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PubMed2004

Inhibitory effect of extracts of Ginkgo biloba leaves on VEGF-induced hyperpermeability of bovine coronary endothelial cells in vitro.

AIM: To study whether extract of Ginkgo biloba (EGb) can protect against atherosclerosis. METHODS: Confluent monolayers of bovine coronary endothelial cells (BCECs), bovine coronary smooth muscle cells (BCSMCs), and cocultures of the two were incubated with medium containing VEGF and/or EGb, and flux of 125I-labeled oxidized low density lipoprotein (ox-LDL) across the monolayers was measured. RESULTS: Incubation with VEGF significantly increased the permeability of BCEC monolayers to 125I-ox-LDL in a time- and concentration-dependent manner, but had no effect on permeability of BCSMCs or endothelial cells-smooth muscle cells cocultures. EGb significantly inhibited the VEGF-induced hyperpermeability of BCECs. CONCLUSION: VEGF was important in the formation and development of atherosclerosis. The inhibition of VEGF-induced permeability by EGb suggests that extracts of Ginkgo biloba leaves may have important clinical applications in the treatment of cardiovascular diseases.

Animals↗
PubMed2006

Comparison of antioxidant activities between salvianolic acid B and Ginkgo biloba extract (EGb 761).

AIM: To investigate and compare the antioxidant activities of salvianolic acid B (SalB) and Ginkgo biloba extract (EGb 761) in aqueous solution, rat microsomes and the cellular system. METHODS: Superoxide anion (O2-.) was generated using xanthine/xanthine oxidase system and phenazine methosulate/NADH system, and the effects of SalB and EGb 761 on the generation of O2-.were achieved by spectrophotometric measurement of the product formed on reduction of nitro blue tetrazolium. Two different methods were used to assess the scavenging effects of the extracts on hydroxyl radical (. OH): HPLC method was used for quantitation of . OH by oxy-radical trapping of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) to form DMPO-OH adducts in Fe2+-EDTA-H2O2 system. To confirm the HPLC data, .OH was also measured by spectrophotometry using a commercial detection kit. The anti-lipid peroxidation effects of the extracts in microsomes of rat brain, liver and kidney induced by ascorbate-NADPH were determined by thiobarbituric acid (TBA) method. The protective effects of the extracts on peroxide hydrogen (H2O2)-induced oxidative damage in SH-SY5Y cells were investigated by assessing cell viability assay, the level of lipid peroxidation, and the lactate dehydrogenase(LDH) release. RESULTS: Both SalB and EGb 761 were able to scavenge O2-. and . OH, inhibit lipid peroxidation of microsomes, and protect SH-SY5Y cells against H2O2-induced oxidative damage. However, the concentration of SalB was far lower than that of EGb 761 when a similar effect was obtained. CONCLUSION: The antioxidant efficiency of SalB was greater than that of EGb 761. These results suggest that SalB, like EGb 761, has promising potential in treating oxidative damage-derived neurodegenerative disorders.

Animals↗
PubMed2005

Short-term ingestion of Ginkgo biloba extract does not alter whole body insulin sensitivity in non-diabetic, pre-diabetic or type 2 diabetic subjects--a randomized double-blind placebo-controlled crossover study.

BACKGROUND & AIMS: Ingestion of Ginkgo biloba Extract (EGb 761) may increase pancreatic beta-cell function in both healthy subjects with normal glucose tolerance (NGT) as well as patients with Type 2 Diabetes mellitus (T2DM). Since hyperinsulinemia is a hallmark of T2DM, it is important to verify that increased insulin production is not due to increased insulin resistance. METHOD: NGT subjects (n = 10; age, 44.2 +/- 13.9 years old), impaired glucose tolerance (IGT) (n = 8; age 51.3 +/- 6.6 years old) and T2DM subjects (n = 8, 51.6 +/- 15.2 years old) completed a randomized, double-blind, placebo-controlled crossover study. After ingesting either EGb 761 (120 mg/day as a single dose) or placebo during each 3-month arm, a 2-step euglycemic insulin clamp was performed. RESULTS: At the low insulin infusion rate (10 mU/m2/min) the glucose metabolic rates (M values) were 3.5 +/- 1.5 vs. 3.0 +/- 0.5 mg/kg (P = 0.16), 3.0 +/- 0.4 vs. 2.8 +/- 0.8 mg/kg (P = 0.19) and 2.6 +/- 0.7 vs. 2.4 +/- 0.5 mg/kg (P = 0.09) for the placebo and EGb 761 cycles, in the NGT, IGT and T2DM subjects, respectively. At the high insulin infusion rate (40 mU/m2/min) the M values were 7.3+/-2.3 vs. 8.1 +/- 2.5mg/kg (P = 0.07), 6.2 +/- 1.6 vs. 6.5 +/- 2.1 mg/kg (P = 0.32) and 3.6 +/- 1.6 vs. 3.5 +/- 1.0 mg/kg (P = 0.34) for placebo vs. EGb 761 cycles, in the NGT, IGT and T2DM subjects, respectively. CONCLUSION: The ingestion of 120 mg of EGb 761 as a single for 3 months did not produce insulin resistance in the non-diabetic or pre-diabetic subjects or exacerbate the disease in the T2DM subjects.

Adult↗
PubMed1990

[Cerebral insufficiency--treatment with Ginkgo-biloba extract. Time of onset of effect in a double-blind study with 60 inpatients].

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.

Adult↗
PubMed2002

The efficacy of Ginkgo special extract EGb 761 in patients with tinnitus.

OBJECTIVE: The objective of the present study in 60 patients with chronic tinnitus aurium was to confirm the efficacy of oral treatment with 2 x 80 mg Ginkgo special extract EGb 761 per day subsequent to 10-day EGb 761 infusion treatment. METHODS: Patients with chronic tinnitus aurium underwent 10 days of in-patient infusion treatment with 200 mg/day EGb 761, after which they were randomized to double-blind, oral out-patient treatment with either 2 x 80 mg/day EGb 761 or placebo, given over a scheduled treatment period of 12 weeks. The primary outcome measure was the change in tinnitus volume in the more severely affected ear during randomized treatment. RESULTS: Fifty-two of 60 patients (89.7%) completed the infusion treatment; complete sets of data were available for 40 (66.7%), 30 (50.0%) and 22 (36.7%) patients after 4, 8 and 12 weeks of randomized treatment, respectively. For the primary outcome measure, significant superiority of EGb 761 over placebo was demonstrated in the intention-to-treat analysis data set after 4, 8 and 12 weeks of out-patient treatment (p < 0.05, 1-tailed), although the absolute treatment group difference was moderate. The results were supported by the secondary outcome measures for efficacy (e.g. decreased hearing loss, improved self-assessment of subjective impairment). During out-patient treatment, there were no attributable adverse events under EGb 761. CONCLUSIONS: A combination of infusion therapy followed by oral administration of Ginkgo special extract EGb 761 appears to be effective and safe in alleviating the symptoms associated with tinnitus aurium.

Administration, Oral↗
PubMed1999

Effects of single intraperitoneal injections of an extract of Ginkgo biloba (EGb 761) and its terpene trilactone constituents on barbital-induced narcosis in the mouse.

A mouse model of barbital-induced narcosis was used to examine the effects of single intraperitoneal injections of an extract of Ginkgo biloba (EGb 761), an extract devoid of terpene trilactones (CP 205), and three terpene trilactone constituents of the extract (ginkgolides A and B, bilobalide). Administration of sodium barbital (180 mg/kg, IP) to the mice caused narcosis, measured as a loss in righting reflex. Single injections of EGb 761 (25 and 50 mg/kg), given 60 min prior to sodium barbital, significantly shortened barbital-induced sleeping time, whereas these same doses of CP 205 were ineffective. Single injections of ginkgolide B (1 mg/kg) and bilobalide (2 and 5 mg/kg) significantly shortened sleeping time, whereas ginkgolide A was ineffective. The effects of ginkgolide B and bilobalide were reflected as increases in latency to onset of sleep and those of EGb 761, ginkgolide B, and bilobalide were correlated with decreases in the number of mice that slept. At the behavioral level, these potent in vivo effects of EGb 761, ginkgolide B, and bilobalide resemble those of certain antidepressants. At the molecular level, it is hypothesized that interactions with the picrotoxinin/TBPT site of GABA-regulated Cl- channels of the CNS may be involved. This information appears useful in explaining the clinically observed "vigilance-enhancing" and "antidepressant-like" actions of EGb 761.

Analysis of Variance↗
PubMed1992

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

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.

Animals↗
PubMed1992

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

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.

Animals↗
PubMedDate not supplied

An open, pilot study to evaluate the potential benefits of coenzyme Q10 combined with Ginkgo biloba extract in fibromyalgia syndrome.

An open, uncontrolled study was undertaken to measure the subjective effects of coenzyme Q10 combined with a Ginkgo biloba extract in volunteer subjects with clinically diagnosed fibromyalgia syndrome. Anecdotal reports from patients with fibromyalgia syndrome have claimed benefits from the use of these supplements. The aim of this study was to determine if these reports could be substantiated in a pilot clinical trial. Patient questioning had determined that poor quality of life was a major factor in the condition and a quality-of-life questionnaire was used to measure potential benefit. Subjects were given oral doses of 200 mg coenzyme Q10 and 200 mg Ginkgo biloba extract daily for 84 days. Quality of life was measured, using the well-validated Dartmouth Primary Care Cooperative Information Project/World Organization of Family Doctors (COOP/WONCA) questionnaire that measures seven different subjective responses, at 0-, 4-, 8-, and 12-week intervals. The subjects were asked for an overall self-rating at the end of the study. A progressive improvement in the quality-of-life scores was observed over the study period and at the end, the scores showed a significant difference from those at the start. This was matched by an improvement in self-rating with 64% claiming to be better and only 9% claiming to feel worse. Adverse effects were minor. A controlled study is now planned.

Antioxidants↗
PubMed1996

Myocardium-protective effects of Ginkgo biloba extract (EGb 761) in old rats against acute isobaric hypoxia. An electron microscopic morphometric study. I. Protection of cardiomyocytes.

Ginkgo biloba extract EGb 761 was used in hypoxia experiments with old rats to investigate its ultrastructure-preserving effects on the myocardium. Hypoxia was performed by means of a hypoxia chamber combined with a commercial narcosis apparatus. N2O/O2-mixture was applied with O2 at 5 vol.% for 20 minutes under normobaric conditions. Ultrastructural-morphometric analysis revealed that EGb 761-pretreatment was able to diminish hypoxic damage at mitochondrial cristae and matrix and also distension of the sarcoplasmic reticulum during acute hypoxic stress. Whereas formation of vacuoles was depressed below the level of controls, the accumulation of lipid drops was not prevented. The preservation of mitochondrial cristae was confirmed by independent secondary morphometric parameters and by cytophotometrically measured activities of mitochondrial enzymes.

Acute Disease↗
PubMed2003

Mechanisms for the vasodilations induced by Ginkgo biloba extract and its main constituent, bilobalide, in rat aorta.

Vasodilating actions of Ginkgo biloba extract (GBE) and bilobalide, a main constituent, were examined using rat aorta ring strips. GBE at the concentration ranges from 0.03 to 3 mg/ml had a potent concentration-dependent relaxation, reaching 70 +/- 4.5% (n = 6, P < 0.001) at 3 mg/ml. Bilobalide at 0.1 to 100 microM also caused the relaxation in a concentration-dependent manner. At 100 microM, bilobalide caused dilation by 17.6 +/- 3.9% (n = 7, P < 0.05). NG-monomethyl-L-arginine acetate (L-NMMA)(100 microM), an NO synthesis inhibitor, reduced the vasodilation of GBE (3 mg/ml) to 57.6 +/- 2.5% (n = 6, P < 0.05), and was accompanied with a decrease in the rate of relaxation. Tetraethylammonium (TEA)(100 microM), a Ca(2+)-activated K(+) channel inhibitor, also decreased the GBE (3 mg/ml)-induced relaxation to 63.1 +/- 4.6% (n = 6), but not significantly. Indomethacin tended to reduce the GBE (3 mg/ml)-induced vasorelaxation to 67.3 +/- 4.1% (n = 6). In contrast, the vasorelaxation of GBE (3 mg/ml) was strongly attenuated to 53 +/- 6.1% (n = 7, P < 0.05) in Ca(2+)-free medium. Similarly, the vasorelaxation induced by bilobalide significantly decreased both by pretreatment with NO inhibitor (L-NMMA) and in Ca(2+)-free solution. These results indicate that the relaxation induced by GBE would be due to the inhibition of Ca(2+) influx through the Ca(2+) channel and the activation of NO release, and might be in part due to the inhibitions of Ca(2+)-activated K(+) current and PGI(2) release, in the endothelium and aortic vascular muscles. Bilobalide possesses the similar mechanisms for the vasodilation.

Animals↗
PubMed2006

The Ginkgo biloba extract EGb761 reduces stress sensitivity, ROS accumulation and expression of catalase and glutathione S-transferase 4 in Caenorhabditis elegans.

The standardised extract EGb761 from the leaves of Ginkgo biloba is a popular herbal dietary supplement and it is used as a phytopharmacon for the therapy of diverse cerebral insufficiencies. The beneficial impact of EGb761 is believed to be conferred by diverse biological actions under physiological conditions as well as in response to stress. In this study we examined effects of EGb761 in the model organism Caenorhabditis elegans. EGb761 reduced the body size but did not affect the reproduction of C. elegans. In fluorescence-based assays performed in microtiter plates we demonstrated the protective action of EGb761 by the increase of resistance to thermal stress and the attenuation of ROS accumulation under conditions of thermal stress in single living worms. Under normal conditions the lifespan of the worms was extended by the EGb761 supporting the beneficial effects found under stress conditions. In a reporter gene approach using individual living worms the expression of the stress-inducible glutathione S-transferase 4 was shown to be reduced by EGb761 under physiological conditions as well as under oxidative stress. EGb761 also led to a decrease in transcription of the stress-inducible catalase genes. These results suggest that the beneficial impact of EGb791 on resistance to thermal stress and lifespan in C. elegans is at least partially due to its ability to relieve oxidative stress.

Animals↗
PubMedDate not supplied

In vitro effect of Ginkgo biloba extract (EGb 761) on the activity of presynaptic cholinergic nerve terminals in rat hippocampus.

The effects of Ginkgo biloba extract (EGb) applied in vitro to hippocampal synaptosomes from young Wistar rats on the specific binding of [3H]hemicholinium-3 ([3H]HCh-3), high-affinity choline uptake (HACU) and activity of Na+,K(+)-ATPase were examined. EGb at a concentration of 100 micrograms/ml markedly elevated the specific binding of [3H]HCh-3 (to 306%) and moderately elevated HACU values (to 115%). Scatchard analysis revealed an increase in the Bmax for [3H]HCh-3 binding. Lineweaver-Burk analysis an increase in the Vmax for choline uptake. No marked changes in the activity of the sodium pump were discovered. EGb was not able to influence the specific 'second messenger' effect of arachidonic acid.

Animals↗
PubMed2000

Protective effects of Ginkgo biloba extract on gastric mucosa.

AIM: To study the protective effects of Ginkgo biloba extract (GbE) on gastric mucosa. METHODS: By means of restaint-cold stress (RCS) in rats and 100% ethanol gavage in mice, the index of gastric mucosal injury was evaluated. The gastric juice was collected using pyloric ligation, and the volume and acidity of juice, and activity of pepsin were determined. The content of malondialdehyde (MDA) was measured by thiobarbituric acid (TBA) method. RESULTS: GbE (25, 50, and 100 mg/kg, bid x 5 d, ig) inhibited dose-dependently the gastric mucosal injury induced by RCS and 100% ethanol gavage. The index of gastric mucosal injury after RCS in groups pretreated with GbE was 58%, 43%, and 31% of control group respectively. The index of gastric mucosal injury induced by ethanol in groups pretreated with GbE was 62%, 36%, and 26% of the control group, respectively. And GbE enhanced the protective effects of cimetidine (Cim) on gastric mucosa. But it did not obviously influence the volume and acidity of gastric juice as well as the activity of pepsin. One hour after the administration of ig 100% ethanol, the contents of MDA in gastric mucosa and serum in mice increased (P < 0.01) vs the control group. But pretreatment with GbE (25, 50, and 100 mg/kg, ig) could inhibit this increase of MDA both in gastric mucosa and in serum. CONCLUSION: GbE had protective effects on gastric mucosa and GbE plus Cim possessed the synergism in the treatment of acute gastric mucosal lesions.

Animals↗
PubMed1986

[Effect of Ginkgo biloba extract on biological endocrine parameters].

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.

Adult↗
PubMed1986

[Effect of Ginkgo biloba extract on the electrophysiology of the isolated retina from a diabetic rat].

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.

Animals↗
PubMed1999

Functional protection of photoreceptors from light-induced damage by dimethylthiourea and Ginkgo biloba extract.

PURPOSE: To investigate the functional protective effect of a synthetic (dimethylthiourea, DMTU) and a natural antioxidant (Ginkgo biloba extract, EGb 761) against light-induced retinal degeneration. METHODS: Wistar rats were exposed for 24 hours to 1700-lux light after treatment with DMTU or EGb 761. Electroretinograms were recorded before and on day (D)1, D3, D8, D15, D22, and D29 after light exposure. The b-wave amplitude was plotted against log L (ganzfeld luminance), providing the b-wave sensitivity curve. The Naka-Rushton function fitted to the sensitivity curve enabled derivation of the parameters Bmax (saturated amplitude) and K (luminance-inducing Bmax/2). In addition, rats from each group were killed for retinal morphometric analyses. RESULTS: In the untreated group, light exposure caused collapse of the b-wave sensitivity curves. Bmax was reduced by 51% at D1 without subsequent recovery. K increased temporarily, reverting to normal values 8 days later. The outer nuclear layer thicknesses decreased markedly in the superior retina. In the treated groups, light exposure had a weaker effect on sensitivity curves. The values of Bmax were not significantly different from those in the unexposed-untreated group, although K increased temporarily. Retinal morphometry was preserved. CONCLUSIONS: Dimethylthiourea and EGb 761 afford functional protection against light-induced retinal damage.

Animals↗
PubMed1999

Effects on skeletal muscle fibres of diabetes and Ginkgo biloba extract treatment.

Combined cytophotometric and morphometric analysis of muscle fibre properties and myosin heavy chain electrophoresis were performed on extensor digitorum longus and soleus muscles from healthy rats and rats with streptozotocin-induced diabetes. Moreover, the protective effect of Ginkgo biloba extract, a potent oxygen radical scavenger, on diabetic muscles was investigated. Changes in fibre type-related enzyme activities, fibre type distribution, fibre cross areas and myosin isoforms were found. In muscles of diabetic rats, a metabolic shift was measured mainly in fibres with oxidative metabolism. Fast-oxidative glycolytic fibres showed a shift to more glycolytic metabolism and about a third transformed into fast-glycolytic fibres. Slow-oxidative fibres became more oxidative. Fibre atrophy was measured in diabetic muscles dependent on fibre type and muscle. Different fibre types atrophied to a different degree. Therefore, a decreased area percentage of slow fibres and an increased area percentage of fast fibres of the whole muscle cross section in both muscles were found. This is supported by reduced slow and increased fast myosin heavy chain isoforms. These alterations of diabetic muscle fibres could be due to less motion of diabetic rats and diabetic neuropathy. After treatment with Ginkgo biloba extract, enzyme activities were increased mainly in oxidative fibres of diabetic muscles, which was interpreted as protective effect. Generally, the soleus muscle with predominant oxidative metabolism was more vulnerable to diabetic alterations and Ginkgo biloba extract treatment than the extensor digitorum longus muscle with predominant glycolytic metabolism.

Animals↗