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PubMed2000

Ginkgo biloba extract (EGb 761) and CNS functions: basic studies and clinical applications.

The effects of EGb 761 on the CNS underlie one of its major therapeutic indications; i.e., individuals suffering from deteriorating cerebral mechanisms related to age-associated impairments of memory, attention and other cognitive functions. EGb 761 is currently used as symptomatic treatment for cerebral insufficiency that occurs during normal ageing or which may be due to degenerative dementia, vascular dementia or mixed forms of both, and for neurosensory disturbances. Depressive symptoms of patients with Alzheimer's disease (AD) and aged non-Alzheimer patients may also respond to treatment with EGb 761 since this extract has an "anti-stress" effect. Basic and clinical studies, conducted both in vitro and in vivo, support these beneficial neuroprotective effects of EGb 761. EGb 761 has several major actions; it enhances cognition, improves blood rheology and tissue metabolism, and opposes the detrimental effects of ischaemia. Several mechanisms of action are useful in explaining how EGb 761 benefits patients with AD and other age-related, neurodegenerative disorders. In animals, EGb 761 possesses antioxidant and free radical-scavenging activities, it reverses age-related losses in brain alpha 1-adrenergic, 5-HT1A and muscarinic receptors, protects against ischaemic neuronal death, preserves the function of the hippocampal mossy fiber system, increases hippocampal high-affinity choline uptake, inhibits the down-regulation of hippocampal glucocorticoid receptors, enhances neuronal plasticity, and counteracts the cognitive deficits that follow stress or traumatic brain injury. Identified chemical constituents of EGb 761 have been associated with certain actions. Both flavonoid and ginkgolide constituents are involved in the free radical-scavenging and antioxidant effects of EGb 761 which decrease tissue levels of reactive oxygen species (ROS) and inhibit membrane lipid peroxidation. Regarding EGb 761-induced regulation of cerebral glucose utilization, bilobalide increases the respiratory control ratio of mitochondria by protecting against uncoupling of oxidative phosphorylation, thereby increasing ATP levels, a result that is supported by the finding that bilobalide increases the expression of the mitochondrial DNA-encoded COX III subunit of cytochrome oxidase. With regard to its "anti-stress" effect, EGb 761 acts via its ginkgolide constituents to decrease the expression of the peripheral benzodiazepine receptor (PBR) of the adrenal cortex.

Alzheimer Disease↗
PubMed2002

Amikacin ototoxicity enhanced by Ginkgo biloba extract (EGb 761).

An animal study was realized to investigate the possible beneficial effect of EGb 761 as an antioxidant agent on amikacin ototoxicity by measuring distortion product otoacoustic emissions (DPOAEs). Twenty-eight adult rats were grouped equally as follows. GROUP AMIKACIN: rats received amikacin 600 mg/kg/day intramuscularly between postnatal days (PND) 30 and PND44. Group amikacin/EGb 761: rats received amikacin 600 mg/kg/day intramuscularly between PND30 and PND44 and EGb 761 100 mg/kg/day orally between PND30 and PND50. Group EGb 761: rats received equivolume saline intramuscularly between PND30 and PND44 and EGb 761 100 mg/kg/day orally between PND30 and PND50. NO TREATMENT GROUP: rats received nothing. Group amikacin was found to be affected only on the last measurement day of study (PND57). The frequencies greater than 2002 Hz were significantly reduced compared with the amplitudes of PND30 (P<0.05). Group amikacin/EGb 761 was most and earliest affected by amikacin-induced ototoxicity. DPOAE amplitudes were found in this group to be decreased at 2-6 kHz starting on PND50. The results of Group EGb 761 and No treatment group were not significantly changed. For the DPOAE input/output amplitude thresholds, Group amikacin (P<0.05) and Group amikacin/EGb 761 (P<0.01) had significantly elevated thresholds on PND57, except at 5 kHz for Group amikacin (P=0,06). According to the results of the study, EGb 761 may be regarded as a facilitating drug for the development of amikacin ototoxicity. The results of the present study may warn against concomitant use of aminoglycosides, specifically amikacin, with EGb 761.

Amikacin↗
PubMed2003

Effects of EGb 761 Ginkgo biloba extract on mitochondrial function and oxidative stress.

As major sources of reactive oxygen species (ROS), mitochondrial structures are exposed to high concentrations of ROS and may therefore be particularly susceptible to oxidative damage. Mitochondrial damage could play a pivotal role in the cell death decision. A decrease in mitochondrial energy charge and redox state, loss of transmembrane potential (depolarization), mitochondrial respiratory chain impairment, and release of substances such as calcium and cytochrome c all contribute to apoptosis. These mitochondrial abnormalities may constitute a part of the spectrum of chronic oxidative stress in Alzheimer's disease. Accumulation of amyloid beta (Abeta) in form of senile plaques is also thought to play a central role in the pathogenesis of Alzheimer's disease mediated by oxidative stress. In addition, increasing evidence shows that Abeta generates free radicals in vitro, which mediate the toxicity of this peptide. In our study, PC12 cells were used to examine the protective features of EGb 761(definition see editorial) on mitochondria stressed with hydrogen peroxide and antimycin, an inhibitor of complex III. In addition, we investigated the efficacy of EGb 761 in Abeta-induced MTT reduction in PC12 cells. Moreover, we examined the effects of EGb 761 on ROS levels and ROS-induced apoptosis in lymphocytes from aged mice after in vivo administration. Here, we will report that EGb 761 was able to protect mitochondria from the attack of hydrogen peroxide, antimycin and Abeta. Furthermore, EGb 761 reduced ROS levels and ROS-induced apoptosis in lymphocytes from aged mice treated orally with EGb 761 for 2 weeks. Our data further emphasize neuroprotective properties of EGb 761, such as protection against Abeta-toxicity, and antiapoptotic properties, which are probably due to its preventive effects on mitochondria.

Amyloid beta-Peptides↗
PubMed2004

The ingestion of Ginkgo biloba extract (EGb 761) inhibits arachidonic acid-mediated platelet aggregation and thromboxane B2 production in healthy volunteers.

Twelve non-diabetic volunteers (age = 39 +/- 13 years, BMI = 23.5 +/- 3.5) undertook a randomized double-blind placebo-controlled crossover study in which they ingested either 120 mg of EGb 761 or a placebo daily for 3 months and then switched to the other test capsules for the next 3 months. Platelet aggregation in platelet-rich plasma (PRP) was performed at the end of each 3-month arm, with or without 1-min incubation with graded doses of EGb 761. In the placebo cycles, AA-stimulated TXB2 production was 2581 +/-1337 pg/10(6) platelets (range 897-5485) compared to 1668 +/- 992 pg/10(6) platelets (range 6-1668) in the EGb 761 cycles (p < 0.005). Incubation of PRP with EGb 761 (150 microg/ml) completely inhibited platelet aggregation accompanied by inhibition of TXB2 synthesis in all subjects both in the placebo (<200 pg TXB2/10(6) platelets) and EGb 761 cycles (< 120 TXB2/10(6) platelets) (p < 0.0001). These results support EGb 761-mediated inhibition of platelet TXB2 synthesis in vivo.

Adult↗
PubMed1995

Protection of hypoxia-induced ATP decrease in endothelial cells by ginkgo biloba extract and bilobalide.

Due to their localization at the interface between blood and tissue, endothelial cells are the first target of any change occurring within the blood, and alterations of their functions can seriously impair organs. During hypoxia, which mimics in vivo ischemia, a cascade of events occurs in the endothelial cells, starting with a decrease in ATP content and leading to their activation and release of inflammatory mediators. EGb 761 and one of its constituents, bilobalide, were shown to inhibit the hypoxia-induced decrease in ATP content in endothelial cells in vitro. Under these conditions, glycolysis was activated, as evidenced by increased glucose transport, as well as increased lactate production. Bilobalide was found to increase glucose transport under normoxic but not hypoxic conditions. In addition, EGb and bilobalide prevented the increase in total lactate production observed after 60 min of hypoxia. However, after 120 min of hypoxia, the total lactate production was similar under normoxic and hypoxic conditions, and both compounds increased this production. These results indicate that glycolysis slowed down between the 60th and 120th minute of hypoxia, while EGb and bilobalide delayed the onset of glycolysis activation. In another experimental model, both compounds were shown to increase the respiratory control ratio of mitochondria isolated from liver of rats treated orally. Since ischemia is known to uncouple mitochondria, the protection of ATP content and the delay in glycolysis activation observed during hypoxia in the presence of EGb 761 or bilobalide is best explained by a protection of mitochondrial respiratory activity, at least during the first 60 min of hypoxia incubation. Both products retain the ability to form ATP, thereby reducing the cell's need to induce glycolysis, probably by preserving ATP regeneration by mitochondria as long as oxygen is available.

Adenosine Triphosphate↗
PubMedDate not supplied

A 26-week analysis of a double-blind, placebo-controlled trial of the ginkgo biloba extract EGb 761 in dementia.

This intent-to-treat (ITT) analysis was performed to provide a realistic image of the efficacy that could be expected after 26 weeks treatment with a 120-mg dose (40 mg t.i.d.) of EGb 761 (EGb). The data were collected during a 52-week, double-blind, placebo-controlled, fixed dose, parallel-group, multicenter study. Patients were mildly to severely impaired and diagnosed with uncomplicated Alzheimer's disease or multi-infarct dementia according to ICD-10 and DSM-III-R criteria. The primary outcome measures included the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Geriatric Evaluation by Relative's Rating Instrument (GERRI) and Clinical Global Impression of Change. From 309 patients included in the ITT analysis, 244 patients (76% for placebo and 73% for EGb) actually reached the 26th week visit. In comparison to the baseline values, the placebo group showed a statistically significant worsening in all domains of assessment, while the group receiving EGb was considered slightly improved on the cognitive assessment and the daily living and social behavior. Mean treatment differences favored EGb with 1.3 and 0.12 points, respectively, on the ADAS-Cog (p = 0.04) and the GERRI (p = 0.007). In the group receiving EGb, 26% of the patients achieved at least a 4-point improvement on the ADAS-Cog, compared to 17% with placebo (p = 0.04). On the GERRI, 30% of the EGb group improved and 17% worsened, while the placebo group showed an opposite trend with 37% of patients worsening for 25% improved (p = 0.006). Regarding safety, no differences between EGb and placebo were observed.

Aged↗
PubMed2002

Ginkgo biloba extract (EGb 761) protects Na,K-ATPase isoenzymes during cerebral ischemia.

Disturbances of Na,K-ATPase activity are implicated in the pathophysiology of cerebral ischemia. Previous experiments have shown that EGb 761 protects NaK-ATPase activity against one hour of cerebral ischemia. In the brain however, the 3 isoenzymes responsible for Na,K-ATPase activity may be differentially affected by various times of ischemia. In the present study, we investigated the effect of a longer period of ischemia, and the protection provided by a pre-treatment with EGb 761 on each of the 3 cerebral NaK-ATPase isoenzymes. In control and EGb 761 pre-treated mice exposed to a 6 hr unilateral occlusion of the middle cerebral artery, Na,K-ATPase activity was decreased by 60% and lipid peroxidation was increased by 40% in the ipsilateral (ischemic) cortex compared to the contralateral one. In parallel, membrane integrity was altered. The alteration of NaK-ATPase activity, as a whole, resulted from a decrease in the activity of the 3 isoenzymes. The two isoenzymes of high ouabain affinity however, had their affinities decreased while the sensitivity of the lowest affinity isoenzyme was increased. Pre-treatment with EGb 761 abolished the differences observed between ipsi- and contralateral cortex, with the exception of the change in ouabain affinity of the low affinity isoenzyme. Ischemia also induced changes in Na,K-ATPase isoenzyme ouabain affinities in the contralateral cortex that where not prevented by EGb 761.

Animals↗
PubMed2005

Hepatotoxicity associated with acarbose therapy.

OBJECTIVE: To report a case of acarbose-induced hepatotoxicity and compare other reported cases from the literature. CASE SUMMARY: A 57-year-old woman with type 2 diabetes mellitus for about 10 years had been treated with insulin glargine 20 units/day since December 19, 2002. Acarbose 100 mg 3-times-daily add-on therapy for inadequate glycemic control was started on June 5, 2003. Six months later, the woman complained of gastrointestinal discomfort; the acarbose dose was decreased to 50 mg 3 times daily thereafter. Laboratory examination later revealed alanine aminotransferase (ALT) 640 U/L (upper reference value 55). To elucidate the possibilities of adverse reactions caused by concurrent use of nutritional supplements and medication, we discontinued propolis extract, Ginkgo biloba, placeta extract, and estrogen. Although no remarkable symptoms were noted thereafter, the abnormal ALT values persisted, and no definite viral or autoimmune etiologies were identified. Acarbose was discontinued in August 2004; aspartate aminotransferase and ALT values returned to normal in October 2004. DISCUSSION: In addition to ruling out other possible etiologic factors, we assessed the probability of acarbose-induced hepatotoxicity by observing the close time relationship between drug administration and the development of signs and symptoms, as well as the close time relationship between drug withdrawal and the normalization of abnormal liver function test values. An objective causality assessment revealed that an adverse drug reaction was probable as determined by both the Naranjo probability scale and the Roussel Uclaf Causality Assessment Method score. CONCLUSIONS: Although acarbose-induced hepatotoxicity appears to be uncommon, diabetic patients receiving long-term acarbose therapy should be closely monitored for this adverse effect.

Acarbose↗
PubMed2001

Protective effect and mechanism of Ginkgo biloba leaf extracts for Parkinson disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

AIM: To observe the effects of extracts of Ginkgo biloba leaves (EGb) on the Parkinson disease (PD) models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its ion 1-methyl-4-phenylpyridinium (MPP+). METHODS: MPTP was microinjected into substantia nigra of rats to induce a behavior change of rotation. EGb (ip, 50 or 100 mg.kg(1 . d-1) was pretreated consecutively for 19 d before MPTP administered and 1 d after MPTP administered. The contents of malondialdehyde (MDA), superoxide dismutase (SOD), and dopamine (DA) in substantia nigra of model rats were determined. Apoptosis of PC12 cells was induced by MPP+, and the protective effect of EGb (25, 50, and 100 mg/L) was also observed. The cells of apoptosis were observed under a microscope and counted under a fluoroscope after stained with AO/EB. RESULTS: EGb (100 mg . kg-1 . d-1) decreased the duration and frequency of the rotation of rats (P < 0.05, n = 10 ) while EGb (50 or 100 mg/L)inhibited the decreases of DA and SOD and the increase of MDA induced by MPTP, (P < 0.05 or P < 0.01, n = 10). MPP+ (10 micromol/L) induced the apoptosis of PC12 cells, and EGb (50 or 100 mg/L) prevented cells from apoptosis at 6 h, 12 h, and 24 h (P < 0.05 or P < 0.01, n = 3). CONCLUSION: EGb possesses protective effect on the PD models in vivo and in vitro. The anti-oxidation and anti-apoptosis may be one of the mechanisms underlying the neuroprotective effect of EGb.

Animals↗
PubMed1992

[The effect of ginkgo biloba special extract (EGb 761, Tebofortan)].

Ginkgo biloba special extract exerts positive effects on hemorheology and platelet aggregation, is a free radical scavenger and possesses PAD antagonistic properties, protects against hypoxia and ischemia, hampers an experimentally induced cerebral edema, has favourable properties on neurotransmitters and enhances cerebral bloodflow. Clinically EGb has proven favourable effects on intellectual deficiency, equilibrium disturbances and peripheral artery occlusions thus being a drug with a clear cut indication for these diseases.

Animals↗
PubMed2005

The effect of extract of ginkgo biloba addition to olanzapine on therapeutic effect and antioxidant enzyme levels in patients with schizophrenia.

It has been suggested that the extract of gingko biloba (EGb) may enhance the efficiency of the classic antipsychotic haloperidol in patients with chronic schizophrenia, especially on positive symptoms, and reduce serum superoxide dismutase (SOD) levels. Therefore, we decided to evaluate the therapeutic effect of EGb and to examine the effect of it on the levels of antioxidant enzymes in schizophrenic patients on olanzapine treatment. We hypothesized that EGb would have the beneficial effects on schizophrenic symptoms and might cause reductions in antioxidant enzymes. The subjects were randomly assigned to the two groups: olanzapine plus EGb (group I) (n=15) and olanzapine alone (group II) (n=14). The patients were evaluated at baseline and at week 8 with respect to the Positive and Negative Syndrome Scale (PANSS), serum SOD, catalase (CAT), and glutathion peroxidase (GPX) levels. At baseline, no statistically significant difference regarding the mean total PANSS scores between treatment groups was found. At the evaluation of week 8, a significant difference in mean Scale for the Assessment of Postive Symptoms (SAPS) scores but not in Scale for the Assessment of Negative Symptoms scores between groups was found. Total patients had statistically significant higher serum SOD, CAT and GPX levels compared to control groups at baseline. At 8 weeks, there were significant differences in the mean decrease in SOD and CAT levels but not in GPX levels between treatment groups. The changes in SOD and CAT levels were correlated with the change in SAPS in group I, but not in the group II. The present study supported the findings of the previous study demonstrating that EGb might enhance the efficiency of antipsychotic in patients with schizophrenia, particularly on positive symptoms of the disorder.

Adult↗
PubMed1994

Ginkgo biloba extract (EGb 761) improves postischemic function in isolated preconditioned working rat hearts.

BACKGROUND: We studied the effect of preconditioning and Gikgo biloba extract (EGb 761) in relation to the recovery of contractile function after global ischemia in the isolated working rat heart. METHODS: Hearts (n = 12 in each group) were randomly divided into five groups: In group I, hearts were subjected to 30 min of normothermic global ischemia followed by 30 min of reperfusion; in group II, they were subjected to one cycle of preconditioning consisting of 5 min ischemia and 10 min reperfusion before the induction of 30 min of ischemia and 30 min of reperfusion; group III hearts underwent two cycles of preconditioning; group IV hearts underwent three cycles of preconditioning; and group hearts underwent four cycles of preconditioning before the onset of 30 min ischemia followed by 30 min of reperfusion. RESULTS: Ventricular fibrillation (total) and ventricular tachycardia (no preconditioning) both fell from 100% to 50% (P < 0.05) after four cycles of preconditioning. In relation to ventricular fibrillation, preconditioning significantly reduced the formation of oxygen free radicals, measured by electron spin resonance spectroscopy (ESR), but recovery of cardiac function was low in all preconditioned groups. Because of the relatively low incidence of arrhythmias (50% ventricular fibrillation and 50% ventricular tachycardia) and relatively low cardiac function in Group V, EGb 761, a free-radical scavenger, was chosen to improve myocardial contractile function in preconditioned hearts. Fifty and 100 mg/kg of EGb 761 (per os) significantly improved coronary flow, aortic flow, left ventricular developed pressure (LVDP), and the first derivative of LVDP (LVDdP/dtmax) in the four-cycle preconditioned group. Thus, after 30 min of reperfusion, aortic flow was improved from 11.6 +/- 0.9 ml/min to 19.7 +/- 1.2 ml/min (P < 0.05) with a dose of 50 mg/kg of EGb 761 and to 22.0 +/- 1.5 ml/min (P < 0.05) with a dose 100 mg/kg of EGb 761, in the four-cycle preconditioned group. During reperfusion, the formation of free radicals was reduced by approximately 50 and 60% using 50 mg/kg and 100 mg/kg of EGb 761, respectively, when compared with the four-cycle preconditioned drug-free control group. CONCLUSION: We have demonstrated that EGb 761 can improve contractile function after global ischemia in the isolated working rat heart by reducing the formation of oxygen free radicals, and we have shown that this protection is additive to that of ischemia-induced preconditioning.

Animals↗
PubMed2003

[The effect of ginkgo biloba on healthy elderly subjects].

BACKGROUND AND AIM: Over the past 25 years, numerous studies have confirmed the positive effect of the special ginkgo extract EGb 761 on the mental ability and emotional well-being of patients with cognitive disorders of vascular genesis, and Alzheimer-type dementia. The following study investigated the short-term effect of the special ginkgo extract EGb 761 on the subjective emotional well-being of healthy elderly subjects. STUDY POPULATION AND METHOD: The study was designed as a randomized double-blind, monocenter study with parallel groups. It included 66 healthy subjects of both sexes aged between 50 and 65 with no age-related cognitive impairments. For a period of 4 weeks, 34 subjects received a daily dose of 240 mg EGb 761, and 32 a placebo. Prior to starting medication and after 28 days of treatment, subjects completed the following scales and questionnaires to establish subjective emotional well-being: the Profile of Mood States (POMS), the Self Rating Depression Scale (SDS), three Visual Analog Scales to assess the quality of life (VAS-QoL), general health (VAS-GH) and mental health (VAS-MH), and a new instrument for assessing changes in general subjective well-being, the Subjective Intensity Score Mood (SIS Mood). Depending on the underlying distribution of the variables analyzed, parametric (t-tests) or nonparametric tests (U-tests) were performed to compare mean values and distributions both within and between the treatment groups. RESULTS: The final examination revealed a statistically significant difference between the two groups for the VAS mental health and quality of life, as also for SIS Mood at the telephone interview in week 2. A comparison of baseline with the final examination within the groups showed a statistically significant improvement in the EGb 761 group for the variables: depression, fatigue, anger and SDS. For none of the variables investigated was a worsening observed in the EGb 761 group. CONCLUSIONS: The results suggest a positive effect of EGb 761 on the subjective emotional well-being of healthy elderly persons.

Activities of Daily Living↗
PubMedDate not supplied

Liquid chromatography-atmospheric pressure chemical ionisation/mass spectrometry: a rapid and selective method for the quantitative determination of ginkgolides and bilobalide in ginkgo leaf extracts and phytopharmaceuticals.

In order to evaluate the composition of active constituents in phytopharmaceutical preparations, valid analytical methods are required. For the determination of the active terpene constituents of Ginkgo biloba (the ginkgolides and bilobalide), a liquid chromatography-mass spectrometry (LC-MS) method has been developed using atmospheric pressure chemical ionisation (APCI) in the negative ion mode. This detection mode was found to be much more sensitive and selective compared to UV; indeed the ginkgo terpene trilactones lack strong UV chromophores and flavonoids interfere with their UV detection. LC-APCI/MS detection allowed a considerable reduction in analysis time when compared to LC-UV, because LC resolution was only needed between the pair of isomers ginkgolide B and ginkgolide J. All compounds were selectively detected by single ion monitoring of their specific deprotonated molecules [M-H]-. The samples were directly injected without pre-purification, and a fast gradient was applied, reducing the total time of analysis to 14 min. With this method, the ginkgo terpene trilactones were detected on-line in the picogram range. Several commercial ginkgo preparations on the Swiss market were analysed, and the ginkgolide and bilobalide contents were evaluated using the method described.

Atmospheric Pressure↗