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PubMed1999

Ginkgo biloba leaf extract: review of biological actions and clinical applications.

The number of studies on Ginkgo biloba leaves is rapidly increasing. A variety of effects of Ginkgo biloba leaf extract (GBLE) have been identified. GBLE contains many different flavone glycosides and terpenoides. GBLE has an antioxidant action as a free radical scavenger, a relaxing effect on vascular walls, an antagonistic action on platelet-activating factor, an improving effect on blood flow or microcirculation, and a stimulating effect on neurotransmitters. Besides a direct scavenging action on active oxygen species, GBLE exerts an anti-inflammatory effect on inflammatory cells by suppressing the production of active oxygen and nitrogen species. GBLE inhibited the increase in the products of the oxidative decomposition low-density lipoprotein (LDL), reduced the cell death in various types of neuropathy, and prevented the oxidative damage to mitochondria, suggesting that GBLE exhibits beneficial effects on neuron degenerative diseases by preventing chronic oxidative damage. The study using a model of ischemia-reperfusion injury has also demonstrated the protective effect of GBLE on cardiac muscle and its antioxidative action in vivo. Favorable results have been obtained in double-blind, placebo-controlled, comparative trials of patients with memory disorders, obstructive arteriosclerosis, and dementia. We review the recent studies on GBLE with respect to its various pharmacological actions, such as a scavenging activity on free radicals and an inhibitory action on lipid peroxidation. GBLE shows a very strong scavenging action on free radicals, and is thus considered to be useful for the treatment of diseases related to the production of free radicals, such as ischemic heart disease, cerebral infarction, chronic inflammation, and aging.

Animals↗
PubMedDate not supplied

Clinical efficacy of Ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type.

Among the psychiatric illnesses associated with old age primary degenerative dementia of the Alzheimer type (DAT) has gained increasing importance in recent years. Even though a curative treatment of the disease is currently impossible, various drugs can be used to slow down its progression. In the present study the influence of oral treatment with 240 mg/day of Ginkgo bilabo special extract EGb 761 (Tebonin forte, manufactured by Dr Willmar Schwabe, Karlsruhe) on the clinical course of DAT was investigated in a double-blind, randomized, placebo-controlled parallel-group design in 20 outpatients. The duration of treatment was 3 months. The primary outcome variable was the sum score in the SKT-test for the determination of attention and memory. Other psychometric tests (trailmaking test, ADAS, CGI) and electrophysiological investigations (EEG topography) were evaluated descriptively. Although the active-treatment group, with a mean sum score of 19.67 points in the, S.K.T., had a poorer baseline level than the placebo group (18.11 points), it experienced an improvement to 16.78 points under treatment with EGb 761 whereas the placebo group deteriorated to 18.89 points. The differences between the baseline and final values formed the basis for a statistical group comparison, which gave a result favourable to EGb 761, at a significance level of p < .013. In addition to this psychometric confirmation of efficacy, certain descriptive trends were found at the psychopathological (Clinical Global Impression) and dynamic functional (EEG findings) levels, which can be interpreted as evidence of effectiveness of Ginkgo biloba special extract EGb 761 in mild to moderate dementia and of local effects in the central nervous system. Inter-group differences in the ADAS cognitive and non-cognitive subscales did not reach statistical significance, probably because of the small sample size.

Aged↗
PubMed2002

Enhanced conditioned inhibitory avoidance by a combined extract of Zingiber officinale and Ginkgo biloba.

Previous work has shown that intragastric administration of Zingicomb, a preparation consisting of Zingiber officinale and Ginkgo biloba extracts, has anxiolytic-like properties. The aim of the present study was to assess the effects of acute treatment with this preparation on inhibitory avoidance learning. The influence of pre-trial administered Zingicomb (ZC) on inhibitory avoidance conditioning was investigated in adult male Wistar rats, with a one-trial step-through avoidance task. The animals were treated intragastrically with either vehicle, 0.5, 1, 10 or 100 mg/kg ZC 60 min prior to the acquisition trial. When tested 24 h after training, rats which had received 10 mg/kg ZC exhibited significantly longer step-through latencies than vehicle treated animals. This result, thus, demonstrates the beneficial effects of Zingicomb on conditioned inhibitory avoidance. Unlike conventional anxiolytic drugs, such as the benzodiazepines, which tend to have amnesic properties, this phytopharmacon is a potent anxiolytic agent which, additionally, can facilitate performance on a learning task, indicating promising clinical applications.

Administration, Oral↗
PubMed2003

Ginkgo biloba leaf extract enhances levels of caspase-3 and amyloid precursor protein in normal rat hippocampus.

AIM: To explore the effect of Ginkgo biloba extract (GbE) on the levels of caspase-3 and amyloid precursor protein (APP) in normal rats' hippocampus. METHODS: Immunohistochemistry method was used for qualitative analysis of the expressions of caspase-3 and APP, and an image analysis method was used for the quantification of the levels of caspase-3 and APP after GbE was administered to rats of different ages for 14 d. RESULTS: The mean absorbance of staining of caspase-3 and APP was markedly higher in GbE group than that in control groups. The expressions of caspase-3 and APP were intensified in the hippocampus of rats after GbE administration. CONCLUSION: GbE can raise the levels of caspase-3 and APP in the hippocampus of normal rats.

Amyloid beta-Protein Precursor↗
PubMed2001

[The safety of herbal medicines in the psychiatric practice].

The use of alternative medicines is increasing world-wide and in Israel. These drugs, considered by the Ministry of Health as food supplements, are to be obtained at pharmacies and health stores and are being sold freely, without any professional advice. Many of the herbs are used by patients to treat psychiatric disorders. These herbs have a pharmacological activity, adverse effects and interactions with conventional drugs, which can produce changes in mood, cognition, and behavior. We present the most commonly used herbal drugs, and discuss their safety and efficacy in psychiatric practice. Hypericum--used as an antidepressant and as an antiviral medicine, was reported in 23 randomized clinical trials reviewed from the MEDLINE. It was found to be significantly more effective than placebo and had a similar level of effectiveness as standard antidepressants. Recent studies almost clearly prove that this herb, like most of the conventional antidepressants, can induce mania. Valerian--is used as an anti-anxiety drug, and reported to have sedative as well as antidepressant properties. In contrast to the significant improvement in sleep that was found with the use of valerian, compared to placebo, there are several reports on the valerian root toxicity. This includes nephrotoxicity, headaches, chest tightness, mydriasis, abdominal pain, and tremor of the hands and feet. Ginseng--another plant that is widely used as an aphrodisiac and a stimulant. It has been associated with the occurrence of vaginal bleeding, mastalgia, mental status changes and Stevens-Johnson syndrome after it's chronic administration. It has interactions with digoxin, phenelzine and warfarin. Ginkgo--in clinical trials the ginkgo extract has shown a significant improvement in symptoms such as memory loss, difficulties in concentration, fatigue, anxiety, and depressed mood. Long-term use has been associated with increased bleeding time and spontaneous hemorrhage. Ginkgo should be used cautiously in patients receiving aspirin, NSAIDs, anticoagulants or other platelet inhibitors. Health care professionals can no longer ignore the widespread use of alternative medicines and cannot continue with the "don't ask, don't tell" policy. Clinicians should ask the patients about their use of herbs in a non-judgmental way, and should document the patient's use of these drugs. Finally, we must be more aware of the side effects and the potential drug interactions of these herbs, and advise our patients to avoid long term use of these drugs due to lack of information regarding the safety of these medicines.

Ginkgo biloba↗
PubMed2004

A new experimental design for screening Chinese medicine formula.

In this paper, an appropriate scale screening for traditional Chinese medicine formula was developed in according to verified pharmacological experiments with uniform optimized experimental design and orthogonal optimized experimental design. Meanwhile, a most appropriate match of prescription dosage for curing vascular disease was got, which was based on NO value of pharmacodynamics experimental data and the endothelial cells configuration which would changed in a degree when damaged by hydration diamine. The appropriate scale of the formula was Ginkgo extraction: substance A:B:C = 100:20:50:0.01. This formula was more optimized and effective than other formula compared by pharmacological and validated experiments.

Cells, Cultured↗
PubMed2004

Studies on interactions between functional foods or dietary supplements and medicines. IV. Effects of ginkgo biloba leaf extract on the pharmacokinetics and pharmacodynamics of nifedipine in healthy volunteers.

The effects of Ginkgo biloba leaf extract (GBE), a widely used herbal dietary supplement in Japan, on the pharmacokinetics and pharmacodynamics of nifedipine (NFP), a calcium-channel blocker, were studied using 8 healthy volunteers. Simultaneous oral ingestion of GBE (240 mg) did not significantly affect any of the mean pharmacokinetic parameters of either NFP or dehydronifedipine, a major metabolite of NFP, after oral administration of NFP (10 mg). However, the maximal plasma NFP concentrations in 2 subjects were approximately doubled by GBE, and they had severer and longer-lasting headaches with GBE than without GBE, with dizziness or hot flushes in combination with GBE. The mean heart rate after oral administration of NFP with GBE tended to be faster than that without GBE at every time point. Accordingly, it was concluded that GBE and NFP should not be simultaneously ingested as much as possible, and careful monitoring is needed when administering NFP concomitantly with GBE to humans.

Administration, Oral↗
PubMed2006

Ginkgo biloba and ovarian cancer prevention: epidemiological and biological evidence.

There is considerable interest in herbal therapies for cancer prevention but often with little scientific evidence to support their use. In this study, we examined epidemiological data regarding effects of commonly used herbal supplements on risk for ovarian cancer and sought supporting biological evidence. 4.2% of 721 controls compared to 1.6% of 668 cases regularly used Ginkgo biloba for an estimated relative risk (and 95% confidence interval) of 0.41 (0.20,0.84) (p=0.01); and the effect was most apparent in women with non-mucinous types of ovarian cancer, RR=0.33 (0.15,0.74) (p=0.007). In vitro experiments with normal and ovarian cancer cells showed that Ginkgo extract and its components, quercetin and ginkgolide A and B, have significant anti-proliferative effects ( approximately 40%) in serous ovarian cancer cells, but little effect in mucinous (RMUG-L) cells. For the ginkgolides, the inhibitory effect appeared to be cell cycle blockage at G0/G1 to S phase. This combined epidemiological and biological data provide supportive evidence for further studies of the chemopreventive or therapeutic effects of Ginkgo and ginkgolides on ovarian cancer.

Case-Control Studies↗
PubMed2006

Does Ginkgo biloba special extract EGb 761 provide additional effects on coagulation and bleeding when added to acetylsalicylic acid 500 mg daily?

OBJECTIVE: The aim of this study was to determine whether Ginkgo biloba special extract EGb 761 amplifies the known effects of acetylsalicylic acid (ASA) on platelet aggregation, bleeding time or other coagulation parameters in healthy subjects. METHODS: In a double-blind, double-dummy procedure, 50 healthy male subjects (20-44 years) were randomly allocated in equal numbers to one of two possible treatment sequences, i.e. ASA followed by ASA + EGb 761 or ASA + EGb 761 followed by ASA. Each treatment lasted 7 days; the washout period between treatments was 3 weeks. Study medication was taken twice daily (ASA group: ASA 500 mg tablet + placebo-coated tablet in the morning and placebo tablet + placebo-coated tablet in the evening; ASA + EGb 761 group: ASA 500 mg tablet + EGb 761 120 mg-coated tablet in the morning and placebo tablet + EGb 761 120 mg-coated tablet in the evening), resulting in a daily dose of ASA 500 mg in the ASA group and 500 mg ASA + 240 mg EGb 761 in the ASA + EGb 761 group. Bleeding time, coagulation parameters and platelet activity in response to various agonists were determined. In addition, adverse events, laboratory variables and vital signs were measured. The primary variable bleeding time was assessed in confirmatory analysis, all other variables were evaluated descriptively. The coagulation variables were analysed by ANOVA under the crossover model. RESULTS: ASA given alone clearly prolonged bleeding time. ASA and the combination of ASA + EGb 761 exerted quite similar effects on all coagulation parameters measured, including bleeding time (ASA alone: 4.1 min before therapy, 6.2 min after therapy; ASA + EGb 761: 4.2 min before therapy, 6.3 min after therapy; ratio of means: 1.01, 90% CI 0.86, 1.19) and agonist-induced platelet aggregation (collagen-induced platelet aggregation - ASA: 84.5% before therapy, 81.0% after therapy; ASA + EGb 761: 86.6% before therapy, 81.0% after therapy; ratio of means: 1.00, 90% CI 0.95, 1.05; adenosine diphosphate-induced platelet aggregation - ASA: 72.6% before therapy, 47.2% after therapy; ASA + EGb 761: 71.7% before therapy, 44.8% after therapy; ratio of means: 0.95, 90% CI 0.85, 1.06). Both treatments were well tolerated, and both the number and nature of adverse events in the two groups were similar. CONCLUSIONS: Our findings suggest that co-administration of ASA and EGb 761 does not constitute a safety risk, including in an elderly patient population undergoing treatment with EGb 761.

Adult↗
PubMed2006

Identification of class 2 1-deoxy-D-xylulose 5-phosphate synthase and 1-deoxy-D-xylulose 5-phosphate reductoisomerase genes from Ginkgo biloba and their transcription in embryo culture with respect to ginkgolide biosynthesis.

Diterpenoid ginkgolides having potent platelet-activating factor antagonist activity are major active ingredients of ginkgo extract. Class 2-type 1-deoxy-D-xylulose 5-phosphate synthase (GbDXS2) and 1-deoxy-D-xylulose 5-phosphate reductoisomerase (GbDXR), the first two enzymes in 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, operating in the earlier step of ginkgolide biosynthesis, were cloned from embryonic roots of Ginkgo biloba through a homology-based polymerase chain reaction for role assessment of the enzymes. Plasmids harboring each gene rescued the respective knockout E. coli mutants. The levopimaradiene synthase gene (LPS), responsible for the first committed step in ginkgolide biosynthesis, and GbDXS2 were transcribed exclusively in embryonic root, suggesting a specific role of GbDXS2 in ginkgolide biosynthesis. GbDXR retained a higher transcription level in roots than in leaves, whereas class 1 DXS (GbDXS1) showed 30 to 50 % higher level in leaves. Ginkgolides and bilobalide were found both in leaves and roots from an earlier stage of the embryo culture. Exclusive transcription of ginkgolide biosynthesis-specific LPS and GbDXS2 in roots and the appearance of ginkgolides in leaves was consistent with translocation of the compounds from roots to leaves.

Aldose-Ketose Isomerases↗
PubMed1998

Demonstration of the efficacy of ginkgo biloba special extract EGb 761 on intermittent claudication--a placebo-controlled, double-blind multicenter trial.

BACKGROUND: A multicentric, randomized, placebo-controlled double-blind study on ginkgo biloba special extract EGb 761 (Tebonin forte) in patients suffering from peripheral occlusive arterial disease (POAD) in Fontaine stage II b was carried out in order to prove its clinical efficacy in this indication according to guidelines of European Community authorities and the German Angiological Society and to confirm the results of former clinical studies with EGb 761. PATIENTS AND METHODS: In total, 111 patients with angiographically proven POAD in Fontaine stage II b and intermittent claudication (pain-free walking distance < 150 m on the treadmill) were recruited in 5 centers and treated with either EGb 761 or placebo at a daily dose of 3 times 1 film-coated tablet over a duration of 24 weeks following a 2-week placebo run-in period. The primary response variable was the difference of the pain-free walking distance between the start of treatment and after 8, 16 and 24 weeks as measured on the treadmill (walking speed 3 km/h and slope of 12%) under standardized conditions. RESULTS: At the start of the treatment period, the mean pain-free walking distances were very similar with 108.5 m in the EGb 761 group and 105.2 m in the placebo group. At the end of the treatment period these values increased to 153.2 m and 126.6 m, respectively. The group differences were statistically significant at all three control visits with p = 0.017, p = 0.007, and p = 0.016. The differences for the maximum walking distance and the relative increases of the pain-free walking distance and the maximum distance were also significantly higher in the EGb 761 group with p-values < 0.05 each. In both groups Doppler indices remained nearly unchanged during therapy. The subjective assessment of the patients demonstrated an amelioration of complaints in both groups. Tolerability was very good with no adverse events under EGb 761 and one case of heartburn and gastric pain in the placebo group. CONCLUSIONS: It can be concluded from the results of this study that treatment with EGb 761 in POAD patients with Fontaine stage II b is very safe and causes a significant and therapeutically relevant prolongation of the patients' walking distance.

Aged↗
PubMed2000

Evidence that gingko biloba extract does not inhibit MAO A and B in living human brain.

Extracts of Ginkgo biloba have been reported to reversibly inhibit both monoamine oxidase (MAO) A and B in rat brain in vitro leading to speculation that MAO inhibition may contribute to some of its central nervous system effects. Here we have used positron emission tomography (PET) to measure the effects of Ginkgo biloba on human brain MAO A and B in 10 subjects treated for 1 month with 120 mg/day of the Ginkgo biloba extract EGb 761, using [11C]clorgyline and [11C]L-deprenyl-D2 to measure MAO A and B respectively. A three-compartment model was used to calculate the plasma to brain transfer constant K1 which is related to blood flow, and lambdak3, a model term which is a function of the concentration of catalytically active MAO molecules. Ginkgo biloba administration did not produce significant changes in brain MAO A or MAO B suggesting that mechanisms other than MAO inhibition need to be considered as mediating some of its CNS effects.

Adult↗
PubMed1999

Medicinal plants and Alzheimer's disease: from ethnobotany to phytotherapy.

The use of complementary medicines, such as plant extracts, in dementia therapy varies according to the different cultural traditions. In orthodox Western medicine, contrasting with that in China and the Far East for example, pharmacological properties of traditional cognitive- or memory-enhancing plants have not been widely investigated in the context of current models of Alzheimer's disease. An exception is Gingko biloba in which the gingkolides have antioxidant, neuroprotective and cholinergic activities relevant to Alzheimer's disease mechanisms. The therapeutic efficacy of Ginkgo extracts in Alzheimer's disease in placebo controlled clinical trials is reportedly similar to currently prescribed drugs such as tacrine or donepezil and, importantly, undesirable side effects of Gingko are minimal. Old European reference books, such as those on medicinal herbs, document a variety of other plants such as Salvia officinalis (sage) and Melissa officinalis (balm) with memory-improving properties, and cholinergic activities have recently been identified in extracts of these plants. Precedents for modern discovery of clinically relevant pharmacological activity in plants with long-established medicinal use include, for example, the interaction of alkaloid opioids in Papaver somniferum (opium poppy) with endogenous opiate receptors in the brain. With recent major advances in understanding the neurobiology of Alzheimer's disease, and as yet limited efficacy of so-called rationally designed therapies, it may be timely to re-explore historical archives for new directions in drug development. This article considers not only the value of an integrative traditional and modern scientific approach to developing new treatments for dementia, but also in the understanding of disease mechanisms. Long before the current biologically-based hypothesis of cholinergic derangement in Alzheimer' s disease emerged, plants now known to contain cholinergic antagonists were recorded for their amnesia- and dementia-inducing properties.

Alzheimer Disease↗
PubMed2001

Liquid chromatography/atmospheric pressure chemical ionization mass spectrometry of terpene lactones in plasma of volunteers dosed with Ginkgo biloba L. extracts.

Liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (LC/APCI-ITMS) was applied to evaluate the levels of ginkgolides A and B and bilobalide in plasma of volunteers after administration of Ginkgo biloba extracts in free (Ginkgoselect) or phospholipid complex (Ginkgoselect Phytosome) forms, providing 9.6 mg of total terpene lactones. The maximum plasma concentrations, C(max), of total ginkgolides A, B and bilobalide were 85.0 and 181.8 microg/mL for Ginkgoselect and Ginkgoselect Phytosome, respectively. The C(max) values were reached at 120 min for the free form and at 180--240 min for the phospholipid complex form. In both cases, the mean elimination half-life of each terpene lactone was in the range 120--180 min. Due to its sensitivity (about 1 ng/mL) and specificity, LC/APCI-ITMS proved to be a very powerful tool for pharmacokinetic studies of these phytochemicals.

Adult↗
PubMed2003

Analysis of ginkgolides and bilobalide in Ginkgo biloba L. extract injections by high-performance liquid chromatography with evaporative light scattering detection.

A RP-HPLC method with evaporative light scattering detection (ELSD) was developed for the determination of ginkgolides and bilobalide in Ginkgo biloba L. extract injections. The samples were extracted with ethyl acetate and the resulting extract was purified by aluminum oxide column. The resultant solution was determined by HPLC on a C(18) column with methanol-water (33:67, v/v) as eluent. The optimum ELSD parameters were set. The recovery of the method was between 98.3 and 102.1%. The method is suitable for routine quantitation of terpenes in Ginkgo biloba L. extract injections.

Chromatography, High Pressure Liquid↗
PubMed2006

[Plant metabolites as nootropics and cognitives].

Nowadays several millions of people suffer from Alzheimer's disease and other types of dementia. Etiology of these diseases is not known very well. There occur different levels of neurotransmitters, the level of acetylcholine in the brain is decreased and pathological changes affect the brain tissue. Organic and toxic damage of the brain, free radicals, and other changes participate in the development of these diseases. Drugs as nootropics, cognitives, and neuroprotectives are commonly used to treat these diseases. Some of these drugs have often side and undesirable effects. In recent years some natural substances (galanthamine, huperzine A, vinpocetine), and standardized plant extracts (Ginkgo biloba L., Centella asiatica L.) Urban, Bacopa monniera L., Evolvulus alsinoides L.) are often used. These plant preparations produce fewer undesirable effects and the same effectiveness as the classic therapy, or these preparations are used as a supplement to the classic therapy.

Alzheimer Disease↗
PubMed2000

[Protective effect of extract of folium ginkgo on repeated cerebral ischemia-reperfusion injury].

OBJECTIVE: To study the protective effect of extract of Folium Ginkgo (FGE) on repeated cerebral ischemia-reperfusion injury. METHODS: The model in waking mice induced by repeated cerebral ischemia-reperfusion were used in the experiment to observe the effect of FGE on behavior, oxygen free radical metabolism and prostaglandin E2 (PGE2) content by step-through experiment, diving stand and colorimetric method. RESULTS: FGE could obviously improve the learning ability and memory of model animals, and could lower obviously the content of malonyldialdehyde, nitric oxide and PGE2, restore the lowered activity of superoxide dismutase and catalase in cerebral tissue. CONCLUSION: FGE has highly protective effect against repeated ischemia-reperfusion injury, the mechanism might be related with its action on anti-lipid oxidatin, improve the activity of antioxidase and inhibit the producing of PGE2.

Animals↗
PubMed2006

[Brain protective effects of ginkgo biloba leaf extract (ginaton) in patients undergoing hypothermic cardiopulmonary bypass].

OBJECTIVE: To investigate the brain protective effects of Ginkgo biloba leaf extract (Ginaton) in patients who underwent hypothermic cardiopulmonary bypass (CPB). METHODS: Sixty patients with rheumatic heart disease of ASA grade II-III, who were scheduled for mitral valve replacement with intravenous anaesthesia, were randomly assigned to two groups, the Ginaton group (30 patients) treated with Ginaton 1 mg/kg by intravenous dripping before open heart for CPB, and the control group (30 patients) with normal saline instead. Blood was synchronously collected from arteriae radialis and vena jugularis interna at 5 time points, namely, before CPB (T1), nasopharyngeal temperature (lowered to 30-31 degrees C) stabilized stage (T2), nasopharyngeal temperature restoration (36 degrees C) stage (T3), 30 min after CPB (T4) and 3 after CPB (Ts) for determining blood gas, lactate acid concentration, activity of superoxide dismutase (SOD) and malonaldehyde (MDA) content. And the oxygen content in artery (CaO2) and jugular vein (CjvO2), the difference of oxygen contents in arterial and jugular vein (Ca-jvO2), the cerebral oxygen extraction ratio (ERO2) as well as the arteriojugular lactate difference (ADVL) were calculated. RESULTS: After the beginning of CPB, as compared with those in the control group, in the Ginaton group, the reduction of Ca-jvO2 and ERO2 was significantly higher (P < 0.05 or P < 0.01) and the increase of lactate acid, ADVL and MDA were significantly lower, and with a remarkably higher SOD activity (P < 0.01). CONCLUSION: Ginaton could improve cerebral oxygen supply, promote SOD activity to inhibit production of free radicals in patients undergoing CPB, and thus shows an evident protective effect in the brain.

Adult↗