€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ACTA HISTOCHEMICA***** Punkt K Welt K Schaffranietz L Changes of enzyme activities in the rat myocardium caused by experimental hypoxia with and without ginkgo biloba extract EGb 761 pretreatment. A cytophotometrical study. In: Acta Histochem (1995 Jan) 97(1):67-79 Using cytophotometry activity changes of succinate dehydrogenase, glycerol-3-phosphate dehydrogenase and myofibrillar adenosine triphosphatase, were measured in the rat myocardium under normal and different experimental conditions. After hypoxia all enzyme activities were significantly decreased in comparison to the normal situation, and the alterations differed in both ventricles. Ginkgo biloba extract treatment over three months before exposition to hypoxia resulted in a lower inhibition of succinate dehydrogenase, a higher inhibition of glycerol-3-phosphate dehydrogenase and an unchanged activity of adenosine triphosphatase after hypoxia of 20 min. These results were interpreted as a protective effect of the Ginkgo biloba extract on the hypoxic myocardium. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ACTA MEDICA AUSTRIACA***** Koltringer P Langsteger W Lind P Wakonig P Klima G Eber O [Ginkgo biloba extract and folic acid in the therapy of changes caused by autonomic neuropathy] Ginkgo-biloba-Extrakt und Folsaure in der Therapie von autonomen neuropathischen Veranderungen. In: Acta Med Austriaca (1989) 16(2):35-7 (Published in German) 10 patients suffering from neuropathies caused by various diseases and with an autonomic disregulation of skin were treated intravenously with a new combination of 87.5 mg Ginkgo-biloba-extract standardized to 21.0 mg Flavonglycosids and 3 mg folic acid during 14 days. The autonomic nerve-function was measured immediately before onset and after the end of therapy with the hyperthermal laser- Doppler-Flowmetry. Additionally pain, superficial and deep sensibility were described. After the end of treatment the autonomic nerve-function was improved in a significant manner (p less than 0.01). An improvement of the described parameters for pain and for perception could be observed too. Therefore this new combination seems to be suited for treatment of polyneuropathies. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ACTA NEUROPATHOLOGICA***** 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. *****ACTA OPHTHALMOLOGICA***** 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****AGENTS AND ACTIONS***** Touvay C Etienne A Braquet P Inhibition of antigen-induced lung anaphylaxis in the guinea-pig by BN 52021 a new specific paf-acether receptor antagonist isolated from Ginkgo biloba. In: Agents Actions (1986 Jan) 17(3-4):371-2 Paf-acether appears to be a potent mediator released in response to allergen exposure in sensitized animals and it could contribute to clinical manifestations of allergic asthma. In order to ascertain this assumption the inhibition of antigen-induced lung anaphylaxis in guinea-pig by BN 52021, a new highly specific paf-acether antagonist, was studied. Ovalbumin injected into passively sensitized guinea-pig induced a large bronchoconstriction which was accompanied by thrombocytopenia and leukopenia. Treatment of animals with BN 52021 i.v., five minutes before challenge, strongly (at the doses of 1 and 2 mg/kg) or totally (at 0.1 mg/kg) inhibited the bronchoconstriction and partially reduced the thrombocytopenia and leukopenia the thrombocytopenia occurring after challenge. These results confirm that paf-acether and platelets might play a key role in asthma. BN 52021 and other paf-acether antagonist could provide a new group of potent prophylactic anti-asthma drugs. *****ANTIMICROBIAL AGENTS AND CHEMOTHERAPY***** Atzori C Bruno A Chichino G Bombardelli E Scaglia M Ghione M Activity of bilobalide, a sesquiterpene from Ginkgo biloba, on Pneumocystis carinii [see comments] 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS***** Duke MV Salin ML Purification and characterization of an iron-containing superoxide dismutase from a eucaryote, Ginkgo biloba. In: Arch Biochem Biophys (1985 Nov 15) 243(1):305-14 A cyanide-insensitive superoxide dismutase was purified to electrophoretic homogeneity from leaves of the eucaryote, Ginkgo biloba L. A molecular mass of 47,000 was determined for the enzyme, which consisted of two subunits of equal size. The enzyme preparation contained two isoenzymes with isoelectric points of 5.25 and 5.15. Metal analysis after dialysis against EDTA revealed the presence of 1.4 gram atoms of iron per molecule. Approximately 2 gram atoms each of copper and zinc per enzyme molecule were also detected, although removal of copper by other chelators had no effect on enzymatic activity. The purified Ginkgo enzyme exhibited a sensitivity to hydrogen peroxide and insensitivity to cyanide, which is typical of iron-containing superoxide dismutases. Ginkgo iron superoxide dismutase was localized in the stroma of chloroplasts, but was absent from mitochondria. The enzyme from Ginkgo was most similar to iron superoxide dismutases of Nuphar, Brassica, and Escherichia coli when compared on the basis of S delta Q analysis of amino acid composition. Peptide fragments formed by proteolytic digestion of these four enzymes were compared qualitatively; similar-sized fragments which denote possible areas of homology were observed. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ARCHIVES OF DERMATOLOGICAL RESEARCH***** Lepoittevin JP Benezra C Asakawa Y Allergic contact dermatitis to Ginkgo biloba L.: relationship with urushiol. In: Arch Dermatol Res (1989) 281(4):227-30 A Ginkgo biloba L. fruit extract was prepared and purified. Three groups of guinea pigs were sensitized to the crude extract, anacardic acids 1, and cardanols 2 respectively, using the FCAT method, and the fourth group to urushiol using the epicutaneous route. Each group was tested for reaction to the primary sensitizer and to the different main aromatic compounds isolated from Ginkgo fruits. Anacardic acids were found to be good sensitizers, while cardanols failed to induce allergic contact dermatitis (ACD). No cross-reactions were observed among the compounds tested. Ginkgolic acids 1 seem to be the main allergens of Ginkgo biloba L. and the hypothesis of a biotransformation of 1 into catechol 4 is not supported by experiment. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ARCHIVES INTERNATIONALES DE PHARMACODYNAMIE ET DE THERAPIE***** Le Poncin Lafitte M Rapin J Rapin JR Effects of Ginkgo Biloba on changes induced by quantitative cerebral microembolization in rats. In: Arch Int Pharmacodyn Ther (1980 Feb) 243(2):236-44 Unilateral embolization of the brain was performed in rats by the intracarotid injection of 4000 radioactive microspheres (50 micron). The local blood flow was determined using the iodoantipyrine technique in the hippocampus, hypothalamus, striatum and remainder of the brain. Embolization resulted in a decrease in the blood flow and a modification of the distribution of microflow. Besides, the embolization produced changes in energy metabolism, specially a fall in ATP and glucose levels and an increase in lactate level. Subsequently severe vasogenic cerebral edema developed. There was a correlation between the number of microspheres injected and the extent of edema. Pretreatment with an extract of Ginkgo Biloba leaves partially suppressed the effects of the embolization. An increase in the blood flow associated with normalization of cellular energy metabolism explained the decrease in brain edema. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ARCHIVES OF OTO-RHINO-LARYNGOLOGY***** Stange G Benning CD [The influence on sound damages by an extract of ginkgo biloba (author's transl)] Beeinflussung des akustischen Traumas durch einen Ginkgo-biloba- Extrakt In: Arch Otorhinolaryngol (1975 Jul 8) 209(3):203-15 (Published in German) A fraction of Ginkgo biloba, used in experiments with animals ensured significantly the diminution of sound damages caused by white noise or by a pure tone of 4.5 kHz. Higher amplitudes of the acoustic nerve potentials show the protective effect of this fraction of Ginkgo biloba at acute sound damages. It is moreover possible to hold physiologically the adaptation of excitation of the hair cells of the organ of Corti by the fraction of Ginkgo biloba before and after sound damage caused by white noise or during a pure tone of 4.5 kHz. The influence of the fraction of Ginkgo biloba can be seen by a significantly slower recovery of the noise damaged evoked potentials of the acoustic cortex. An efferent protective influence on the neurons of the acoustic cortex is discussed. The fraction of Ginkgo biloba in this form of solution has not been tested for clinical use but it seems to be rich in meaning. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ARZNEIMITTEL-FORSCHUNG***** Schneider B [Ginkgo biloba extract in peripheral arterial diseases. Meta-analysis of controlled clinical studies] Ginkgo-biloba-Extrakt bei peripheren arteriellen Verschlusskrankheiten. Meta-Analyse von kontrollierten klinischen Studien. 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Jung F Mrowietz C Kiesewetter H Wenzel E Effect of Ginkgo biloba on fluidity of blood and peripheral microcirculation in volunteers. In: Arzneimittelforschung (1990 May) 40(5):589-93 In a randomized placebo controlled single-blind cross-over study of n = 10 apparently healthy subjects the influence of Ginkgo biloba (Kaveri) on blood fluidity and cutaneous microcirculation was studied. Microcirculation was measured before and every 30 min for 4 h after administration of Ginkgo biloba; fluidity of blood was determined before and after 1, 2 and 4 h. Significant changes in blood pressure or heart rate were found neither during Ginkgo phase nor placebo phase. Haematocrit, plasma viscosity, erythrocyte rigidity, thrombocyte and leukocyte count as well as thrombocyte aggregation and the number of circulating thrombocyte aggregates were also not influenced by the Ginkgo nor the placebo solution. In contrast a remarkable influence on the erythrocyte aggregation was observed: comparing two samples a significant decrease by 15.6% (p less than 0.001) with regard to the initial value was observed after 2 h. The blood flow in the nail fold capillaries also increased significantly by about 57% (p less than 0.004) 1 h after administration. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Bauer U 6-Month double-blind randomised clinical trial of Ginkgo biloba extract versus placebo in two parallel groups in patients suffering from peripheral arterial insufficiency. In: Arzneimittelforschung (1984) 34(6):716-20 79 patients suffering from peripheral arteriopathy (Fontaine's stage IIb) completed a 6-month double-blind randomised clinical trial of Ginkgo biloba extract (GBE) (as coated tablets containing 40 mg GBE; rokan) versus placebo in two parallel groups. From the results of measurements of pain-free walking distance, maximum walking distance and plethysmography recordings, GBE was shown to be active and significantly superior to placebo. These results correlated with the physician's and patients' overall assessment of response to treatment. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hofferberth B [The effect of Ginkgo biloba extract on neurophysiological and psychometric measurement results in patients with psychotic organic brain syndrome. A double-blind study against placebo] Einfluss von Ginkgo biloba-Extrakt auf neurophysiologische und psychometrische Messergebnisse bei Patienten mit hirnorganischem Psychosyndrom. Eine Doppelblindstudie gegen Plazebo. In: Arzneimittelforschung (1989 Aug) 39(8):918-22 (Published in German) The range of typical symptoms of cerebro-organic syndrome such as dizziness, memory and concentration loss, and orientation disorders can either be measured objectively within a clinical trial or can be observed subjectively. Thirty-six patients with classical symptoms of organic syndrome were recruited into a placebo-controlled double- blind trial in which the therapeutic effect of Ginkgo biloba extract EGb 761 (rokan) was measured by the following objective criteria: quantified EEG, saccadic eye movements and psychometric tests (Wiener Determination Test, Number Connection Test). Following 2 weeks' wash- out, 40 mg. EGb 761 was administered 3 times daily (= 120 mg daily dose) for 8 weeks. The control group received placebo capsules of identical external appearance. The tests listed above were carried out prior to treatment and after 4 and 8 weeks' therapy with the exception of quantitative EEG which was recorded at the beginning and end of treatment only. Patients presenting with pathological findings for at least two of the four test criteria were admitted to the trial. Patients receiving unpermitted supplementary medication or suffering from acute cardiovascular disturbances or digestive and metabolic disorders were excluded from the trial. A highly significant difference could already been seen after 4 weeks of therapy and also after 8 weeks in the results of both the saccadic test and the psychometric tests compared to the placebo control group. Saccade duration was shortened and the latency reduced. In parallel, the number of correct answers given in the Wiener Determination Test and Number Connection Test increased significantly compared to the control group. (ABSTRACT TRUNCATED AT 250 WORDS) Institutional address: Klinik fur Neurologie der Westf~alischen Wilhelms-Universitat Munster/Westf €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hopfenmuller W [Evidence for a therapeutic effect of Ginkgo biloba special extract. Meta-analysis of 11 clinical studies in patients with cerebrovascular insufficiency in old age] Nachweis der therapeutischen Wirksamkeit eines Ginkgo biloba- Spezialextraktes. Meta-Analyse von 11 klinischen Studien bei Patienten mit Hirnleistungsstorungen im Alter. In: Arzneimittelforschung (1994 Sep) 44(9):1005-13 (Published in German) Eleven controlled clinical trials were evaluated in a meta-analysis in order to proof the effectiveness of the ginkgo biloba special extract LI 1370 (Kaveri forte). All included studies were placebo controlled randomized double blind studies, using in most of the cases a daily dosage of 150 mg extract. The requirements for the quality of the studies were the basic criteria for the performance of clinical drug tests analysed from the biometrical scope. The analysis of the individual studies revealed that three studies had to be excluded from the meta-analysis according to methodological or objective reasons. In two further studies the evaluation of the physician or the patients was missing, therefore the studies could not be used for the analysis of the "global effectiveness". All other studies were comparable with regard to diagnoses, inclusion and exclusion criteria as well as methodology. Therefore a statistical meta-analysis could be performed for them, analysing the parameters "single symptoms", total score of clinical symptoms and "global effectiveness". For all analyzed single symptoms significant differences could be concluded, indicating the superiority of ginkgo biloba in comparison to placebo. The analysis of the total score of clinical symptoms from all relevant studies indicated that 7 studies confirmed the effectiveness (Ginkgo biloba being better compared to placebo) while only one study was inconclusive (the medications were not different). This relation confirms the therapeutical effectiveness of ginkgo biloba regarding the clinical symptom complex. Finally the parameter "global effectiveness" was evaluated.(ABSTRACT TRUNCATED AT 250 WORDS) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ 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 The action of a Ginkgo biloba extract (rokan, Tanakan, G.B.E.) in promoting blood flow has been demonstrated in several animal and human pharmacological studies. The aim of this present study was to estimate the action of the substance on the central nervous system in order to be able to assess its potential use as a therapeutic agent in geriatric patients with cerebral insufficiency. Quantitative pharmaco-EEG is the method of choice for studying the vigilance- promoting effects of a drug. It is incomparable for confirming the findings of behavioural and psychometric studies. 60 volunteers of either sex participated in the double-blind trial. They were aged 57- 77 years and showed mental deterioration corresponding to their age. They were randomly divided into three experimental groups: 20 subjects received 3 X 40 mg/day G.B.E., 20 received 5 mg nicergoline and 20 received a placebo of similar appearance. The subjects underwent an extensive series of examinations before and 4, 8 and 12 weeks after the start of medication. Analysis of the EEG results for the whole group revealed no significant advantage of G.B.E. over the two reference substances with regard to vigilance. However, a subclassification of the subjects showed that the vigilance of those persons with a more unfavourable initial situation measured in the resting EEG could be clearly improved by chronic G.B.E. medication. This increase in vigilance was reflected at the behavioural level by an improvement of reaction times in the G.B.E. group by comparison with the reference substances.(ABSTRACT TRUNCATED AT 250 WORDS) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Schaffler K Reeh PW [Double blind study of the hypoxia protective effect of a standardized Ginkgo biloba preparation after repeated administration in healthy subjects] Doppelblindstudie zur hypoxieprotektiven Wirkung eines standardisierten Ginkgo-Biloba-Praparates nach Mehrfachverabreichung an gesunden Probanden. In: Arzneimittelforschung (1985) 35(8):1283-6 (Published in German) A randomised, placebo-controlled, double-blind, crossover study was run in 8 healthy, male subjects (mean age 27.3 +/- 2.6 years, mean BW 75.3 +/- 9.7 kg) to demonstrate a possible hypoxia-protective effect of standardised Ginkgo flavone glycosides after subchronical administration. After a 14-days' treatment with Ginkgo bilobae extract (Tebonin) performance of subjects was studied--concerning assessments of oculomotor and complex choice reaction system as well as simple cardiorespiratory parameters under multiple exposure to hypoxic hypoxia (10.5% oxygen, 89.5% nitrogen)--using oculodynamic methodology (ODT). Hypoxia increased the corneoretinal resting- potential of the eye and stimulated respiration. Both parameters were significantly reduced by verum administration. Under cumulative exposure to hypoxic hypoxia fixation time of saccadic eye movements and complex choice reaction time were significantly improved by Ginkgo flavone glycosides vs placebo. These results could be explained as a hypoxia-protective phenomenon--supporting the therapy of cerebral insufficiency. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****AUDIOLOGY***** 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS***** Yan LJ Droy-Lefaix MT Packer L Ginkgo biloba extract (EGb 761) protects human low density lipoproteins against oxidative modification mediated by copper. In: Biochem Biophys Res Commun (1995 Jul 17) 212(2):360-6 The antioxidant effects of Ginkgo biloba extract (EGb 761) on copper- mediated human low density lipoprotein (LDL) oxidative modification were evaluated by several techniques. Human LDL (0.5 mg/ml) in phosphate buffered saline, pH 7.4, was incubated with 10 microM cupric sulfate at 37 degrees C under air for 8 hours and 24 hours in the presence of varying concentrations of EGb 761. Increases in LDL apoB carbonylation, lipid peroxidation, apoB electrophoretic mobility and LDL fluorescence were all inhibited when the incubation mixture contained EGb 761 at concentrations less than 100 micrograms/ml. This inhibition was EGb 761-concentration-dependent. Thus, EGb 761 has powerful antioxidant effects on copper-mediated LDL oxidative modification. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BIOCHEMICAL JOURNAL***** Ibata K Mizuno M Takigawa T Tanaka Y Long-chain betulaprenol-type polyprenols from the leaves of Ginkgo biloba. In: Biochem J (1983 Aug 1) 213(2):305-11 A long-chain betulaprenol-type polyprenol mixture was isolated from the leaves of Ginkgo biloba mainly as acetate. The structure was determined by mass spectroscopy, 1H-n.m.r. spectroscopy and 13C- n.m.r. spectroscopy. The mixture contained polyprenols-14-22, predominantly polyprenols-17, -18 and -19, and consisted of the dimethylallyl terminal unit (omega-terminal), two trans-isoprene residues, a sequence of 11-19 cis-isoprene residues and a terminal hydroxylated isoprene unit (alpha-terminal) aligned in that order. The concentration of these polyprenols in leaves increased from 0.04 to 2.0% of dry wt. with maturing of the leaves, though the content of total lipids was constant. The distribution of chain length in these polyprenols showed little variation throughout the whole life of the leaves. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL***** Shen JG Zhou DY Efficiency of Ginkgo biloba extract (EGb 761) in antioxidant protection against myocardial ischemia and reperfusion injury. In: Biochem Mol Biol Int (1995 Jan) 35(1):125-34 The cardio-protective mechanisms of EGb 761, an extract of Ginkgo biloba leaves, on myocardial ischemia-reperfusion injury were investigated using rabbits subjected to 30 minutes of regional cardiac ischemia and 120 min of reperfusion under anesthesia. Compared to the saline perfused group, EGb 761 treatment (10 mg/kg, injected into the coronary artery) significantly inhibited the increase in lipid peroxidation and maintained total and CuZn-SOD levels in both plasma and tissue during and at the end of reperfusion. Both the decrease in tissue type plasminogen activator (t-PA) and the increase in plasminogen activator inhibitor-1 (PAI-1) caused by ischemia-reperfusion were also significantly suppressed by EGb 761 treatment. Furthermore, the ultrastructure of the myocytes of the EGb 761 treated heart was slightly damaged after ischemia- reperfusion, while the control ischemic-reperfused hearts demonstrated severe histological damages such as swelling and vacuolization of the mitochondria. These results suggest that EGb 761 protects hearts by its antioxidant properties and by its ability to adjust fibrinolytic activity. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BIOCHEMICAL PHARMACOLOGY***** Barth SA Inselmann G Engemann R Heidemann HT Influences of Ginkgo biloba on cyclosporin A induced lipid peroxidation in human liver microsomes in comparison to vitamin E, glutathione and N-acetylcysteine. In: Biochem Pharmacol (1991 May 15) 41(10):1521-6 The in vitro effect of cyclosporin A (CsA) on lipid peroxidation in human liver microsomes was investigated, and efforts were made to prevent the resulting toxic effect of CsA. Microsomes were prepared from human liver resection material and incubated with CsA (0, 10, 30, 100, 300, 1000 micrograms/mL) for one hour (pH 7.4, 37 degrees, 95% O2, 5% CO2). Subsequently the resulting concentrations of malondialdehyde equivalents (MDA) were determined, a breakdown product of lipid peroxidation. Furthermore the duration of incubation was varied (0, 15, 30, 60, 90 min) using a CsA concentration of 300 micrograms/mL. CsA was shown to stimulate MDA-formation to up to 10- fold of the control value in both a time and concentration dependent manner. The dosage dependent experiment stated above was repeated, adding alpha-tocopherol (vitamin E, 1 mM), reduced glutathione (GSH, 1 mM), N-acetylcysteine (0.1, 0.3, 1, 3 mM), and Ginkgo biloba extract (Gbe, 15, 50, 150 micrograms/mL), respectively, to the medium of incubation. Vitamin E, a potent radical scavenger, proved to inhibit lipid peroxidation almost totally. Both GSH and N- acetylcysteine were also able to prevent lipid peroxidation, suggesting that the antioxidant effect of GSH might be caused by its thiol group and does not depend on the integrity of the whole molecule. Gbe inhibited CsA induced lipid peroxidation in a concentration dependent manner. This effect of Gbe was diminished yet not totally abolished when FeCl3 was added to the medium of incubation, whereas N-acetylcysteine even slightly enhanced CsA stimulated lipid peroxidation in the presence of iron. These results suggest that Gbe might be able to prevent radical mediated damage to human membranes caused by CsA. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Maitra I Marcocci L Droy-Lefaix MT Packer L Peroxyl radical scavenging activity of Ginkgo biloba extract EGb 761. In: Biochem Pharmacol (1995 May 26) 49(11):1649-55 Antioxidant mechanisms have been proposed to underlie the beneficial pharmacological effects of EGb 761, an extract from Ginkgo biloba leaves used for treating peripheral vascular diseases and cerebrovascular insufficiency in the elderly. In vitro evidence has been reported that EGb 761 scavenges various reactive oxygen species, i.e. nitric oxide, and the superoxide, hydroxyl, and oxoferryl radicals. However, the ability of EGb 761 to scavenge peroxyl radicals (reactive species mainly involved in the propagation step of lipid peroxidation) has not been investigated. To characterize further the antioxidant action of EGb 761, we measured the protective effects of EGb 761 during: (1) the oxidation of B-phycoerythrin by peroxyl radicals generated in aqueous solution by 2,2'-azobis (2- amidinopropane) hydrochloride (AAPH); and (2) the reaction of luminol or cis-parinaric acid with peroxyl radicals generated from 2,2'- azobis (2,4-dimethylvaleronitrile) (AMVN) in liposomes or in human low density lipoprotein (LDL), respectively. To evaluate the peroxyl radical scavenging activity of EGb 761 in a more physiologically relevant model of damage to lipid-containing systems, we also analyzed the effect of the extract on the oxidation of human LDL exposed to the azo-initiators in terms of: (1) accumulation of cholesterol linoleate ester hydroperoxides, (2) depletion of alpha- tocopherol and beta-carotene, and (3) changes in intrinsic tryptophan fluorescence. EGb 761 afforded protection against oxidative damage in all the systems we analyzed; thus, it is an efficient scavenger of peroxyl radicals. This result extends the oxygen radical scavenging properties of the extract and supports the hypothesis of an antioxidant therapeutic action of EGb 761. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Lamant V Mauco G Braquet P Chap H Douste-Blazy L Inhibition of the metabolism of platelet activating factor (PAF- acether) by three specific antagonists from Ginkgo biloba. In: Biochem Pharmacol (1987 Sep 1) 36(17):2749-52 Washed rabbit platelet suspensions were incubated in the presence of 1-[3H]O-alkyl-2-acetyl-sn-glycero-3-phosphocholine ([3H] PAF- acether), which was metabolized into 1-[3H]O-alkyl-2-acyl-sn-glycero- 3-phosphocholine (alkylacyl-GPC) through the sequential action of cytosolic acetylhydrolase and membrane transacylase. Within 60 min at 37 degrees, percentage of [3H] PAF-acether metabolized was 50.3 +/- 5.2% (9 experiments). This conversion was inhibited in a dose- dependent manner by various concentrations of ginkgolides A, B and C (BN 52020, 52021, 52022) known as specific antagonists of PAF- acether. The three compounds displayed the following order of potency: BN 52021 (IC50 = 3.6 X 10(-6) M) greater than BN 52020 (IC50 = 9.7 X 10(-6) M) greater than BN 52022 (IC50 = 37.6 X 10(-6) M). As this order is the same as that previously defined for inhibition of platelet aggregation to PAF-acether or for inhibition of PAF-acether binding to platelets, our data bring further support to the view that PAF-acether metabolism in platelets involves in some way its binding to its membrane receptor. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BIOCHIMICA ET BIOPHYSICA ACTA***** Gellerman JL Anderson WH Schlenk H Synthesis of anacardic acids in seeds of Ginkgo biloba. In: Biochim Biophys Acta (1976 Apr 22) 431(1):16-21 Anacardic (6-alkylsalicylic) acids and common lipids are efficiently synthesized by immature seeds of Ginkgo biloba. The seeds were incubated with 14C-labeled acetic, malonic and palmitoleic acids, glucose, and other potential precursors. Levels of 14C in common lipids and in anacardic acids, and the distribution of 14C in anacardic acids were determined. The results show that the salicylic moiety is synthesized by a polyketide pathway via malonic acid. The chain moiety for anacardic acid synthesis is in a different state of activation and/or site than chains that are used for synthesis of the common lipids. Labeled shikimic acid did not contribute 14C to anacardic acids, nor to other lipids, and palmitoleic acid was incorporated only into common lipids. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BIOLOGICAL AND PHARMACEUTICAL BULLETIN***** 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BIOMEDICA BIOCHIMICA ACTA***** Delaflotte S Auguet M DeFeudis FV Baranes J Clostre F Drieu K Braquet P Endothelium-dependent relaxations of rabbit isolated aorta produced by carbachol and by Ginkgo biloba extract. In: Biomed Biochim Acta (1984) 43(8-9):S212-6 Spirally-cut strips of rabbit aorta were used to examine the relaxations produced by carbachol and extract of Ginkgo biloba (Gb) under isometric conditions. After precontracting the strips with phenylephrine (10(-7) M), carbachol produced a dose-related relaxation (PD2 congruent to 6.2 +/- 0.1) and this effect was antagonized competitively by atropine (PA2 congruent to 9.4 +/- 0.1). Gb (0.2 or 0.3 mg/ml) also relaxed the strips. Removal of the endothelium or a 30-min pre-treatment of the strips with a substance that has lipoxygenase-inhibitor activity (nordihydroguaiaretic acid, NDGA, 10(-5) M) abolished the relaxant effect of carbachol and partially blocked the relaxant effect of Gb. Thus, at least part of the relaxant effect of Gb is mediated by a factor(s) (e.g., EDRF) that is released from endothelial cells. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Becker K Braquet P Forster W Influence of the specific antagonist of PAF-acether, BN 52021, and of Ginkgo extract on the rejection of murine tail skin allografts and the PAF-acether mortality in mice in particular consideration of the role of TXB2. In: Biomed Biochim Acta (1988) 47(10-11):S165-8 An oral application of 2 x 10 mg/kg daily of the PAF antagonist, BN 52021, significantly prolonged the distal allograft survival in the murine tail skin model of cell-mediated allograft rejection. BN 52021 diminished the TXB2 content in the skin at and near to the transplantation site by two thirds whereas PAF-acether significantly enhanced the TXB2 content in murine tail skin. Similar to the tail skin BN 52021 also reduced by more than 70% the TXB2 release from human granulocytes stimulated by calcium ionophore A 23187. The PAF- acether mortality (LD75) in NMRI mice was decreased to 20% by BN 52021 with a lower dose than by BN 52020. Comparing Ginkgo total extract in doses which significantly diminished the 75% mortality by PAF-acether in mice with BN 52021 and BN 52020 in doses that produced the same inhibitory effect, a potentiated effect of Ginkgo extract resulted with respect to the share of BN 52021 and BN 52020 in Ginkgo extract. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BRITISH JOURNAL OF CLINICAL PHARMACOLOGY***** 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BRAIN RESEARCH***** 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CHEMICAL AND PHARMACEUTICAL BULLETIN***** Itokawa H Totsuka N Nakahara K Maezuru M Takeya K Kondo M Inamatsu M Morita H A quantitative structure-activity relationship for antitumor activity of long-chain phenols from Ginkgo biloba L. In: Chem Pharm Bull (Tokyo) (1989 Jun) 37(6):1619-21 With the aim of obtaining compounds with strong antitumor activity, a quantitative structure-activity relationship (QSAR) of antitumor phenolic compounds (long-chain phenols) was derived using the Hansch- Fujita equation. The ED50 values against Chinese hamster V-79 cells were analyzed in terms of log P as the hydrophobic parameter and the energy of the lowest unoccupied molecular orbital (ELUMO) calculated by using the modified neglect of differential overlap (MNDO) method as the electronic parameter, by means of multiple regression analysis. It was found that the activities mainly depended on log P (an optimum log P of 8.3) and a low-lying ELUMO value. 4- Undecylcatechol, selected on the basis of the above results, exhibited strong antitumor activity against Sarcoma 180 ascites and P- 388 lymphocytic leukemia. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ **CHUNG-KUO CHUNG YAO TSA CHIH CHINA JOURNAL OF CHINESE MATERIA MEDICA* Chen C Jin RM Li Y Sheng Y Zhou M Chen S Zhou Z [Improvement of memory in mice by extracts from leaves of Ginkgo biloba L.] In: Chung Kuo Chung Yao Tsa Chih (1991 Nov) 16(11):681-3, 704 (Published in Chinese) The study has shown that the extracts from leaves of Ginkgo biloba can significantly improve the NaNO2 and scopolamine induced impaired memory in mice. The potency of the ethanolic extract is greater than that of the aqueous extract. The ethanolic extract acts favorably on the memory function of normal animals. Both extracts help to prolong the survival time of mice receiving 200 mg/kg(ip)NaNO2. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Zhang H Xu L Jin Q Zhou L Cheng P [Anti-anaphylactic pharmacological action of water-soluble constituents of Ginkgo biloba L. episperm] In: Chung Kuo Chung Yao Tsa Chih (1990 Aug) 15(8):496-7, 513 (Published in Chinese) Water-soluble constituents of Ginkgo biloba episperm 100 or 200 mg/kg po given to mice inhibited passive cutaneous allergic response and the same dose given to rats ip inhibited mast cell degranulation. It antagonized the contractile effect of isolated guinea pig ileum smooth muscles induced by the antigen. It inhibited the deliverance of SRS-A from anaphylactic lung of guinea pig. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CLINICAL THERAPEUTICS***** 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CONTACT DERMATITIS***** Tomb RR Foussereau J Sell Y Mini-epidemic of contact dermatitis from ginkgo tree fruit (Ginkgo biloba L.). In: Contact Dermatitis (1988 Oct) 19(4):281-3 3 cases of contact dermatitis from ginkgo fruit are reported. Swelling of the prepuce can be the only clinical sign of intolerance, as was observed in 1 case. Diagnosis of contact dermatitis to ginkgo fruit should be made in cities where female ginkgo trees grow, in Chinese, Japanese and South-East Asian subjects, who are aware of the ginkgo nut's culinary qualities within the fruit, as well as in children who play with the fallen fruits as "marbles". €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CORONARY ARTERY DISEASE***** Tosaki A Engelman DT Pali T Engelman RM Droy-Lefaix MT Ginkgo biloba extract (EGb 761) improves postischemic function in isolated preconditioned working rat hearts. In: Coron Artery Dis (1994 May) 5(5):443-50 BACKGROUND: We studied the effect of preconditioning and Gikgo biloba extract (EGb 761) in relation to the recovery of contractile function after global ischemia in the isolated working rat heart. METHODS: Hearts (n = 12 in each group) were randomly divided into five groups: In group I, hearts were subjected to 30 min of normothermic global ischemia followed by 30 min of reperfusion; in group II, they were subjected to one cycle of preconditioning consisting of 5 min ischemia and 10 min reperfusion before the induction of 30 min of ischemia and 30 min of reperfusion; group III hearts underwent two cycles of preconditioning; group IV hearts underwent three cycles of preconditioning; and group hearts underwent four cycles of preconditioning before the onset of 30 min ischemia followed by 30 min of reperfusion. RESULTS: Ventricular fibrillation (total) and ventricular tachycardia (no preconditioning) both fell from 100% to 50% (P < 0.05) after four cycles of preconditioning. In relation to ventricular fibrillation, preconditioning significantly reduced the formation of oxygen free radicals, measured by electron spin resonance spectroscopy (ESR), but recovery of cardiac function was low in all preconditioned groups. Because of the relatively low incidence of arrhythmias (50% ventricular fibrillation and 50% ventricular tachycardia) and relatively low cardiac function in Group V, EGb 761, a free-radical scavenger, was chosen to improve myocardial contractile function in preconditioned hearts. Fifty and 100 mg/kg of EGb 761 (per os) significantly improved coronary flow, aortic flow, left ventricular developed pressure (LVDP), and the first derivative of LVDP (LVDdP/dtmax) in the four-cycle preconditioned group. Thus, after 30 min of reperfusion, aortic flow was improved from 11.6 +/- 0.9 ml/min to 19.7 +/- 1.2 ml/min (P < 0.05) with a dose of 50 mg/kg of EGb 761 and to 22.0 +/- 1.5 ml/min (P < 0.05) with a dose 100 mg/kg of EGb 761, in the four-cycle preconditioned group. During reperfusion, the formation of free radicals was reduced by approximately 50 and 60% using 50 mg/kg and 100 mg/kg of EGb 761, respectively, when compared with the four-cycle preconditioned drug-free control group. CONCLUSION: We have demonstrated that EGb 761 can improve contractile function after global ischemia in the isolated working rat heart by reducing the formation of oxygen free radicals, and we have shown that this protection is additive to that of ischemia-induced preconditioning. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CURRENT MEDICAL RESEARCH AND OPINION***** Rai GS Shovlin C Wesnes KA A double-blind, placebo controlled study of Ginkgo biloba extract ('tanakan') in elderly outpatients with mild to moderate memory impairment. In: Curr Med Res Opin (1991) 12(6):350-5 Thirty-one patients over the age of 50 years and showing a mild to moderate degree of memory impairment entered a 6-month double-blind, placebo controlled, parallel group design study to assess the effects of a standardized Ginkgo biloba extract (containing 24% flavonoid glycosides and 6% terpenes) on cognitive function. Patients were allocated at random to receive oral doses of 40 mg Ginkgo biloba extract or identical placebo 3-times daily. Assessments were made at baseline and after 12 and 24 weeks of treatment using a range of psychometric tests. Efficacy data were available for 27 patients (15 in the placebo group and 12 in the active treatment group). Statistical analysis of the data as compared to baseline suggests that Ginkgo biloba extract had a beneficial effect on cognitive function in this group of patients. Performance on the Digit Copying sub-test of the Kendrick battery was significantly improved at both 12 and 24 weeks, while the median speed of response on a computerized version of a classification task also showed a significant superiority over placebo at 24 weeks. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****DRUGS UNDER EXPERIMENTAL AND CLINICAL RESEARCH***** Droy-Lefaix MT Bonhomme B Doly M Protective effect of Ginkgo biloba extract (EGB 761) on free radical- induced changes in the electroretinogram of isolated rat retina. In: Drugs Exp Clin Res (1991) 17(12):571-4 The retina is a tissue particularly rich in polyunsaturated fatty acids and thus highly sensitive to lipid peroxidation initiated by oxygenated free radicals. By recording the electroretinogram (ERG) b wave amplitude on isolated rat retina, the authors have investigated the anti-oxidant properties of Ginkgo biloba extract (EGB 761). Two groups of rats were used: one group was treated with EGB 761 at a dose of 100 mg/kg/day per os for 10 days; the other one of untreated animals served as a control. At the end of the treatment (10 days), rats were sacrificed, one retina isolated and perfused in order to record ERG. Lipid peroxidation was induced by adding a mixture of (FeSO4 + Na ascorbate) to the perfusion solution. In the untreated rats a 50% decrease in ERG was observed after only 55 min. Such a delay in the decrease and subsequent maintenance of ERG b wave amplitude confirm that the anti-oxidant properties of EGB 761 can protect the retina against lipoperoxidation. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****EXPERIENTIA***** Pincemail J Dupuis M Nasr C Hans P Haag-Berrurier M Anton R Deby C Superoxide anion scavenging effect and superoxide dismutase activity of Ginkgo biloba extract. In: Experientia (1989 Aug 15) 45(8):708-12 Ginkgo biloba extract is known to be efficient in diseases associated with free radical generation. The purpose of this work was to study, under in vitro conditions, the action of Ginkgo biloba extract (Gbe) against superoxide anion (O2-.), which is directly or indirectly implicated in cell damage. Gbe appears to have both an O2-. scavenging effect and also a superoxide dismutase activity. Its antiradical effect was demonstrated by low temperature electron spin resonance and in a non-enzymatic system (phenazine methosulfate- NADH), and its enzymatic activity was shown by polarographic determination. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Pincemail J Thirion A Dupuis M Braquet P Drieu K Deby C Ginkgo biloba extract inhibits oxygen species production generated by phorbol myristate acetate stimulated human leukocytes. In: Experientia (1987 Feb 15) 43(2):181-4 A Ginkgo biloba extract (Gbe) containing flavonoids, among other compounds, was tested for the release of activated oxygen species (O- 2, H2O2, OH.) during the stimulation of human neutrophils (PMNs) by a soluble agonist. The extract slows down O2 consumption (respiratory burst) of stimulated cells by its inhibitory action on NADPH-oxidase, the enzyme responsible for the reduction of O2 to O-2. Consequently, superoxide anion (O-.2) and hydrogen peroxide (H2O2) production is significantly decreased when the PMNs stimulation is done in the presence of the extract at concentrations of 500, 250 and 125 micrograms/ml. Moreover, the hydroxyl radical generation (OH.) is very much decreased at concentrations as low as 15.6 micrograms Gbe/ml, which indicates that the extract also has free radical scavenging activity. Gbe is able at least to reduce very severely the activity of myeloperoxidase contained in neutrophils. This enzyme, secreted into the intra and extracellular medium, catalyzes the oxidation of chloride (Cl-) by H2O2 to yield strong oxidants (HOCl, chloramines) which are implicated in inflammatory processes. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****EXPERIMENTAL NEUROLOGY***** Attella MJ Hoffman SW Stasio MJ Stein DG Ginkgo biloba extract facilitates recovery from penetrating brain injury in adult male rats. In: Exp Neurol (1989 Jul) 105(1):62-71 Adult, male Sprague-Dawley rats received 100 mg/kg Ginkgo biloba extract (GBE) intraperitoneally for 30 days. GBE reduced overall activity and decreased sensitivity to light in the open field maze. The rats were also less responsive to noxious stimuli after 13 days of treatment with GBE. After the last injection, all subjects were trained on a delayed-spatial alternation task. Subsequent to acquisition of the spatial task, the rats received either sham operations and saline or bilateral frontal cortex lesions treated with either saline or GBE. Thirty additional days of treatment began on the day of injury, and open field behavior, analgesia, and metabolic activity measurements were again measured. The rats with lesions treated with saline were more active than their GBE-treated counterparts and sham controls but there were no differences in response to illumination or noxious stimuli. Retention of the delayed- spatial alternation indicated that rats with lesions treated with GBE were less impaired than brain-injured subjects receiving saline treatment. Histological examination showed that GBE reduced the extent of brain swelling in response to the injury. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****FORTSCHRITTE DER MEDIZIN***** Witte S Anadere I Walitza E [Improvement of hemorheology with ginkgo biloba extract. Decreasing a cardiovascular risk factor] Verbesserung der Hamorheologie durch Ginkgo-biloba-Extrakt. Verminderung eines kardiovaskularen Risikofaktors. 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Grassel E [Effect of Ginkgo-biloba extract on mental performance. Double-blind study using computerized measurement conditions in patients with cerebral insufficiency] Einfluss von Ginkgo-biloba-Extrakt auf die geistige Leistungsfahigkeit. Doppelblindstudie unter computerisierten Messbedingungen bei Patienten mit Zerebralinsuffizienz. 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Eckmann F [Cerebral insufficiency--treatment with Ginkgo-biloba extract. Time of onset of effect in a double-blind study with 60 inpatients] Hirnleistungsstorungen--Behandlung mit Ginkgo-biloba-Extrakt. Zeitpunkt des Wirkungseintrits in einer Doppelblindstudie mit 60 stationaren Patienten. In: Fortschr Med (1990 Oct 10) 108(29):557-60 (Published in German) Sixty inpatients with cerebral insufficiency and the leading symptom depressive mood, were treated in a double-blind study for 6 weeks with a daily dose of 160 mg Ginkgo biloba extract or placebo. After 2, 4 and 6 weeks, changes in 12 typical symptoms in comparison with the last examination, were evaluated. In the group receiving placebo, small, but progressive improvements were observed. In the Ginkgo- biloba group, the overall number of improvements was significantly larger. After 2 weeks the differences were marked for only a few of the symptoms; after 4 and 6 weeks in contrast, in 11 of the 12 symptoms. The largest number of improvements in the Ginkgo-biloba group was observed between the 2nd and 4th weeks of treatment. In this period, about two-thirds of the patients on Ginkgo-biloba, and about one-fifth of the patients on placebo showed improvements. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Gerhardt G Rogalla K Jaeger J [Drug therapy of disorders of cerebral performance. Randomized comparative study of dihydroergotoxine and Ginkgo biloba extract] Medikamentose Therapie von Hirnleistungsstorungen. Randomisierte Vergleichsstudie mit Dihydroergotoxin und Ginkgo-biloba-Extrakt. In: Fortschr Med (1990 Jun 30) 108(19):384-8 (Published in German) In a randomized trial lasting six weeks and involving 80 elderly patients with cerebrovascular disorders, the effectiveness and tolerance of dihydroergotoxine was compared with an extract of Ginkgo biloba. On the basis of psychometric tests and assessment scales, it was shown that treatment with either substance improved the condition of the patients. While, for the most part, intergroup comparison revealed no major statistically significant differences, such changes, affecting various parameters, were found during follow-up-- more frequently within the dihydroergotoxine group than within the group treated with Ginkgo biloba extract. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ 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] Hamorheologische Effekte des Ginkgo-biloba-Extrakts EGb 761. Dosisabhangige Wirkung von EGb 761 auf Mikrozirkulation und Viskoelastizitat des Blutes. 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****FREE RADICAL BIOLOGY AND MEDICINE***** 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 (EGb 761). 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Emerit I Arutyunyan R Oganesian N Levy A Cernjavsky L Sarkisian T Pogossian A Asrian K Radiation-induced clastogenic factors: anticlastogenic effect of Ginkgo biloba extract. In: Free Radic Biol Med (1995 Jun) 18(6):985-91 Clastogenic factors (CFs) were first described in the blood of persons irradiated accidentally or for therapeutic reasons. Work of our laboratory has shown that they occur also under other circumstances, which are characterized by oxidative stress, and that CF-induced chromosome damage is regularly prevented by superoxide dismutase (SOD). Recently we found CFs in a high percentage of salvage personnel of the Chernobyl reactor accident. These liquidators represent a high-risk population and might benefit from cancer chemoprevention by antioxidants. SOD would have to be injected and is not appropriate for long-term prophylactic treatment. In the present study, we therefore evaluated the anticlastogenic effect of the Ginkgo biloba extract EGb 761, which is known for its superoxide scavenging properties. EGb 761 was tested on CF-treated blood cultures of healthy donors. After establishing the optimal protective EGb concentration, using CFs produced by irradiation of whole blood from healthy volunteers, the extract was tested on cultures exposed to CFs from plasma of persons irradiated as liquidators. The anticlastogenic effect could be confirmed for a final concentration of 100 micrograms/ml. In 12 consecutive experiments, CFs induced an average of 18.00 +/- 4.41 aberrations/100 cells. This was reduced to 7.33 +/- 3.08 in the parallel cultures receiving 100 micrograms/ml EGb 761 (p < .001). SOD was anticlastogenic in the same system at concentrations of 30 cytochrome C units/ml (approximately 10 micrograms/ml). Preliminary results obtained in a small series of liquidators showed regression or complete disappearance of CFs in the plasma after 2 months of treatment with EGb 761 (3 x 40 mg/d). €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Haramaki N Aggarwal S Kawabata T Droy-Lefaix MT Packer L Effects of natural antioxidant ginkgo biloba extract (EGB 761) on myocardial ischemia-reperfusion injury. In: Free Radic Biol Med (1994 Jun) 16(6):789-94 Recently, it was reported that Ginkgo biloba extract (EGb 761), which is known to have antioxidant properties, also has antiarrhythmic effects on cardiac reperfusion-induced arrhythmias. In the present study, effects of EGb 761 on cardiac ischemia-reperfusion injury were investigated from the point of view of recovery of mechanical function as well as the endogenous antioxidant status of ascorbate. Isolated rat hearts were perfused using the Langendorff technique, and 40 min of global ischemia were followed by 20 min of reperfusion. EGb 761 improved cardiac mechanical recovery and suppressed the leakage of lactate dehydrogenase (LDH) during reperfusion. Furthermore, EGb 761 diminished the decrease of myocardial ascorbate content after 40 min of ischemia and 20 min of reperfusion. Interestingly, EGb 761 also suppressed the increase of dehydroascorbate. These results indicate that EGb 761 protects against cardiac ischemia-reperfusion injury and suggest that the protective effects of EGb 761 depend on its antioxidant properties. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****FREE RADICAL RESEARCH COMMUNICATIONS***** Ramassamy C Girbe F Christen Y Costentin J Ginkgo biloba extract EGb 761 or trolox C prevent the ascorbic 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****FUNDAMENTAL AND CLINICAL PHARMACOLOGY***** Bolanos-Jimenez F Manhaes de Castro R Sarhan H Prudhomme N Drieu K Fillion G Stress-induced 5-HT1A receptor desensitization: protective effects of Ginkgo biloba extract (EGb 761). In: Fundam Clin Pharmacol (1995) 9(2):169-74 The effects of sub-chronic cold stress on the functioning of hippocampal 5-HT1A receptors in old isolated rats and the possible protective effects of Ginkgo biloba extract (EGb 761) were investigated. Cold exposure during five days, produced a significant reduction of the inhibitory effect of 8-hydroxy-2-(di-n- propylamino)tetraline (8-OH-DPAT) on forskolin-stimulated adenylyl cyclase activity. In contrast, neither the affinity nor the density of hippocampal [3H]8-OH-DPAT binding sites were affected indicating that the reduced sensitivity of 5-HT1A receptors induced by stress is probably due to a modification of their coupling mechanisms to adenylyl cyclase. The stress-induced desensitization of 5-HT1A receptors was prevented by the administration of EGb 761 (50 mg/kg per os/14 days). These results clearly indicate that 5-HT1A receptors are desensitized by stress and point out the reduced capacity of old rats to cope with the adverse effects of a chronic stressor. EGb 761 appears to restore the age-related decreased capacity to adapt to a chronic stressor. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****GENERAL PHARMACOLOGY***** Auguet M Clostre F Effects of an extract of Ginkgo biloba and diverse substances on the phasic and tonic components of the contraction of an isolated rabbit aorta. In: Gen Pharmacol (1983) 14(2):277-80 1. The effects of phentolamine, propranolol, D 600, theophylline, papaverine and an extract of Ginkgo biloba were studied with respect to the two phases of the contractile response induced by norepinephrine in an isolated rabbit aorta. 2. Phentolamine (3 x 10(- 6) M) inhibits the rapid phase of the contraction of the rabbit aorta brought on by norepinephrine (NE) 10(-5) M more strongly than the tonic phase. Propranolol (10(-6) M) potentiates this rapid phase. 3. D 600 inhibits the slow phase with an EC50 = to 3.8 x 10(-8) M. 4. Papaverine and theophylline increase the relaxation that follows the rapid phase of contraction. The slow phase is inhibited only by papaverine. 5. The extract of Ginkgo biloba (Gb) at a concentration of 3 mg/ml has the same type of effect as papaverine 3 X 10(-5) M. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Vilain B DeFeudis FV Clostre F Effect of an extract of Ginkgo biloba on the isolated ileum of the guinea-pig. In: Gen Pharmacol (1982) 13(5):401-5 1. The effects of an extract of Ginkgo biloba (Gb) were studied using the guinea-pig isolated ileum. 2. Using isometric recording, the dose- response relation for the action of Gb was complex, and at 400 micrograms/ml was reproducibly biphasic--a relaxation followed by a contraction. 3. Droperidol (3 X 10(-7) M - 10(-6) M), cyproheptadine (10(-7) M), and diphenhydramine (10(-7) M) prolonged the relaxation and usually decreased the amplitude of the contraction produced by Gb (400 micrograms/ml), whereas phentolamine, hexamethonium, methysergide, or cimetidine (10(-7) or 10(-6) M) did not affect the response to Gb. 4. The action of Gb on the guinea-pig ileum might involve mechanisms associated with dopamine and/or histamine. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Auguet M DeFeudis FV Clostre F Deghenghi R Effects of an extract of Ginkgo biloba on rabbit isolated aorta. In: Gen Pharmacol (1982) 13(3):225-30 1. Extract of Ginkgo biloba (Gb) provoked a dose-dependent contraction of spirally-cut rabbit aortic strips (EC50 congruent to 1.0 mg/ml) by an action that was antagonized by phentolamine (10(-7) M). 2. Inhibitors of catecholamine re-uptake, cocaine (10(-5) M) and desipramine (10(-7) M) potentiated the contractile effect of norepinephrine (NE), but inhibited the contractile effects of Gb and tyramine. 3. A comparison of the actions of Gb, NE and tyramine using aortic strips prepared from control and reserpine-treated rabbits revealed that reserpine treatment increased the response to NE but decreased the response to Gb and tyramine. 4. The contractile action of Gb on rabbit isolated aorta involves, at least in part, a release of catecholamines from endogenous tissue stores. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Auguet M DeFeudis FV Clostre F Effects of Ginkgo biloba on arterial smooth muscle responses to vasoactive stimuli. In: Gen Pharmacol (1982) 13(2):169-71 1. An extract of Ginkgo biloba (Gb), at a concentration (100 microgram/ml) that did not provoke isometrically-recorded contractions of rabbit aorta, was tested on the contractile effects of norepinephrine (NE), serotonin (5-HT) and dopamine (DA). 2. Gb potentiated the contractile effect of NE (reduced the EC50 from 75 to 36 nM), but had no obvious action on the contractile effects of 5-HT or DA. 3. These results indicate that low concentrations of Gb might influence catecholaminergic systems by an indirect mechanism. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Rapin JR Lamproglou I Drieu K DeFeudis FV Demonstration of the "anti-stress" activity of an extract of Ginkgo biloba (EGb 761) using a discrimination learning task. In: Gen Pharmacol (1994 Sep) 25(5):1009-16 1. Young (4-month-old) and old (20-month-old) rats, maintained under water restriction, were trained to discriminate to obtain a small amount of drinking water as a reward. Each animal had to learn to press a lever corresponding to a light that was randomly distributed on the left or right. 2. Introduction of an auditory perturbation ("stress") during the discriminative phase of learning modified the capacity and rate of acquisition in both young and old animals, changes that were correlated with increases in plasma concentrations of epinephrine, norepinephrine and corticosterone. 3. Stress-induced detrimental changes in both discrimination learning and plasma hormones were suppressed by 20 days of oral treatment with an extract of Ginkgo biloba leaves (EGb 761; 50 or 100 mg/kg/day) in both young and old rats, effects that became statistically significant by the third day of learning (time of maximal acquisition rate). 4. EGb 761 treatment was less effective in increasing the percentage of efficient lever presses in old than in young rats, but more effective in decreasing the number of inefficient lever presses and reaction time in the older animals. 5. These results indicate that EGb 761 can facilitate behavioral adaptation despite adverse environmental influences, a property that supports its clinical use in treating cognitive impairment, especially in elderly patients. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hellegouarch A Baranes J Clostre F Drieu K Braquet P DeFeudis FV Comparison of the contractile effects of an extract of Ginkgo biloba and some neurotransmitters on rabbit isolated vena cava. In: Gen Pharmacol (1985) 16(2):129-32 Dose-related contractions were elicited in strips of rabbit isolated vena cava by norepinephrine (NE, IC50 approximately equal to 2.3 X 10(-7) M), dopamine (IC50 approximately equal to 6.9 X 10(-6) M), histamine (IC50 approximately equal to 2.1 X 10(-6) M) and extract of Ginkgo biloba (Gb, IC50 approximately equal to 86 micrograms/ml). Serotonin and tyramine elicited very weak contractile effects in this preparation. Phenoxybenzamine (10(-7) M) abolished the contractions elicited by NE, and blocked the effect of Gb by about 50%. Further support is provided for the therapeutic action of Gb in cardiovascular disorders. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ 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). €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY RESEARCH***** Subhan Z Hindmarch I The psychopharmacological effects of Ginkgo biloba extract in normal healthy volunteers. In: Int J Clin Pharmacol Res (1984) 4(2):89-93 Eight healthy female volunteers received Ginkgo biloba extract (G.B.E.) 120, 240, 600 mg and placebo according to a randomized, double-blind crossover design. One hour following treatment, subjects completed a battery of psychological tests including critical flicker fusion (CFF), choice reaction time (CRT), subjective ratings of drug effects (LARS) and a Sternberg memory scanning test. No statistically significant changes from placebo were observed on CFF, CRT or subjective ratings of drug effects. However, memory as assessed using the Sternberg technique was found to be significantly improved following treatment with G.B.E. 600 mg when compared to placebo and results suggested a localized effect of the drug on the serial comparison stage of the reaction process. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Duche JC Barre J Guinot P Duchier J Cournot A Tillement JP Effect of Ginkgo biloba extract on microsomal enzyme induction. In: Int J Clin Pharmacol Res (1989) 9(3):165-8 Twenty-four healthy volunteers were divided in three groups who were randomly assigned different treatments for 13 days: group I received 400 mg/day of a defined Ginkgo biloba extract (GBE), group II 300 mg/day of phenytoin and group III a placebo. The elimination half- life of antipyrine was measured with a high performance liquid chromatographic technique initially and on the last day of the administration of the treatments. The results show that the half-life of antipyrine was not affected by GBE and placebo treatments, whereas it was significantly decreased (p less than 0.05) frm 12.2 to 6.8 h after phenytoin control treatment. This study demonstrates that GBE has no effect on the hepatic microsomal drug oxidation system. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****INTERNATIONAL JOURNAL OF NEUROSCIENCE***** Agar A Yargicoglu P Apaydin KC Oguz Y The effect of ginkgo biloba extract on EEG spectra in experimental diabetes: no relation to lipid peroxidation. In: Int J Neurosci (1994 Jun) 76(3-4):259-66 Forty four Swiss albino rats aged two months, weighing 180-250 g, were used in the experiment. They were divided into four equal groups as control, alloxan-diabetic, diabetic + GbE and control + GbE. After the onset of experimental period, diabetic + GbE and control + GbE groups received ginkgo biloba extract and the other groups were given saline solution for ten weeks. Diabetic and diabetic + GbE groups were made diabetic by injecting alloxan on 16th day. Spectral analysis of EEGs recorded from parietal lobes of all groups of rats were computed by Fast Fourier Transform (FFT) algorithm. Their amplitude maxima were found to occupy the frequency bands of 1-2, 2- 4, 4-6, 6-8, 8-16 and 16-30 Hz. Significant amplitude increase was found in 1-2 and 2-4 Hz frequency bands in diabetic + GbE group compared with control, but no differences were found for other groups. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION***** Lo HM Lin FY Tseng CD Chiang FT Hsu KL Tseng YZ Effect of EGb 761, a ginkgo biloba extract, on early arrhythmia induced by coronary occlusion and reperfusion in dogs. In: J Formos Med Assoc (1994 Jul) 93(7):592-7 EGb 761 is a preparation of Ginkgo biloba extract, which has complex biologic actions including free radical scavenging activity. To examine the anti-arrhythmic effect of EGb 761, a canine preparation of coronary artery occlusion-reperfusion was tested. Under intravenous anesthesia and open chest conditions, 32 dogs were subjected to 30 min of coronary occlusion, followed by reperfusion. Twelve received EGb 761 by intravenous injection, 1 mg/kg five minutes before coronary occlusion, followed by a continuous infusion of 0.1 mg/kg/min until five minutes after reperfusion. Immediately prior to reperfusion, an additional bolus dose of EGb 761 (1 mg/kg) was again injected (group A). The remaining 20 dogs received saline injection, and served as the control (group B). The electrocardiographic changes were recorded during the whole experimental course. The results showed that, during coronary occlusion, group A dogs had a lower count of ventricular premature beats than group B dogs. However, there was no difference in the incidence of ventricular tachycardia (VT) between the two groups. The duration of VT of the treated dogs was similar to that of the control dogs. The incidence of ventricular fibrillation (VF) was also similar. Upon reperfusion, the treated dogs were shown to be protected from VF. The duration of VT was also shorter in the treated group, although the incidence of VT was not different between the two groups. EGb 761 is effective in preventing early VF induced by coronary reperfusion while ineffective in protecting the ischemic VT and VF. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL FRANCAIS D OPHTALMOLOGIE***** Lanthony P Cosson JP [The course of color vision in early diabetic retinopathy treated with Ginkgo biloba extract. A preliminary double-blind versus placebo study] Evolution de la vision des couleurs dans la retinopathie diabetique debutante traitee par extrait de Ginkgo biloba. Etude preliminaire a double insu contre placebo. In: J Fr Ophtalmol (1988) 11(10):671-4 (Published in French) The therapeutic efficiency of the Ginkgo biloba extract was estimated in a double-blind trial, during a 6 months period, in 29 diabetic subjects with an early diabetic retinopathy evidenced by angiography, and associated with a blue-yellow dyschromatopsia. The functional criterion was the color vision evolution, studied by the Desaturated Panel D-15 and the 100-Hue Farnsworth test at the beginning of the trial and 6 months later. An improvement tendency was evidenced in subjects treated by Ginkgo biloba extract, and an aggravation in subjects with placebo, this improvement being statistically significative with the Desaturated Panel D-15 among subjects without retinal ischemia. These clinical results on visual function corroborate the pharmacological actions of Ginkgo biloba extract on diabetic retina. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF INTERNATIONAL MEDICAL RESEARCH***** Kose K Dogan P Lipoperoxidation induced by hydrogen peroxide in human erythrocyte membranes. 2. Comparison of the antioxidant effect of Ginkgo biloba extract (EGb 761) with those of water-soluble and lipid-soluble antioxidants. In: J Int Med Res (1995 Jan-Feb) 23(1):9-18 An in vitro model using healthy human erythrocyte suspensions was used to compare the antioxidant effect of standardized Ginkgo biloba extract (EGb 761) with those of water-soluble (ascorbic acid, glutathione and uric acid) and lipid-soluble (alpha-tocopherol and retinol acetate) antioxidants. Lipid peroxidation was induced by hydrogen peroxide in the absence (control) and presence of antioxidants at low (25 micrograms/ml) and high (250 micrograms/ml) concentrations. Malondialdehyde production was determined as the indicator of lipid peroxidation during the incubation period. The results suggest that all of the antioxidants, except ascorbic acid, have antioxidant potential in this system in a concentration- dependent manner. When the antioxidants were compared, EGb 761 was found to be more effective than water-soluble antioxidants, and as effective as lipid-soluble antioxidants. Among the lipid-soluble antioxidants there was no significant difference in potency between alpha-tocopherol and retinol acetate, but uric acid was the most potent of the water-soluble antioxidants. The antioxidant potency of EGb 761 appears to be comparable with that of the well-known antioxidants alpha-tocopherol and retinol acetate. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Kose K Dogan P Lipoperoxidation induced by hydrogen peroxide in human erythrocyte membranes. 1. Protective effect of Ginkgo biloba extract (EGb 761). In: J Int Med Res (1995 Jan-Feb) 23(1):1-8 The antioxidant potential of Ginkgo biloba extract (EGb 761) on healthy human erythrocyte membranes was investigated. Lipoperoxidation was induced in erythrocyte suspensions using hydrogen peroxide, in the presence of EGb 761 at 37 degrees C; malondialdehyde production was determined as the indicator of lipoperoxidation during the incubation period. The results for EGb 761 at concentrations of 0, 25, 50, 125, 250 and 500 micrograms/ml suggest that the antioxidant potential of EGb 761 in erythrocyte membranes increases with dose. Similarly, using different incubation periods (0, 15, 30, 45 or 60 min) indicated that the antioxidant effect of EGb 761 increased by the incubation time. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL DES MALADIES VASCULAIRES***** Saudreau F Serise JM Pillet J Maiza D Mercier V Kretz JG Thibert A [Efficacy of an extract of Ginkgo biloba in the treatment of chronic obliterating arteriopathies of the lower limbs in stage III of Fontaine's classification] Efficacite de l'extrait de Ginkgo biloba dans le traitement des arteriopathies obliterantes chroniques des membres inferieurs au stade III de la classification de Fontaine. In: J Mal Vasc (1989) 14(3):177-82 (Published in French) A controlled trial of Ginkgo biloba extract in injectable form (Tanakan 50 mg, a lyophilizate for parenteral use) was carried out versus a placebo as a preoperative medical treatment of stage III (Fontaine classification) chronic occlusive arterial disease of the lower limbs (with pain in decubitus). The 64 men and women patients in this multicenter study (32 in each group) were over 18 years of age and had a cultural and intellectual level as well as a physical condition allowing them to play an active role in the experiment (self-evaluation of pain). During 8 days they received two daily infusions of 500 cc of normal saline solution containing either 100 mg of Ginkgo biloba extract or a placebo of identical appearance. During this period, anticoagulants were authorized; hemodilution, vasoactive drugs and platelet anti-aggregates were forbidden; pentazocine (Fortal, 50-mg tablets) was allowed at the patient's request. Pain was rated according to a visual scale, with each patient marking a point between two extremes ("maximum imaginable pain" and "total absence of pain") 100 mm apart. A questionnaire based on that of Melzack (McGill Pain Questionnaire) completed this qualitative as well as quantitative self-evaluation of pain. The results of these questionnaires were assessed on the basis of 4 scores, each determined by the patient's choice among 3 evaluation figures. The chi square, Student and Wilcoxon tests were used for statistical analysis. Results: The two randomly-composed groups with Ginkgo biloba extract and a placebo were comparable (Table I). Analysis was based on 55 observations (26 in the extract group and 29 in the placebo group).(ABSTRACT TRUNCATED AT 250 WORDS) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF NEUROCHEMISTRY***** Macovschi O Prigent AF Nemoz G Pacheco H Effects of an extract of Ginkgo biloba on the 3',5'-cyclic AMP phosphodiesterase activity of the brain of normal and triethyltin- intoxicated rats. In: J Neurochem (1987 Jul) 49(1):107-14 For clarification of the beneficial effects of the extract of Ginkgo biloba (EGB) on triethyltin (TET) toxicity in rats, the phosphodiesterase (PDE) activities of the cerebral tissue were measured under in vitro and ex vivo conditions. Under in vitro conditions, low concentrations of EGB (0.25-4.0 mg/L) activated the enzyme, whereas after higher concentrations (5-250 mg/L), dose- dependent inhibition of the enzyme activity was observed. In the lower concentration range, the extract also partially restored the high-affinity PDE activity (measured with 0.25 microM cyclic AMP) of the particulate fraction of the brain inhibited by TET in vitro. In contrast, the inhibitory influence of TET on the low-affinity PDE activity (measured with 50 microM cyclic AMP) of the particulate fraction was enhanced by the extract. Although treatment with a single large dose of EGB lowered the particulate PDE activities of the brain of normal rats, no effects of the extract could be detected in animals after repeated daily administrations of EGB during a 4-day period. Curative treatment of the TET-intoxicated rats with EGB during a 7-day period accelerated the recovery of the edematous state of the white matter caused by the intoxication and also normalized the lowered PDE activity of the particulate fraction of the edematous brain tissue. Furthermore, when preventively administered, EGB counteracted both the edema formation and the fall in PDE activity observed with treatment by TET alone. These observations strongly suggest that some beneficial effects of EGB might be due to its modulating influences on cellular cyclic AMP levels via activation of membrane-bound PDE. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF NEUROSURGICAL SCIENCES***** Iliff LD Auer LM The effect of intravenous infusion of Tebonin (Ginkgo biloba) on pial arteries in cats. In: J Neurosurg Sci (1983 Oct-Dec) 27(4):227-31 The dilatory effect of intravenously infused Tebonin (extract of Ginkgo biloba) on pial arterial vessels (less than 100 micron diameter), has been measured using a multichannel videoangiometer through a closed cranial window in cats. After 20 minutes there was a significant dilatation of 7% which increased to 21% by one hour. Results from 6 cats treated with 0.3 mg/kg/min. Tebonin were compared with a group of 6 control cats; the same blood gas "steady state" situation applying to both groups. Results imply a cerebral metabolic effect of Ginkgo biloba that induced a slow rise in cerebral blood flow. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF PHARMACY AND PHARMACOLOGY***** 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Ramassamy C Clostre F Christen Y Costentin J Prevention by a Ginkgo biloba extract (GBE 761) of the dopaminergic neurotoxicity of MPTP. In: J Pharm Pharmacol (1990 Nov) 42(11):785-9 In mice implanted subcutaneously with osmotic minipumps releasing the neurotoxic agent N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 days (105 micrograms h-1/mouse) (approximately 100 mg kg-1 day- 1) a significant reduction (approximately 25%) in the striatal dopaminergic nerve endings was observed. This neurotoxic effect was prevented by the semi-chronic ingestion of a Ginkgo biloba extract for 17 days (GBE 761, approximately 100 mg kg-1 day-1). The high concentrations (approximately 1 g L-1) at which GBE 761 in-vitro either prevented the uptake of [3H]dopamine by synaptosomes prepared from striatum, or prevented the specific binding of the pure dopamine uptake inhibitor [3H]GBR 12783 to membranes prepared from striatum suggests that the prevention of the MPTP neurotoxicity does not depend on an inhibition of the MPTP uptake by dopamine neurons. This is also suggested by the lack of prevention of the in-vitro striatal binding of [3H]GBR 12783 administered i.v. at a tracer dose, in mice pretreated for 8 days with GBE 761 (100 mg kg-1 p.o.) and receiving a supplementary gastric administration of GBE 761 (100 mg kg-1) 1 h before testing. Similar treatment with GBE 761 did not modify the toxicity for dopamine neurons of 6-hydroxydopamine (20 micrograms) directly injected into the striatum of rats. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Huguet F Drieu K Piriou A Decreased cerebral 5-HT1A receptors during ageing: reversal by Ginkgo biloba extract (EGb 761). In: J Pharm Pharmacol (1994 Apr) 46(4):316-8 Investigation of [3H]8-hydroxy-2(di-n-propylamino)tetralin binding to 5-HT1A receptors in cerebral cortex membranes of Wistar rats showed that the maximal number of binding sites (Bmax) was reduced significantly (22%) in aged (24-month-old) as compared with young (4- month-old) animals. Chronic treatment with Ginkgo biloba extract did not alter binding in young rats but increased binding density significantly (33%) in aged rats. These results confirm previously described age-related 5-hydroxytryptaminergic alterations. Together with data in the literature, they also suggest a restorative effect in aged rats, associated with decreased receptor density resulting from the protective action of Ginkgo biloba extract treatment on neuronal membrane. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL DE PHARMACOLOGIE***** Etienne A Hecquet F Clostre F Defeudis FV [Comparative effects of an extract of Ginkgo biloba and chlorpromazine on the in vitro osmotic fragility of rat erythrocytes (author's transl)] Comparison des effets d'un extrait de Ginkgo biloba et de la chlorpromazine sur la fragilite osmotique, in vitro, d'erythrocytes de rat. In: J Pharmacol (1982 Apr-Jun) 13(2):291-8 (Published in French) The effects of different concentrations of an extract of Ginkgo biloba (Gb) and of chlorpromazine (CPZ) on the osmotic lysis of rat erythrocytes (produced by dilution of the incubation medium by 30%- 70%) were compared in vitro. The erythrocytes were incubated together with Gb or Cpz at the time of the hemolytic reaction at 25 degrees or 37 degrees C in either a simple phosphate buffer or in a more complete buffer containing inorganic salts at physiological concentrations. CPZ produced a dose-dependent increase in the membrane resistance, the maximum effect occurring at 10(-4) M regardless of the experimental conditions used. Gb also increased membrane resistance, but to a lesser extent than CPZ. In addition, Gb was more effective under conditions which increased erythrocyte membrane fragility; i.e., 37 degrees C, simple phosphate buffer. The mechanism of action of Gb seems to differ from that of CPZ. The activity of CPZ (as a membrane stabilizer) is, in part, due to its penetration into the membrane phospholipid layer. Gb might act in a similar manner, but could also modify Na+ transport across the cell membrane by an action on adrenergic receptors, or could stimulate Na+, K+-ATP-ase activity, as has been described for norepinephrine. As Gb contains many molecular constituents: its action on the membrane is likely to be quite complex; but this effect could be associate with its vascular therapeutic action. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF VESTIBULAR RESEARCH***** Tighilet B Lacour M Pharmacological activity of the Ginkgo biloba extract (EGb 761) on equilibrium function recovery in the unilateral vestibular neurectomized cat. In: J Vestib Res (1995 May-Jun) 5(3):187-200 Locomotor balance recovery after unilateral vestibular neurectomy has been found strongly accelerated in the cat when the animals received a postoperative treatment with Ginkgo biloba Extract (EGb 761:50 mg/kg/d, i.p.), a result due to the improvement of plasticity mechanisms involved in vestibular compensation. The aim of this study was to determine which of the two main biochemical components (terpenes vs. flavonoids) contained in the extract was the most active in the recovery process, to test the influence of the route of administration, and to look for dose-dependent effects. Experiments were performed in six experimental groups of cats that were compared with each other and with three control groups. Comparisons were done on the recovery profile and time course of equilibrium function restoration, as quantified by the rotating beam test. Four experimental groups were treated with the standardized extract EGb 761 given orally (p.o.:2 groups; 40 mg and 80 mg/kg) or intraperitoneally (i.p.: 2 groups; 50 mg and 25 mg/kg), whereas the two others received only a special extract that did not contain the terpenes (i.p. administration: 25 mg and 10 mg/kg). Treatment was always given until complete recovery of locomotor balance function. The control groups received either no treatment (untreated cats), an oral vehicle (placebo cats), or a sham i.p. injection (sham cats). Results showed that locomotor balance recovery was significantly improved in all the experimental groups as compared to the control groups of cats, which recovered similarly and more slowly. Efficacy of the special extract without the terpenes was comparable to that of the total extract, indicating that the nonterpenic fraction was the most active biochemical constituent in this experimental model of central nervous system (CNS) plasticity. Pharmacological activity of the extract was also significantly better when given i.p. as compared to the p.o. route of administration, and dose-dependent effects were evidenced with the i.p. administration of the special extract without the terpenes, with a lower efficacy for the lowest dose (10 mg/kg). These data confirm that EGb 761 treatment serves as useful therapy in supporting brain functional recovery in this animal model of vestibular compensation and lead to a more precise understanding of the biochemical component that is active in this recovery process. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JAPANESE JOURNAL OF PHARMACOLOGY***** 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****KLINISCHE MONATSBLATTER FUR AUGENHEILKUNDE***** Raabe A Raabe M Ihm P [Therapeutic follow-up using automatic perimetry in chronic cerebroretinal ischemia in elderly patients. Prospective double-blind study with graduated dose ginkgo biloba treatment (EGb 761)] Therapieverlaufskontrolle mittels automatisierter Perimetrie bei chronischer zerebroretinaler Mangelversorgung alterer Patienten. Prospektive randomisierte Doppelblinduntersuchung mit dosisgestaffelter Ginkgo biloba-Behandlung (EGb 761). In: Klin Monatsbl Augenheilkd (1991 Dec) 199(6):432-8 (Published in German) The chronic cerebral retinal insufficiency syndrome in elderly patients is an organ specific expression of a generalized vascular cerebral deficiency. The progress of the disease is characterized by complex symptoms, variation in course, spontaneous remissions and, until recently inadequate diagnostic measurement methods. The new method of automated perimetry with the octopus 2000 P offers a patient-friendly procedure for indirect non-invasive diagnosis of circulatory state in limited cerebral retinal perfusion. In the present study measurements were made with this method on 24 patients (4 men and 20 women with an age of 74.9 +/- 6.9 years). The effect of the extract of Ginkgo biloba (EGb 761) on the reversibility of visual field disturbances was tested using a randomized and double blind study-design in two phases and with two dose levels. The main parameter investigated in this study was the change in the luminous density difference threshold after therapy with EGb 761. In group B (EGb 761 dose 160 mg/day) a significant increase in retinal sensitivity was seen within 4 weeks (p less than 0.05). In the lower dose (80 mg EGb 761/day) group (A), this change in retinal sensitivity was first seen after increasing the dose to 160 mg/day (p less than 0.01). The relative sensitivity of damaged retinal areas was more strongly influenced than "healthy" areas. The assessment by both doctors and patients of the general condition of the patients showed a significant improvement after the course of therapy. The results presented here show that damage to the visual field by chronic lack of bloodflow are significantly reversible.(ABSTRACT TRUNCATED AT 250 WORDS) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****LARYNGO- RHINO- OTOLOGIE***** 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] Ginkgoextrakt EGb 761 (Tebonin)/HAES versus Naftidrofuryl (Dusodril)/HAES. Eine randomisierte Studie zur Horsturztherapie. 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****LIFE SCIENCES***** Krieglstein J Beck T Seibert A Influence of an extract of Ginkgo biloba on cerebral blood flow and metabolism. In: Life Sci (1986 Dec 15) 39(24):2327-34 The purpose of the present investigation was to examine the effects of an extract of Ginkgo biloba (EGB) on blood glucose levels, on local cerebral blood flow as well as on cerebral glucose concentration and consumption. The local cerebral blood flow (LCBF) was measured in conscious rats by means of the 14C-iodoantipyrine technique and local cerebral glucose utilization (LCGU) by 14C-2- deoxy-glucose autoradiography. EGB increased the LCBF in 39 analyzed, anatomically defined brain structures by 50 to 100 per cent. No influence of EGB on LCGU was demonstrable. However, EGB enhanced the blood glucose level dose-dependently. Substrates and metabolites of energy metabolism were measured in the cortex of the isolated rat brain perfused at constant rate and with 7 mmol/l glucose added to the perfusion medium. In these experiments EGB decreased the cortical glucose concentration without other substrate levels being changed. These results suggest that glucose uptake may be inhibited by EGB. It is argued that the effects of EGB on brain glucose concentration and blood flow may contribute to its protection of brain tissue against ischemic or hypoxic damage. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY***** Dumont E D'Arbigny P Nouvelot A Protection of polyunsaturated fatty acids against iron-dependent lipid peroxidation by a Ginkgo biloba extract (EGb 761). In: Methods Find Exp Clin Pharmacol (1995 Mar) 17(2):83-8 Iron can induce a peroxidative degradation of the membrane polyunsaturated fatty acids by the well-known Fenton reaction. Chelated iron can also form a complex with oxygen, called perferryl ion, which is able to induce lipoperoxidation without a detectable production of hydroxyl radicals. The antioxidant properties of a titrated and standardized extract of Ginkgo biloba leaves (EGb 761) against iron-dependent peroxidative degradation of the membrane polyunsaturated fatty acids were studied. Rat liver microsomes were exposed to a mixture of NADPH, ADP and FeCl3 hypothesized to produce iron-oxygen complexes. The results of the analysis of the microsomal polyunsaturated fatty acids by gas chromatography show that the susceptibility to peroxidation of the different polyunsaturated fatty acids increases with their unsaturation level, and that EGb 761 protects these membrane polyunsaturated fatty acids regardless of their susceptibility to peroxidation. This protective effect is correlated with the decrease in the thiobarbituric acid-reactive substances concentration, but the calculation of the antioxidant potency of EGb 761 as an IC50 value using results of the thiobarbituric acid reaction leads to an underestimated evaluation when the reaction is carried out in the presence of iron ions. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY***** Karcher L Zagermann P Krieglstein J Effect of an extract of Ginkgo biloba on rat brain energy metabolism in hypoxia. In: Naunyn Schmiedebergs Arch Pharmacol (1984 Aug) 327(1):31-5 The purpose of the present investigation was to determine brain energy metabolism under hypoxic conditions as influenced by an extract of Ginkgo biloba (EGB). Male Sprague-Dawley rats treated with EGB were exposed to hypobaric or hypoxic hypoxia, and at various time points during or after hypoxia the levels of high-energy phosphates and some substrates of glycolysis were measured in brain cortical tissue. Rats treated with EGB (100 mg/kg, intraperitoneally) survived hypobaric hypoxia for a much longer period than controls (e.g. controls: 3.9 +/- 1.8 min, EGB-treated: 23.6 +/- 10.5 min). The brain glucose level was elevated by EGB in most experimental series, and the lactate concentration was slightly lower than in control brains. The lowering of lactate/pyruvate ratio was due to the decreased level of lactate and to the enhanced concentration of pyruvate as well. When hypoxia was sufficiently severe the breakdown of high-energy phosphates was less pronounced in EGB-treated animals. After oral application of EGB for 14 days the rats survived hypobaric hypoxia for 25.7 +/- 2.5 min whereas controls survived for 11.5 +/- 5.1 min. However, brain energy metabolism was not significantly influenced by this oral treatment. It is suggested that changes in brain energy metabolism and blood flow may contribute to the protective effect of EGB against hypoxia. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****NEUROPSYCHOBIOLOGY***** 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****OPHTHALMIC RESEARCH***** 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHARMACEUTISCH WEEKBLAD. SCIENTIFIC EDITION***** 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHARMACOLOGY, BIOCHEMISTRY AND BEHAVIOR***** 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 Previous studies have demonstrated that the administration of Ginkgo biloba extract (EGb 761) improves the compensation of the vestibular syndrome induced by transection of the VIIIth nerve. To investigate the mechanisms at play, the vestibular nuclei of alert guinea pigs were perfused with EGb 761. This perfusion always induced a stereotyped reversible postural syndrome that was the mirror image of the syndrome provoked by the unilateral lesion of the otolithical receptors. This result supports the hypothesis that EGb 761 has a direct excitatory effect on the lateral vestibular nuclei (LVN) neurons. In a second step, we quantified the horizontal vestibuloocular reflex (HVOR) of the normal guinea pig following IP injection of EGb 761. In normal guinea pig, IP administration of EGb 761 led to a reversible, dose-dependent decrease of the HVOR gain without affecting the phase of the reflex. These data help to explain the therapeutic effects of EGb 761 during vestibular syndromes and strongly suggest an impact at the neuronal level. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Lacour M Ez-Zaher L Raymond J Plasticity mechanisms in vestibular compensation in the cat are improved by an extract of Ginkgo biloba (EGb 761). In: Pharmacol Biochem Behav (1991 Oct) 40(2):367-79 The effects of administration of an extract of Ginkgo biloba (EGb 761) on vestibular compensation was studied in unilateral vestibular neurectomized cats. This experimental model of CNS plasticity was investigated by using behavioral tests (postural disorders compensation, locomotor balance recovery), electrophysiological (spontaneous and evoked neck muscle activity) and neurophysiological (spontaneous firing rate recovery of deafferented vestibular cells) recordings, and immunocytochemical methods (synaptic loss and synaptic reoccupation within the deafferented vestibular nuclei). In all experiments, EGb 761 was administered over 30 days at daily doses of 50 mg/kg IP. The results showed a faster recovery in the EGb- treated group of cats as compared to an untreated control group. EGb administration strongly accelerated postural and locomotor balance recovery. Concomitantly, spontaneous neck muscle activity, vestibulo- collic reflexes and spontaneous firing rate of vestibular units located on the lesioned side were restored earlier. Morphological correlates characterized by a more rapid synaptic reoccupation were found in the deafferented medial vestibular nucleus by means of immunoreactive labelling using an antibody against a synaptic vesicle- associated protein (synaptophysin), but they displayed a longer time- constant in comparison with the behavioral and neurophysiological data. These results clearly demonstrate that EGb 761 acts on recovery mechanisms considered as key processes in vestibular compensation. They suggest that this substance would possess neurotrophic and/or neuritogenic properties improving functional recovery after CNS injury. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Winter E Effects of an extract of Ginkgo biloba on learning and memory in mice. In: Pharmacol Biochem Behav (1991 Jan) 38(1):109-14 The effects of an extract of Ginkgo biloba (EGb 761) on acquisition, performance, and retention of mice in an appetitive operant conditioning were investigated. The animals were trained for 30 consecutive days to acquire a two-lever response sequence followed by food reward. EGb 761 was administered daily at a dose level of 100 mg/kg PO. Drug treatment started four and eight weeks before the training and was maintained until a retention test 10 weeks after it. The results indicated that EGb 761 facilitated memory processes. EGb 761 quickened the acquisition and improved the performance of the two- response sequence: The number of correct responses was increased and correct responses were performed more frequently in the most effective manner. Besides, incorrect responses were reduced sooner and faster and to a lower level in EGb 761-treated mice. With regard to the retention EGb 761 improved the retrieval of the learned response. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Porsolt RD Martin P Lenegre A Fromage S Drieu K Effects of an extract of Ginkgo Biloba (EGB 761) on "learned helplessness" and other models of stress in rodents. In: Pharmacol Biochem Behav (1990 Aug) 36(4):963-71 The effects of repeated oral administration of an extract of Ginkgo Biloba (EGB 761) on various behavioral models of stress in rodents were investigated. The models in rats included "learned helplessness," shock-suppressed licking (Vogel conflict test) and forced swimming-induced immobility ("behavioral despair"). The models in mice included shock-suppressed exploration (four plates test), spontaneous exploration (staircase test) and food consumption in a novel situation (emotional hypophagia). Further tests in rats examined the effects of EGB 761 on memory (passive avoidance test) and responsiveness to shock to determine whether the preventive effects observed with EGB 761 in the learned helplessness procedure were due either to drug-induced impairment of memory or to reduced shock sensitivity. In all experiments EGB 761 was administered over 5 days at daily doses of 50 and 100 mg/kg PO. In some experiments (Vogel test, four plates test, staircase test, emotional hypophagia) the effects of acute administration were also investigated. The results showed that repeated administration of EGB 761 (50 and 100 mg/kg/day) before exposure to unavoidable shock (preventive treatment) clearly reduced the subsequent avoidance deficits in the learned helplessness procedure but was less effective when first administered after "helplessness" induction (curative treatment). EGB 761 did not affect performance in the passive avoidance task or alter the animals' response to electric shock, suggesting that the effects observed in the learned helplessness procedure were not due to impaired memory or reduced shock sensitivity. Anxiolytic-like activity was also seen in the emotional hypophagia test in mice where repeated administration of EGB 761 increased the amount of food consumed.(ABSTRACT TRUNCATED AT 250 WORDS) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHARMACOLOGICAL RESEARCH***** Bruel A Gardette J Berrou E Droy-Lefaix MT Picard J Effects of Ginkgo biloba extract on glucose transport and glycogen synthesis of cultured smooth muscle cells from pig aorta. In: Pharmacol Res (1989 Jul-Aug) 21(4):421-9 We have examined the effect of an extract of Ginkgo biloba (Gbe) on glucose uptake and on glycogen synthesis in cultured smooth muscle cells (SMC) from pig aorta. Initial rates of glucose transport were determined by measurements of 2-deoxy-D-glucose (2-DG) uptake. From kinetic analyses apparent KM and Vmax values of facilitated glucose transport in cultured SMC were evaluated at 2.2 mM and 9.1 nmol/min/10(6) cells respectively. Gbe stimulated glucose transport in a dose-dependent manner; the maximum effect was reached at a Gbe concentration of 0.25 micrograms/ml and represented an increase of 35 +/- 4% above basal activity. This stimulation mainly occurred on facilitated glucose transport. The passive diffusion measured when cells were treated with cytochalasin B represented 15 +/- 3% of glucose total transport activity either in the absence or the presence of Gbe. The effect of Gbe on glycogen synthesis in cultured SMC was then tested by the incorporation of U14C-glucose into cellular glycogen. This process was enhanced by Gbe, the maximal effect was observed at a Gbe concentration of 0.25 micrograms/ml, and represented a 41 +r4% increase above basal activity. These data argue for a direct effect of Gbe upon glucose transport and glucose utilization in cultured SMC thus allowing a better nutriment disposal in the vascular wall. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHARMACOLOGICAL RESEARCH COMMUNICATIONS***** Puglisi L Salvadori S Gabrielli G Pasargiklian R Pharmacology of natural compounds. I. Smooth muscle relaxant activity induced by a Ginkgo biloba L. extract on guinea-pig trachea. In: Pharmacol Res Commun (1988 Jul) 20(7):573-89 A standardized Ginkgo biloba L. extract containing flavonol glycosides induces a concentration-dependent relaxation of guinea-pig trachea in vitro and antagonizes in vivo bronchoconstriction induced by various agonists. The action of the extract appears to be mediated partially by an interaction with the eicosanoid system particularly through specific stimulation of the PGE2 biosynthesis and partially by beta-adrenoceptor activation. The relaxation of guinea-pig trachea induced by the extract is in fact antagonized by indomethacin (2 x 10(-8)M), ETYA (3.4 x 10(-8)M) and sotalol (4 x 10(-6)M). The concentration-response curves obtained with tracheal preparation from reserpinized guinea-pig and those performed in the presence of a glutathione depletor (CDNB 1 x 10(-5)M) are modified in a similar manner confirming that the extract can act on both the systems: adrenergic as well as prostaglandinergic. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Oberpichler H Beck T Abdel-Rahman MM Bielenberg GW Krieglstein J Effects of Ginkgo biloba constituents related to protection against brain damage caused by hypoxia. In: Pharmacol Res Commun (1988 May) 20(5):349-68 The purpose of the present study was to approach the compound(s) responsible for the beneficial effects of an extract of Ginkgo biloba leaves (EGB) on animals subjected to hypoxia. In this first approach we compared the effects of the flavone and the non-flavone fraction of EGB with those of the whole extract on mice in lethal hypoxia (3.5% O2), on brain energy metabolism of artificially ventilated rats inspiring 7% O2, and on local cerebral blood flow (LCBF) of normoxic rats. The latter two experimental settings should also extend the knowledge about the underlying mechanisms of the antihypoxidotic actions. EGB as well as its non-flavone fraction considerably prolonged the survival time of mice under lethal hypoxia. EGB retarded the breakdown of brain energy metabolism in the hypoxic artificially ventilated rat. A corresponding effect was exerted by the non-flavone fraction while the flavone fraction even worsened the metabolic state. The non-flavone fraction increased LCBF in the majority of 35 examined brain regions; a similar effect could be seen after EGB-treatment, while the flavone fraction caused only minor alterations of LCBF. We conclude that the non-flavone fraction of EGB carries the antihypoxidotic activity. Metabolic effects are suggested to cause this activity. Further studies are necessary to elucidate the effective compound within this fraction. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Brunello N Racagni G Clostre F Drieu K Braquet P Effects of an extract of Ginkgo biloba on noradrenergic systems of rat cerebral cortex. In: Pharmacol Res Commun (1985 Nov) 17(11):1063-72 Oral treatment of rats with Ginkgo biloba extract (Gb) elicited a biphasic effect on normetanephrine (NMN) content of cerebral cortex; an initial decrease was evident after 45 minutes, followed by a marked increase that was evident after 14 days. Chronic treatment with Gb led to decreases in the density of 3H-dihydroalprenolol binding (after 27 days or 2 months) and in isoproterenol-stimulated adenylate cyclase activity (after 2 months) of the cerebral cortex. Taken together, these results indicate that the effects of Gb on the central beta-adrenergic system might be involved in its therapeutic actions. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PHYTOCHEMISTRY***** Markham KR Geiger H Jaggy H Kaempferol-3-O-glucosyl(1-2)rhamnoside from Ginkgo biloba and a reappraisal of other gluco(1-2, 1-3 and 1-4)rhamnoside structures. In: Phytochemistry (1992 Mar) 31(3):1009-11 A kaempferol-3-O-glucorhamnoside from Ginkgo biloba is defined as the 3-O-alpha-L-[ beta-D-glucopyranosyl(1-2)rhamnopyranoside] on the basis of 2D NMR evidence. Complete assignments of the 1H and 13C NMR spectra of this compound and of its known p-coumaroyl derivative are presented for the first time. The NMR distinctions of 1-2, 1-3 and 1- 4 linked glucopyranosylrhamnopyranosides are discussed and indicate (i) that the 13C NMR assignments for one published gluco(1- 3)rhamnoside are in need of modification, (ii) that the published structure of hordenine-O-[6-O-t-cinnamoyl-beta-glucosyl(1-4)-alpha- rhamnoside] from Selaginella doederleinii is not distinguished from the 1-3 linked glucorhamnoside structure, and (iii) that the 8- prenylkaempferol-3-O-[glucosyl(1-4)rhamnoside]-7-O-glucoside and the equivalent 4'-O-methylated xylosyl(1-4)rhamnoside from Epimedium pubescens and E. washanense, respectively, are (1-2)-linked. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hager KP Jensen U Gilroy J Richardson M The N-terminal amino acid sequence of the beta-subunit of the legumin- like protein from seeds of Ginkgo biloba. In: Phytochemistry (1992 Feb) 31(2):523-5 The sequence of the first 52 amino acids at the N-terminus of the beta-subunit of a legumin-like protein from seeds of the gymnosperm Ginkgo biloba were determined by automated sequencing and DABITC/PITC microsequence analyses of peptides derived from the protein by enzymatic digestions and chemical cleavage with CNBr. The protein from Ginkgo exhibits sequence homologies (32-49% identities) with the 11S globulins and legume-like proteins from seeds of various angiosperm monocotyledons and dicotyledons. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Kraus J Water-soluble polysaccharides from Ginkgo biloba leaves. In: Phytochemistry (1991) 30(9):3017-20 The water-soluble polysaccharides from dried Ginkgo biloba leaves were isolated after exhaustive extraction with organic solvents. The polysaccharide mixture could be separated into a neutral (GF1) and two acidic (GF2 and GF3) polysaccharide fractions by ion exchange chromatography. According to the Mr distribution GF1 and GF3 seemed to be homogenous, whereas GF2 could be further fractionated into two subfractions (GF2a and GF2b) by gel permeation chromatography. GF1 (Mr 23,000) showed the structural features of a branched arabinan. The main chain was composed of 1,5-linked arabinose residues and three in 12 arabinose molecules were branched via C-2 or C-3. GF2a (Mr 500,000) consisted mainly of 1,2,4-branched mannose (29%), 1,4- linked glucuronic (32%) and galacturonic (8%) acid as well as terminal rhamnose (25%). After removal of ca 70% of the terminal rhamnose the remaining polysaccharide showed a decrease in 1,2,4- branched mannose and an increase in 1,2-linked mannose indicating that at least half of the rhamnose residues were linked to mannose via C-4. GF3 (Mr 40,000) consisted of 1,4-linked galacturonic (30%) and glucuronic (16) acid, 1,3,6-branched galactose (15%), 1,2-linked (5%) and 1,2,4-branched (3.5%) rhamnose as well as 1,5-linked arabinose (11%). Rhamnose (5%) and arabinose (10%) were present as terminal groups. Mild acid hydrolysis selectively cleaved arabinose and the remaining polysaccharide showed an increased amount of 1,6- linked and terminal galactose and a decreased quantity of 1,3,6- branched galactose. These results indicated that the terminal as well as the 1,5-linked arabinose were mainly connected to galactose via C- 3. The GF3 polysaccharide appeared to be a rhamnogalacturonan with arabinogalactan side chains. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PLANT PHYSIOLOGY***** Chinn E Silverthorne J Hohtola A Light-regulated and organ-specific expression of types 1, 2, and 3 light-harvesting complex b mRNAs in Ginkgo biloba. In: Plant Physiol (1995 Feb) 107(2):593-602 In a prior study (E. Chinn and J. Silverthorne [1993] Plant Physiol 103: 727-732) we showed that the gymnosperm Ginkgo biloba was completely dependent on light for chlorophyll synthesis and chloroplast development and that expression of light-harvesting complex b (Lhcb) mRNAs was substantially increased by light. However, dark-grown seedlings that were transferred to constant white light took significantly longer than angiosperm seedlings to initiate a program of photomorphogenesis and the stems failed to green completely. We have prepared type-specific probes for mRNAs encoding major polypeptides of light-harvesting complex II (Lhcb1, Lhcb2, and Lhcb3) and have used these to analyze the expression of individual Lhcb mRNAs during greening. All three sequences accumulated in the top portions of dark-grown seedlings transferred to light, but, as was seen previously for total Lhcb mRNAs, there was a transient, reproducible decline in the levels of all three mRNAs after 4 d in the light. This transient decrease in Lhcb mRNA levels was not paralleled by a decrease in Chl accumulation. By contrast, there were significantly lower levels of all three Lhcb mRNAs in the lower portions of greening dark-grown stems as well as lower Chl levels. We conclude that although the tops of the plants have the capacity to etiolate and green, Gingko seedling stems continue a program of development into woody tissue in darkness that precludes greening when the seedlings are transferred to the light. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Chinn E Silverthorne J Light-dependent chloroplast development and expression of a light- harvesting chlorophyll a/b-binding protein gene in the gymnosperm Ginkgo biloba. In: Plant Physiol (1993 Nov) 103(3):727-32 Unlike conifers, the gymnosperm Ginkgo biloba is dependent on light for chlorophyll (Chl) synthesis and initiation of chloroplast development. Dark-grown seedlings show complete etiolation, including no detectable Chl accumulation, no leaf expansion, and increased hypocotyl elongation. When dark-grown seedlings are placed in white light, Chl synthesis and leaf expansion are initiated, but unlike angiosperms, which initiate rapid photomorphogenesis, Ginkgo takes at least 1 week to change to a normal light-regulated pattern of growth. A cDNA clone (pLhcb*Gb1) encoding a Chl a/b-binding protein of light- harvesting complex II from Ginkgo mRNA has been used as a probe for the expression of this family of mRNAs. We have found that, in common with angiosperms but in marked contrast to pines, Lhcb mRNA is expressed in a highly light-dependent manner. In addition to being expressed in light-grown leaves, this sequence is also expressed in the green tissues of immature seeds. The Lhcb mRNA appears during greening in parallel with the onset of Chl synthesis. The complete sequence of pLhcb*Gb1 has been determined and the deduced amino acid sequence was found to be of type I based on comparison with signature sequences of angiosperm and gymnosperm sequences. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PLANTA MEDICA***** Joyeux M Lobstein A Anton R Mortier F Comparative antilipoperoxidant, antinecrotic and scavenging properties of terpenes and biflavones from Ginkgo and some flavonoids. In: Planta Med (1995 Apr) 61(2):126-9 Ginkgo biloba extract is known to be efficient in diseases associated with free radical generation. This study compares the in vitro effect of some constituents of Ginkgo against lipid peroxidation and cell necrosis of isolated rat hepatocytes, and against superoxide anion which is generally implicated in cell damages. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Steinke B Muller B Wagner H [Biological standardization of Ginkgo extracts] Biologische Standardisierungsmethode fur Ginkgo-Extrakte. 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PRESSE MEDICALE***** Warburton DM [Clinical psychopharmacology of Ginkgo biloba extract] Psycho-pharmacologie clinique de l'extrait de Ginkgo biloba. 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hindmarch I [Activity of Ginkgo biloba extract on short-term memory] Activite de l'extrait de Ginkgo biloba sur la memoire a court terme. In: Presse Med (1986 Sep 25) 15(31):1592-4 (Published in French) Eight healthy female volunteers were included in a double-blind, cross-over trial comparing Ginkgo biloba extract in acute and ascending doses (120, 240, 600 mg) with a placebo. One hour after treatment they were subjected to a battery of tests, including: critical flicker fusion, choice reaction time, subjective rating scale and Sternberg memory scanning test. No statistically significant differences with the placebo were observed in the first three tests. In contrast, short term memory, as assessed by the Sternberg technique, was very significantly improved following 600 mg of Ginkgo biloba extract, as compared with the placebo. These results differentiate Ginkgo biloba extract from sedative and stimulant drugs and suggest a specific effect on memory processes. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ 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 (Published in French) Electroencephalography is the only convenient method for functional exploration of the brain. The recent introduction of signal analysis techniques has given it a quantitative dimension and has resulted in pharmacological studies of electoencephalograms. In four studies of this kind the effects of Ginkgo biloba extract were investigated on three pathological animal models, in young healthy volunteers and in elderly people with dementia disorders. In man, the EEG tracings could be analyzed in relation to different psychometric tests. The results obtained confirm those of clinical trials, and notably the activity of Ginkgo biloba extract on alertness. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Taillandier J Ammar A Rabourdin JP Ribeyre JP Pichon J Niddam S Pierart H [Treatment of cerebral aging disorders with Ginkgo biloba extract. A longitudinal multicenter double-blind drug vs. placebo study] Traitement des troubles du vieillissement cerebral par l'extrait de Ginkgo biloba. Etude longitudinale multicentrique a double insu face au placebo. In: Presse Med (1986 Sep 25) 15(31):1583-7 (Published in French) The effectiveness of Ginkgo biloba extract in the treatment of cerebral disorders due to ageing was evaluated in a multicentric, double-blind, drug versus placebo trial involving 166 patients. In this study carried out under strict methodological conditions a specially devised geriatric clinical evaluation scale was used. The results confirmed that Ginkgo biloba extract is effective against cerebral disorders due to ageing. The difference between control and treatment groups became significant at 3 months and increased during the following months. These results were concordant with the overall clinical assessment made by the specialist in charge. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hannequin D Thibert A Vaschalde Y [Development of a model to study the anti-edema properties of Ginkgo biloba extract] Mise au point d'un modele d'etude des proprietes anti-oedemateuses de l'extrait de Ginkgo biloba. In: Presse Med (1986 Sep 25) 15(31):1575-6 (Published in French) The vasogenic edema observed after irradiation of the brain constitutes a new and interesting model to study the anti-oedema properties of drugs. We have just completed a first pharmaco-clinical study of Ginkgo biloba extract with the dual purpose of assessing the feasibility of a therapeutic protocol and of deciding on simple and non-invasive criteria that would quantity cerebral oedema. The results of this pilot study have encouraged us to pursue our investigations under strict methodological conditions, in view of their therapeutic but also epidemiological interest. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Felber JP [Effect of Ginkgo biloba extract on biological endocrine parameters] Effet de l'extrait de Ginkgo biloba sur les parametres biologiques endocriniens. In: Presse Med (1986 Sep 25) 15(31):1573-4 (Published in French) In order to find out whether Ginkgo biloba extract has an influence on endocrine balance, 7 male volunteers (mean age: 26.1 years) received twice the usual dose of the drug for 8 weeks. Different hormonal assays and stimulation tests with LHRH and TRH were performed before, and 4 and 8 weeks after treatment. No significant change or tendency to change was observed. The other, usual blood tests also were unmodified. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Haguenauer JP Cantenot F Koskas H Pierart H [Treatment of equilibrium disorders with Ginkgo biloba extract. A multicenter double-blind drug vs. placebo study] Traitement des troubles de l'equilibre par l'extrait de Ginkgo biloba. Etude multicentrique a double insu face au placebo. In: Presse Med (1986 Sep 25) 15(31):1569-72 (Published in French) This study, conducted in 3 centres, included 70 patients with vertiginous syndrome of recent onset and undetermined origin. In a double-blind trial extending over a 3-month period they were given either Ginkgo biloba extract or a placebo. The effectiveness of Ginkgo biloba extract on the intensity, frequency and duration of the disorder was statistically significant. At the end of the trial, 47% of the patients treated were rid of their symptoms as against 18% of those who received the placebo. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Meyer B [Multicenter randomized double-blind drug vs. placebo study of the treatment of tinnitus with Ginkgo biloba extract] Etude multicentrique randomisee a double insu face au placebo du traitement des acouphenes par l'extrait de Ginkgo biloba. In: Presse Med (1986 Sep 25) 15(31):1562-4 (Published in French) This important multicenter study of 103 tinnitus out-patients during a 13-month treatment period was carried out by ten E.N.T. specialists, using the double blind, drug versus placebo method. The results were conclusive as regards the effectiveness of Ginkgo biloba extract and made it possible to determine the prognostic value of different parameters. Of special importance among these parameters were site and periodicity of the disease. However, the Ginkgo biloba extract treatment improved the condition of all the tinnitus patients, irrespective of the prognostic factor. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Dubreuil C [Therapeutic trial in acute cochlear deafness. A comparative study of Ginkgo biloba extract and nicergoline] Essai therapeutique dans les surdites cochleaires aigues. Etude comparative de l'extrait de Ginkgo biloba et de la nicergoline. In: Presse Med (1986 Sep 25) 15(31):1559-61 (Published in French) Ischemia and the metabolic disorder it entails would seem to be the pathogenic mechanism behind acute cochlear deafness, irrespective of the triggering process. The prognosis is entirely dependent on the rapid initiation of an effective treatment. At the end of a double- blind therapeutic trial comparing Ginkgo biloba extract and a standard alpha blocker (nicergoline), a significant recovery was observed in both therapeutic groups, but improvement was distinctly better in the Ginkgo biloba group. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Lebuisson DA Leroy L Rigal G [Treatment of senile macular degeneration with Ginkgo biloba extract. A preliminary double-blind drug vs. placebo study] Traitement des degenerescences "maculaires seniles" par l'extrait de Ginkgo biloba. Etude preliminaire a double insu face au placebo. In: Presse Med (1986 Sep 25) 15(31):1556-8 (Published in French) Senile macular degeneration is a frequent cause of blindness for which there is no satisfactory medical treatment. A double-blind trial comparing Ginkgo biloba extract with a placebo was conducted in 10 out-patients at the Hopital Foch. Drug effectiveness was assessed on the results of fundoscopy and of measurements of visual acuity and visual field. In spite of the small population sample, a statistically significant improvement in long distance visual acuity was observed after treatment with Ginkgo biloba extract. The assumed pathogenesis of senile macular degeneration is discussed with emphasis on free oxygenated radicals. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Lagrue G Rahbar K Behar A Sobel A Laurent J [Recurrent shock with monoclonal gammopathy. Treatment in the acute and chronic phases with oral and parenteral Ginkgo biloba extract] Choc recidivant avec gammapathie monoclonale. Traitement en phase aigue et chronique par l'extrait de Ginkgo biloba oral et parenteral. In: Presse Med (1986 Sep 25) 15(31):1554-5 (Published in French) In a rare but severe case of hypovolaemic shock related to monoclonal gammapathy, intravenous infusion of Ginkgo biloba extract resulted in dramatic recovery. Treatment was pursued with the oral form. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Lagrue G Behar A Kazandjian M Rahbar K [Idiopathic cyclic edema. The role of capillary hyperpermeability and its correction by Ginkgo biloba extract] Oedemes cycliques idiopathiques. Role de l'hyperpermeabilite capillaire et correction par extrait de Ginkgo biloba. In: Presse Med (1986 Sep 25) 15(31):1550-3 (Published in French) Idiopathic cyclic oedema is a frequent and often unrecognized condition in young women. It is characterized by water and sodium retention with secondary hyperaldosteronism due to capillary hyperpermeability. Treatment is not easy. It includes spironolactone, sometimes sympathomimetics and hygienic-dietetic measures. Thiazide diuretics and laxatives must be avoided. Correcting the capillary defect is of paramount importance. This defect is detected and measured by Landis' labelled albumin test. The authors have tried Ginkgo biloba extract administered either orally or by intravenous infusion. Full correction of the biological anomaly was obtained in 10 cases in which Landis' test was performed before and after oral treatment, and in the 5 cases treated by intravenous infusion. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Bauer U [Ginkgo biloba extract in the treatment of arteriopathy of the lower extremities. A 65-week trial] L'extrait de Ginkgo biloba dans le traitement de l'arteriopathie des membres inferieurs. Etude sur 65 semaines. In: Presse Med (1986 Sep 25) 15(31):1546-9 (Published in French) Thirty-six patients with arteritis were treated with Ginkgo biloba extract for sixty-five weeks. For the first six months of the treatment period, these patients participated in a double-blind randomised comparison with 35 well matched patients taking placebo. Subsequently, those patients taking Ginkgo biloba extract were given the option to continue treatment on an open basis with follow-up at regular three-monthly intervals. Ginkgo biloba extract therapy gave significantly greater pain relief and walking tolerance than the placebo after 6 months of treatment, and this improvement continued throughout the whole duration of the study. This symptomatic and measurable improvement was combined with excellent tolerance of the drug. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Allard M [Treatment of the disorders of aging with Ginkgo biloba extract. From pharmacology to clinical medicine] Traitement des troubles du vieillissement par extrait de Ginkgo biloba. De la pharmacologie a la clinique. 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Clostre F [From the body to the cell membrane: the different levels of pharmacological action of Ginkgo biloba extract] De l'organisme aux membranes cellulaires: les differents niveaux d'actions pharmacologiques de l'extrait de Ginkgo biloba. 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: different 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Auguet M Delaflotte S Hellegouarch A Clostre F [Pharmacological bases of the vascular impact of Ginkgo biloba extract] Bases pharmacologiques de l'impact vasculaire de l'extrait de Ginkgo biloba. In: Presse Med (1986 Sep 25) 15(31):1524-8 (Published in French) The preferential tissue irrigatory effect of Ginkgo biloba extract in ischaemic areas is largely explained by the direct impact of this product on both arteries and veins. The adrenergic vasoregulatory system and the vascular endothelium are the preferential targets for arterial impact. Ginkgo biloba extract reinforces the physiological vasoregulation of the sympathetic nervous system directly, by acting on neuromediator release, and indirectly, by inhibiting their extraneuronal degradation by catechol-orthomethyltransferase (C.O.M.T.) In the arterial endothelium Ginkgo biloba extract stimulates the release of endogenous relaxing factors, such as endothelium-derived relaxing factor, (EDRF) and prostacyclin. The action of Ginkgo biloba extract on the venous system has been shown to have a venoconstrictor component that maintains the degree of parietal tonus essential to the dynamic clearing of toxic metabolites accumulated during tissue ischaemia. The originality of the vascular impact mechanisms of Ginkgo biloba extract is due to the fact that the product can at the same time combat the phenomena resulting from vascular spasm and with the same efficiency restore circulation in areas subject to vasomotor paralysis. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Reuse-Blom S Drieu K [Effect of Ginkgo biloba extract on arteriolar spasm in rabbits] Effet de l'extrait de Ginkgo biloba sur le spasme arteriolaire chez le lapin. In: Presse Med (1986 Sep 25) 15(31):1520-3 (Published in French) Injectable Ginkgo biloba extract, administered intravenously to rabbits, suppressed the vasospasm induced by the topic application of autologous serum on brain surface. This effect was dose-dependent as for as the normalization of the arterial diameter and duration of spasm were concerned. In animals previously treated with oral Ginkgo biloba extract, the almost complete disappearance of spasm was observed at intervals of time similar to those observed after intravenous injection. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Guillon JM Rochette L Baranes J [Effects of Ginkgo biloba extract on 2 models of experimental myocardial ischemia] Effets de l'extrait de Ginkgo biloba sur deux modeles d'ischemie myocardique experimentale. In: Presse Med (1986 Sep 25) 15(31):1516-9 (Published in French) Ginkgo biloba extract, a free radical scavenger containing kaempferol and quercetin esters, which are potent radical scavengers, was studied on various models of cardiac ischaemia, both in vitro and in vivo. On the two in vitro models of ischaemia-reperfusion described (rat and guinea-pig hearts) Ginkgo biloba extract was without effect on cardiac functional parameters. However, it induced a significant decrease in the intensity of ventricular fibrillation during the reperfusion stage. On normal or hypertrophied heart in vivo, Ginkgo biloba extract provided effective protection against the electrocardiographic disorders induced by ischaemia. On the different models of global or localized ischaemia (followed or not by reperfusion), a decrease of arrhythmia without change in cardiovascular parameters was regularly noted. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Spinnewyn B Blavet N Clostre F [Effects of Ginkgo biloba extract on a cerebral ischemia model in gerbils] Effets de l'extrait de Ginkgo biloba sur un modele d'ischemie cerebrale chez la gerbille. In: Presse Med (1986 Sep 25) 15(31):1511-5 (Published in French) Certain anatomical characteristics peculiar to the gerbil make it the animal model best adapted to experimental pathology studies of acute ischaemia. In this animal species, devoid of any substitute vertebro- basilar vascular tissue, unilateral ligature of the carotid artery produces a cerebral ischaemia with neurological signs (well quantifiable), metabolic perturbations (especially mitochondrial) and cerebral oedema development closely resembling the symptoms revealed by physiopathology in human clinical studies. Using this model and under the experimental conditions described, clear-cut, highly significant results were obtained with Ginkgo biloba, whether by oral or intravenous administration. These results were normalization of mitochondrial respiration, diminution of cerebral oedema, correction of the accompanying ionic perturbations, and practically total functional restoration revealed by a normal neurological index in the gerbils treated with Ginkgo biloba extract. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ 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 (Published in French) 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Grosdemouge C Le Poncin-Lafitte M Rapin JR [Protective effects of Ginkgo biloba extract on the early rupture of the hemato-encephalic barrier in the rat] Effets protecteurs de l'extrait de Ginkgo biloba sur la rupture precoce de la barriere hemoencephalique chez le rat. In: Presse Med (1986 Sep 25) 15(31):1502-5 (Published in French) During the hours immediately following an hypertensive burst or a cerebral ischemia induced by the intracarotid administration of microspheres, damage to the blood brain barrier can be observed with molecules of low molecular weight, such as angiotensin, whereas albumin or large proteins will not yet have been able to cross over and there is virtually no edema. Gingko biloba extract causes the brain uptake index of angiotensin hypertensive animals. This effect is proportional to the dose of extract used (500-100 mg/kg). A similar effect can be observed in animals showing embolism in one hemisphere. The process can therefore doubtlessly be explained by the stabilizing effect of Ginkgo biloba on membranes. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ 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 (Published in French) 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Rapin JR Le Poncin Lafitte M [Cerebral glucose consumption. The effect of Ginkgo biloba extract] Consommation cerebrale du glucose. Effet de l'extrait de Ginkgo biloba. In: Presse Med (1986 Sep 25) 15(31):1494-7 (Published in French) Deoxyglucose is transported under the same conditions as glucose from blood to cerebral tissue. Deoxyglucose-6-phosphate, which cannot be neither metabolized nor eliminated, accumulates in cells. This accumulation is correlated with glucose consumption. In this study, two parameters, transfer rate of deoxyglucose and glucose consumption were measured by means of quantitative autoradiography in two experimental models: normobaric hypoxia and carotid clamping in rats. Normobaric hypoxia induced a decrease in both transfer rate and glucose consumption. Ligature of the carotid artery induced a diminution of glucose consumption greater than that of transfer rate. After administration of Ginkgo biloba extract, glucose consumption was partly reestablished in both experimental models, but the transfer rate of deoxyglucose was increased only in normobaric hypoxia. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Taylor JE [Neuromediator binding to receptors in the rat brain. The effect of chronic administration of Ginkgo biloba extract] Liaisons des neuromediateurs a leurs recepteurs dans le cerveau de rats. Effet de l'administration chronique de l'extrait de Ginkgo biloba. In: Presse Med (1986 Sep 25) 15(31):1491-3 (Published in French) The present data confirm the results of others that post-synaptic receptor changes may contribute to the decline in brain cholinergic function in ageing and dementia. We have also shown that chronic oral treatment with an extract of Gingko biloba increases the apparent muscarinic receptor population in the hippocampus of the aged Fisher 344 rat. The possible effect on (3H) kainic acid binding to the kainate-excitatory amino acid site is also interesting because of the proposed association of neurodegenerative disease and excessive excitatory amino neurotransmission. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ 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 (Published in French) 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Raymond J [Effects of Ginkgo biloba extract on the morphological preservation of vestibular sensory epithelia in mice] Effets de l'extrait de Ginkgo biloba sur la preservation morphologique des epitheliums sensoriels vestibulaires chez la souris. In: Presse Med (1986 Sep 25) 15(31):1484-7 (Published in French) Oral or parenteral Ginkgo biloba extract seems to uniformly improve the ultrastructural qualities of vestibular sensorial epithelia when fixed by vascular perfusions. The improvements observed may be consequential to the effects of Ginkgo biloba extract on capillary permeability and general microcirculation, which would accelerate penetration of the fixator into vestibular tissues, and/or to more complex processes associated with cellular metabolism and membrane protective systems. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Doly M Droy-Lefaix MT Bonhomme B Braquet P [Effect of Ginkgo biloba extract on the electrophysiology of the isolated retina from a diabetic rat] Effet de l'extrait de Ginkgo biloba sur l'electrophysiologie de la retine isolee de rat diabetique. In: Presse Med (1986 Sep 25) 15(31):1480-3 (Published in French) The purposes of the experimental work presented here were to ascertain that diabetes causes impairment of the visual function and to test the protective properties of Ginkgo biloba extract against this impairment. The experimental method selected was the isolated albino rat retina maintained in survival by perfusion. Retinal function was evaluated by electroretinographic recording in response to a light stimulus. The rats were made diabetics by injection of alloxan. After one month of diabetes the electroretinogram amplitude was significantly decreased in diabetic rats as compared with control animals. This decrease in amplitude was more pronounced after 2 months of diabetes, which confirmed that retinal function was worse. In rats treated with Ginkgo biloba extract, after 2 months of diabetes the electroretinograms had a significantly greater amplitude that that observed in untreated rats. These results are attributed to the specific role played by free oxygenated radicals on the retina of diabetic rats and to the free radical scavenger property of Ginkgo biloba extract. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Pincemail J Deby C [Antiradical properties of Ginkgo biloba extract] Proprietes antiradicalaires de l'extrait de Ginkgo biloba. In: Presse Med (1986 Sep 25) 15(31):1475-9 (Published in French) The anti-radical properties of Ginkgo biloba extract have been determined on several in vitro models. The products is as effective as uric acid, an anti-radical agent known to entrap the hydroxyl and diphenylpicrylhydrazyl radicals. In addition, it inactivates the formation of radicals, such as adriamycyl, which escape uric acid activity. It also inhibits membrane lipid peroxidation and owes to its anti-radical activity exerts a stimulant effect on the biosynthesis of prostanoids. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Moreau JP Eck CR McCabe J Skinner S [Absorption, distribution and elimination of a labelled extract of Ginkgo biloba leaves in the rat] Absorption, distribution et elimination de l'extrait marque de feuilles de Ginkgo biloba chez le rat. In: Presse Med (1986 Sep 25) 15(31):1458-61 (Published in French) The absorption, distribution and elimination of a radiolabelled 14C extract prepared from Ginkgo biloba leaves have been studied in rats. Following oral administration, expired 14C-CO2 represented 16% of the administered dose excreted within the first 3 hours post-dose out of a total of 38% after 72 hours. An additional 21% of the administered dose was eliminated in the urine. The absorption of the radiolabelled Ginkgo biloba extract was at least 60%. The pharmacokinetics of the drug, based on blood specific activity data versus time course, were characteristic of a two-compartment model with an apparent first order phase and a biological half-life of approximatively 4.5 h. During the first 3 hours, radioactivity was primarily associated with the plasma, but through a gradual uptake after 48 h. The specific activity in erythrocytes matched that of plasma. A site of absorption in the upper gastrointestinal tract is suspected since specific activity in blood peaked after 1.5 hours. Glandular and neuronal tissues and eyes showed a high affinity for the labelled substance. These results provide the first tentative link between the therapeutic effectiveness of Ginkgo biloba extract and the biological fate of some of its constituents. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Drieu K [Preparation and definition of Ginkgo biloba extract] Preparation et definition de l'extrait de Ginkgo biloba. In: Presse Med (1986 Sep 25) 15(31):1455-7 (Published in French) Ginkgo biloba extract is a well-defined and complex product prepared from green leaves of Ginkgo biloba. The leaves are harvested from trees growing in plantations in South Corea, Japan and France. The mode of culture, harvesting and extraction are perfectly standardized and controlled. Analysis of Ginkgo biloba extract makes it possible to confirm that undesirable substances have been eliminated and to measure the amount of active principles. The extract contains flavonoid substances, such as the Ginkgo-flavone glycosides and terponoids which are characteristic of Ginkgo and have a unique structure (ginkgolides, bilobalide). €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Michel PF [The doyen of trees: the Ginkgo biloba] Le doyen des arbres: le Ginkgo biloba. In: Presse Med (1986 Sep 25) 15(31):1450-4 (Published in French) The Ginkgo biloba tree is the sole representative of a once flourishing botanical division, that of the so-called ginkgophytes. It is in fact a living fossil, the most ancient of all trees, and this claim to fame is accompanied by numerous peculiarities as diverse as its reproduction cycle (it scatters neither seeds nor spores but ovules), its extraordinary resistance to pollution, viruses and fungi, or again its extremely original biochemistry; in particular, Ginkgo biloba leaves countain specific terpens namely bilobalide and ginkgolides. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PROGRESS IN CLINICAL AND BIOLOGICAL RESEARCH***** Funfgeld EW A natural and broad spectrum nootropic substance for treatment of SDAT--the Ginkgo biloba extract. In: Prog Clin Biol Res (1989) 317:1247-60 The efficacy of the Ginkgo biloba extract was not only found clinically or in standardised ratings but also documented by objective data, obtained by a computerized EEG method, the DYNAMIC BRAIN MAPPING and BRAIN FUNCTION MONITORING SYSTEM (Dr. T. Itil, New York). A one year open trial comprise 25 parkinson patients with additional signs of SDAT. Data from 3 selected cases were given: The short time efficacy of the substance after the infusion and the long- term result after the oral medication. The maps showed less slower and more faster waves. Without any side effects the Ginkgo biloba extract seems to be a substance with a broad spectrum of influence. Our therapeutic findings in parkinsonian patients with SDAT and the data taken from healthy elderly volunteers revealed that the computerized EEG method may have another big advantage: It seems that the so-called anteriorisation of the Theta waves can be taken as a preclinical sign of an incipient change in brain metabolism. As a consequence--it might be that these changes are reversible by an adequate nootropic treatment. Further studies and treatment experiences must confirm these preliminary findings. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PROSTAGLANDINS***** 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****PSYCHOPHARMACOLOGY BULLETIN***** Itil T Martorano D Natural substances in psychiatry (Ginkgo biloba in dementia). In: Psychopharmacol Bull (1995) 31(1):147-58 Natural substances and/or their synthetically developed active ingredients are frequently used in medicine. In psychiatry, two of the most well known natural compounds are reserpine and Ginkgo biloba extract (EGb). EGb is among the most popular over-the-counter medicines in Europe and is also available in the United States, primarily in health food stores. Already the European medical community has recognized EGb as an effective compound in the treatment of cerebral insufficiency. In a pilot bioequivalency study, the effects of three different commercially available EGb products were examined. Findings indicated significant quantitative central nervous system (CNS) effects in, at least, one of the three. Furthermore, the CNS effects of Ginkgold were similar to other psychoactive compounds classified as cognitive activators. Recent studies in which EGb 761 demonstrated therapeutic effects in the treatment of dementia have earned EGb the approval of the German BGA (Bundesgesundheit Amt) for use in the treatment of dementia. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****RESEARCH IN EXPERIMENTAL MEDICINE***** Koc RK Akdemir H Kurtsoy A Pasaoglu H Kavuncu I Pasaoglu A Karakucuk I Lipid peroxidation in experimental spinal cord injury. Comparison of treatment with Ginkgo biloba, TRH and methylprednisolone. In: Res Exp Med (Berl) (1995) 195(2):117-23 Ischaemia-induced lipid peroxidation is one of the most important factors producing tissue damage in spinal cord injury. In our study, the protective effects of Ginkgo biloba, thyroid releasing hormone (TRH) and methylprednisolone (MP) on compression injury of the rat spinal cord were investigated. For this study 45 rats in four groups, including control, MP, TRH and Gingko biloba, were used to determine the formation of malondialdehyde (MDA). All the animals were made paraplegic by the application clip method of Rivlin and Tator. Rats were divided randomly and blindly to one of four treatment groups (ten animals in each). MP and Ginkgo biloba treatments significantly decreased MDA levels (F = 54.138, P < 0.01). These results suggest that MP and Ginkgo biloba may have a protective effect against ischaemic spinal cord injury by the antioxidant effect. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****REVUE FRANCAISE DE GYNECOLOGIE ET D OBSTETRIQUE***** Tamborini A Taurelle R [Value of standardized Ginkgo biloba extract (EGb 761) in the management of congestive symptoms of premenstrual syndrome] Interet de l'extrait standardise de Ginkgo biloba (EGb 761) dans la prise en charge des symptomes congestifs du syndrome premenstruel. 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY***** Otamiri T Tagesson C Ginkgo biloba extract prevents mucosal damage associated with small- intestinal ischaemia. In: Scand J Gastroenterol (1989 Aug) 24(6):666-70 We have examined how a Ginkgo biloba extract influences the damaging effects of ischaemia in the small-intestinal mucosa. We used a rat experimental model in which a ligated loop of the distal ileum was subjected to ischaemia and revascularization, and the ensuing mucosal damage assessed by lysosomal enzyme release and intestinal permeability measurements. We also determined the mucosal content of malondialdehyde, a lipid peroxidation product, and the mucosal activity of myeloperoxidase, a neutrophil granulocyte marker. Ischaemia and revascularization alone caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-beta- glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content in the mucosa, and increased myeloperoxidase activity in the mucosa. Intravenous injection of G. biloba extract caused a dose-dependent attenuation of all these effects of ischaemia. It is suggested, therefore, that G. biloba extract may protect the intestinal mucosa against ischaemic damage by reducing neutrophil infiltration and lipid peroxidation. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****SCHWEIZERISCHE RUNDSCHAU FUR MEDIZIN PRAXIS***** Z'Brun A [Ginkgo--myth and reality] Ginkgo--Dichtung und Wahrheit. In: Schweiz Rundsch Med Prax (1995 Jan 3) 84(1):1-6 (Published in German) Ginkgo biloba is one of the oldest, still existing plants. Extracts from its leaves were already used in ancient China whereas in the Western World, they have been utilized only since the Sixties when it became technically possible and feasible to isolate the essential substances of Ginkgo biloba. Pharmacologically, there are two groups of substances which are of some significance: the flavonoids, effective as oxygen-free radical scavengers, and the terpenes (i.e. the ginkgolides) with their highly specific action as platelet activating factor (PAF) inhibitors. Clinically important indications for Ginkgo biloba extracts are cerebral insufficiency and atherosclerotic disease of peripheral arteries of intermediate severity. In several placebo-controlled clinical studies, symptoms of cerebral insufficiency have been effectively and significantly influenced. Most of these investigations have examined the efficacy of Ginkgo biloba extracts such as EGb 761 and LI 1370. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****SEMAINE DES HOPITAUX DE PARIS***** Le Poncin-Lafitte M Martin P Lespinasse P Rapin JR [Cerebral ischemia after ligature of both carotid arteries in rats: effect of ginkgo biloba extracts (author's transl)] Ischemie cerebrale apres ligature non simultanee des arteres carotides chez le rat: effet de l'extrait de Ginkgo biloba. In: Sem Hop (1982 Feb 18) 58(7):403-6 (Published in French) Simultaneous ligature of both carotid arteries in Long Evans rats results in death for all animals. 50% of the animals survive if the ligatures are separated by a four-day interval. Studies of variations in cerebral blood flow according to the time interval between the two ligatures show that alternative vascularization develops and that the balance between both hemibrains is restored. After giving L-dopa3H to animals with ligature of both carotids, increased synthesis of cerebral dopamine 3H and norepinephrine 3H can be demonstrated. When animals are given extracts of Ginkgo biloba leaves prior to carotid ligatures, survival rate is improved and dopamine synthesis increased, without marked changes in cerebral blood flow. This is related to increased brain cell activity in spite of hypoxia due to carotid ligature. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Borzeix MG Labos M Hartl C [Researches on the antiaggregative activity of Ginkgo biloba extract (author's transl)] Recherches sur l'action antiagregante de l'extrait de Ginko biloba. Activite au niveau des arteres et des veines de la pie-mere chez le lapin. In: Sem Hop (1980 Feb 18-25) 56(7-8):393-8 (Published in French) Sodium lactate applied on the pia-mater of the rabbit induces the appearance of venous platelets thrombi. The same phenomenon occurs in the arteries after electric stimulation of the arterial wall. Gingo biloba extract, i.v. and per os, has been shown capable to partially antagonize these effects, particularly in the venous microcirculation. The ratio between the activity following the two modes of administration is about 1 to 5. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Rapin JR Le Poncin-Lafitte M [Experimental model of cerebral ischemia preventive activity of Ginkgo biloba extract (author's transl)] Modele experimental d'ischemie cerebrale. Action preventive de l'extrait de Ginkgo. In: Sem Hop (1979 Dec 18-25) 55(43-44):2047-50 (Published in French) Unilateral embolization of the brain was performed in rats by intracarotid injection of 4 000 radioactive microspheres (50 mu). Local blood flow in hippocampus, striatum, hypothalamus and remainder of the brain were determined using the iodoantipyrine technique. Embolization resulted in a decreases in blood flow and modificationof the distribution of microflow. Furthermore, embolization produces changes in energy metabolism : particularly a fall in ATP and glucose levels and an increase in lactate level. Subsequently, severe vasogenic edema developed. There was a correlation between the number of microspheres injected and the amount of edema. Pretreatment using an extracted of Ginkgo biloba leaves partially suppressed the effect of embolization. An improvement of the flow in the ischemic areas associated with an improvement of the energy metabolism explain the decreases of the edema. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****THERAPIE***** Warot D Lacomblez L Danjou P Weiller E Payan C Puech AJ [Comparative effects of ginkgo biloba extracts on psychomotor performances and memory in healthy subjects] Comparaison des effets d'extraits de Ginkgo biloba sur les performances psychomotrices et la memoire chez le sujet sain. In: Therapie (1991 Jan-Feb) 46(1):33-6 (Published in French) The effect on psychomotor and mnesic performances of acute oral dose (600 mg) of 2 Ginkgo biloba extracts were evaluated in twelve healthy female in a dummy placebo-controlled double blind study. Tests were performed comprising: objective measures of vigilance [critical flicker frequency (CFF), choice reaction time (CRT)], memory tasks (pictures and Sternberg scanning tests) and self-rating evaluation (visual analogue scales). Tests session took place before and 1 hour post-dosing. No statistically significant changes from placebo were observed on CFF, CRT or subjective rating of drug effects. No differences between treatment were evidenced on Sternberg scanning test and pictures recognition. Comparing to baseline, free recall score, while decreasing under placebo and Ginkgo, remained the same under Tanakan. As the differences between treatment are localized on one test, it appears important to examine the reproductility in healthy subjects. In order to verify the clinical relevance of these results, they need to be replicated in older healthy volunteers with age-associated memory impairment. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Fourtillan JB Brisson AM Girault J Ingrand I Decourt JP Drieu K Jouenne P Biber A [Pharmacokinetic properties of Bilobalide and Ginkgolides A and B in healthy subjects after intravenous and oral administration of Ginkgo biloba extract (EGb 761)] Proprietes pharmacocinetiques du Bilobalide et des Ginkgolides A et B chez le sujet sain apres administrations intraveineuses et orales d'extrait de Ginkgo biloba (EGb 761). In: Therapie (1995 Mar-Apr) 50(2):137-44 (Published in French) The pharmacokinetics of Ginkgolide A, Ginkgolide B and Bilobalide, which are compounds extracted from the dried leaves of the Ginkgo biloba tree, were investigated in 12 young healthy volunteers (six men and six women; mean +/- SD age = 25 +/- 5 years) after single- dose administration of Ginkgo biloba extract. Subjects were given, on three occasions, Ginkgo biloba extract as a solution either orally (in fasting conditions and after a standard meal) or intravenously; corresponding to single doses of Ginkgolide A, Ginkgolide B and Bilobalide ranging from 0.90 mg to 3.36 mg. After each dosing, blood and urine samples were collected for up to 36 h and 48 h, for measurements of Ginkgolide A, Ginkgolide B and Bilobalide. Plasma and urine concentrations of these compounds were quantitatively measured by gas chromatography/mass spectrometry using negative chemical ionization, by applying a very sensitive method which allowed plasma concentrations as low as 0.2 ng/ml of each compound to be measured. When given orally, while fasting, the extents of bioavailability are high, as shown by bioavailability coefficients (FAUC) mean (+/- SD) values equal to 0.80 (+/- 0.09), 0.88 (+/- 0.21) and 0.79 (+/- 0.30) for Ginkgolide A, Ginkgolide B and Bilobalide respectively. Food intake does not change AUC quantitatively but increases Tmax. For the three compounds of interest, after oral dosing while fasting, differences can be noted for the elimination half-lives (T1/2Z), which exhibit mean values equal to 4.50, 10.57 and 3.21 h, as well as mean residence times (MRT), equal to 5.86, 11.25 and 4.89 h, for Ginkgolide A, Ginkgolide B and Bilobalide respectively.(ABSTRACT TRUNCATED AT 250 WORDS) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****WIENER KLINISCHE WOCHENSCHRIFT***** Koltringer P Eber O Klima G Rothlauer W Wakonig P Langsteger W Lind P [Microcirculation in parenteral Ginkgo biloba extract therapy] Die Mikrozirkulation unter parenteraler Ginkgo-biloba-Extrakt- Therapie. In: Wien Klin Wochenschr (1989 Mar 17) 101(6):198-200 (Published in German) 15 patients with arteriosclerotic lesions in the extracranial brain arteries, randomly selected, were treated with an infusion of 250 ml physiological NaCl and 25 ml Ginkgo biloba extract (Tebonin). A second group (n = 15) received 250 ml NaCl without drugs stimulating blood flow. The skin microcirculation was measured in vivo by means of a helium-neon laser at one of the 4 extremities. Perfusion increased significantly (p less than or equal to 0.01) in response to Ginkgo biloba extract als composed with the response in the control group. The results justify the administration of Ginkgo biloba extract in vascular diseases. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****WIENER MEDIZINISCHE WOCHENSCHRIFT***** P Eber O [Collagen-induced thrombocyte aggregation in parenteral therapy using Ginkgo biloba] Die kollageninduzierte Thrombozytenaggregation unter parenteraler Ginkgo-biloba-Therapie. In: Wien Med Wochenschr (1989 Mar 15) 139(5):92-4 (Published in German) 24 patients suffering from arteriosclerotic disorders were divided into 2 groups. One half received 250 ml NaCl with 25 ml Ginkgo-biloba- extract the other 12 were treated with 250 ml NaCl without this substance. The collagen induced platelet aggregation was determined before, immediately after infusion and on the next day. The platelet aggregation increased in both collectives after infusion. In the group treated with Ginkgo-biloba-extract after 1 day values returned into normal range while the aggregation remained increased in the NaCl-group. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hitzenberger G [The effect of ginkgo biloba special extract (EGb 761, Tebofortan)] Zur Wirkung von Ginkgo-biloba-Spezialextrakt (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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****YAKUGAKU ZASSHI. JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN***** 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ZEITSCHRIFT FUR DIE GESAMTE INNERE MEDIZIN UND IHRE GRENZGEBIETE***** Diwok M Kuklinski B Ernst B [Superoxide dismutase activity of Ginkgo biloba extract] Superoxiddismutasenaktivitat von Ginkgo-biloba-Extrakt. 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. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€