Extract of Ginkgo biloba added to haloperidol was effective for positive symptoms in refractory schizophrenia.
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The effect of intravenously administered Ginkbo biloba extract (EGb 761) on the vasospastic response to platelet activation has been assessed using a cutaneous flap preparation in anaesthetized mice. Arterioles of the axillary artery were observed by intravital microscopy, and platelets were activated by topical application of ADP under two steady state conditions: normothermia (37 degrees C) and hypothermia (24 degrees C). Responses of the cutaneous arterioles to stimulation by topical application of a thromboxane agonist (U46619) were also compared in animals treated intravenously with EGb 761 or with a thromboxane synthesis inhibitor (U63557). ADP induced a 34% constriction of the arterioles in control animals. However, no arteriolar constriction occurred in response to ADP in platelet-depleted animals (collagen-induced thrombocytopenia) or in animals treated with EGb 761 (60 mg/kg, i.v.). Exposure of the arterioles to hypothermia (24 degrees C) for 10 min induced constriction of 7-12% in all experimental groups of animals. Under these hypothermic conditions, either EGb 761 or thrombocytopenia abolished ADP-induced arteriolar constriction which was substituted by arteriolar dilation, indicating that EGb 761 can inhibit the vasospasm that is produced by platelet activation. As topically applied U46619 (10(-5) M) induced arterioles constriction (about 22%) that was abolished by intravenous treatment with EGb 761, the extract appears to act directly rather than as a thromboxane synthase inhibitor. Collectively, these findings indicate that platelet factors can play a significant role in cutaneous vasospasm, and that EGb 761, via an action on the thromboxane pathway, could be useful in treating Raynaud's phenomenon and other vascular disorders which involve increased thromboxane production.
Effects of EGb on cultured bovine aortic endothelial cells (BAEC) damaged by lysophosphatidylcholine (LPC) were investigated. When endothelial cells were incubated with LPC (2.5 micrograms.ml-1) for 24 h, the endothelial cells turned round pyknotic, exfoliated and broken, and the contents of malondialdehyde (MDA), lactate dehydrogenase (LDH) and plasminogen activator inhibitor (PAI) were markedly increased and the superoxide dismutase (SOD) activity was inhibited. Treatment with EGb at concentrations of 125 and 250 micrograms.ml-1, caused a reduction in MDA, LDH and PAI contents, while the SOD activity in the medium was increased and the morphologically damaged BAECs were alleviated. These results suggest that EGb afforded protection against BAECs damages induced by LPC and that the protective effect of EGb may be due to anti-lipid peroxidation via free-radical scavenging activity.
Thiobarbituric acid reacting (TBAR) substances were measured in washed platelets before and after ingesting 120 mg of standardized Gingko biloba extract daily for 3 months, in both normocholesterolemic (total cholesterol, 160 +/- 27 mg/dl; age 40 +/- 13 years; n = 18) and hypercholesterolemic subjects (total cholesterol, 229 +/- 35; age, 45 +/- 8 years, n = 12). Gingko biloba extract significantly reduced cellular content of TBAR substances; 42 +/- 21 vs. 28 +/- 16 pmol/10(7 platelets (p < 0.0025) and 50 +/- 17 vs. 29 +/- 13 pmol/10(7) platelets (P < 0.004), for the normo- and hypercholemic subjects, respectively. In conclusion, Gingko biloba extract is a potent antioxidant for both groups, reducing TBAR substances possibly by inhibiting platelet COX-1 isoform activity.
OBJECTIVE: This study was designed to investigate whether EGB protect against ethanol-induced oxidative injury in rat testes. METHODS: The rats were pretreated with EGB (4.8,9.6 mg/100g bw per day) before 30% ethanol administration (2.37g/kg bw by gastric incubation). Ninety days later, the rats were killed in order to measure the activities of Superoxide Dismutase (SOD), Glutathione Reductase (GST), Glutathione Peroxidase (GSH-Px), Catalase (CAT) and the contents of Glutathione (GSH), Reactive Oxygen Species (ROS), Malondialdehyde (MDA)in rat testes. The microsomal fractions were obtained by the method of differential centrifugation, and HO-1 (Heme Oxygenase-1) activity in testicular microsomal was measured. To examine the expression of HO-1 mRNA by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Compared with ethanol group, ROS, and MDA contents significantly decreased in EGB group testes, respectively (P < 0.05). GST, GSH-Px, CAT, SOD activities, and GSH content in EGB group testes elevated markedly (P <0.05). EGB could enhance HO-1 mRNA expression remarkably. CONCLUSION: It is suggested that EGB as a preventive antioxidant can protect against ethanol-induced testicular injury, which may be associated with HO-1 activity enhancement, free radicals elimination, lipid per-oxidation reaction inhibition.
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The present data confirm the results of others that post-synaptic receptor changes may contribute to the decline in brain cholinergic function in ageing and dementia. We have also shown that chronic oral treatment with an extract of Gingko biloba increases the apparent muscarinic receptor population in the hippocampus of the aged Fisher 344 rat. The possible effect on (3H) kainic acid binding to the kainate-excitatory amino acid site is also interesting because of the proposed association of neurodegenerative disease and excessive excitatory amino neurotransmission.
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Sodium lactate applied on the pia-mater of the rabbit induces the appearance of venous platelets thrombi. The same phenomenon occurs in the arteries after electric stimulation of the arterial wall. Gingo biloba extract, i.v. and per os, has been shown capable to partially antagonize these effects, particularly in the venous microcirculation. The ratio between the activity following the two modes of administration is about 1 to 5.
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Ginkgo biloba extract EGb 761 has been reported to have therapeutic effects which have been attributed to anti-oxidant and free radical-scavenging activities, including a direct action on nitric oxide production. L G-nitro-arginine (L-NOARG), a nitric oxide synthase inhibitor, and haloperidol, a drug that blocks dopamine receptors, are both known to induce catalepsy in rodents. Nitric oxide has been shown to influence dopaminergic transmission in the striatum. The purpose of the present study was to evaluate the effect of the extract obtained from leaves of Ginkgo biloba tree EGb 761 on catalepsy induced by haloperidol or by L-NOARG. Albino Swiss mice (35-45 g, N = 8-12) received by gavage a single or repeated oral dose (twice a day for 4 days) of EGb 761 followed by ip injection of haloperidol or L-NOARG. After the treatments, the animals were submitted to behavioral evaluation using the catalepsy test. Acute treatment with 80 mg/kg EGb did not modify the catalepsy induced by L-NOARG but, the dose of 40 mg/kg significantly enhanced haloperidol-induced catalepsy measured at the 10th min of the test. After repeated treatment with 80 mg/kg EGb 761, a significant increase in the cataleptic effect produced by both haloperidol and L-NOARG was observed. These data show that repeated EGb 761 administration increases the effects of drugs that modify motor behavior in mice. Since the catalepsy test has predictive value regarding extrapyramidal effects, the possibility of pharmacological interactions between haloperidol and Ginkgo biloba extracts should be further investigated in clinical studies.
Several studies have tested the efficacy of ginkgo biloba using compromised visual systems and have found improvement in vision. We measured functional changes in the visual system of older, healthy adults to see if ginkgo extract EGb 761 would increase performance in the normal visual system. Two electrophysiological measures were taken during baseline, placebo, and treatment conditions: visual evoked potentials were used to assess changes in low-level functioning of the visual pathways, and P300 recognition responses were measured to assess higher order processing. No significant effect was found in the lower level visual pathways. However, when using regression analysis across age to assess higher order functioning, an improvement was found. The results suggest that the higher order processing stages, which may be influenced by cognition, decline more rapidly than do lower level processing stages in healthy adults as a function of age, and that the use of ginkgo biloba extract may improve the functioning of this system.
BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating neurological disease afflicting young and middle-aged adults, resulting in problems with coordination, strength, cognition, affect, and sensation. OBJECTIVE: The objective of this study was to determine whether a ginkgo extract (EGb 761) improved functional performance in individuals with MS. DESIGN: This study used a double-blind, placebo-controlled, parallel group design. The end point was change between baseline (ie, preintervention) and follow-up evaluation following a regimen of four tablets per day at 60 mg per tablet for four weeks. SETTING: The study was conducted in academic and clinical-based settings. PATIENTS/PARTICIPANTS: Twenty-two individuals with MS were randomly assigned to either the treatment or control condition. Groups did not differ with respect to age, IQ, and education. INTERVENTION: Half of the subjects received 240 mg per day of ginkgo special extract (EGb 761), and the other half received placebo. MAIN OUTCOME MEASURE: The main outcome measures assessed depression (Center for Epidemiologic Studies of Depression Scale [CES-D]), anxiety (State-Trait Anxiety Inventory [STAI]), fatigue (Modified Fatigue Impact Scale [MFIS]); symptom severity (Symptom Inventory [SI]) and functional performance (Functional Assessment of Multiple Sclerosis [FAMS]). RESULTS: The ginkgo group had significantly more individuals showing improvement on four or more measures with improvements associated with significantly larger effect sizes on measures of fatigue, symptom severity, and functionality. The ginkgo group also exhibited less fatigue at follow-up compared with the placebo group. CONCLUSIONS: This exploratory pilot study showed that no adverse events or side effects were reported and that ginkgo exerted modest beneficial effects on select functional measures (eg, fatigue) among some individuals with MS.
Free radical scavenging activities of water-soluble extracts from some natural sources, health foods, and antioxidant substances were measured using the JES-FR30 JEOL spectrometer. The objective was to develop a standardized method whereby comparison could be made between the radical scavenging activities of complex mixtures. Scavenging of hydroxyl radical was determined using DMPO. Activity was calibrated using a standard material, L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1- benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1), an analog of vitamin C and vitamin E which is water soluble and stable at room temperature. The order of greatest hydroxyl radical scavenging activity was green tea extract, pine bark extract (Pycnogenol), Ginkgo Biloba extract (EGb 761), a flavonoid blend of several fruit and vegetable extracts (GNLD), and Bio-Normalizer (Sun-O Corp). Activity was determined after treatment of samples with ascorbic acid oxidase. This treatment revealed the presence of ascorbate in some natural extracts and commercial preparations. The pine bark extract was the most heat resistant and had ascorbate-like activity in the preparations. Scavenging of superoxide anion was determined using the spin trap, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), and analyzed by comparison with a standard curve made with superoxide dismutase. Comparison of the water solubilized components of natural source antioxidants showed that filtrates fractionated using centrifuge type Millipore filter tubes (M.W. < 100,000; M.W. < 10,000) also had almost the same SOD-like activity. Samples were also treated with ascorbate oxidase or by heating (100 degrees C for 10 min). The order of activity, from greatest to least, was Ginkgo biloba extract EGb 761, pycnogenol, beta-catechin, tea and BioNormalizer.
Extracts of Ginkgo biloba (EGb) are among the most prescribed drugs in France and Germany. EGb is claimed to be effective in peripheral arterial disorders and in "cerebral insufficiency." The mechanism of action is not yet well understood. Three of the ingredients of the extract have been isolated and found to be pharmacologically active, but which one alone or in combination is responsible for clinical effects is unknown. The recommended daily dose (3 x 40 mg extract) is based more on empirical data than on clinical dose-findings studies. However, despite these, according to double-blind, placebo-controlled clinical trials, EGb has therapeutic effects, at least, on the diagnostic entity of "cerebral insufficiency," which is used in Europe as synonymous with early dementia. To determine whether EGb has significant pharmacological effects on the human brain, a pharmacodynamic study was conducted using the Quantitative Pharmacoelectroencephalogram (QPEEG(R)) method. It was established that the pharmacological effects (based on a predetermined 7.5--13.0-Hz alpha frequency band in a computer-analyzed electroencephalogram = CEEG(R)) of EGb on the central nervous system (CNS) are significantly different than placebo, and the high and low doses could be discriminated from each other. The 120-mg, but particularly the 240-mg, single doses showed the most consistent CNS effects with an earlier onset (1 h) and longer duration (7 h). Furthermore, it was established that the electrophysiological effects of EGb in CNS are similar to those of well-known cognitive activators such as "nootropics" as well as tacrine, the only marketed "antidementia" drug currently available in the United States.