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[A multicenter study of tinnitus. Epidemiology and therapy].

A comparative, randomized multicenter study of 259 patients with tinnitus had three objectives. First, to conduct an epidemiology survey of cases of tinnitus of less than one year duration. Second, to determine prognostic factors to establish profiles of patients with different courses of the disorder. Third, to quantify therapeutic efficacy of three medicines of the same therapeutic class but with different modes of action: Ginkgo biloba extract, almitrine-raubasine and nicergoline. Statistical analysis of findings showed prognostic significance for 3 parameters: chronicity, periodicity and uni- or bilateral nature of symptom, as well as the value of Ginkgo biloba in the treatment of tinnitus unrelated to its initial description.

Almitrine↗

Ginkgo biloba precipitating epileptic seizures.

BACKGROUND: The herbal remedy Ginkgo biloba is promoted as a treatment for a variety of ailments including memory loss and dementia, poor concentration and mood, glaucoma, 'cerebral insufficiency' and 'peripheral circulatory disturbances'. It is gaining worldwide popularity, particularly as a potential treatment for dementia. CASE REPORTS: Two patients with well-controlled epilepsy presented with recurrent seizures within 2 weeks of commencing extract of Ginkgo biloba. The herbal remedy was discontinued and both patients are seizure-free several months later. DISCUSSION: Ginkgo biloba may have precipitated seizures in these two patients. This and other potential adverse effects should be highlighted on the packaging of the drug.

Aged↗

IgE immune response to Ginkgo biloba pollen.

BACKGROUND: The ginkgo (Ginkgo biloba L.) continues to be planted as a shade tree in preference to other species in Seoul, Korea. The proportion of ginkgo to total shade trees was 43.2% in 1998, but the allergenic characteristics of ginkgo pollen has not been elucidated. OBJECTIVES: This study was undertaken to obtain information regarding the skin reactivity rate to ginkgo pollen in a population of Korean subjects with respiratory allergy. Possible ginkgo pollen allergens and the cross-reactivity of ginkgo pollen with other prevalent pollens were also examined. METHODS: Four hundred and forty-seven patients with asthma and/or allergic rhinitis were skin prick tested with extract of ginkgo pollen (1:20 wt/vol). Of these patients, positive skin responders (A/H ratio > or =2+) were selected for ELISA and immunoblot experiments. RESULTS: A total of 21 patients (4.7%) showed skin reactivity (A/H ratio > or =2+) to ginkgo pollen in the skin prick test. They were also cosensitized to many other tree, grass, and weed pollens. Sixteen (76%) of the 21 positive skin responders showed specific IgE responses to ginkgo pollen in ELISA. In inhibitory ELISA, IgE binding to ginkgo pollen was inhibited by more than 80% by oak, ryegrass, mugwort, and ragweed; and 34% by hop Japanese; and 10% by rBet v 2 at 10 microg/mL. In immunoblot, 10 out of 21 sera (48%) reacted to the 15-kD protein of ginkgo pollen, 9 (43%) to 33-35 kD, and 8 (38%) to 36-38 kD. In inhibitory immunoblot, IgE binding to ginkgo pollen proteins was almost completely inhibited by oak, ryegrass, mugwort and ragweed, but only partially by hop Japanese and rBet v 2. CONCLUSION: The skin reactivity rate to ginkgo pollen is approximately 4.7% in a population of Korean subjects with respiratory allergy. Since ginkgo pollen has a high cross-reactivity with other prevalent pollens, it could cause clinical symptoms during its pollen season by cross-reacting with the IgE produced in response to other pollens in patients sensitized to multiple pollens.

Adolescent↗

Self-assembly of Abeta(1-42) into globular neurotoxins.

Amyloid beta 1-42 (Abeta(1-42)) is a self-associating peptide that becomes neurotoxic upon aggregation. Toxicity originally was attributed to the presence of large, readily formed Abeta fibrils, but a variety of other toxic species are now known. The current study shows that Abeta(1-42) can self-assemble into small, stable globular assemblies free of fibrils and protofibrils. Absence of large molecules was verified by atomic force microscopy (AFM) and nondenaturing gel electrophoresis. Denaturing electrophoresis revealed that the globular assemblies comprised oligomers ranging from trimers to 24mers. Oligomers prepared at 4 degrees C stayed fibril-free for days and remained so when shifted to 37 degrees C, although the spectrum of sizes shifted toward larger oligomers at the higher temperature. The soluble, globular Abeta(1-42) oligomers were toxic to PC12 cells, impairing reduction of MTT and interfering with ERK and Rac signal transduction. Occasionally, oligomers were neither toxic nor recognized by toxicity-neutralizing antibodies, suggesting that oligomers could assume alternative conformations. Tests for oligomerization-blocking activity were carried out by dot-blot immunoassays and showed that neuroprotective extracts of Ginkgo biloba could inhibit oligomer formation at very low doses. The observed neurotoxicity, structure, and stability of synthetic Abeta(1-42) globular assemblies support the hypothesis that Abeta(1-42) oligomers play a role in triggering nerve cell dysfunction and death in Alzheimer's disease.

Amyloid beta-Peptides↗

Effectiveness of oral Ginkgo biloba in treating limited, slowly spreading vitiligo.

For effective treatment of vitiligo, it is as important to arrest the progression of the disease as it is to induce repigmentation. Recently, oxidative stress has been shown to play an important role in the pathogenesis of vitiligo. Ginkgo biloba extract has been shown to have antioxidant and immunomodulatory properties. In a double-blind placebo-controlled trial, we evaluated the efficacy of G. biloba extract in controlling the activity of the disease process in patients with limited and slow-spreading vitiligo and in inducing repigmentation of vitiliginous areas. Fifty-two patients were assigned to two treatment groups (A and B) in a double-blind fashion, but only 47 patients could be evaluated, because one patient in group A and four patients in group B withdrew for reasons unrelated to the study. Patients in group A were given G. biloba extract 40 mg three times daily whereas patients in group B received placebo in similar doses. A statistically significant cessation of active progression of depigmentation was noted in patients treated with G. biloba (P = 0.006). Marked to complete repigmentation was seen in 10 patients in group A, whereas only two patients in group B showed similar repigmentation. The G. biloba extract was well tolerated. G. biloba extract seems to be a simple, safe and fairly effective therapy for arresting the progression of the disease.

Adolescent↗

Medicinal plants and Alzheimer's disease: Integrating ethnobotanical and contemporary scientific evidence.

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 Ginkgo biloba in which the ginkgolides have antioxidant, neuroprotective, and cholinergic activities relevant to Alzheimer's disease mechanisms. The therapeutic efficacy of Ginkgo biloba 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 Ginkgo biloba are minimal. Old European reference books (eg, medical herbals) 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 activities 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 amnesic and dementia-inducing properties.

Alzheimer Disease↗

Quantitative determination of major active components in Ginkgo biloba dietary supplements by liquid chromatography/mass spectrometry.

A reversed-phase high-performance liquid chromatography/electrospray ionisation mass spectrometry (RP-HPLC/ESI-MS) method was developed and validated for the simultaneous determination of ten major active components in Ginkgo biloba extract (bilobalide, ginkgolides A, B, C, quercetin, kaempferol, isorhamnetin, rutin hydrate, quercetin-3-beta-D-glucoside and quercitrin hydrate) which have not been previously reported to be quantified in a single analysis. The ten components exhibit baseline separation in 50 min by C18 chromatography using a water/1:1 (v/v) methanol/acetonitrile gradient. Quantitation was performed using negative ESI-MS in selected ion monitoring (SIM) mode. Good reproducibility and recovery were obtained by this method. The sensitivity of both UV and different mass spectrometry modes (full scan, selected ion monitoring (SIM), and selected reaction monitoring (SRM)) were compared and both quantitation with and without internal standard were evaluated. The analysis of Ginkgo biloba commercial products showed remarkable variations in the rutin and quercetin content as well as the terpene lactone contents although all the products satisfy the conventional quality control method.

Chromatography, High Pressure Liquid↗

[The cellular mechanism of angiotensin II inhibition on BKCa of ECV304 cell and the protective effect of gingko leaf extract].

OBJECTIVE: To observe the cellular mechanism of A II inhibition on Maxi-conductance calcium activated potassium channel (BKCa) in ECV304 cell membrane. METHOD: Using the cell-attached configuration of patch clamp technique. RESULTS: A II receptor antagonist saralasin (10(-7) mol/L) may block the inhibitory effect of A II (10(-7) mol/L). Phorbol ester (5 x 10(-8) mol/L) potentiated the effect of A II, while NO (10(-10) mol/L SNP) decreased the effect of A II and gingko leaf extract (800 micrograms/ml) activated BKCa and opposed the effects of A II. CONCLUSION: A II receptor mediates the inhibitory effect of A II on BKCa in ECV304, and PKC is involved in this inhibition. NO and ginkgo leaf extract protect BKCa from the inhibition of A II.

Angiotensin II↗

Ginkgo biloba normalizes stress- and corticosterone-induced impairment of recall in rats.

Exposure to chronic restraint stress in rats and psychosocial stress in humans has been shown to alter cognitive functions such as learning and memory and has been linked to the pathophysiology of mood and anxiety disorders. Antianxiety or sedative agents used in the management of stress have several disadvantages and side effects. Therefore, in this study, we investigated efficacy of a natural medicine, the extract of Ginkgo biloba (EGB 761), in prevention and treatment of the post-stress memory dysfunctions. The results showed that chronic restraint stress (2h for 21 days) or an 'equivalent' dose of exogenous corticosterone (5 mg kg(-1)) decreased re-entry latencies in the passive avoidance situation showing thus impairment of recall. Preventive doses of EGB 761 (100 mg kg(-1)), given 30 min before each restraint stress episode or corticosterone injection, abolished cognitive deficits seen in unprotected rats. There was no influence of stress, corticosterone, and EGB 761 on the acquisition of conditioned avoidance responses (CARs).

Animals↗

Ginkgo biloba attenuates mucosal damage in a rat model of ulcerative colitis.

Intestinal inflammatory states, regardless of specific initiating events, share common immunologically mediated pathways of tissue injury and repair. The efficacy of various drugs used to treat ulcerative colitis (UC) was investigated. The aim of the present study is to evaluate the effects of ginkgo biloba extract on the extent and severity of UC caused by intracolonic administration of acetic acid in rats. The inflammatory response was assessed by histology and measurement of myeloperoxidase activity (MPO), reduced glutathione (GSH), tumor necrosis factor (TNF-alpha) and interleukin-1beta (IL-1beta) levels in colon mucosa. Oral pretreatment with Ginkgo biloba in doses of (30, 60, 120 mg kg(-1) body weight) and sulfasalazine in a dose of (500 mg kg(-1) body weight used as reference) for 2 days before induction of colitis and continued for 5 consecutive days, significantly decreased colonic MPO activity, TNF-alpha, and IL-1beta levels and increased GSH concentration. Moreover, Ginkgo biloba attenuated the macroscopic colonic damage and the histopathological changes-induced by acetic acid. These results suggest that Ginkgo biloba may be effective in the treatment of UC through its scavenging effect on oxygen-derived free radicals.

Acetic Acid↗

Zoosporicidal activities of anacardic acids against Aphanomyces cochlioides.

The EtOAc soluble constituents of the unripe fruits of Ginkgo biloba showed motility inhibition followed by lysis of zoospores of the phytopathogenic Aphanomyces cochlioides. We purified 22:1-omega7-anacardic acid (1), 24:1-omega9-anacardic acid (2) and 22:0-anacardic acid (3), together with other related compounds, 21:1-omega7-cardol (4) and 21:1-omega7-cardanol (5) from the crude extracts of Ginkgo fruits. Amongst them, compound 1 was a major active agent in quality and quantity, and showed potent motility inhibition (98% in 30 min) followed by lysis (55% in 3 h) of the zoospores at 1 x 10(-7) M. The 2-O-methyl derivative (1-c) of 1 displayed antibacterial activity against Bacillus subtilis, but practically inactive to Escherichia coli. A brief study on structure-activity relationships revealed that a carboxyl group on the aromatic ring and an unsaturated side chain in the anacardic acid derivative are important for strong motility inhibitory and lytic activities against the zoospore.

Acetates↗

Comparison of relative antioxidant activities of British medicinal plant species in vitro.

We have determined the relative levels of endogenous antioxidant activity in a range of British medicinal plant species (representative of a variety of plant families, selected on the basis of their widespread use in traditional herbal medicine), via competitive scavenging of the ABTS(z.rad)(+) or O(2)(-)(z.rad) radicals in vitro. A number of plant species with appreciable levels (i.e. greater than or comparable with the activity in corresponding extracts of Ginkgo biloba or Panax ginseng, as recognised phytological sources of antioxidant activity) of antioxidant activity against the ABTS(z.rad)(+) radical were identified as potentially novel sources of free radical scavenging compounds; however none of these extracts showed measurable antioxidant activity when assayed against the O(2)(-)(z.rad) radical. It, therefore, follows that any comparative determination of antioxidant activity should clearly define the radical species and assay method employed. For those extracts showing activity against the ABTS(z.rad)(+) radical, in general, it was not possible to predict the potential antioxidant capacity of a given plant species (or the most active part of the plant) on a taxonomical basis, or from its use in traditional or modern medicine. In the longer term further characterisation of the active compounds from plant species with appreciable antioxidant activity identified in the present investigation may prove of value for treatment of disorders such as Alzheimer's disease, in which free radical induced tissue damage has been implicated.

Antioxidants↗

Liquid chromatography/atmospheric pressure chemical ionization ion trap mass spectrometry of terpene lactones in plasma of animals.

Liquid chromatography/atmospheric pressure chemical ionization ion trap mass spectrometry (LC/APCI-ITMS) was applied to evaluate the bioavailibility of two different forms (free and complexed with soy phospholipids) of pure bilobalide and ginkgolide B in rats after acute administration. The same technique was used to measure the levels of ginkgolide A, B and bilobalide in plasma of guinea pigs fed Ginkgo biloba extract enriched in terpene lactones after chronic administration. The ratio R(P)/R(A) increased two to four times after the administration in the phytosomic form, where R(P) and R(A) represent the percentage ratio between the concentration of each terpene lactone in plasma and in the administrated form, respectively.

Animals↗

[Phytotherapy in cardiovascular medicine].

There is widespread use of herbal medicine in patients suffering from cardiovascular diseases. The discussion about the benefit of these drugs is still controversial because of lack of scientific evidence. Ginkgo biloba, Crataegus and Garlic are often recommended substances for patients with cardiovascular diseases. For these substances there is a lot of data available from experimental and clinical studies, unfortunately not always adhering to the criteria of evidence based medicine. Extracts from ginkgo biloba contain several active constituents, mainly flavonoids and terpens, which have antioxidative properties and an inhibitory effect on platelet aggregation by inhibiting platelet activation factor PAF. Ginkgo is mainly used in vascular dementia and peripheral vascular disease. Garlic shows a modest lipid-lowering effect in the same range as a low-cholesterol diet. Effect on blood pressure seems to be at best minor. Crataegus is often used in patients with heart failure because of its positive inotropic effect. Additionally, crataegus acts as an antiarrhythmic substance by prolonging refractory period of the action potential.

Cardiovascular Diseases↗

Coumaroyl flavonol glycosides from the leaves of Ginkgo biloba.

Two coumaroyl flavonol glycosides, isorhamnetin 3-O-alpha-L-[6"'-p-coumaroyl-(beta-D)-glucopyranosyl-(1,2)-rhamnopyranoside], and kaempferol 3-O-alpha-L-[6"'-p-coumaroyl-(beta-D)-glucopyranosyl-(1,2)-rhamnopyranoside]-7-O-beta-D-glucopyranoside, were isolated from the n-BuOH extract of Ginkgo biloba leaves. These two, together with six other flavonol glycosides, kaempferol 3-O-alpha-L-[6"'-p-coumaroyl-(beta-D)-glucopyranosyl-(1,2)-rhamnopyranoside], quercetin 3-O-alpha-L-[6"'-p-coumaroyl-(beta-D)-glucopyranosyl-(1,2)-rhamnopyranoside], quercetin 3-O-alpha-L-[6"'-p-coumaroyl-(beta-D)-glucopyranosyl-(1,2)-rhamnopyranoside]-7-O-beta-D-glucopyranoside, quercetin 3-O-beta-D-glucopyranosyl-(1-2)-alpha-L-rhamnopyranoside, quercetin 3-O-beta-rutinoside, and quercetin 3-O-beta-D-glucopyranoside, showed profound antioxidant activities in DPPH and cytochrome-c reduction assays using the HL-60 cell culture system.

Antioxidants↗

The protozoan Tetrahymena as a bioindicator to screen bioactive substances.

Tetrahymena thermophila has been used as a "swimming receptor" to study its chemotaxis in the presence of various bioactive substances from herbal plants. Chemotaxis of this ciliated protozoan is, in part, controlled by a cyclic GMP-dependent protein kinase (PKG), which can adjust ciliary beating. In this paper, the effects of Ginkgo biloba extract (GBE) and its main functional constituents, terpene lactones, flavonol glycosides and aglycones, on the chemotaxis and PKG activity of ciliates, were systematically investigated. GBE and its constituents exerted significant inhibition of chemotaxis and PKG activity in cells of T. thermophila. The minimal concentrations to completely inhibit chemotaxis of T. thermophila were 12, 25, 50, 100, 300, 400, 400, 500 microM, 2 mg/ml for isorhamnetin, kaempferol, quercetin, myricetin, isoquercitrin, quercetin-3-beta-d-galactoside, rutin, quercitrin, and GBE, respectively. The IC(50) values for PKG were 14, 17, 20, 25, 186, 78 microM, 0.157 mg/ml for isorhamnetin, kaempferol, quercetin, myricetin, isoquercitrin, rutin and GBE, respectively. The results indicate that the chemotaxis inhibition by GBE and its constituents and their effects on PKG are similar. This suggests that T. thermophila may be a potential experimental organism for screening other bioactive substances.

Animals↗

Effect of compatibility on the pharmacokinetic characteristics of ginsenosides.

Pharmacokinetic research, which is one of the most important parts of preclinic research, plays an important role in guiding medicine compatibility and preparation improvement. In this paper, the influence of the compatibility of GGV on pharmacokinetics of ginsenosides (GS) was studied, which consisted of ginsenosides, ginkgo biloba extract (GBE) and a chemical monomer V. The result indicated that the addition of either GBE or V could influence the pharmacokinetic parameters of ginsenosides and the influence was different when different administering routes were adopted. Therefore, it could be concluded that there are interactions among GS, GBE and V, and the synergetic and inhibitory effects of the three ingredients contribute to the pharmacological effect of GGV.

Animals↗

[Nephroprotective effect of bilobil in experimental acute kidney failure].

Bilobil, a commercial preparation based on Ginkgo biloba extract, improves the functional state of kidney and increases the survival of rats with glycerol-induced acute renal insufficiency. One possible mechanism of this effect is related to the ability of bilobil to simulate the renal antioxidant system, thus decreasing the rate of lipid peroxidation processes and reducing the renal damage. The results show good prospects for the use of bilobil in nephrology.

Acute Kidney Injury↗