Ginkgo biloba extract rokan liquid could be made evident.

Droy-Lefaix-M-T; Szabo-M-E; Doly-M

Ischaemia and reperfusion-induced injury in rat retina obtained from normotensive and spontaneously hypertensive rats: Effects of free radical scavengers.

In: International Journal of Tissue Reactions (1993)15(2): 85-91

The authors have studied the effects of free radical scavengers, superoxide dismutase (SOD) and extract of Ginkgo biloba (EGb 761, flavone-rich extract) on ion shifts (Na, K and Ca) induced by ischaemia and reperfusion in rat retina obtained from normotensive and spontaneously hypertensive rats. Eyes were subjected to 90 min of ischaemia by occlusion of the retinal artery, followed by 4 and 24 hours of reperfusion. SOD (15, 000 U/kg, i.v.) or EGb 761 (50 mg/kg, per os) was administered in a daily dose for 10 days. In the drug-free control groups, 90 min of ischaemia significantly increased tissue Na gains from their pre-ischaemic control values of 63 +- 7 mu-M/g dry weight (in retina obtained from normotensive rats) and 76 mu-M/g dry weight (in retina obtained from hypertensive rats) to 89 +- 9 mu-M/g dry weight and 101 +- 7 mu-M/g dry weight, respectively. During reperfusion, a further elevation was found in retinal Na in both the normotensive and hypertensive groups. Probably, because of the ischaemia-induced inhibition of Na-K-ATPase, retinal K loss was detected after ischaemia and reperfusion, respectively. An accumulation of retinal Ca was measured after ischaemia and reperfusion in the normotensive and spontaneously hypertensive groups. Both free radical scavengers significantly reduced the maldistribution of ions induced by ischaemia and reperfusion, but the effectiveness of drugs was more evident in normotensive than hypertensive groups. The present results indicate that the elimination of free radicals by free radical scavengers may reduce, probably via an indirect mode, the reperfusion-induced ionic imbalance and improve the ionic homeostasis in injured retinal cells obtained from normotensive and spontaneously hypertensive rats.

Dumont E Petit E Tarrade T Nouvelot A

UV-C irradiation-induced peroxidative degradation of microsomal fatty acids and proteins: protection by an extract of Ginkgo biloba (EGb761).

In: Free Radic Biol Med (1992 Sep) 13(3):197-203

After exposure of rat liver microsomes to UV-C irradiation, analysis of membrane fatty acids by gas chromatography confirmed that EGb 761, a drug containing a dosed and standardized extract of Ginkgo biloba, provides effective protection against free radical attack in vitro. This analysis, coupled with thiobarbituric acid (TBA) reaction, permitted qualitative and overall quantitative evaluation of radical- induced damage to polyunsaturated fatty acids (PUFA), as well as evidence of the antioxidant properties of the Ginkgo biloba extract. Assay of thiobarbituric acid reactive substances (TBARS) showed a correlation between TBARS concentration and the state of degradation of the polyunsaturated fatty acids. Mannitol (5.5 mM) did not prevent degradation of microsomal PUFA or malondialdehyde (MDA) production, nor did it prevent polymerization of membrane proteins. Low doses of EGb 761 were found to provide efficient protection of membrane PUFA regardless of individual susceptibility to peroxidation. This protection was accompanied by a decrease in the production of TBARS. EGb 761 also protected membrane proteins from the irreversible polymerization induced by these degradation products, but did not appear to prevent thiols oxidation into disulfide bonds.

Eckmann F., Schlag H.:

Etude controlee, a double insu, de l'activite de l'Extrait de Ginkgo biloba chez des malades atteints d'insuffisance cerebrale chronique.

In: Fortschritte der Medizin, 1982, 31132, 1474-1478.

Etienne A Hecquet F Clostre F

[Mechanism of action of Ginkgo biloba extract in experimental cerebral edema]

Mecanismes d'action de l'extrait de Ginkgo biloba sur l'oedeme cerebral experimental.

In: Presse Med (1986 Sep 25) 15(31):1506-10

Oedema is one of the major complication of cerebral ischaemia being at the same time a consequence and an aggravating factor. Its first phase is intracellular and cytotoxic, with breakdown of ionic pumps through loss of energy, resulting in a whole sequence of ionic perturbations characterized by loss of intracellular K+ and accumulation of water and Na+, Cl-, and Ca2+ ions in the cells of the ischaemic zone. The second phase, termed vasogenic, applies to the accumulation of lactates, inorganic phosphates and free polyunsaturated fatty acids and in particular, arachidonic acid. This last compound is responsible for the production of membrane "aggressors", amongst which free radicals play an important role. Ginkgo biloba extract limits the formation of cerebral oedema and suppresses its neurological consequences, whether the oedema is of cytotoxic (triethyltin) or vasogenic (unilateral traumatic oedema) origin. Several membrane mechanisms could be implicated in the protective action manifested by Ginkgo biloba extract against cerebral oedema.

Gautherie M Bourjat P Grosshans E Quenneville Y

[Vasodilator effect of Gingko biloba extract determined by skin thermometry and thermography]

In: THERAPIE (Sep-Oct 72) 27(5):881-92

Gessner B Voelp A Klasser M

Study of the long-term action of a Ginkgo biloba extract on vigilance and mental performance as determined by means of quantitative pharmaco-EEG and psychometric measurements.

In: Arzneimittelforschung (1985) 35(9):1459-65

Gonda R Takeda K Shimizu N Tomoda M

Characterization of a neutral polysaccharide having activity on the reticuloendothelial system from the rhizome of Curcuma longa.

In: Chem Pharm Bull (Tokyo) (1992 Jan) 40(1):185-8

A neutral polysaccharide, named ukonan D, was isolated from the rhizome of Curcuma longa L. It produced a single band on electrophoresis and a single peak on gel chromatography, and its molecular mass was estimated to be 28, 000. It showed remarkable reticuloendothelial system-potentiating activity in a carbon clearance test. Ukonan D is composed of L-arabinose: D-galactose: D- glucose: D-mannose in the molar ratio of 1:1:12:0.2, in addition to small amounts of peptide moiety. Methylation analysis, carbon-13 nuclear magnetic resonance and enzymic degradation studies indicated that its structural features include mainly both alpha-1, 5-linked L- arabino-beta-3, 6-branched D-galactan type and alpha-4, 6-branched D- glucan type structural units. The influence of degradation with alpha- amylase followed by the elimination of glucan side chains on its immunological activity was discussed.

Gonda R Tomoda M Ohara N Takada K

Arabinogalactan core structure and immunological activities of ukonan C, an acidic polysaccharide from the rhizome of Curcuma longa.

In: Biol Pharm Bull (1993 Mar) 16(3):235-8

Controlled Smith degradation of ukonan C, a phagocytosis-activating polysaccharide isolated from the rhizome of Curcuma longa L., was performed. The reticuloendothelial system-potentiating, anti- complementary and alkaline phosphatase-inducing activities of ukonan C and its degradation products were investigated. Methylation analyses of the primary and secondary Smith degradation products and of a de-arabinosylated product indicated that structural features of the arabinogalactan core of ukonan C include a backbone chain composed of beta-1, 3-linked D-galactose and beta-1, 4-linked D-xylose. All of the galactose units in the backbone carry side chains composed of beta-1, 6-linked D-galactosyl residues with or without terminal alpha-L-arabinose units at position 3. Ukonan C showed remarkable effects on both reticuloendothelial system-potentiating and alkaline phosphatase-inducing activities. Periodate oxidation caused a decrease in or disappearance of the immunological activities, but the controlled Smith degradation product having the arabinogalactan core structure of polysaccharide showed a pronounced effect on anti- complementary activity.

Gonda R Tomoda M Takada K Ohara N Shimizu N

The core structure of ukonan A, a phagocytosis-activating polysaccharide from the rhizome of Curcuma longa, and immunological activities of degradation products.

In: Chem Pharm Bull (Tokyo) (1992 Apr) 40(4):990-3

The controlled Smith degradation of ukonan A, a phagocytosis- activating polysaccharide isolated from the rhizome of Curcuma longa L., was performed. The reticuloendothelial system-potentiating, anti- complementary and alkaline phosphatase-inducing activities of ukonan A and its degradation products were investigated. Methylation analyses of both the primary and the secondary Smith degradation products indicated that the core structural features of ukonan A include a backbone chain mainly composed of beta-1, 3-linked D- galactose, beta-1, 4-linked D-xylose and alpha-1, 2-linked L-rhamnose residues. All of the galactose units in the backbone carry side chains composed of alpha-L-arabino-beta-D-galactosyl or beta-D- galactosyl residues at position 6. Ukonan A has a remarkable effect on each of the three kinds of immunological activities. Periodate oxidation caused pronounced decrease or disappearance of the activities, but the controlled Smith degradation product having the core structure of polysaccharide showed considerable restoration of these activities.

Grassel E

[Effect of Ginkgo-biloba extract on mental performance. Double-blind study using computerized measurement conditions in patients with cerebral insufficiency]

In: Fortschr Med (1992 Feb 20) 110(5):73-6 (Published in German)

Problem: The effect of ginkgo biloba extract EGb 761 on basic parameters of mental performance. Patients: Seventy-two outpatients with cerebral insufficiency at three test centers. Study design: Double-blind, randomized placebo-controlled study of 24 weeks duration. Test parameters: Psychometric computer-aided examination of the short-term memory and basic learning rate. Results: Statistically significant improvement in the shortterm memory after 6 weeks and of the learning rate after 24 weeks in the test substance group, but not in the placebo group (longitudinal analysis). The difference between the test substance and placebo groups (horizontal analysis) reached statistical significance in the 24th week. Conclusions: Treatment with ginkgo biloba extract EGb 761 improves mental/mnestic performance.

Hitzenberger G

[The effect of ginkgo biloba special extract (EGb 761, Tebofortan)]

In: Wien Med Wochenschr (1992) 142(17):371-9 (Published in German)

Ginkgo biloba special extract exerts positive effects on hemorheology and platelet aggregation, is a free radical scavenger and possesses PAD antagonistic properties, protects against hypoxia and ischemia, hampers an experimentally induced cerebral edema, has favourable properties on neurotransmitters and enhances cerebral bloodflow. Clinically EGb has proven favourable effects on intellectual deficiency, equilibrium disturbances and peripheral artery occlusions thus being a drug with a clear cut indication for these diseases.

Hofferberth, B.:

The influence of Ginkgo Biloba Extract (GBE) on the Neuro physiological and Psychometrical Test results in patients suffering from organic cerebral Psychosyndrome: A Double-Blind Study Versus Placebo.

In: Conference at The Third Congress of the International Psychogeriatric Association, Chicago, August 1987

Hoffmann F Beck C Schutz A Offermann P

[Ginkgo extract EGb 761 (tenobin)/HAES versus naftidrofuryl

(Dusodril)/HAES. A randomized study of therapy of sudden deafness]

In: Laryngorhinootologie (1994 Mar) 73(3):149-52 (Published in German)

80 patients with idiopathic sudden hearing loss existing no longer than 10 days were included in a randomised reference-controlled study. The therapeutic value of Ginkgo EGb 761 (Tebonin) + HAES was compared to that of Naftidrofuryl (Dusodril)+HAES. The main mechanisms of action of EGb 761 are a vasoregulating activity (increased blood flow), the platelet activating factor antagonism and a prevention of membrane damage caused by free radicals. Naftidrofuryl has antiserotonergic and therefore vasodilatory properties. The statistical analysis of the audiometric data was performed in measuring the relative hearing gain as described by Eibach 1979. After one week of observation, 40% of the patients in each group showed a complete remission of hearing loss. This was also observed by other authors who had compared other drugs. Therefore, in these cases, it is most likely that spontaneous recovery is the most important factor. After two and three weeks of observation, measuring the relative hearing gain, there was a significant borderline benefit of EGb 761 (p = 0.06) without any side effects. Some patients of the reference group developed side effects such as orthostatic dysregulation or headache or sleep disturbances. Minimising side effects should be one of the most important goals in therapy of sudden hearing loss until the efficiency of infusion therapy is proved.

Holgers KM Axelsson A Pringle I

Ginkgo biloba extract for the treatment of tinnitus.

In: Audiology (1994 Mar-Apr) 33(2):85-92

Previous studies have shown contradictory results of Ginkgo biloba extract (GBE) treatment of tinnitus. The present study was divided into two parts: first an open part, without placebo control (n = 80), followed by a double-blind placebo-controlled study (n = 20). The patients included in the open study were patients who had been referred to the Department of Audiology, Sahlgren's Hospital, Goteborg, Sweden, due to persistent severe tinnitus. Patients reporting a positive effect on tinnitus in the open study were included in the double-blind placebo-controlled study (20 out of 21 patients participated). 7 patients preferred GBE to placebo, 7 placebo to GBE and 6 patients had no preference. Statistical group analysis gives no support to the hypothesis that GBE has any effect on tinnitus, although it is possible that GBE has an effect on some patients due to several reasons, e.g. the diverse etiology of tinnitus. Since there is no objective method to measure the symptom, the search for an effective drug can only be made on an individual basis.

Huguet F Tarrade T

Alpha 2-adrenoceptor changes during cerebral ageing. The effect of Ginkgo biloba extract.

In: J Pharm Pharmacol (1992 Jan) 44(1):24-7

[3H]Rauwolscine binding to alpha 2-adrenoceptors in cerebral cortex and hippocampus membranes of young (4 months) and aged (24 months) Wistar rats has been investigated. In aged rats, Bmax values of [3H]rauwolscine binding were significantly reduced (25-32%) in the cerebral cortex and hippocampus, as compared with the number of alpha 2-adrenoceptors found in young rats. Chronic treatment with Ginkgo biloba extract did not alter [3H]rauwolscine binding in the hippocampus of young rats, but significantly increased (28%) the [3H]rauwolscine binding density in aged rats. These data confirm the previously described age-related noradrenergic alteration and suggest that noradrenergic activity in aged rats is more susceptible to Ginkgo biloba extract treatment.

Kenzelmann R Kade F

Limitation of the deterioration of lipid parameters by a standardized garlic-ginkgo combination product. A multicenter placebo-controlled double-blind study.

In: Arzneimittelforschung (1993 Sep) 43(9):978-81

The efficacy of a garlic-ginkgo combination product (Allium plus) was analyzed in a randomized placebo-controlled double-blind study under extreme dietary conditions. The Christmas/New Year's season was chosen for this 2 months lasting investigation analyzing whether the known cholesterol lowering effect of garlic was even effective during the period of the year with the most cholesterol-rich meals. 43 patients with elevated total cholesterol levels ranging between 230- 390 mg/dl completed the study. There were no significant changes of the total cholesterol values in both treatment groups. Nevertheless the analysis of improvement or deterioration of total cholesterol values revealed a clear difference between verum and placebo. 20% of the patients in the placebo group showed an improvement of their total cholesterol level, while there was a significant greater improvement rate of 35% in the verum group (p < 0.05). The responders of the verum group showed a reduction in the total cholesterol values from 298.5 +/- 53.8 to 293.0 +/- 56.4 mg/dl after 1 month and a total reduction of 10.4% after 2 months to 267.6 +/- 44.4 mg/dl. The difference after 2 months of treatment was significantly different from the starting value (p < 0.05). After the 2 months treatment phase there was a 2 weeks wash-out period. During this period the total cholesterol value returned to 293.5 +/- 90.1 mg/dl showing the effectiveness of garlic treatment, but indicating the need for a continuous long-term therapy.

Kimbel KH

Ginkgo biloba [letter; comment]

In: Lancet (1992 Dec 12) 340(8833):1474

Kleijnen J Knipschild P

Ginkgo biloba [see comments]

In: Lancet (1992 Nov 7) 340(8828):1136-9

Kleijnen J Knipschild P

Ginkgo biloba for cerebral insufficiency.

In: Br J Clin Pharmacol (1992 Oct) 34(4):352-8

1. By means of a critical review we tried to establish whether there is evidence from controlled trials in humans on the efficacy of Ginkgo biloba extracts in cerebral insufficiency. 2. The methodological quality of 40 trials on Ginkgo and cerebral insufficiency was assessed using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. A comparison of the quality was made with trials of co-dergocrine, which is registered for the same indication. 3. There were eight well performed trials out of a total of 40. Shortcomings were limited numbers of patients included, and incomplete description of randomization procedures, patient characteristics, effect measurement and data presentation. In no trial was double-blindness checked. Virtually all trials reported positive results, in most trials the dosage was 120 mg Ginkgo extract a day, given for at least 4-6 weeks. For the best trials, there were no marked differences in the quality of the evidence of the efficacy of Ginkgo in cerebral insufficiency compared with co-dergocrine. The results of the review may be complicated by a combination of publication bias and other biases, because there were no negative results reported in many trials of low methodological quality. 4. Positive results have been reported for Ginkgo biloba extracts in the treatment of cerebral insufficiency. The clinical evidence is similar to that of a registered product which is prescribed for the same indication. However, further studies should be conducted for a more detailed assessment of the efficacy.

Kleijnen J Knipschild P

The comprehensiveness of Medline and Embase computer searches. Searches for controlled trials of homoeopathy, ascorbic acid for common cold and ginkgo biloba for cerebral insufficiency and intermittent claudication.

In: Pharm Weekbl Sci (1992 Oct 16) 14(5):316-20

OBJECTIVE: To assess the comprehensiveness of Medline and Embase computer searches for controlled trials. DESIGN: Comparison of articles found after an exhaustive search of the literature with the yield of a Medline or Embase search. This was performed for controlled clinical trials on the efficacy of three interventions: homoeopathy, ascorbic acid for common cold, and ginkgo biloba for intermittent claudication and cerebral insufficiency. The number of controlled trials found by exhaustive search of the literature was 107, 61 and 45, respectively. RESULTS: For homoeopathy, ascorbic acid and ginkgo the proportion of all trials found by Medline was 17%, 36% and 31% respectively and for Embase 13%, 25% and 58% respectively. After checking of the references in the Medline articles 44%, 79% and 76% of all trials were identified. After checking of the references in the Embase articles 42%, 72% and 93% of all trials were identified. About 20% of the articles was not correctly indexed. Of the best trials 68%, 91% and 83% could be found with Medline and 55%, 82% and 92% of the best trials were identified through Embase. CONCLUSIONS: For the topics mentioned, Medline and Embase searches are sufficient to get an impression of the evidence from controlled trials, but only if references in the articles are followed for further evidence. If one wants to get a more complete picture, additional search strategies make sense. Of course, this picture may be different for other topics.

Kobayashi N Suzuki R Koide C Suzuki T Matsuda H Kubo M

[Effect of leaves of Ginkgo biloba on hair regrowth in C3H strain mice]

In: Yakugaku Zasshi (1993 Oct) 113(10):718-24 (Published in Japanese)

Effects of 70% ethanolic extract from leaves of Ginkgo biloba (GBE) on the hair regrowth in normal and high butter diet-pretreated C3H strain mice which posterior hair we shaved were investigated. GBE showed a promoting effect on the hair regrowth. GBE had the inhibitory effects on blood platelet aggregation, thrombin activity and fibrinolysis. GBE inhibited the increase of serum the triglyceride level in high cholesterol diet-treated rats. These results suggested that GBE promotes the hair regrowth and could be used as a hair tonic.

Koltringer P Langsteger W Klima G Reisecker F Eber O

[Hemorheologic effects of ginkgo biloba extract EGb 761. Dose- dependent effect of EGb 761 on microcirculation and viscoelasticity of blood]

In: Fortschr Med (1993 Apr 10) 111(10):170-2 (Published in German)

Method: In a randomized open clinical trial involving 42 patients with pathological visco-elasticity values, the effect of a single intravenous injection of 50, 100, 150 or 200 mg of the Ginkgo biloba extract EGb 761, commercially available as Tebonin p.i. on the microcirculation of the skin (Doppler flowmetry) and the visco- elasticity of whole blood was investigated. Results: A dose-dependent significant increase in the microcirculation was found. In the case of visco-elasticity, this dose-dependence was less marked. The present study thus confirms the positive effect of EGb 761 on the microcirculation and whole-blood visco-elasticity in patients with pathological visco-elasticity values, already found in earlier studies, and shows it to be dependent on the dose employed.

Krauskopf R., Guinot Ph., Peetz H.G.:

Long term on line EEG analysei de monstrating the pharmaco-dynamic effect of a defined Ginkgo biloba extract.

In: Beaufour -Schwabe Internat. Report, 1983.

Kunkel H

EEG profile of three different extractions of Ginkgo biloba.

In: Neuropsychobiology (1993) 27(1):40-5

Two experiment were conducted to assess the electroencephalographic effects of (1) three different dosages of a total extract of Ginkgo biloba (EGb 761, Tebonin) and (2) three different extractions of G. biloba (Tebonin and two fractions from it). The medicament was tested against placebo using a double-blind cross-over design in 12 normal healthy males for each experiment. Medication was administered for 3 days preceding the recording sessions. 25 parameters were computed from the EEG spectra. Medication-related effects were obtained for most of the power measures, whereas dominant frequencies of the respective frequency band remained largely unchanged. The differences between the EEG effects of the two studies are critically discussed.

Lee K Ku JR Koh SD Kim KS

Effects of methanol extract of ginkgo biloba (EGb), its ethylacetate fraction (EAF) and butanol fraction (BF) on the isolated aorta.

In: Jpn J Pharmacol (1992) 58 Suppl 2:377P

Long R Yin R Zhen Y

[Partial purification and analysis of allergenicity, immunogenicity of Ginkgo biloba L. pollen]

In: Hua Hsi I Ko Ta Hsueh Hsueh Pao (1992 Sep) 23(4):429-32 (Published in Chinese)

Pollens of Ginkgo biloba L. (G.b.l.p) have been found to be a kind of important allergen which causes pollinosis in Chengdu. The goal of this study is to purify G.b.l.p and to determine the allergenicity and immunogenicity of various fractions. Crude extract was purified by gel filtration with Sephadex G25, then G75. Two elution peaks were observed. On SDS-PAGE, the molecular weights of protein of the 1st peak and the valley were 30-42 kd and 13-18kd, respectively, and that of the 2nd peak was less than 13 kd. 40 patients with allergic rhinitis and/or asthma underwent the skin test with crude extract and various fractions of gel filtration; it revealed that the strongest allergenic activity existed in the 1st peak and there was mild allergenic activity in the 2nd peak. The in vitro allergenic activity and immunogenic activity of various fractions were examined by ELISA inhibition test. It was further confirmed that the allergenic activity and immunogenic activity of the 1st peak were the strongest, and those of the 2nd peak were the lowest. It is suggested that diagnosing reagents can be made satisfactorily by partial purification, i.e. discarding the inactive fractions, since allergenicity exists in various fragments. But fractions of allergen with high IgG immunogenicity should be selected to produce immunotherapy agents so as to enhance the production of blocking antibody and thus improve the therapeutic effect.

Marcocci L Maguire JJ Droy-Lefaix MT Packer L

The nitric oxide-scavenging properties of Ginkgo biloba extract EGb 761.

In: Biochem Biophys Res Commun (1994 Jun 15) 201(2):748-55

Ginkgo biloba extract EGb 761 was found to be a scavenger of nitric oxide in in vitro acellular systems, under physiological conditions. EGb 761 competed with oxyhemoglobin for reaction with nitric oxide generated during the interaction of hydroxylamine with Complex I of catalase. An EGb 761 dose-dependent decrease in the amount of nitrite formed in the reaction of oxygen with nitric oxide produced from solution of 5 mM sodium nitroprusside was also observed. These data implicate it as a potential therapeutic agent in conditions of altered production of nitric oxide.

Olivier-J; Plath-P

Combined low power laser therapy and extracts of Ginkgo biloba in a blind trial of treatment for tinnitus.

In: Laser Therapy (1993) 5(3): 137-139

Tinnitus is an annoying and often debilitating condition of neurootologic origin but of uncertain aetiology. Many treatment methods have been tried, but to date none has been consistently successful. The present preliminary study presents a blind trial of laser therapy (c/w HeNe 632.8 nm and pulsed GaAs 904 nm) combined with doses of an extract of Ginkgo biloba (50 mg) in two groups of 20 patients, one experimental and one control. All 40 patients received the biloba extract injection, but only the 20 experimental patients received real laser irradiation, 8 days, 8 min per day. The control group received sham irradiation in a blind arrangement. Fifty percent of the experimental group was assessed to have a reduction in tinnitus of more than 10 dB, compared with 5% in the control group in both self-assessment and audiometric findings. Although only a preliminary report, the results are very encouraging, and the authors suggest that this combined photochemotherapy is a promising treatment for tinnitus.

Otani M Chatterjee SS Gabard B Kreutzberg GW

Effect of an extract of Ginkgo biloba on triethyltin-induced cerebral edema.

In: ACTA NEUROPATHOL (BERL) (1986) 69(1-2):54-65

The effect of an extract of Ginkgo biloba was studied on cerebral edema in rats intoxicated with triethyltin chloride (TET). Brains of TET-treated rats showed elevated water and sodium levels and a significant increase in the sodium/potassium ratio. Animals treated with TET plus the extract did not show water and electrolyte changes. The course of intoxication and treatment was studied light- and electron-microscopically. A severe edema with extensive vacuolization was seen in the cerebral and cerebellar white matter. Morphometric measurements revealed a significant decrease in these manifestations of the cytotoxic edema when the animals were treated with an extract of Ginkgo biloba. Thus, we conclude that this extract has a protective effect on the development of a cytotoxic edema in the white matter of the brain.

Oyama Y Fuchs PA Katayama N Noda K

Myricetin and quercetin, the flavonoid constituents of Ginkgo biloba extract, greatly reduce oxidative metabolism in both resting and Ca(2+)-loaded brain neurons.

In: Brain Res (1994 Jan 28) 635(1-2):125-9

The antioxidant action of myricetin and quercetin, the flavonoid constituents of the extract of Ginkgo biloba (EGb), on oxidative metabolism of brain neurons dissociated from the rats was examined using 2', 7'-dichlorofluorescin (DCFH) which is retained within the neuron and then is oxidized by cellular hydrogen peroxide to be highly fluorescent. Incubation with myricetin or quercetin reduced the oxidation of DCFH in resting brain neurons, more profoundly than EGb. Myricetin decreased the oxidative metabolism at concentrations of 3 nM or more. It was 10 nM or more for the case of quercetin. Incubation with each flavonoid constituent also reduced the Ca(2+)- induced increase in the oxidative metabolism without affecting the cellular content of DCFH or the intracellular concentrations of Ca2+. Such an antioxidant action of myricetin or quercetin may be responsible for a part of the beneficial effects of EGb on brain neurons subject to ischemia.

Oyama Y Hayashi A Ueha T

Ca(2+)-induced increase in oxidative metabolism of dissociated mammalian brain neurons: effect of extract of ginkgo biloba leaves.

In: Jpn J Pharmacol (1993 Apr) 61(4):367-70

Effect of an extract of Ginkgo biloba leaves (EGb) on oxidative metabolism was studied using rat brain neurons and 2', 7'- dichlorofluorescin fluorescence. Ionomycin (100 nM to 1 microM), a Ca(2+)-ionophore, dose-dependently augmented the 2', 7'- dichlorofluorescin fluorescence in the presence of external Ca2+, but not under the external Ca(2+)-free condition. Preincubation of neurons with EGb (3 micrograms/ml) greatly reduced the ionomycin- induced increase in 2', 7'-dichlorofluorescin fluorescence. Results suggest that EGb may reduce the Ca(2+)-induced increase in the oxidative metabolism of brain neurons.

Oyama Y Ueha T Hayashi A Chikahisa L Noda K

Flow cytometric estimation of the effect of Ginkgo biloba extract on the content of hydrogen peroxide in dissociated mammalian brain neurons.

In: Jpn J Pharmacol (1992 Dec) 60(4):385-8

The effect of Ginkgo biloba extract (GBE) on the content of hydrogen peroxide was estimated in cerebellar neurons dissociated from rats, by means of a flow-cytometer and 2', 7'-dichlorofluorescein (DCF) diacetate, a fluorescent dye for intracellular hydrogen peroxide. The GBE started to reduce the DCF fluorescence of the neuron at 0.1 microgram/ml to 0.3 microgram/ml. Further increases in the GBE concentration (up to 3 micrograms/ml) produced a dose-dependent decrease in the DCF fluorescence, suggesting that GBE reduces the content of hydrogen peroxide or suppresses the reactive oxygen species (ROS) formation of cerebellar neurons. The present technique may be useful for preliminary evaluations of agents affecting the ROS formation in mammalian brain neurons.

Petkov VD Kehayov R Belcheva S Konstantinova E Petkov VV Getova D Markovska V

Memory effects of standardized extracts of Panax ginseng (G115), Ginkgo biloba (GK 501) and their combination Gincosan (PHL-00701).

In: Planta Med (1993 Apr) 59(2):106-14

In experiments on young (aged 3 months) and old (aged 26 months) rats, using some conditioned-reflex methods with punishment or positive reinforcement for active and passive avoidance (shuttle-box, step-down, step-through, and water maze), we studied the effects of the standardized extracts of Panax ginseng (G115), Ginkgo biloba (GK501) and their combination Gincosan (PHL-00701). The extracts were administered orally for 7 days before training at three increasing doses: 17, 50, and 150 mg/kg for G115; 10, 30, and 90 mg/kg for GK501; and 27, 80, and 240 mg/kg for PHL-00701. The two extracts and their combination improved the retention of learned behavior. This effect varied considerably with the extracts, with the dose and with the behavioral method used. The results suggest that the Panax ginseng G115 and the Ginkgo biloba GK501 extracts possess properties similar in every respect to those of nootropic drugs. The favorable effects on learning and memory of the combination of G115 plus GK501 and the other pharmacological activities inherent in the extracts characterize this combination, offered as Gincosan as a particularly promising drug in geriatric practice.

Pidoux B

[Effects of Ginkgo biloba extract on functional brain activity. An assessment of clinical and experimental studies]

Effets sur l'activite fonctionnelle cerebrale de l'extrait de Ginkgo biloba. Bilan d'etudes cliniques et experimentales.

In: Presse Med (1986 Sep 25) 15(31):1588-91

Electroencephalography is the only convenient method for functional exploration of the brain and recent developments allows for pharmacological studies of electoencephalograms. Using such techniques has confirmed those of clinical trials, and notably the activity of Ginkgo on alertness.

Pidoux B., Bastien C., Niddam S.:

Clinical and quantitative EEG double-blind study of GBE.

In: J. Cerebral Blood Flow Metabolism, 1983, 3, 5556-5557.

Pidoux B., Bastien C., Niddam S.:

Normalization of electroencephalographic activity in ageing brain by an extract of Ginkgo biloba;

In: Bes. A. Braquet P., Paoletti R., Siesjo B.K. Eds., Cerebral Ischemia, Amsterdam, Excerpta Medica, 1984, 385-388.

Pietta P Mauri P Rava A

Rapid liquid chromatography of terpenes in Ginkgo biloba L. extracts and products.

In: J Pharm Biomed Anal (1992 Oct-Dec) 10(10-12):1077-9

Pritz-Hohmeier S Chao TI Krenzlin J Reichenbach A

Effect of in vivo application of the ginkgo biloba extract EGb 761 (Rokan) on the susceptibility of mammalian retinal cells to proteolytic enzymes.

In: Ophthalmic Res (1994) 26(2):80-6

Lesions, inflammations, or degenerative insults of the human retina are accompanied by the release of proteolytic enzymes. Their deleterious effect may be enhanced by the release of free radicals. Ginkgo biloba extracts are known to exert protective influences against the action of free radicals, and this prompted us to ask whether the application of such extracts might protect retinal tissue against proteolytic damage. Eighteen adult rabbits were fed for 3 weeks (+/- 3 days) with 40 mg/kg of G. biloba extract (EGb 761) or a terpene-free fraction of this extract, dissolved in their drinking water. Twelve control rabbits received no G. biloba extract. The animals were then euthanatized and their retinae isolated. After appropriate enzymatic treatment, the tissue was dissociated and the number of isolated Muller cells counted as an indication of the strength of the proteolytic effects. There was a significant protective action of EGb 761: in an average control rabbit 5, 200 cells per milligram retinal tissue were isolated; application of EGb 761 markedly reduced this number to 2, 500 (terpene-free fraction; CP 205) or 3, 050 (terpene-containing fraction). It is concluded that G. biloba extracts may have a significant therapeutic value in cases of retinal damage.

Racagni G Brunello N Paoletti R

[Neuromediator changes during cerebral aging. The effect of Ginkgo biloba extract]

Variations des neuromediateurs lors du vieillissement cerebral. Effet de l'extrait de Ginkgo biloba.

In: Presse Med (1986 Sep 25) 15(31):1488-90

Ginkgo biloba extract exerts a specific effect on the noradrenergic system and on beta-receptors. No variation was found in alpha 2- receptors and serotonin uptake. These findings provide the first evidence of central effects of a drug acting on cerebral ageing, connected specifically to reactivation of the noradrenergic system in the cerebral cortex.

Ramassamy C Christen Y Clostre F Costentin J

The Ginkgo biloba extract, EGb761, increases synaptosomal uptake of 5- hydroxytryptamine: in-vitro and ex-vivo studies.

In: J Pharm Pharmacol (1992 Nov) 44(11):943-5

The Ginkgo biloba extract (EGb 761) added to a synaptosomal fraction prepared from mice cerebral cortex modified [3H]5-hydroxytryptamine ([3H]5-HT) uptake in a biphasic manner. Between 4 and 16 micrograms mL-1 EGb 761 increased significantly the [3H]5-HT uptake (maximum + 23%). A similar increase was also obtained when synaptosomes were prepared from the cortex of mice treated orally with EGb 761, either acutely (100 mg kg-1, 14 h and 2 h before death) or semi-chronically (2 x 100 mg-1 kg daily for 4 consecutive days). The in-vitro increase in [3H]5-HT uptake induced by EGb 761 was not observed in the presence of 10(-6) M clomipramine, a 5-HT-uptake inhibitor. EGb 761 did not increase [3H]dopamine uptake by synaptosomes prepared from striatum of mice. We investigated different fractions of EGb 761 in order to determine the compounds inducing the increase in [3H]5-HT uptake. The BN 52063 extract (corresponding to the EGb 761 devoid of flavonoid substances) did not increase [3H]5-HT uptake. The Cp 202 extract (corresponding to the EGb 761 devoid of terpenic substances and containing mostly flavonoid substances) increased [3H]5-HT uptake. Among the flavonoids, quercetin has been tested and had no effect on the [3H]5-HT uptake. Since at the usual therapeutic doses of EGb 761, the effective concentrations of the components responsible for this increase are likely to be reached in the brain, one may suggest that this effect could contribute to the therapeutic effect of EGb 761.

Ramassamy C Girbe F Christen Y Costentin J

Ginkgo biloba extract EGb 761 or trolox C prevent the ascorbi acid/Fe2+ induced decrease in synaptosomal membrane fluidity.

In: Free Radic Res Commun (1993) 19(5):341-50

The ability of synaptosomes, prepared from striata, to take up 3H- dopamine declined rapidly during incubation at 37 degrees C, in an oxygenated Krebs-Ringer medium with 0.1 mM ascorbic acid. Ascorbic acid was responsible for this decrease. Its effectiveness after a 60 min incubation was concentration dependent from 1 microM and virtually complete for 0.1 mM. Furthermore, a decrease of synaptosomal membrane fluidity was revealed by measurements of fluorescence polarization using 1, 6-diphenyl-1, 3, 5-hexatriene. This decrease was potentiated by Fe2+ ions (1 microM). In contrast, it was prevented by the Fe2+ ion chelator, desferrioxamine (0.1 mM), by the Ginkgo biloba extract EGb 761 [2-16 micrograms/ml], as well as by the flavonoid quercetin (0.1 microM). This preventive effect was shared by trolox C (from 0.1 mM). It is concluded that peroxidation of neuronal membrane lipids induced by ascorbic acid/Fe2+ is associated with a decrease in membrane fluidity which, in turn, reduces the ability of the dopamine transporter to take up dopamine.

Ramassamy C Naudin B Christen Y Clostre F Costentin J

Prevention by Ginkgo biloba extract (EGb 761) and trolox C of the decrease in synaptosomal dopamine or serotonin uptake following incubation.

In: Biochem Pharmacol (1992 Dec 15) 44(12):2395-401

Prolonged incubation of synaptosomes in Krebs-Ringer oxygenated medium in the presence of ascorbic acid (10(-4) M) led, after 20 min, to a decrease in [3H]dopamine (DA) (synaptosomes prepared from the striatum) and [3H]serotonin (5HT) (synaptosomes prepared from the cortex) uptake. The decrease was progressive and uptake was virtually abolished after a 60 min incubation period. A concentration-dependent (from 5 x 10(-6) M) role of ascorbic acid in the decrease of [3H]DA or [3H]5HT uptake was demonstrated. This decrease was potentiated by Fe2+ ions and prevented by the ferrous chelating agent desferrioxamine. Thus, the progressive decrease in synaptosomal uptake of either [3H]DA or [3H]5HT could depend on the generation of free radicals by the association of ascorbic acid with Fe2+ ions. The decrease in synaptosomal uptake was prevented, in a concentration- dependent manner, by the Ginkgo biloba extract EGb 761 (4-16 micrograms/mL) and the vitamin E analog trolox C (10(-4) M). The terpenic fraction of EGb 761, Bn 52063 (up to 0.5 microgram/mL), did not prevent the reduction of [3H]amine uptake. In contrast, the flavonoidic fraction, Cp 202, was effective (from 1 microgram/mL) and its efficacy was shared by the flavonoid quercetin (from 0.1 microgram/mL). The prolongation of the ability of synaptosomes to take up [3H]amine elicited by EGb 761, in particular its flavonoidic fraction, as well as by trolox C could be due to their free radical scavenger properties.

Rodriguez de Turco EB Droy-Lefaix MT Bazan NG

Decreased electroconvulsive shock-induced diacylglycerols and free fatty acid accumulation in the rat brain by Ginkgo biloba extract (EGb 761): selective effect in hippocampus as compared with cerebral cortex.

In: J Neurochem (1993 Oct) 61(4):1438-44

The effect of Ginkgo biloba extract (EGb 761) treatment (100 mg/kg/day, per os, for 14 days) on electroconvulsive shock (ECS)- induced accumulation of free fatty acids (FFA) and diacylglycerols (DAG) was analyzed in rat cerebral cortex and hippocampus. EGb 761 reduced the FFA pool size by 33% and increased the DAG pool by 36% in the hippocampus. These endogenous lipids were unaffected in cerebral cortex. During the tonic seizure (10 s after ECS) the fast accumulation of FFA, mainly 20:4, was similar in sham- and EGb 761- treated rats, in both the cerebral cortex and hippocampus. However, further accumulation of free 18:0 and 20:4, observed in the hippocampus of sham-treated rats during clonic seizures (30 s to 2 min after ECS), did not occur in EGb 761-treated animals. The rise in DAG content triggered in the cortex and hippocampus by ECS was delayed by EGb 761 treatment from 10 s to 1 min, when values similar to those in sham animals were attained. Moreover, in the hippocampus the size of the total DAG pool was decreased by 19% during the tonic seizure. At later times, DAG content showed a faster decrease in EGb 761-treated rats. By 2 min levels of all DAG acyl groups decreased to values significantly lower than in sham animals in both cortex and hippocampus. This study shows that EGb 761 treatment affects, with high selectivity, lipid metabolism and lipid-derived second messenger release and removal in the hippocampus, while affecting to a lesser extent the cerebral cortex.

Schneider B

[Ginkgo biloba extract in peripheral arterial diseases. Meta-analysis of controlled clinical studies]

In: Arzneimittelforschung (1992 Apr) 42(4):428-36 (Published in German)

In the first part the statistical methods of meta-analysis are discussed. Meta-analysis is considered as a statistical tool for quantitatively summarizing the results of clinical trials with comparable aims (treatments) and designs. Meta-analysis can be based on the significance probabilities or effect values. The last procedure is preferable as it gives an estimate (and confidence interval) for the global effect of the treatment of interest, if homogeneity of the effects between the trials can be assumed. Such a homogeneity can be often achieved by a suitable standardization of the effect variables within the trials. In the second part the methods of meta-analysis are applied to controlled clinical trials with Ginkgo biloba extract EGb 761 in patients with peripheral arterial disease. Included were 5 placebo-controlled clinical trials with similar design and inclusion criteria. In all studies treatment effect was quantified by the increase of walking distance (measured in standardized treadmill exercise). The effect value of EGb 761 treatment was expressed by the standardized mean difference in walking distance increase between EGb 761 and placebo, standardized by the standard deviation. It could be shown that this effect value is homogeneous in all trials. The global effect size was estimated as 0.75. This means that the mean increase in walking distance achieved by EGb 761 is 0.75 times of the standard deviation higher than that achieved by placebo. This value is highly significant different from zero. So the meta-analysis revealed a highly significant therapeutic effect of EGb 761 for the treatment of peripheral arterial disease.

Stange G Benning CD Degenhardt M Ottinger E

[Adaptational behaviour of peripheral and central acoustic responses in guinea pigs under the influence of various fractions of an extract from Gingko biloba (author's transl)]

In: ARZNEIM FORSCH (1976) 26(3):367-74

Experimental studies on guinea pigs clearly demonstrated the influence of an extract from Ginkgo biloba on the acoustic system. With the Ginkgo biloba extract it is probably possible to diminish sound damages caused by white noise.

Steinke B Muller B Wagner H

[Biological standardization of Ginkgo extracts]

In: Planta Med (1993 Apr) 59(2):155-60 (Published in German)

The determination of the inhibition of PAF (platelet-activating factor)-induced platelet aggregation has been proposed as a biological standardization method for commercially available Ginkgo biloba extracts by measuring the characteristic pharmacological effect of ginkgolides in vitro. The determination is specific for ginkgolides A, B, C, and J and is not influenced by other constituents present in Ginkgo biloba extracts. IC50 values of ginkgolide B can be used to standardize various Ginkgo extracts produced by special extraction methods with respect to equi-effective ginkgolide B contents. In order to compare values obtained by a chemical-analytical procedure with those obtained by the biological assay, the equi-effective total ginkgolide content of each Ginkgo extract had to be calculated. Accordingly, the concentrations of the individual ginkgolides in the various Ginkgo extracts were determined chromatographically by assaying ginkgolides as trime-thylsilyl derivatives. Their individual contributions towards the measured in vitro effects were derived from their respective IC50 values. The calculated equi-effective total ginkgolide contents of the Ginkgo extracts were in good agreement with those obtained by gas chromatography. The results demonstrate that, in addition to a chemical standardization, the biological standardization of Ginkgo extract preparations is also feasible.

Sticher O

Quality of Ginkgo preparations.

In: Planta Med (1993 Feb) 59(1):2-11

A survey of known and of recently isolated constituents from Ginkgo leaves is given. The structures of flavonoids and terpene lactones which are considered to be the active compounds as well as their qualitative and quantitative determination in Ginkgo leaves and phytomedicines are presented. In the case of flavonoid analysis three selective methods worked out in our laboratories are described. The quality control of terpene lactones is discussed on the basis of a recently published paper. Finally, the standardization methods used for the quality control of Ginkgo preparations as well as the question as to whether or not phytomedicine generics--so called "phytogenerics"--exist, is discussed.

Sticher-O

Ginkgo biloba: A modern phytomedicine.

In: Vierteljahrsschrift der Naturforschenden Gesellschaft in Zuerich (1993)138(3): 125-168

Phytomedicines based on extracts from the leaves of Ginkgo biloba are used in the Federal Republic of Germany and in France a rather long time for the treatment of peripheral vascular insufficiency and cerebrovascular insufficiency, and disturbances of cerebral function. In Europe, commercially available preparations based on the special extract EGb 761 have a turnover of about 500 million US dollars. Meanwhile also in Switzerland various Ginkgo preparations are on the market. In this review taxonomy, botany, chemistry, pharmacology and clinical applications as well as quality control of Ginkgo biloba and phytomedicines based on leaf extracts of this plant are described. Research work of the own laboratory dealing with quality control is discussed in detail.

Subhan Z., Hindmarch 1.:

The psychopharmacological effects of Ginkgo biloba extract in normal healthy volunteers.

In: Internat. J. Clin. Pharmacol. Res., 1984, 4, 89-93.

Tamborini A Taurelle R

[Value of standardized Ginkgo biloba extract (EGb 761) in the management of congestive symptoms of premenstrual syndrome]

In: Rev Fr Gynecol Obstet (1993 Jul-Sep) 88(7-9):447-57 (Published in French)

The efficacy of standardized Ginkgo biloba extract (EGb 761) in treating congestive symptoms of premenstrual syndrome (PMS) was evaluated in a controlled multicentric double blind study versus placebo. The population studied was a group of 165 women aged between 18 to 45, in genital activity period, suffering since 3 cycles from congestive premenstrual troubles during at least 7 days per cycle. The characteristics of patients and PMS were the same in both groups (EGb 761 and placebo). The observation of one menstrual cycle confirmed the diagnosis of PMS. Then, during the 2 following cycles, each patient received either EGb 761 or placebo from the 16th day of the first cycle till the 5th day of the next cycle. A double evaluation of the symptoms was realized by the patient using a daily rating scale (auto-evaluation), by the practitioner during visits at the premenstrual phase before and after the two cycles treatment. From 165 patients included, 143 observations were available. With a good acceptability, EGb 761 was effective against the congestive symptoms of PMS, particularly breast symptoms with a statistical significance between EGb 761 and placebo. Neuropsychological symptoms were also improved. EGb 761 is an alternative of interest to therapeutics already used in treating PMS or can be associated without any inconvenience.

Taylor J.E.:

The effects of chronic, oral Ginkgo biloba extract administration on neurotransmitter receptor binding in young and aged Fisher 344 rats.

In: Effects of Ginkgo biloba extract on organic cerebral impairment, Paris, London, John Lilley, 1985.

Tea S., Celsis P., Clanet M., Marc-Vergnes J.P.:

Effets cliniques, hemodyna miques et metaboliques de l'extrait de Ginkgo biloba en pathologie vasculaire cerebrale.

In: Gazette Medicale de France, 1979, 86, 4149-4152.

Vasseur M Jean T DeFeudis FV Drieu K

Effects of repeated treatments with an extract of Ginkgo biloba (EGb 761), bilobalide and ginkgolide B on the electrical activity of pancreatic beta cells of normal or alloxan-diabetic mice: an ex vivo study with intracellular microelectrodes.

In: Gen Pharmacol (1994 Jan) 25(1):31-46

1. The effects of repeated (5-day) treatments with an extract of Ginkgo biloba leaves (EGb 761), bilobalide, and ginkgolide B on the in vitro electrical activity of insulin-secreting pancreatic beta cells of mice have been examined using intracellular microelectrodes. 2. EGb 761 (200 mg/kg/day, p.o.) protected beta cells against the toxic effects of alloxan (50 mg/kg, i.v.), an effect characterized by a restoration of membrane potential (Vr) and an increase in spike frequency (Fs/30), an indicator of insulin secretion. 3. Treatment of non-diabetic mice with EGb 761 (200 mg/kg/day, p.o.) increased Fs/30 of their beta cells, as tested by in vitro exposure of the cells to 11.1 mM glucose, an effect that also occurred with bilobalide (8 mg/kg/day, i.p.) but not with ginkgolide B (4 mg/kg/day, i.p.). 4. Since bilobalide and ginkgolide B caused opposite effects on the sensitivity of beta cells to glucose, the stimulatory effect of EGb 761 on Fs/30 may be attributed to its content of bilobalide. 5. In contrast to its ex vivo effect, the direct in vitro effect of EGb 761 (10 and 25 micrograms/ml) on beta cells favors a decrease in electrical activity, indicating that its in vivo action might be indirect (e.g. via the formation of an active metabolite).

Volkner JH

Inhalations of extracts from Gingko biloba in vasomotor rhinitis and in the bronchitic syndrome

In: DTSCH MED J (5 Sep 67) 18(17):527-33

Wada K Sasaki K Miura K Yagi M Kubota Y Matsumoto T Haga M

Isolation of bilobalide and ginkgolide A from Ginkgo biloba L. shorten the sleeping time induced in mice by anesthetics.

In: Biol Pharm Bull (1993 Feb) 16(2):210-2

The leaves of Ginkgo biloba L. and aqueous extract from them shortened the sleeping time induced in mice by anesthetics (hexobarbital, alpha-chloralose and urethane, i.p.). Two characteristic terpenoids in G. biloba, bilobalide and ginkgolide A, significantly shortened the sleeping time induced by anesthetics. A toxic substance, 4-O-methylpyridoxine (MPN), responsible for "gin-nan food poisoning" isolated from the seed of G. biloba, was not detected from the extract of the leaves of G. biloba. Therefore, the Ginkgo biloba extract has no toxicities for MPN.

Warburton DM

Ginkgo biloba extract and cognitive decline [letter]

In: Br J Clin Pharmacol (1993 Aug) 36(2):137

Warburton DM :

Clinical psychopharmacology of Ginkgo biloba extract

In: PRESSE MED 1986 Sep 25; 15(31):1595-604 (Published in FRENCH)

From this general review of the pharmacological, psychopharmacological and clinical studies performed with Ginkgo biloba extract, the following conclusions can be drawn: the drug seems to be effective in patients with vascular disorders, in all types of dementia and even in patients suffering from cognitive disorders secondary to depression, because of its beneficial effects on mood. Of special concern are people who are just beginning to experience deterioration in their cognitive function. Ginkgo biloba extract might delay deterioration and enable these subject to maintain a normal life and escape institutionalization. In addition, Ginkgo biloba extract appears to be a safe drug, being well tolerated, even in doses many times higher than those usually recommended.

Witte S Anadere I Walitza E

[Improvement of hemorheology with ginkgo biloba extract. Decreasing a cardiovascular risk factor]

In: Fortschr Med (1992 May 10) 110(13):247-50 (Published in German)

STUDY DESIGN: Open prospective study. Patients: 20 outpatients with a long history of elevated fibrinogen levels and plasma viscosity, and a variety of underlying diseases. INTERVENTION: Treatment with the special ginkgo biloba extract (EGb 761), 240 mg tablets a day for a period of 12 weeks. RESULTS: The clinical diagnoses included coronary heart disease, hypertension, hypercholesterolemia and diabetes mellitus. A significant improvement in the fibrinogen levels and hemorrheological properties was seen. The medication can thus positively influence these cardiovascular risk factors over the long term.

Yabe T Chat M Malherbe E Vidal PP

Effects of Ginkgo biloba extract (EGb 761) on the guinea pig vestibular system.

In: Pharmacol Biochem Behav (1992 Aug) 42(4):595-604