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Antioxidative activity of ginkgolides against superoxide in an aprotic environment.

The terpene lactones ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J and bilobalide, which are components of a standardized extract (EGb 761) from leaves of Ginkgo biloba, as well as ginkgolide M from roots of G. biloba were studied regarding their reaction against superoxide (O2-) and hydroperoxyl radicals (HO2) in dimethyl sulfoxide as an aprotic solvent. It was found that the ginkgolides B, C, J, M as well as bilobalide react with superoxide and its protonated form as demonstrated by EPR and UV/VIS spectroscopy. The initial reaction rate with these oxygen-derived radicals is in the order of 100 M-1/s and below. Ginkgolide A does not react with superoxide under these conditions. From these findings it can be suggested that the superoxide scavenging effect of the ginkgolides B, C, J, M and bilobalide contributes to the antioxidant properties of G. biloba.

Antioxidants↗

The effect of EGb 761 on the doxorubicin cardiomyopathy.

Doxorubicin (Dx) is used to treat a number of types of cancer. The drug produces many toxic reactions and cardiomyopathy. Many drugs have been used to prevent this myocardial damage caused by peroxidative alterations. EGb 761 is being used to prevent arrhythmias in ischemic myocardium. We decided to establish the tissue protective effect of EGb 761 against myocardial toxic effects of Dx in three groups of rats. Cardiotoxicity signs of Dx were found to be dose-related, beginning at 30 mg/kg dose and being apparent at 45 mg/kg dose. 48 hr after a single i.v. injection, myocardial tissues showed a marked edema, vacuolization and fragmentation. We compared the changes in heart tissue biochemically and histopathologically among the control, Dx treated and EGb 761 (100 mg/kg/d.x 4, i.p.) + Dx treated groups. Biochemical results of CK-MB and MDA values showed a significant decrease in Dx + EGb 761 group when compared with Dx treated group. Histopathologically, myocardial tissues of Dx + EGb 761 treated group were found to have diminished vacuolization and fragmentation. These results suggest that EGb 761 might have the same therapeutic potential in Dx related cardiomyopathy.

Animals↗

[Therapeutic effect of shuxuening combining neuroleptics for the treatment of chronic schizophrenia--a double blind study].

OBJECTIVE: To assess the therapeutic effect of Shuxuening (SXN), the extractum of Ginkgo biloba761 (EGb761) in treating chronic schizophrenia. METHODS: A double-blind, placebo-controlled multi-center research on the treatment of chronic schizophrenics with SXN was used. Five hundred and forty-five patients were randomly divided into either SXN group or the control group. Patients in the former group received SXN 120 mg three times daily. Patients in both groups received their maintenance neuroleptics throughout the 16-week research treatment. RESULTS: The patients' rating scores of brief psychiatric rating scale (BPRS) and Scale for the Assessment of Negative Symptoms reduced much greater in SXN group than those in the control group from the sixth week of treatment (P < 0.01). The effect of SXN for BPRS factors of retardation and thought disturbance was better than that of the control. SXN presented a better therapeutic effect for chronic schizophrenics than the control when rated with traditional global rating method as well, in which 44.98% marked improvement was obtained in SXN group compared to 20.98% in the control group. CONCLUSION: SXN combining neuroleptics, was an effective medicine for chronic schizophrenics. Moreover, it appeared few side-effects within the recommended dose range.

Adult↗

[Clinical study on the effect of shuxuening tablet in treatment of coronary heart disease].

Shuxuening was made of extract of Folium Ginkgo, the Shuxuening tablet No. 2 was a pure extract and No. 1 was a crude extract. Forty-six coronary heart disease patients were divided randomly into two groups according to the ratio of 2:1, Shuxuening tablet No. 1 and No. 2 were given to the two groups respectively. Results showed that both of them could alleviate the symptom of angina, the total effective rate of 2 groups were 60.00% and 83.87%, there was no significant difference between the two groups. But for the angina of middle and severe degree, the total effective rate of No. 2 was 83.33%, while that of No. 1 was 33.33%, the difference was significant (P < 0.01). They could also improve the abnormal electrocardiogram, the total effective rate of two groups were 60.00% and 74.19%, no significant difference between them was found. The two drugs could decrease the blood lipid as well.

Aged↗

Isolation of bilobalide and ginkgolide A from Ginkgo biloba L. shorten the sleeping time induced in mice by anesthetics.

The leaves of Ginkgo biloba L. and aqueous extract from them shortened the sleeping time induced in mice by anesthetics (hexobarbital, alpha-chloralose and urethane, i.p.). Two characteristic terpenoids in G. biloba, bilobalide and ginkgolide A, significantly shortened the sleeping time induced by anesthetics. A toxic substance, 4-O-methylpyridoxine (MPN), responsible for "gin-nan food poisoning" isolated from the seed of G. biloba, was not detected from the extract of the leaves of G. biloba. Therefore, the Ginkgo biloba extract has no toxicities for MPN.

Anesthetics↗

Assays of physical stability and antioxidant activity of a topical formulation added with different plant extracts.

In the present investigation the changes on physical stability (pH, viscosity, flow index and tixotropy) of topical formulations were evaluated following inclusion of different plant extracts containing flavonoids. Also, the antioxidant effect of these plant extracts alone and after addition in the formulation was evaluated using chemiluminescence and the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH(.-)) assays, as well as the inhibition of lipid peroxidation. Formulation added with dl-alpha-tocopherol was used to compare the physical stability and antioxidant activity. Formulations with plant extracts showed pseudoplastic behavior with decreasing on viscosity and tixotropy. The Glycyrrhiza glabra (GG) and Ginkgo biloba (GB) extracts alone and the formulations containing these extracts showed great antioxidant and free radical scavenging activities while the other extracts studied (mixture of Glycyrrhiza glabra, Symphytum officinale L and Arctium majus root, Nelumbium speciosum and soybean) showed lower activity. The results suggest that GG and GB extracts may be used in topical formulations in order to protect skin against damage caused by free radical and reactive oxygen species.

Administration, Topical↗

Sample preparation and determination of ginkgo terpene trilactones in selected beverage, snack, and dietary supplement products by liquid chromatography with evaporative light-scattering detection.

Ginkgo biloba leaf extract has been widely used in dietary supplements and more recently in some foods and beverages. Sample preparation procedures for determination of ginkgo terpene trilactones (including bilobalide and ginkgolides A, B, C, and J) in various sample matrixes were developed in this study. Ginkgo leaves and capsules were extracted with 5% KH2PO4 aqueous solution under sonication. Tea bags were extracted with boiling water, whereas drink samples were taken directly from the bottles. After filtration and the addition of NaCl to approximately 30% (w/v), the terpene trilactones in aqueous solutions were quantitatively extracted with ethyl acetate-tetrahydrofuran (4 + 1, v/v). Puff samples (a cereal-based fried snack item) were first defatted by using hexane or by using supercritical fluid extraction and then extracting under sonication with methanol-acetic acid (99 + 1, v/v). After evaporation of the organic phase, the terpene trilactones were redissolved in methanol and determined on a C18 reversed-phase column by liquid chromatography (LC) with evaporative light-scattering detection. The method of standard additions and gas chromatography with flame ionization detection were used for method validation. For most samples, the relative standard deviation was <10%. The identities of target compounds in ginkgo leaves and drink samples were confirmed by LC/electrospray ionization-tandem mass spectrometry.

Algorithms↗

Cognitive psychophysiology in nootropic drug research: effects of Ginkgo biloba on event-related potentials (P300) in age-associated memory impairment.

Extracts from the leaves of Ginkgo biloba have been suggested to be useful in the treatment of various symptoms of impaired brain functions in advanced age. To elucidate specific mechanisms of the possible clinical benefit, the effects of Ginkgo biloba extract Ginkobene on cognitive information-processing were investigated by means of long-latency auditory event-related potentials. In a double-blind placebo-controlled study, 48 patients (29 women and 19 men) aged between 51 and 79 years with the diagnosis of age-associated memory impairment had 57 days' treatment with a daily dosage of 3 x 40 mg Ginkobene or placebo. To evaluate acute, chronic, and superimposed drug effects, psychophysiological investigations were carried out on day 1 and day 57 before and 3 hours after drug administration. ERP investigations were carried out by means of a two-tone auditory oddball paradigm. In addition to 17 EEG leads, vertical and horizontal EOGs were recorded. After minimizing ocular artifacts and visual artifact rejection, latencies and topographic distributions of N1 and P2 components (non-targets) and N2 and P300 components (targets) were calculated by an automatic procedure. When compared to the placebo group, in the Ginkobene group no consistent and unequivocal changes on N1, P2, N2, and P300 amplitudes or on N1, P2, and N2 latencies were observed. P300 latency was shortened by 31 ms, 38 ms, and 32 ms in the Ginkgo biloba group after acute, chronic, and superimposed drug administration. It may therefore be hypothesized that the decrease of P300 latency in the Ginkgo biloba group may reflect shorter stimulus-evaluation time.(ABSTRACT TRUNCATED AT 250 WORDS)

Affect↗

Acaricidal activity against Panonychus citri of a ginkgolic acid from the external seed coat of Ginkgo biloba.

An acaricidal substance extracted from the external seed coat of Ginkgo biloba L. was identified by UV (ultraviolet), IR (infrared), EI-MS (electron impact ion source mass spectrometry), (1)H NMR (nuclear magnetic resonance) and (13)C NMR as 6-[(Z)-10-heptadecenyl]-2-hydroxybenzoic acid (compound 1). Laboratory bioassay on citrus red mite, Panonychus citri (Mcg), showed that compound 1 possessed the following properties. (i) Powerful contact toxicity with an LC(50) of 5.2 mg litre(-1) after 24 h that was similar to that of pyridaben (LC(50) = 3.4 mg litre(-1)) and significantly superior to that of omethoate (LC(50) = 122 mg litre(-1)). Furthermore, its LC(90) was 13.4 mg litre(-1) after 24 h, which is significantly superior to both pyridaben (LC(90) = 69.6 mg litre(-1)) and omethoate (LC(90) = 453 mg litre(-1)). (ii) Quick-acting acaricidal activity. At identical concentrations, compound 1 was much faster-acting than pyridaben or omethoate. (iii) Compound 1 had strong corrosive action on the cuticle of P. citri but no phytotoxicity to plants.

Animals↗

[The role of rheological changes of blood and hemostasis in the development of acute neurosensory hypoacusis].

We studied blood rheology and hemostasis in patients with acute neurosensory hypoacusis (ANH) of different genesis to clarify correlations of these disorders with an ANH form. After examination 72 ANH patients (60 male and 12 female, age 19-68) were divided into three groups by ANH etiology: ANH of vascular genesis (group 1, 47 patients), ANH of viral genesis (group 2, 19 patients), ANH of traumatic genesis (group 3, 6 patients). Blood rheology was studied on viscosimeter Low-Shear 30 (Switzerland); hematocrit--on Autocrit (USA) centrifuge, platelet aggregation--on aggregometer Elvi 840 (Italy), coagulation--on coagulometer Tetra (Spain). Blood rheology and hemostasis in groups 2 and 3 were changed insignificantly, while in group 1 we registered disturbed microcirculation. Treatment with vasoactive drugs normalized both clinical picture of the disease and blood rheology, hemostasis. The highest activity was seen in use of the drugs tanakan and gincor fort.

Acute Disease↗

The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers.

RATIONALE: Chronic administration of extracts from the leaves of the tree Ginkgo biloba is known to improve aspects of cognitive performance. However, little is known about the effects of acute doses of Ginkgo on coherent cognitive domains. Recent factor analysis of test measures from subtasks of the Cognitive Drug Research (CDR) computerised assessment battery has revealed that four primary cognitive 'factors' corresponding to speed of attention, accuracy of attention, speed of memory and quality of memory can be useful to describe cognitive function changes. OBJECTIVE: The present study aimed at assessing whether acute administration of Ginkgo biloba had any consistent effect on the four CDR factors. METHODS: The study utilised a placebo-controlled, multi-dose, double-blind, balanced, crossover design. Twenty participants received 120 mg, 240 mg and 360 mg of a standardised extract of Ginkgo (GK501, Pharmaton, SA) or a matching placebo. Cognitive performance was assessed using the CDR computerised test battery immediately prior to dosing and at 1, 2.5, 4 and 6 h thereafter. The primary outcome measures were the four aspects of cognitive performance, which have previously been derived by factor analysis of CDR subtests. RESULTS: Compared with the placebo, administration of Ginkgo produced a number of significant changes on the performance measures. The most striking of these was a dose-dependent improvement of the 'speed of attention' factor following both 240 mg and 360 mg of the extract, which was evident at 2.5 h and was still present at 6 h. Additionally, there were a number of time- and dose-specific changes (both positive and negative) in performance of the other factors. CONCLUSIONS: We conclude that acute administration of Ginkgo biloba is capable of producing a sustained improvement in attention in healthy young volunteers.

Adult↗

[Soft laser therapy in combination with tebonin i.v. in tinnitus].

28 patients were treated with soft-laser therapy. Two-thirds of them had suffered from tinnitus for more than six months and had undergone different therapies before. Each patient was treated twelve times, treatment lasting ten minutes. Before therapy six ml of Tebonin were given i.v. Four minutes later, the laser was positioned at a distance of one centimetre from the patients' mastoid. The laser beam was directed two fingers above the mastoid tip aiming at the lateral wall of the contralateral orbit. Before and three weeks after treatment each patient underwent pure tone audiometry and determination of the tinnitus intensity. Patients were asked to score symptoms before and three weeks after therapy. Hearing levels before and after soft-laser therapy did not show any statistic difference. Three weeks after the last treatment, twenty patients denied any change in tinnitus. Two patients felt an improvement of tinnitus and one patient had recovered completely. Five patients remained undecided about the outcome of therapy. To sum up, according to our results, the trial so far failed to show clear benefits of soft-laser therapy for patients suffering from chronic tinnitus.

Adult↗

Enteric disposition and recycling of flavonoids and ginkgo flavonoids.

OBJECTIVE: The objective of this study was to determine the intestinal and microbial disposition of flavonoids and how these disposition processes affect their enteric recycling. DESIGN: Studies were performed using a perfused rat intestinal model or using enrichment cultures and a pure isolate of Enterococcus avium (LY1). RESULTS: In the rat intestine, aglycones, such as quercetin and apigenin, were as permeable (P*(eff) > or = 2) as compounds such as propranolol (100% absorption). However, a significant portion of the absorbed aglycones was conjugated and the metabolites were excreted into the lumen. Flavonoid glycosides, such as isoquercitrin and apigenin-7-O-glucoside, also had high apparent P*(eff) values (> or = 2) in the upper small intestine because of rapid hydrolysis. However, isoquercitrin was absorbed much slower (P*(eff) < or = 0.7, p < 0.05) when hydrolysis was absent or inhibited by 20 mmol gluconolactone. Absorption of other intact glycosides was similar to intact isoquercitrin and was much slower than the corresponding aglycones (P*(eff) < or = 0.7, p < 0.05). Intestinal bacteria, such as LY1, hydrolyzed the flavonoid glycosides used in the study. Excreted glycosidases were involved in the hydrolysis of glycosides because glycosides were poorly taken up by LY1. In conclusion, glycosidase-catalyzed hydrolysis is a critical first step in the intestinal and microbial disposition of flavonoid glycosides. Aglycones were not only rapidly absorbed, but also rapidly metabolized into phase II conjugates, which were then excreted back into the lumen. Therefore, intestinal and microbial glycosidases and intestinal phase II enzymes make a significant contribution to the disposition of flavonoids via the proposed enteric and enterohepatic recycling scheme.

Animals↗

[A comparative study of the protective effect of different phlebotonic agents on endothelial cells in hypoxia].

Numerous reported findings indicate that the etiology of venous diseases is multifactorial. One of the chief factors is certainly stasis of blood in the veins of the lower limbs during long periods spent standing up. This stasis causes tissue hypoxia which first affects the venous wall. Because of their location at the interface between blood and vein wall and because of their fragility, endothelial cells are the first to suffer from the lack of oxygen. With the aim of understanding these events, the authors have developed a model of endothelial cells in culture subjected to hypoxia in vitro which mimics the conditions encountered clinically. This model has enabled us to test various drugs commonly used in venous disease. These included GbE, the active ingredient of GINKOR FORT, diosmin and procyanidol oligomers. It was thus shown that only GbE was not toxic to endothelial cells. GbE was also found to be capable of effectively protecting cells exposed to hypoxia. Protection under the influence of diosmin was obtained only at concentrations very close to toxic doses. In contrast, procyanidol oligomers offered no protection. The protective effect of GbE is believed to be due to the action of terpenes on the energy metabolism of the cell.

Antihypertensive Agents↗

Chronic daily administration of selegiline and EGb 761 increases brain's resistance to ischemia in mice.

Brief cerebral ischemia is reported to cause selective neuronal necrosis, apoptotic cell death, silent infarcts and, when recurrent, cognitive decline. Acute administration of selegiline and EGb 761 have been shown to have anti-apoptotic and neuroprotective effects in experimental ischemia. Their daily use is currently advised to slow down cognitive decline in patients with vascular dementia. Hence, unlike previous studies, we studied the neuroprotective action of chronic daily administration of these drugs in Swiss mice subjected to 30-min middle cerebral artery occlusion and 72 h of reperfusion since this model was reported to induce a slowly evolving infarct with profuse apoptotic cell death. Infarct area was evaluated by H&E staining on coronal brain sections and, apoptotic cells were identified by histological criteria, terminal transferase-mediated d-UTP nick-end labeling (TUNEL) and by immunohistochemical detection of caspase-cleaved actin fragments (fractin). Fifty-one mice received daily intraperitoneal injections of 10 mg/kg selegiline (n=18) or 50 mg/kg EGb 761 (n=17) or equal volume of saline (n=16) for 10-14 days before but not on the day of insult. The infarct volume, number of TUNEL- and fractin-positive cells were significantly reduced in treatment groups by 30, 42 and 51% (selegiline) and, 27, 27 and 29% (EGb 761), respectively. These data suggest that prophylactic use of selegiline and EGb 761 could increase the brain's resistance to mild ischemic injury.

Actins↗

Pharmacokinetics of the ginkgo B following intravenous administration of ginkgo B emulsion in rats.

Ginkgo B (GB) is an extract from the leaves of Ginkgo biloba, used in the treatment of dementia, cerebral insufficiency or related cognitive decline. In this paper, the main features of the pharmacokinetics of GB emulsion in rats were reviewed and the binding rate of GB to rat plasma and human plasma protein were investigated meanwhile. The concentrations of GB in plasma, tissue, and excretion of rats after i.v. administration of GB were measured using HPLC-ESI-MS. The metabolite was qualitated by LC-MS/MS. Intravenously administered GB was eliminated in a biphasic manner with a prominent initial phase (half-life of 0.3 h) followed by a slower terminal phase (half-life of 1.5 h). After i.v. 4, 12 and 36 mg/kg GB emulsion, the pharmacokinetic parameters from a two compartment model analysis of plasma samples were AUC(0-tau) (microg x min/ml): 53.7, 165.5 and 649.7; CL (l/min/kg): 0.07, 0.07 and 0.05; V(C) (l/kg): 2.27, 3.27 and 2.76, respectively. Peak concentrations generally occurred at 10 min except brain and fat. Tissue concentration then declined by several-fold during 6 h although still present in most tissues at 6 h. Single intravenous dose was mainly excreted in the urine (40-50%), feces contained less than 30%. The binding rate to rat plasma was little higher than to human plasma, but the difference was negligible. Some metabolites were found in urine and bile through qualitative analysis on the urine and bile by LC-MS/MS.

Animals↗

Ginkgo biloba.

Ginkgo biloba is commonly used in the treatment of early-stage Alzheimer's disease, vascular dementia, peripheral claudication, and tinnitus of vascular origin. Multiple trials investigating the efficacy of ginkgo for treating cerebrovascular disease and dementia have been performed, and systematic reviews suggest the herb can improve the symptoms of dementia. Ginkgo is generally well tolerated, but it can increase the risk of bleeding if used in combination with warfarin, antiplatelet agents, and certain other herbal medications. Clinical issues of safety, dosing, use in the perioperative period, and pharmacology are addressed in this review.

Clinical Trials as Topic↗