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[Depiction of ultraviolet spectrum group draft of EGB761].

By the combinative method of fingerprint spectrums, the ultraviolet spectrum group draft of EGB761 was depicted. The established method is characteristic and reproducible and can be used in the identification and quality control of the medical materials, extracts and preparations. The ultraviolet spectrum group draft of EGB761 was tentatively depicted as: lambda max (nm): H2O solution (C = 0.02 mg/ml) 265.00 +/- 1.00, 201.00 +/- 1.00; EtOH solution (C = 0.02 mg/ml) 267.00 +/- 1.00, 210.00 +/- 1.00; CHCl3 solution (C = 0.4 mg/ml) 241.00 +/- 1.00; petroleum benzine solution (C = 0.4 mg/ml) 211.00 +/- 1.00.

Ethanol↗

Can the cognitive enhancing effects of ginkgo biloba be explained by its pharmacology?

Pre-clinical and clinical studies have shown that the extract of the leaves of Ginkgo biloba has modest therapeutic potential as a cognitive enhancing drug. The pharmacology of Ginkgo biloba is complex due to its multiple active constituents. While Ginkgo biloba's cognitive enhancing effects have been attributed to its platelet-activating factor antagonistic effects and its free-radical scavenger activity, recent evidence suggests it may have direct effects on the cholinergic system which might explain both its acute and chronic cognitive enhancing effects. Ginkgo biloba's direct cholinergic actions include reduction of scopolamine-induced amnesia, modulation of pre-synaptic choline uptake and acetylcholine release, upregulation of post-synaptic muscarnic receptors and indirect effects on cholinergic function by modulation of the serotonergic system. The overall pharmacodynamic effect of Ginkgo biloba is likely due to a combination of platelet activating factor antagonistic effects, free radical scavenging activity and modulation of cholinergic function.

Acetylcholine↗

[Effect of tanakan on psychophysiological status of patients with asthenic disorders].

A clinical pharmacological 56-day trial was devoted to the effect of tanakan on the psychophysiological state of 26 patients with psychogenic and post-traumatic asthenic disorders. The drug was found to produce a positive effect on the psychophysiological state, with most pronounced improvement in the attention characteristics, short-term visual memory, operational component, and integral operator performance index. The results confirmed the positive action of tanakan on the cognitive and mnestic functions, which is analogous to the effect of nootropes. The antiasthenic, anxiolytic, antiamnesic, and vegetotropic components in the pharmacological spectrum of tanakan correlate with the positive psychophysiological effects. It is shown that positive changes in the psychophysiological state play an important role in the complex therapeutic action of tanakan in the treatment of asthenic disorders.

Adolescent↗

Analysis of ginkgolides and bilobalide in food products using LC-APCI-MS.

A method was developed for the extraction and quantification of five marker compounds characteristic of Ginkgo biloba. Five ginkgo terpene trilactones: bilobalide and ginkgolides A, B, C, and J, were selected as marker compounds for this study. Initial studies produced a simple methanol extraction method for determination of gingko markers in solid dietary supplements. Five dietary supplements were analyzed and the results were later compared to the concentrations detected in the analysis of beverages. Beverage samples were prepared by extracting the ginkgo terpene trilactones using an optimized solid phase extraction (SPE) method. The extracts were analyzed using LC-atmospheric pressure chemical ionization (APCI)-MS in the negative ionization mode. The limits of detection of the extraction method ranged from 6.8 to 3.2 ng mL(-1). Using the optimized method, 14 drinks and 3 tea products were analyzed. Concentrations of total marker compounds in drinks ranged between 1685 and 21.4 ng mL(-1) with individual ginkgo terpene trilactones being detected at ppb concentrations. Analysis of brewed tea products presented much higher total marker compound concentrations ranging from 8.12 and 16.6 microg mL(-1). Analytical results reproducibility data, and recovery of the SPE method are presented.

Beverages↗

Standardized extracts of flavonoids increase the viability of PC12 cells treated with hydrogen peroxide: effects on oxidative injury.

Oxidative stress plays an important role in cell death associated with many diseases. In the present study, concentration-dependence of hydrogen peroxide on rat pheochromocytoma (PC12) cell viability was studied. Preventive effects of antioxidants on the viability of these cells treated with 2 mM hydrogen peroxide were compared. Trolox and Stobadine, as chain-breaking antioxidants were studied in comparison with standardized extracts of flavonoids of Ginkgo biloba and Pycnogenol, known as agents effective in several diseases. All antioxidants increased the viability of hydrogen peroxide-treated PC12 cells. Flavonoid extracts were more effective than Trolox and Stobadine. Antioxidants were most effective if present after the oxidative treatment. As expected, the preloading with antioxidants was without effect on cell viability. Correlations between viability increase induced by antioxidants, and content of oxidation products of proteins and lipids were studied at concentrations of antioxidants mostly effective in preventing cell death: Trolox (10 microM), Stobadine (30 microM), Ginkgo biloba (160 microg/ml), Pycnogenol (100 microg/ml). In these concentrations, antioxidants did not statistically significantly decrease the content of protein carbonyls, with exception of Stobadine, which had no effect. Ginkgo biloba, Trolox and Stobadine intensively decreased the content of malondialdehyde, a product of lipid peroxidation. Pycnogenol was without any preventive effect. Concentrations of antioxidants with a large effect on viability of PC12 cells were not effective in preventing oxygen radical-induced injury of proteins. Antioxidants prevented the oxidative injury of lipids more effectively than that of proteins.

Animals↗

Ginkgo biloba medicines and food supplements on the Belgian market: a comparative study.

Medicines and food supplements based on the dry extract of the leaves of Ginkgo biloba L. were evaluated by determination of the content of total flavonoids, rutin and terpene lactones by means of liquid chromatography. All examined medicines complied with the fixed requirements whereas all food supplements deviated from 1 or more of the criteria. It could also be demonstrated that some products contained extracts to which rutin was added.

Belgium↗

Memory function and brain glucose metabolism.

Memory formation and memory retrieval are subject to complex cellular and molecular processes. Increasing evidence exists that neuronal glucose metabolism and its control by the insulin signal transduction cascade are the main players in such processes. Acetylcholine synthesis depends on the availability of acetyl CoA, provided from glucose breakdown, and insulin, which controls the activity of acetylcholine transferase. ATP is necessary for both synaptic activity and plasticity. This is also true for APPs, the secreted derivative of APP. Trafficking of the latter protein is controlled by insulin and insulin receptor function also acting on activity-regulated cytoskeleton-associated gene expression, which induces biochemical stimuli involved in synaptic activity and plasticity. Any damage in neuronal glucose metabolism and its control may, therefore, cause disturbances in memory function--as is found for example in sporadic Alzheimer's disease. Mimicking these metabolic and behavioral abnormalities in experimental animals, it was found that EGb 761 (definition see editorial) shows beneficial effects both on brain glucose and energy metabolism and on behavior.

Amyloid beta-Protein Precursor↗

[Treatment with Ginkor Fort in varicose veins].

The study shows the experience acquired in our clinic concerning Ginkor fort administration in varicose veins pathology. The research comprises 32 patients who were treated by the well-known classical procedures (hygienic-dietetic, contention, surgery) and by Ginkor fort administration. The study rendered 71% good results consisting in evident amelioration of symptomatology, both subjective and objective.

Adult↗

Prescribing practice with cognition enhancers in outpatient care: are there differences regarding type of dementia?--Results of a representative survey in lower Saxony, Germany.

Previous studies of cognition enhancers have mainly focused on insufficiently defined groups of cognition disorders, e.g., "cerebral insufficiency". With regard to the various biological changes in senile dementia of Alzheimer's type (SDAT) and in vascular dementia (VD), which together make up the great majority of senile dementias, many authors have encouraged different studies of these types of dementias, especially since both can be diagnosed clinically with satisfying certainty. Since primary care physicians treat the majority of elderly and demented patients, they have their own experience with cognition enhancers. We were therefore interested to know, how far these physicians differ in their treatment of SDAT and VD. We performed a representative survey (response rate 83.2%; 145 family physicians and 14 neuropsychiatrists) in the Goettingen area. A written case vignette described a 70-year-old widow with moderate dementia and vascular risk factors which are easily treated with drugs. Two versions were randomly assigned, in which (version A) either a "typical" VD history or a typical SDAT history (version B) were described. After perusal, the physician was asked whether and which drugs he would choose to treat the cognitive disorders in this patient. Most frequently, piracetam (A/B: 25.6%/30.9%), ginkgo biloba (24.4%/28.4%), and nimodipine (14.1%/25.9%) were considered. Aspirin was cited by 29.5%(A) and 17.3%(B) of the physicians respectively. As far as the type of dementia was concerned, significant differences were found only for co-dergocrine, which was preferred in SDAT. The following inter-group trends were observed: family physicians considered ginkgo biloba more often than nimodipine or co-dergocrine. The results show the apparent importance of cost-and safety aspects, while the type of dementia has hardly any impact. The latter impression corresponds to the results of drug trials demonstrating no different efficacy. In our opinion, aspirin was not sufficiently taken into consideration.

Adult↗

Preparative isolation and dual column high-performance liquid chromatography of ginkgolic acids from Ginkgo biloba.

A chromatographic procedure for the preparative isolation of six different 6-alkylsalicylic acids (syn. ginkgolic acids) with as alkyl substituents C13:0, C15:0, C15:1, C17:1, C17:2 and, tentatively C17:3 from Ginkgo biloba leaves was developed. The procedure consisted of a combination of normal-phase, reversed-phase and argentation chromatography. The compounds were characterised by means of UV, 1H-NMR and 13C-NMR spectroscopy, and mass spectrometry after silylation. A 15 cm C18 RP-HPLC column connected in series with a 20 cm silver(I) loaded cation exchanger HPLC column in combination with the solvent methanol-water (93:7) acidified with 0.1% formic acid was capable of separating the ginkgolic acids C13:0, C15:1, C17:2, C15:0 and C17:1 within 21 min on an analytical scale. The separation is based on a combination of reversed-phase mechanisms and double bond complexation. Detection took place by UV at 311 nm. The separation is a good starting point for the development of a quantitative procedure for the five major ginkgolic acids in Ginkgo leaves and standardised extracts.

Chromatography, High Pressure Liquid↗

Effect of Ginkgo biloba (EGb 761) on staurosporine-induced neuronal death and caspase activity in cortical cultured neurons.

Previous studies suggest the protective potentiality of Ginkgo biloba (EGb 761) against apoptotic cell death induced by hydroxyl radicals, staurosporine, serum deprivation and beta-amyloid (betaA) peptide. We have extended these observations to cultured cortical neurons and studied the effect of EGb 761 on neuronal survival (evaluated as MTT reduction), the presence of condensed nuclei (monitored as Hoechst staining), the time-course of caspase-1, caspase-3 and caspase-9 activation (measured by cleavage of specific fluorescent substrates) and superoxide anion production (evaluated by hydroethidine staining) after the exposure to staurosporine. Results show that 200 microg/ml of EGb 761 increased cell survival and reduced the number of condensed nuclei after the exposure to 200 nM staurosporine. Vitamin E and the spin trapper alpha-phenyl-N-tert-butylnitrone (PBN) also significantly increased cell survival. In contrast, the broad-spectrum caspase inhibitors ZVAD and ZBIOT showed no protection. Similarly, selective inhibitors of caspase-1 (YVAD-CHO), caspase-2 (VDVAD-CHO), caspase-3 (DEVD-CHO) and caspase-8 (IETD-CHO) did not protect against cell damage induced by staurosporine. The protective effect of EGb 761 was not enhanced when coincubated with vitamin E or DEVD-CHO. Caspase-3 activity was maximally induced 5-8 h after staurosporine exposure. Both EGb 761 and vitamin E showed a tendency to decrease caspase-3 activity. In contrast, activation of caspase-1 and caspase-9 was not observed at any of the times studied after STS exposure. Exposure to staurosporine resulted in increased superoxide production that was maximal at 5 h. EGb 761 significantly inhibited superoxide production at short times after staurosporine exposure. Vitamin E and PBN also significantly reduced superoxide production. Results suggest that EGb 761 neuroprotective effect might be mediated by its well-known antioxidant activity, which might also influence caspase-3 activation. Inhibition of capase-3 induced by EGb 761 and vitamin E does not seem to contribute to their observed protective action.

Animals↗

The GuidAge study: methodological issues. A 5-year double-blind randomized trial of the efficacy of EGb 761 for prevention of Alzheimer disease in patients over 70 with a memory complaint.

BACKGROUND: Preventive approaches in the field of Alzheimer disease (AD) is important but these trials raise many questions. Which protective factor should be studied? What population should be studied? With which principal and secondary criteria? We present here the design of the ongoing GuidAge Study. In the past, several studies suggest that Ginkgo biloba could have a potential benefit effect on cognitive function. The aim of the GuidAge Study is to evaluate the efficacy of 240 mg/d of EGb 761 in the prevention of AD. METHODS: GuidAge is a 5-year double-blind randomized trial conducted in France by a private practice/hospital network of general practitioners and hospital practitioners specializing in memory disorders. This study enrolled elderly subjects with spontaneous memory complaint and the primary outcome is the incidence of AD during a 5 years follow-up period. A total of 2854 subjects were enrolled between March 2002 and September 2004. The age of the study population was 76.8 +/- 4.4 with mean MMSE at entry 27.8 +/- 1.7. CONCLUSION: The GuidAge study is the largest study carried out in Europe on the prevention of AD. Final results should be available in 2010.

Aged↗

[Effect of Ginkgo biloba L leaves on oxidation of human low density lipoproteins in vitro].

OBJECTIVE: To study the effects of Ginkgo biloba L leave on oxidation of human low density lipoproteins (LDL) induced by Fe2+ or Cu2+ in vitro. METHODS: LDL was oxidized by Fe2+ or Cu2+ for 1, 2, 4, 6h, while it was protected by extracts from leaves of Ginkgo biloba L. ( EGB761), ginkgo flavonids(GF) and ginkgo terpenlactones (GT). Lipofusion (LF), malondialdehyde (MDA) and vitamin E (VitE) were measured as the index of the oxidation of LDL by means of Fluorescence spectroscopy methods. RESULTS: Each extract can inhibit the oxidation of LDL, the inhibition of each extract is increasing during the first 4 hours and subsequently decrease, after 6 hours all the inhibitor have almost lost their ability on antioxidation. CONCLUSION: EGB761, GF and GT are effective antioxidant and the anti-oxidation vary with time.

Antioxidants↗

The protection of the retina from ischemic injury by the free radical scavenger EGb 761 and zinc in the cat retina.

We investigated the effects of a free radical scavenger (EGb 761) and zinc in experimentally induced ischemic injury in the cat retina. Total retinal ischemia for 90 min was produced in the left eyes of 40 cats by raising intraocular pressure. In group 1, 10 cats were used as control. The free radical scavenger (EGb 761, 100 mg/kg) in group 2 (10 cats) and zinc chloride (250 microg/kg) in group 3 (10 cats) were administered intravenously at the end of ischemia. In group 4, both EGb 761 (100 mg/kg) and zinc chloride (250 microg/kg) were injected into 10 cats. ERG and a histologic study were performed 1 h, 1 day, 3 days, 1 week and 2 weeks after ischemia. The amplitude of the ERG b-wave was 62.73+/-0.32, 84.31+/-6.10, 83.65+/-12.23 and 102.4+/-14.27%, and the summed amplitude of oscillatory potentials was 66.16+/-16.42, 99.44+/-14.92, 95.45+/-6.42 and 99.62+/-12.32% in each group 2 weeks after ischemia. There was no significant effect in animals that received zinc alone (group 3) by the end of 1 week but some additive effect in combining EGb 761 and zinc chloride (group 4) 1 h after ischemia. These findings suggest that the free radical scavenger EGb 761 may efficiently protect the retina from ischemic injury and zinc may have an additive effect when combined with a radical scavenger.

Animals↗

Ginkgo biloba: local experiences.

Ginkgo biloba (EGb 761) as a phytotherapeutic agent used in otoneurology, psychiatry, and ophthalmology. We studied the efficacy of therapy with EGb 761 in 72 patients (44 male and 28 female) with chronic cochleovestibular disorders. We used pure-tone audiology, measuring pure-tone average, speech reception threshold, and speech discrimination score. Then we used craniocorpography to measure lateral body sway and angular deviation. Finally, we used nystagmography (central nystagmic frequency). Also, we assessed subjectively the variation in patients' comfort. We concluded that EGb 761 has a very good effect on both postural and oculovestibular reflexes. Also, hearing was improved, and patients' comfort was considered to be heightened by the therapy.

Audiometry↗