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[Microcirculation in parenteral Ginkgo biloba extract therapy].

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.

Aged↗

Pharmacokinetics and bioavailability of a Ginkgo biloba extract.

The aim of the present study was to assess the bioavailability of the main active ingredient in Ginkgo biloba extract, ginkgolid B. The study also focused on the pharmacokinetics of two different dosage regimens for orally administered Gingko biloba extract, 80 mg once daily and 40 mg twice daily for 7 days. Twelve healthy volunteers took part in the study. They were randomly assigned to one of the two treatment groups: 40 mg twice daily or 80 mg once daily, with an interval of 21 days between cycles. Statistical analysis was used to assess the main pharmacokinetic parameters. The results show that a dosage of 40 mg twice daily (every 12 hrs) is accompanied by a significantly longer half-life (t1/2) and mean residence time (MRT) than a single 80 mg dose, even though the latter causes a higher concentration peak (Cmax). The maximum concentration time (Tmax) is 2.3 hrs after administration in both treatments.

Adult↗

Ginkgo biloba extract protects rat kidney from diabetic and hypoxic damage.

Ginkgo biloba extract EGb 761 was studied for its nephroprotective effects in experimentally diabetic and hypoxic rats. Duration of streptozotocin-induced diabetes was 4 months, that of respiratoric hypoxia of the diabetic group 20 min. The daily dose of 100 mg EGb/kg bodyweight started 1 month after induction of the diabetes. EGb reduced diabetes-induced morphological alterations of the kidney such as increase in volume of glomeruli, capillary tufts, urinary space, and thickening of Bowman's capsule basement membrane. Diabetically increased immunostaining of interstitial collagenes of types I, III, and VI was diminished by the EGb extract. EGb reduced the relative total SOD activity from 163% in diabetic kidney to 46%. Additional hypoxia-induced ultrastructural damage was also diminished.

Animals↗

Comparative vasodilating actions among terpenoids and flavonoids contained in Ginkgo biloba extract.

BACKGROUND: Comparative vasodilating actions of the constituents of Ginkgo biloba extract (GBE), terpenoids (bilobalide, ginkgolides A, B and C) and flavonoids (quercetin and rutin), were examined using rat aorta ring strips. METHODS: Cumulative administrations of GBE and its constituents were followed with the pretreatment of 5 micromol/l NE. RESULTS: GBE at 0.03 to 3 mg/ml had a potent concentration-dependent relaxation; by 70 +/- 4.5% (n = 6, P < 0.001) at 3 mg/ml. Terpenoids and flavonoids at 0.1 to 100 micromol/l had potent concentration-dependent relaxation. At 100 micromol/l, bilobalide dilated by 17.6 +/- 3.9% (n = 7, P < 0.05), and ginkgolides A, B and C also caused it to the almost same extent. Quercetin (100 micromol/l) caused a potent vasorelaxation by 49.9 +/- 4.8% (n = 10, P < 0.001). Rutin at 100 micromol/l had weaker vasorelaxation; by 13.7 +/- 3.2% (n = 6, P < 0.01). CONCLUSIONS: All constituents of GBE have the concentration-dependent vasorelaxtant effect. The potency of GBE's action was not made simply by addition of those of the constituents. Each constituent itself would contribute to the GBE-induced vasodilation, although the constituents have the complicated interactions with each other.

Animals↗

[Activity of Ginkgo biloba extract on short-term memory].

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.

Adult↗

[Effects of Ginkgo biloba extract on the morphological preservation of vestibular sensory epithelia in mice].

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.

Animals↗

Comparison of two dosages of ginkgo biloba extract EGb 761 in patients with peripheral arterial occlusive disease Fontaine's stage IIb. A randomised, double-blind, multicentric clinical trial.

BACKGROUND: Rheologically-active drugs are widely used in the therapy of peripheral arterial occlusive disease (pAOD) Fontaine's stage II. Several clinical trials have demonstrated the efficacy of Ginkgo biloba extract in the treatment of pAOD Fontaine's stage II. A pilot study indicated the superiority of 240 mg Ginkgo biloba extract daily compared with the standard dosage of 120 mg to 160 mg daily. This trial was conducted to confirm the superiority of the higher dosage of Ginkgo biloba extract in patients with pAOD Fontaine's stage IIb statistically. PATIENTS AND METHODS: 74 patients were analysed. Thirty-eight patients received the standard dosage (EGb 761 120 mg/d), and 36 patients received 240 mg EGb 761 daily. The primary efficacy criterion was the difference of the pain-free walking distance between the start of treatment and after 24 weeks measured on a treadmill under standardized conditions. RESULTS: The pain-free walking distance improved in both groups. There was a mean increase of 60.6 m in the group of patients who received 120 mg Ginkgo biloba extract daily and a statistically significant higher (p = 0.0253) mean increase of 107.0 m in the group of patients who were treated with the higher dosage. CONCLUSION: Both dosage regimens investigated in this trial led to a clinically relevant improvement of the pain-free walking distance after 24 weeks of treatment. The superiority of the higher dosage over the standard dosage was statistically significant. Both treatment variations were safe and well tolerated.

Aged↗

Neuroprotective effects of bilobalide, a component of the Ginkgo biloba extract (EGb 761), in gerbil global brain ischemia.

The neuroprotective effect of Ginkgo biloba extract (EGb 761) against ischemic injury has been demonstrated in animal models. In this study, we compared the protective effect of bilobalide, a purified terpene lactone from EGb 761, and EGb 761 against ischemic injury. We measured neuronal loss and the levels of mitochondrial DNA (mtDNA)-encoded cytochrome oxidase (COX) subunit III mRNA in vulnerable hippocampal regions of gerbils. At 7 days of reperfusion after 5 min of transient global forebrain ischemia, a significant increase in neuronal death and a significant decrease in COX III mRNA were observed in the hippocampal CA1 neurons. Oral administration of EGb 761 at 25, 50 and 100 mg/kg/day and bilobalide at 3 and 6 mg/kg/day for 7 days before ischemia progressively protected CA1 neurons from death and from ischemia-induced reductions in COX III mRNA. In addition, both bilobalide and EGb 761 protected against ischemia-induced reductions in COX III mRNA in CA1 neurons prior to their death, at 1 day of reperfusion. These results suggest that oral administration of bilobalide and EGb 761 protect against ischemia-induced neuron death and reductions in mitochondrial gene expression.

Animals↗

Extract of Ginkgo biloba EGb761 facilitates extinction of conditioned fear measured by fear-potentiated startle.

A standard extract of Ginkgo biloba (EGb761) has been used in the treatment of various common geriatric complaints including vertigo, short-term memory loss, hearing loss, lack of attention, or vigilance. We demonstrated that acute systemic administration of EGb761 facilitated the acquisition of conditioned fear. Many studies suggest the neural mechanism underlies extinction is similar to the acquisition. This raises a possibility that EGb761 may modulate and accelerate the fear extinction process. We tested this possibility by using fear-potentiated startle (FPS) on laboratory rats. Acute systemic injection of EGb761 (10, 20, or 50 mg/kg) 30 min before extinction training facilitated extinction in a dose-dependent manner. Intra-amygdaloid infusion of EGb761 (28 ng/side, bilaterally) 10 min before extinction training also facilitated extinction. Control experiments showed that facilitation effect of EGb761 was not the result of impaired expression of conditioned fear or accelerated forgetting. Rats previously injected with EGb761 showed significant FPS after retraining. Extinction of conditioned fear appeared to result from acute drug effects rather than from toxic action. Systemic administration of EGb761 immediately after extinction training did not facilitate extinction, suggested the EGb761 facilitation effect is contributed to the acquisition phase of extinction learning. Western blot results showed that extinction induced amygdaloid extracellular signal-regulated kinase (ERK1/2) phosphorylation was significantly elevated by EGb761 treatment. Intra-amygdala injection of ERK1/2 inhibitor PD98059 completely blocked the EGb761 effect. Therefore, acute EGb761 administration modulated extinction of conditioned fear by activating ERK1/2.

Amygdala↗

A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761 in a sample of cognitively intact older adults: neuropsychological findings.

There appears to be an absence of large-scaled clinical trials that have examined the efficacy of Ginkgo biloba extract on the neuropsychological functioning of cognitively intact older adults. The importance of such clinical research appears paramount in light of the plethora of products containing Ginkgo biloba that are currently being widely marketed to predominantly cognitively intact adults with claims of enhanced cognitive performances. The purpose of this research was to conduct the first known, large-scaled clinical trial of the efficacy of Ginkgo biloba extract (EGb 761) on the neuropsychological functioning of cognitively intact older adults. Two hundred and sixty-two community-dwelling volunteers (both male and female) 60 years of age and older, who reported no history of dementia or significant neurocognitive impairments and obtained Mini-Mental State Examination total scores of at least 26, were examined via a 6-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel-group, clinical trial. Participants were randomly assigned to receive either Ginkgo biloba extract EGb 761(n = 131; 180 mg/day) or placebo (n = 131) for 6 weeks. Efficacy measures consisted of participants' raw change in performance scores from pretreatment baseline to those obtained just prior to termination of treatment on the following standardized neuropsychological measures: Selective Reminding Test (SRT), Wechsler Adult Intelligence Scale-III Block Design (WAIS-III BD) and Digit Symbol-Coding (WAIS-III DS) subtests, and the Wechsler Memory Scale-III Faces I (WMS-III FI) and Faces II (WMS-III FII) subtests. A subjective Follow-up Self-report Questionnaire was also administered to participants just prior to termination of the treatment phase. Analyses of covariance indicated that cognitively intact participants who received 180 mg of EGb 761 daily for 6 weeks exhibited significantly more improvement on SRT tasks involving delayed (30 min) free recall (p < 0.04) and recognition (p < 0.01) of noncontextual, auditory-verbal material, compared with the placebo controls. The EGb 761 group also demonstrated significantly greater improvement on the WMS-III FII subtest assessing delayed (30 min) recognition (p < 0.025) of visual material (i.e. human faces), compared with the placebo group. However, based on the significant difference (p < 0.03) found between the two groups' pretreatment baseline scores on the WMS-III FII, this result should be interpreted with caution. An examination of the participants' subjective ratings of their overall abilities to remember by treatment end on the Follow-up Self-report Questionnaire also revealed that significantly more (p = 0.05) older adults in the EGb 761 group rated their overall abilities to remember by treatment end as 'improved' compared with the placebo controls. Overall, the results from both objective, standardized, neuropsychological tests and a subjective, follow-up self-report questionnaire provided complementary evidence of the potential efficacy of Ginkgo biloba EGb 761 in enhancing certain neuropsychological/memory processes of cognitively intact older adults, 60 years of age and over.

Aged↗

A double-blind, placebo controlled study of Ginkgo biloba extract ('tanakan') in elderly outpatients with mild to moderate memory impairment.

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.

Administration, Oral↗

Protective effects of Ginkgo biloba extract against mercury(II)-induced cardiovascular oxidative damage in rats.

This study was designed to determine the possible protective effect of Ginkgo biloba extract (EGb) against Hg II-induced oxidative damage and also thromboplastic activity in the aorta and heart tissues. Wistar albino rats of either sex (200-250 g) were divided into four groups. Rats were injected intraperitoneally with (1) control (C) group: 0.9% NaCl; (2) EGb group: Ginkgo biloba extract (Abdi Ibrahim Pharmaceutical Company, Istanbul, Turkey) at a dose of 50 mg/kg/day; (3) Hg group: a single dose of 5 mg/kg mercuric chloride (HgCl(2)); and (4) Hg + EGb group: First day EGb at a dose of 50 mg/kg/day, i.p., 1 hour after HgCl(2) (5 mg/kg) injection; following four days EGb at a dose 50 mg/kg/day, i.p. After decapitation of the rats, trunk blood was obtained and serum tumor necrosis factor-alpha (TNF-alpha), lactate dehydrogenase (LDH) activity, and malondialdehyde (MDA) and glutathione (GSH) levels were analysed. In the aorta and heart tissues total protein, MDA, GSH levels and thromboplastic activity were determined. The results revealed that HgCl(2) induced oxidative tissue damage, as evidenced by increases in MDA levels and decreased GSH levels both in serum and tissue samples. Thromboplastic activity was increased significantly following Hg administration, which verifies the cardiotoxic effects of HgCl(2). Serum LDH and TNF-alpha were elevated in the Hg group compared with the control group. Since EGb treatment reversed these responses, it seems likely that Ginkgo biloba extract can protect the cardiovascular tissues against HgCl(2)-induced oxidative damage.

Animals↗

[Treatment of cerebral aging disorders with Ginkgo biloba extract. A longitudinal multicenter double-blind drug vs. placebo study].

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.

Aged↗

Ginkgo biloba extract for the treatment of tinnitus.

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, Göteborg, 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.

Adult↗

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

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.

Aged↗

[Ginkgo biloba extract in the treatment of arteriopathy of the lower extremities. A 65-week trial].

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.

Arterial Occlusive Diseases↗

Effect of Ginkgo biloba extract on beta-adrenergic receptors in different rat brain regions.

The effect of oral administration of Ginkgo biloba extract at a dose of 90 mg/kg for 7 consecutive days on rat brain beta-adrenergic receptors in the frontal cortex, hippocampus, striatum and hypothalamus was studied. Ginkgo biloba treatment induced a significant decrease in the density (B(max)) of beta-adrenoreceptors in the frontal cortex and hippocampus. It has been suggested that modulation of the beta-adrenergic system is implicated in the favourable effects of Ginkgo biloba extracts on learning and memory.

Animals↗

Effects of Ginkgo biloba extract on somatosensory evoked potential, nitric oxide levels in serum and brain tissue in rats with cerebral vasospasm after subarachnoid hemorrhage.

This study aimed to investigate the protective effects of Ginkgo biloba extract on cerebral vasospasm and neural damage following subarachnoid hemorrhage (SAH) in rats. It was found that the regional cerebral blood flow decreased immediately and persistently after SAH in SAH rats. The latency of somatosensory evoked potential delayed progressively. The nitric oxide levels in serum and brain tissue decreased and increased, respectively, after SAH. Ginkgo biloba extract effectively antagonized the changes of above parameters. It was concluded that somatosensory evoked potential is useful for the judgement of cerebral ischemic damage during cerebral vasospasm after SAH. Decrease in serum nitric oxide and increase in brain tissue nitric oxide are important factors leading to cerebral vasospasm and neural damage, respectively, after SAH. Ginkgo biloba extract relieves cerebral vasospasm and cerebral ischemic damage by reversing the pathological alteration of nitric oxide.

Animals↗