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[Neuromediator changes during cerebral aging. The effect of Ginkgo biloba extract].

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.

Aging↗

[Effect of folium ginkgo extract on the erythrocyte immunity function and serum lipid peroxide in asphyxia neonate].

OBJECTIVE: To observe the changes of erythrocyte immunity and serum lipid peroxide in asphyxia neonate, and to study the effect of Folium Ginkgo extract (FGE) on them. METHODS: Thirty asphyxia neonates were randomly divided into 2 groups, the treated group and the control group, 15 in each group. Erythrocyte C3b receptor rosette rate (E-C3bRR), erythrocyte immune complex rosette rate (E-ICR), blood superoxide dismutase (SOD) activity and serum lipid peroxide (LPO) level were determined at 24 hrs after birth. Conventional treatment was given to both groups and FGE (15 mg/kg.d) was given to the treated group additionally for 7-8 days, then the above-mentioned parameters were re-examined and neonatal behavioral neurological assessment (NBNA) was measured as well. RESULTS: E-C3bRR and SOD lowered, E-ICR and serum LPO increased in the asphyxia neonate significantly (P < 0.05). After treatment, comparison between the two groups showed that E-C3bRR and SOD were higher, E-ICR and serum LPO were lower in the treated group than those in the control group, and NBNA scoring was obviously higher in the former than that in the latter (all P < 0.05). CONCLUSION: Decrease of erythrocyte immunity in asphyxia neonate is related to the declined anti-oxidation ability and lipid peroxidase injury. FGE could suppress the free radical production, scavenge free radicals, antagonize the lipid peroxidation injury of cell membrane and up-regulate erythrocyte immunity. It displays the effects of nerve tissue protection and hypoxia-ischemic brain injury alleviation.

Asphyxia Neonatorum↗

[Ginkgo extract in impaired vision--treatment with special extract EGb 761 of impaired vision due to dry senile macular degeneration].

The therapeutic efficacy of Ginkgo special extract Egb 761 was investigated in a controlled, double-blind trial involving 99 patients with impaired vision due to senile, dry macular degeneration. The primary objective target variable was the change in the corrected visual acuity of the more severely impaired eye at baseline, during a six months treatment period with either 240 mg/die (group I = 50 patients) or 60 mg/die (group II = 49 patients) Egb 761. Marked improvement of the study participants' vision was observed in both treatment groups already after four weeks, with more pronounced improvements in group I (acuity increases by 0.13 in group I vs. 0.10 in group II after 24 weeks). The fraction of patients with improvement of visual acuity > or = 0.2 was nearly twice as large in the group treated with 240 mg/die Egb 761 as in patients receiving the lower dosage (p = 0.08). Subjective health impairments, if present, could be improved during treatment as well. The investigator rated a favorable tolerability for both dosages of Egb 761. In conclusion, the results demonstrate the therapeutic efficacy of Egb 761 in patients with senile, dry macular degeneration, with obvious benefits in every-day life.

Aged↗

Ultrastructural, immunohistochemical and biochemical investigations of the rat liver exposed to experimental diabetes und acute hypoxia with and without application of Ginkgo extract.

The aim of this paper was to investigate the effect of streptozotocin-induced diabetes by i.p. bolus injection of streptozotocin at 60 mg per kg bodyweight over four months and additional acute respiratory hypoxia (20 min. duration, 5% oxygen v/v), and also the protective effect of Ginkgo biloba extract (EGb 761) on Wistar rat liver under these experimental conditions. Diabetic and additional hypoxic alterations in histology and ultrastructure were subjected to qualitative and quantitative analysis, collagen was investigated by immunohistochemistry, and some biochemical parameters of oxidative stress were determined. Diabetes caused an increase in the size of the hepatocytes and their nuclei with a decrease in nucleus-to-plasma ratio and glycogen content. Connective tissue was variably increased in individual cases as shown by routine histological staining. EGb did not influence these data. Ultrastructural morphometry revealed a significant reduction in rough endoplasmic reticulum (rER) and a significant increase in smooth endoplasmic reticulum (sER) through diabetes, an increase under EGb protection, with no significant alteration under hypoxia. The volume fraction of mitochondria was significantly increased after induction of diabetes but less increased in the protected group. Additional hypoxia reduced this parameter. The mean cross-section area of mitochondria was significantly elevated in all diabetic groups compared to controls. Volume density of mitochondrial cristae was significantly diminished in all diabetic groups; EGb could only improve this parameter in the diabetic-hypoxic group.

Animals↗

[Ginkgo extract EGb 761 (tenobin)/HAES versus naftidrofuryl (Dusodril)/HAES. A randomized study of therapy of sudden deafness].

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.

Adult↗

Biological activities of Ginkgo extracts.

The biological activity of methanolic the extracts of leaves, roots, leaf-derived callus, root-derived callus, ginkolide A, ginkgolide B, bilobalide and a commercial Ginkgo product (Tanakan) was assessed. Bioassays consisted of the Agrobacterium tumefaciens-induced potato tumor assay and a Kirby-Bauer microbial sensitivity assay with pure strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes. Methanolic extracts of leaves, leaf-derived callus, root-derived callus, bilobalide and Tanakan inhibited tumor formation significantly, but more weakly than the positive control, camptothecin. No activity against E. coli was detected, but extracts from both callus types inhibited the growth of K. pneumonia, P. aeruginosa, S. aureus, S. epidermidis and S. pyogenes. All extracts and reference compounds inhibited the growth of S. pyogenes. Leaf and root tissues contained the highest levels of ginkgolide A, as compared to the callus tissues; leaf tissue contained more of all three marker compounds than the callus tissues.

Anti-Bacterial Agents↗

A new capillary zone electrophoresis method for the analysis of Ginkgo biloba extracts and Ginkgo biloba pharmaceutical products.

Ginkgo biloba, traditional Chinese medicine is now generally accepted. Separation and determination of active components in G. biloba is important for the product quality control. Therefore, the development of an effective and reliable separation method is important. In this work, a new capillary electrophoretic (CZE) method for separation of the G. biloba leaf extracts components was developed and optimized by the use of experimental design and artificial neural network (ANN). Under best separation conditions, in gamma-CD-modified buffer, the separation was reached within 10 min (36 mM borate BGE, pH 9.2, 1 mM gamma-CD), while the hydrodynamic mode for sample injection (2 s) and UV detection at 270 nm were applied. The method developed was validated and applied for analysis of various extracts and G. biloba products.

Cyclodextrins↗

Ginkgo biloba extracts and cancer: a research area in its infancy.

Recent studies conducted with various molecular, cellular and whole animal models have revealed that leaf extracts of Ginkgo biloba may have anticancer (chemopreventive) properties that are related to their antioxidant, anti-angiogenic and gene-regulatory actions. The antioxidant and associated anti-lipoperoxidative effects of Ginkgo extracts appear to involve both their flavonoid and terpenoid constituents. The anti-angiogenic activity of the extracts may involve their antioxidant activity and their ability to inhibit both inducible and endothelial forms of nitric oxide synthase. With regard to gene expression, a Ginkgo extract and one of its terpenoid constituents, ginkgolide B, inhibited the proliferation of a highly aggressive human breast cancer cell line and xenografts of this cell line in nude mice. cDNA microarray analyses have shown that exposure of human breast cancer cells to a Ginkgo extract altered the expression of genes that are involved in the regulation of cell proliferation, cell differentiation or apoptosis, and that exposure of human bladder cancer cells to a Ginkgo extract produced an adaptive transcriptional response that augments antioxidant status and inhibits DNA damage. In humans, Ginkgo extracts inhibit the formation of radiation-induced (chromosome-damaging) clastogenic factors and ultraviolet light-induced oxidative stress - effects that may also be associated with anticancer activity. Flavonoid and terpenoid constituents of Ginkgo extracts may act in a complementary manner to inhibit several carcinogenesis-related processes, and therefore the total extracts may be required for producing optimal effects.

Angiogenesis Inhibitors↗

Bioavailability of ginkgolides and bilobalide from extracts of ginkgo biloba using GC/MS.

The bioavailability of ginkgolides A, B and bilobalide was studied in rats after single oral administration of 30, 55 and 100 mg/kg Ginkgo extract EGb 761. The plasma levels of the terpene lactones were measured by a specific GC/MS method. The pharmacokinetics of the mentioned substances were found to be dose-linear. For the lowest dose maximum concentrations were 68, 40 and 159 ng/ml and half-lives 1.7, 2.0 and 2.2 h for ginkgolide A, B and bilobalide, respectively. Clearance values ranged from 24.2 to 37.6 ml/min/kg.

Animals↗

[Superoxide dismutase activity of Ginkgo biloba extract].

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 rökan liquid could be made evident.

Diterpenes↗

Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract.

The Ginkgo biloba extract EGb761 was tested for its ability to inhibit the major human cytochrome P450 enzymes (CYPs). The full extract was found to strongly inhibit CYP2C9 (Ki = 14+/- 4 microg/mL), and to a lesser extent, CYP1A2 (Ki = 106 +/- 24 microg/mL), CYP2E1 (Ki = 127 +/- 42 microg/mL), and CYP3A4 (Ki = 155 +/- 43 microg/mL). The terpenoidic and flavonoidic fractions of the extract were tested separately against the same P450s to identify the source of inhibition by EGb761. The terpenoidic fraction inhibited only CYP2C9 (Ki = 15 +/-6 microg/mL) whereas the flavonoidic fraction of EGb761 showed high inhibition of CYP2C9, CYP1A2, CYP2E1, and CYP3A4 (Ki's between 4.9 and 55 microg/mL). The flavonoidic fraction was further fractionated using extraction and chromatography. Inhibition studies indicated that the majority of these fractions inhibited P450s at a significant level (IC50 < 40 microg/mL).

Chemical Fractionation↗

Effect of two doses of ginkgo biloba extract (EGb 761) on the dual-coding test in elderly subjects.

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.

Aged↗

EGb 761: ginkgo biloba extract, Ginkor.

EGb 761 [Ginkgo biloba extract EGb 761, Rökan, Tanakan, Tebonin] is a standardised extract of Ginkgo biloba leaves and has antioxidant properties as a free radical scavenger. A standardised extract of Ginkgo biloba leaves is a well defined product and contains approximately 24% flavone glycosides (primarily quercetin, kaempferol and isorhamnetin) and 6% terpene lactones (2.8-3.4% ginkgolides A, B and C, and 2.6-3.2% bilobalide). Ginkgolide B and bilobalide account for about 0.8% and 3% of the total extract, respectively. Other constituents include proanthocyanadins, glucose, rhamnose, organic acids, D-glucaric and ginkgolic acids. EGb 761 promotes vasodilation and improves blood flow through arteries, veins and capillaries. It inhibits platelet aggregation and prolongs bleeding time. EGb 761, which was originated by Dr Willmar Schwabe Pharmaceuticals (Dr Willmar Schwabe Group), has been available in Europe as a herbal extract since the early 1990s. However, products containing EGb 761 are not approved for use by the US FDA. As a dietary supplement, Nature's Way in the US distributes and markets a standardised extract of Ginkgo biloba leaves (the EGb 761 Formula) under the name Gingold Nature's Way. The French company Beaufour-Ipsen and its German subsidiary Ipsen Pharma are co-developing EGb 761 with Dr Willmar Schwabe Group. Beaufour-Ipsen (France) is developing EGb 761 as Tanakan, Dr Willmar Schwabe Pharmaceuticals (Germany) as Tebonin and Ipsen Pharma (Germany) as Rökan. Intersan was formerly developing EGb 761 in Germany, but Intersan appears to have been merged into Ipsen Pharma. However, there has been no recent development for these indications. In the UK and other European countries, the cardioprotective effects of EGb 761 in myocardial ischaemia and reperfusion are being investigated in preclinical studies. The psychological and physiological benefits of ginkgo are said to be based on its primary action of regulating neurotransmitters and exerting neuroprotective effects in the brain, protecting against or retarding nerve cell degeneration. Ginkgo also benefits vascular microcirculation by improving blood flow in small vessels and has antioxidant activity. There has been conflicting evidence about the benefits of ginkgo, e.g. the ginkgo clinical trial published in August 2002 in JAMA concluded that a leading ginkgo supplement did not produce measurable benefits for memory in healthy adults over 60, although a month earlier, another study concluded that the same ginkgo extract is effective in helping normal healthy older adults in memory and concentration. However, in December 2002, the Cochrane Collaboration, the world's most respected scientific reviewer of clinical trials in medicine, concluded that the published literature strongly supports the safety and potential benefits of ginkgo in treating memory loss and cognitive disorders associated with age- related dementia. A phase II study of EGb 761 in combination with fluorouracil is in progress in Germany in patients with pancreatic cancer. German researchers are investigating the potential of EGb 761 for the treatment of sudden deafness and tinnitus in clinical studies. EGb 761 was undergoing preclinical development for the potential treatment of diabetes in France, diabetic neuropathies in Russia, and cancer in Brazil. However, there has been no recent development for these indications. Beaufour-Ipsen has expressed the intention to license out its diabetes projects that may include EGb 761.

Animals↗

Inhibition of platelet activating factor (PAF)-induced aggregation of human thrombocytes by ginkgolides: considerations on possible bleeding complications after oral intake of Ginkgo biloba extracts.

The special Ginkgo biloba leaf extract EGb 761 is marketed for more then two decades. During this time its therapeutic efficacy and favorable safety profile have been proven in numerous clinical trails as well as by postmarketing surveillance in accordance with German drug regulations. During recent years, however, several cases of hemorrhage have been reported to occur in coincidence with the use of Ginkgo products. Although a clear causality between Ginkgo intake and bleeding could not be established, these observations have generally been explained by the platelet-activating factor (PAF)-antagonistic action of ginkgolides, which represent characteristic constituents of Ginkgo extracts. PAF was originally characterized by inducing aggregation and secretion of serotonin and histamine from rabbit platelets. We now confirmed that induction of aggregation of human platelets by PAF requires at least 200 times higher concentration when compared to rabbit cells. Under the chosen experimental conditions, PAF-mediated aggregation of human platelets was half-maximally inhibited by ginkgolide B, A, C and J at concentrations of 2.5, 15.8, 29.8 and 43.5 microg/ml, respectively. These concentrations are generally more than 100 times higher as the peak plasma values measured after oral intake of EGb 761 at recommended doses between 120 and 240 mg. As PAF is a 'weak' platelet activator, which does not appear to be of importance for primary hemostasis, our results rise serious doubts that the PAF antagonistic effect of ginkgolides could be responsible for hemorrhage in patients taking EGb 761.

Administration, Oral↗

The nitric oxide-scavenging properties of Ginkgo biloba extract EGb 761.

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.

Animals↗

[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].

UNLABELLED: 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)

Arterial Occlusive Diseases↗