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The antioxidant activity of standardized extract of Ginkgo biloba (EGb 761) in rats.

The standardized extract of Ginkgo biloba (EGb 761) has been widely employed for its significant benefit in neurodegenerative disorders. Although antioxidative actions have been attributed to this extract, the mechanisms of the multiple principles involved in this pharmacological activity are not completely established. Parkinson's and Alzheimer's diseases are frequently associated with oxidative stress and defects in the cellular protective mechanisms. In this study, the lipid peroxidation (LPO) and the activity of the antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD) were evaluated in the hippocampus, striatum and substantia nigra (SN) of rats treated with EGb 761. An increase in the CAT and SOD activities in the hippocampus, striatum and SN, and a decrease of the LPO in the hippocampus were observed. These data are additional to the antioxidant properties of EGb 761 reported in the literature and indicate a possible role for the extract in the treatment of diseases involving free radicals and oxidative damage.

Animals↗

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

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.

Animals↗

[The course of color vision in early diabetic retinopathy treated with Ginkgo biloba extract. A preliminary double-blind versus placebo study].

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.

Clinical Trials as Topic↗

Reduction of behavioural disturbances in elderly dogs supplemented with a standardised Ginkgo leaf extract.

In this open clinical trial conducted in 10 veterinary practices, Ginkgo leaf extract was administered as a dietary supplement to 42 elderly dogs (mean age 11.4 years) at a daily dose of 40 mg/ 10 kg body weight for 8 weeks. The "severity of the geriatric condition" in dogs with a history of geriatric behavioural disturbances (mean duration 12 months), was significantly reduced after 8 weeks of treatment (P = 0.0002). The positive effect was already apparent after 4 weeks. Thirty-six % of the dogs were completely free of clinical signs at study end. Overall efficacy of treatment as judged by the investigator was good or very good in 79% of the dogs. Five of six clinical sign scores (disorientation, sleep/activity changes, behavioural changes, general behaviour and general physical condition/vitality) also showed a significant decrease over the treatment period. In conclusion, these findings provide promising results that could increase the quality of life in the elderly dog and, as a consequence, that of the pet owner. The Ginkgo leaf extract appears to be an efficacious agent that provides a safe dietary supplement for the elderly dog with age-related behavioural disturbances.

Aging↗

Enhancement of radiation effect by Ginkgo biloba extract in C3H mouse fibrosarcoma.

BACKGROUND AND PURPOSE: Ginkgo biloba leaf extract (GBE) is known to increase peripheral blood circulation. The hypothesis that GBE may be able to enhance radiosensitivity of tumor by improving tumor blood flow and thus decreasing hypoxic fraction was tested. MATERIALS AND METHODS: Fibrosarcoma (FSaII) growing in C3H mouse leg muscle was used as a tumor model. GBE was given i.p. 1 h before irradiation with or without priming dose given 1 day earlier. Effect on tumor and normal tissue radiation reaction was investigated. RESULTS: Tumor growth delay by radiation was more elongated after two doses (1-day interval) of GBE than after a single dose. Radiation dose for 3-day tumor growth delay was decreased from 12.45 (10.97-13.93) Gy to 6.06 (3.89-8.22) Gy by two doses of GBE [enhancement ratio = 2.06 (1.32-2.79)]. Hypoxic cell fraction was 10.6% (6.3-18.2%) for control, 7.2% (3.8-14.0%) after a single dose (P = 0.18) and 2.7% (1.5-5.0%) after two doses (P < 0.001). Radiation effect on normal tissue, estimated by acute skin reaction and jejunal crypt assay, was not affected by GBE. CONCLUSION: Ginkgo biloba extract enhances radiation effect on tumor without increasing acute normal tissue radiation damage in this model system probably by increasing tumor blood flow and further investigation for this possible radiosensitizer is needed.

Animals↗

Magnitude of effect and special approach to Ginkgo biloba extract EGb 761 in cognitive disorders.

In the early 70's, improvements in methodical procedures of extraction and standardization of ginkgo preparation allowed the production of a highly concentrated and stable extract (EGb 761) (definition see editorial) by the company Dr. Willmar Schwabe, which could be systematically tested in scientific programs. Consequently, numerous studies have been undertaken and provided replicable outcomes to demonstrate its efficacy in human population. EGb 761 is currently registered as an ethical drug in more than 50 countries around the world, and is prescribed for a range of neurological and vascular disorders including dementia, arterial occlusive disease, retinal deficit, and tinnitus. The following chapter will focus on the relevant data that support EGb 761 efficacy in the treatment of cognitive disorders in general, and dementia in particular. Besides the published data, the author will provide original results unveiling different factors that could interfere with EGb 761 efficacy and may be the source of the variations observed among studies in the EGb 761 literature. In the author's opinion, such factors should be taken into consideration when implementing the design of future research and optimizing individual EGb 761 response in the clinical practice. Within the framework of this new approach, the author will not only answer the question as to whether EGb 761 works over placebo in cognitive disorders, but also attempt to estimate how well it works in particular conditions.

Alzheimer Disease↗

[Protective effects of a Ginkgo biloba extract (EGb 761) on ischemia-reperfusion injury].

EGb 761 is a standardized extract of dried leaves of Ginkgo biloba. EGb 761 is a neuroprotective and anti-ischaemic drug. Its broad spectrum of pharmacological activities allows it to be adequate to the numerous pathological requirements--haemodynamic, haemorrheological, metabolic--which occur in cerebral, retinal, cochleovestibular, cardiac or peripheral ischaemia. Moreover, EGb 761 has direct effects in retinal and myocardial ischaemia and reperfusion injuries. EGb 761 improves retinal microcirculation, reduces oedema of the retinal inner layer and protects chemoreceptors against free-radical injuries. On myocardial ischaemia-reperfusion models, EGb 761 improves myocardial functional recovery, and reduces the number of ventricular extrasytoles and the duration of ventricular tachycardia induced by reperfusion. EGb 761 protects the retina and the heart against ischaemia-reperfusion damage via its free radical-scavenging and anti-lipoperoxidative properties and its regulation of mitochondrial respiratory function.

Animals↗

Hydrogen peroxide-induced oxidative damage and apoptosis in cerebellar granule cells: protection by Ginkgo biloba extract.

The ability of oxidative stress to induce apoptosis and the protective effects of Ginkgo biloba extract (EGb761) against this induction were studied in cultures of rat cerebellar granule cells. Cells were exposed to oxidative stress by treatment with 50 microm hydrogen peroxide+100 microm ferrous sulphate which generates hydroxyl radicals by Fenton reaction. Both morphological observation and biochemical analysis revealed that H(2)O(2)/FeSO(4)treatment induced apoptotic cell death in cerebellar granule cells, which was characterized by chromatin condensation and DNA fragmentation. During this process, the fluidity of the cell membrane decreased markedly, and the conformation of membrane proteins altered significantly. Pretreating cerebellar granule cells with the antioxidant EGb761 (Ginkgo biloba extract) effectively attenuated oxidative damage induced by H(2)O(2)/FeSO(4), and prevented cells from apoptotic cell death. The results suggested that EGb761 might be used as a potential drug for neuronal diseases associated with the excessive production of reactive oxygen species.

Animals↗

Anti-apoptotic properties of Ginkgo biloba extract EGb 761 in differentiated PC12 cells.

Standard Ginkgo biloba leaf extract (EGb 761) has been known to have neuroprotective effects ranging from molecular and cellular, to animal and human studies, however, the cellular and molecular mechanisms remain unclear. Using PC 12 cells, a well-established model for studying neuroprotection, we have determined the mechanism of action of EGb 761 on cell survival following apoptosis induced by serum-deprivation or treatment with staurosporine (STS). Our results show that EGb 761 treatments of PC12 cells are able to prevent serum deprivation- and STS-induced mitochondrial damage, attenuate release of cytochrome c and DNA fragmentation. EGb 761, but not vitamin E. inhibited STS-induced activation of the caspase-3 enzyme. Two of the EGb 761 components, bilobalide B and ginkgolide C show more significant inhibition than the EGb 761 extract. Furthermore, DNA microarray assay results indicate that transcription of multiple apoptosis-related genes is either up- or down-regulated in cells treated with EGb 761. These results suggest that inhibition of apoptotic machinery may, at least in part, mediate multiple neuroprotective effects of EGb 761, and that EGb 761 and vitamin E act on different molecular paths to provide neuroprotection.

Animals↗

Effects of ginkgo biloba extract on cation currents in rat ventricular myocytes.

Ginkgo biloba extract (GBE), a valuable natural product for cerebral and cardiovascular diseases, is mainly composed of two classes of constituents: terpene lactones (e.g., ginkgolide A and B, bilobalide) and flavone glycosides (e.g., quercetin and kaempferol). Its electrophysiological action in heart is yet unclear. In the present study, using whole-cell patch clamp technique, we investigated electrophysiological effects of GBE on cation channel currents in ventricular myocytes isolated from rat hearts. We found that GBE 0.01-0.1% inhibited significantly the sodium current (I(Na)), L-type calcium current (I(Ca)) and transient outward potassium current (IK(to)) in a concentration-dependent manner. Surprisingly, its main ingredients, ginkgolide A (GB A), ginkgolide B (GB B) and bilobalide (GB BA) at 0.1 mM did not exhibit any significant effect on these cation channel currents. These results suggested that GBE is a potent non-selective cation channel modulator in cardiaomyocytes. Other constituents (rather than GB A, GB B and GB BA) might be responsible for the observed inhibitory effects of GBE on cation channels.

Animals↗

Effect of the Ginkgo biloba extract, EGb 761, on memory formation in day-old chicks.

Previous studies indicate that the Ginkgo biloba extract, EGb 761, has a facilitative effect on deficient memory. The temporal parameters of this effect, however, have not been clearly defined or distinguished from the effect on normal memory. The aim in the current study was to investigate the effects of EGb 761 on memory using a well-controlled animal model. Day-old chicks were trained on either a weakly or strongly reinforced version of a passive avoidance task. Long-term memory formation of the weakly reinforced version of the task was improved significantly by EGb 761 (3 mg/ml) when administered between 10 and 30 min after training. However, the same dose of EGb 761 impaired retention when administered prior to strongly reinforced training. These data provide convincing evidence that posttraining administration of EGb 761 initiates long-term memory in chicks with only short-term memory, but that the same dose-administered pretraining can be deleterious for normal retention. This dual effect has important implications for the clinical use of Ginkgo biloba extracts.

Animals↗

The effects of Ginkgo biloba extracts on the memory and motor functions of rats with chronic cerebral insufficiency.

The main goal of the current study was to investigate the effects of two Ginkgo leaf extracts, EGb 761 and an extract of local Ginkgo leaf (LGb), on the memory and motor functions of rats with chronic cerebral insufficiency (produced by bilateral common carotid artery ligation). After the operation, spatial memory and motor functions were tested for over 80 days. Tests included (1) radial-arm maze test for testing spatial memory and locomotor activity and (2) muscle force and hind limbs for escape. The results indicate that both EGb 761 and LGb improved spatial memory from the second week after operation, but only EGb 761 delayed deterioration of motor functions from the fifth week after operation.

Animals↗

A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group.

CONTEXT: EGb 761 is a particular extract of Ginkgo biloba used in Europe to alleviate symptoms associated with numerous cognitive disorders. Its use in dementias is based on positive results from only a few controlled clinical trials, most of which did not include standard assessments of cognition and behavior. OBJECTIVE: To assess the efficacy and safety of EGb in Alzheimer disease and multi-infarct dementia. DESIGN: A 52-week, randomized double-blind, placebo-controlled, parallel-group, multicenter study. PATIENTS: Mildly to severely demented outpatients with Alzheimer disease or multi-infarct dementia, without other significant medical conditions. INTERVENTION: Patients assigned randomly to treatment with EGb (120 mg/d) or placebo. Safety, compliance, and drug dispensation were monitored every 3 months with complete outcome evaluation at 12, 26, and 52 weeks. PRIMARY OUTCOME MEASURES: Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Geriatric Evaluation by Relative's Rating Instrument (GERRI), and Clinical Global Impression of Change (CGIC). RESULTS: From 309 patients included in an intent-to-treat analysis, 202 provided evaluable data for the 52-week end point analysis. In the intent-to-treat analysis, the EGbgroup had an ADAS-Cog score 1.4 points better than the placebo group (P=.04) and a GERRI score 0.14 points better than the placebo group (P=.004). The same patterns were observed with the evaluable data set in which 27% of patients treated with EGb achieved at least a 4-point improvement on the ADAS-Cog, compared with 14% taking placebo (P=.005); on the GERRI, 37% were considered improved with EGb, compared with 23% taking placebo (P=.003). No difference was seen in the CGIC. Regarding the safety profile of EGb, no significant differences compared with placebo were observed in the number of patients reporting adverse events or in the incidence and severity of these events. CONCLUSIONS: EGb was safe and appears capable of stabilizing and, in a substantial number of cases, improving the cognitive performance and the social functioning of demented patients for 6 months to 1 year. Although modest, the changes induced by EGb were objectively measured by the ADAS-Cog and were of sufficient magnitude to be recognized by the caregivers in the GERRI.

Activities of Daily Living↗

EEG profile of three different extractions of Ginkgo biloba.

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.

Adult↗

Effect of EGb 761, a ginkgo biloba extract, on early arrhythmia induced by coronary occlusion and reperfusion in dogs.

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.

Animals↗

A randomized, double-blind, placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimer's type.

CONTEXT: Previous studies of Ginkgo biloba extract (GbE) in patients with various forms of cognitive impairment or dementia have shown promising results. OBJECTIVE: To determine the clinical efficacy of GbE in mild to moderate dementia of the Alzheimer type. DESIGN: Randomized, placebo-controlled, double-blind, parallel-group, multicenter trial. SETTING: Outpatient clinics of universities and private research centers specialized in dementia. PATIENTS: 513 outpatients with uncomplicated dementia of the Alzheimer's type scoring 10 to 24 on the Mini-Mental State Examination and less than 4 on the modified Hachinski Ischemic Score, free of other serious illnesses and not requiring continuous treatment with any psychoactive drug. INTERVENTION: 26-week treatment with GbE at daily doses of 120 mg or 240 mg or placebo. MAIN OUTCOMES: Cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC). RESULTS: There were no significant between-group differences for the whole sample. There was little cognitive and functional decline of the placebo-treated patients, however. For a subgroup of patients with neuropsychiatric symptoms there was a greater decline of placebo-treated patients and significantly better cognitive performance and global assessment scores for the patients on GbE. CONCLUSION: The trial did not show efficacy of GbE, however, the lack of decline of the placebo patients may have compromised the sensitivity of the trial to detect a treatment effect. Thus, the study remains inconclusive with respect to the efficacy of GbE.

Aged↗

[Protective effects of ginkgo leaf extracts on neurons in spinal cord after ischemia-reperfusion injury in rabbits].

OBJECTIVE: To observe the protective effects of ginkgo leaf extracts on spinal cord after ischemia-reperfusion (IR) injury in rabbits and to find out its possible mechanism. METHODS: Twenty-seven New Zealand white rabbits were randomly divided into three groups, which were sham-operation group, untreated group and ginkgo leaf extracts-treated group. The locomotor scores of hindlimbs in rabbits after 24 and 48 h of reperfusion were evaluated, and the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in ischemia spinal cord were examined. The apoptotic index (AI) of neurons in spinal cord was detected by terminal deoxyribonucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) method. The expressions of Bcl-2 and Bax proteins were examined by streptavidin-biotin peroxidase method. RESULTS: The locomotor scores of hindlimbs in rabbits after 24 and 48 h of reperfusion in the ginkgo leaf extracts-treated group were obviously elevated as compared with those in the untreated group (P<0.05). The activity of SOD was higher and the level of MDA was lower in ischemia spinal cord in the ginkgo leaf extracts-treated group than those in the untreated group (P<0.01). The decreased neuron AI and the expressions of up-regulated Bcl-2 protein and down-regulated Bax protein were also observed in the ginkgo leaf extracts-treated group. CONCLUSION: The protective effects of the ginkgo leaf extracts against spinal cord injury induced by IR may be related to scavenging oxygen free radicals, reducing lipid peroxidation injury and inhibiting apoptosis.

Animals↗