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Effects of Ginkgo biloba on plasma oxidant injury induced by bleomycin in rats.

Bleomycin is an anti-neoplastic agent and its clinical usage is limited by its toxicity, which is mostly induced by oxygen radicals. The aim of this study was to investigate the effect of Ginkgo biloba on plasma indices of oxidants induced by bleomycin in rats. Male Sprague-Dawley rats were divided into five groups: none medicated or 0.9% NaCl injected or only Ginkgo biloba (orally, 100 mg/kg per day for 14 days) or only a single dose of bleomycin (intratracheal, 2.5 U/kg) or Gingko biloba and bleomycin-treated groups. After 14 days, blood was taken before the rats were sacrificed. The plasma was removed and stored at -85 degrees C until the study day. Plasma superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) enzyme activities with malondialdehyde and nitric oxide (NO) levels were studied. The levels of malondialdehyde and NO with activity of XO were higher in plasma of bleomycin group than the other groups (P <0.05). The activities of SOD and GSH-Px were increased in the bleomycin plus Gingko biloba group in comparison with the bleomycin group (P <0.05). There was a positive correlation between malondialdehyde and NO levels in the bleomycin group (r =0.859, P <0.05). There were positive correlations between SOD and GSH-Px activities (r =0.760, P <0.05) and between XO activity and malondialdehyde level (r =0.822, P <0.05) in the bleomycin plus Gingko biloba group. In conclusion, it was thought that bleomycin induced oxidative stress can be prevented by Gingko biloba treatment via high anti-oxidant enzyme activity together with decreased radical production from XO.

Animals↗

Non-cholinergic strategies for treating and preventing Alzheimer's disease.

The pathophysiology of Alzheimer's disease is complex and involves several different biochemical pathways. These include defective beta-amyloid (Abeta) protein metabolism, abnormalities of glutamatergic, adrenergic, serotonergic and dopaminergic neurotransmission, and the potential involvement of inflammatory, oxidative and hormonal pathways. Consequently, these pathways are all potential targets for Alzheimer's disease treatment and prevention strategies. Currently, the mainstay treatments for Alzheimer's disease are the cholinesterase inhibitors, which increase the availability of acetylcholine at cholinergic synapses. Since the cholinesterase inhibitors confer only modest benefits, additional non-cholinergic Alzheimer's disease therapies are urgently needed. Several non-cholinergic agents are currently under development for the treatment and/or prevention of Alzheimer's disease. These include anti-amyloid strategies (e.g. immunisation, aggregation inhibitors, secretase inhibitors), transition metal chelators (e.g. clioquinol), growth factors, hormones (e.g. estradiol), herbs (e.g. Ginkgo biloba), nonsteroidal anti-inflammatory drugs (NSAIDs, e.g. indomethacin), antioxidants, lipid-lowering agents, antihypertensives, selective phosphodiesterase inhibitors, vitamins (E, B12, B6, folic acid) and agents that target neurotransmitter or neuropeptide alterations. Neurotransmitter receptor-based approaches include agents that modulate certain receptors (e.g. nicotinic, muscarinic, alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid [AMPA], gamma-aminobutyric acid [GABA], N-methyl-D-aspartate [NMDA]) and agents that increase the availability of neurotransmitters (e.g. noradrenergic reuptake inhibitors). Of these strategies, the NMDA receptor antagonist memantine is in the most advanced stage of development in the US and is already approved in Europe as the first treatment for moderately severe to severe Alzheimer's disease. Memantine is proposed to counteract cellular damage due to pathological activation of NMDA receptors by glutamate. Results with Ginkgo biloba have been mixed. Data for neurotrophic therapies and vitamin E (tocopherol) appear promising but require confirmation. NSAIDs and conjugated estrogens have not proven to be of value to date for the treatment of Alzheimer's disease. Statins may have a potential role in reducing the risk or delaying the onset of Alzheimer's disease, although this has yet to be confirmed in randomised trials. There are currently no data to support the use of statins as a treatment for dementia. This article provides an update on the current status of selected agents, focusing primarily on those agents with the most extensive clinical evidence at present.

Alzheimer Disease↗

[Phytotherapeutic medicines. A possible source of drug interactions].

Herbal drugs are popular. Coming from nature, many people are still reluctant to link them with the risk of adverse effects. Many of these products do not require a prescription. Thus, their use and any potential risks may easily escape the physician's attention. Interactions, causing either adverse effects or treatment failures, with synthetic drugs have attracted increasing interest and recent case reports (e.g. about patients suffering from transplant rejection upon using of St John's wort with subsequently insufficient cyclosporine levels) have triggered some systematic research. As of yet, however, a substantial part of knowledge is based on case reports only. In this situation, the assessment of potential risks arising from herb drug interactions is difficult. More research is needed. This review is a brief account of interactions involving garlic, ginkgo, ginseng, echinacea, and St John's wort.

Drug Interactions↗

Differential cognitive effects of Ginkgo biloba after acute and chronic treatment in healthy young volunteers.

RATIONALE: Acute doses of Ginkgo biloba have been shown to improve attention and memory in young, healthy participants, but there has been a lack of investigation into possible effects on executive function. In addition, only one study has investigated the effects of chronic treatment in young volunteers. OBJECTIVES: This study was conducted to compare the effects of ginkgo after acute and chronic treatment on tests of attention, memory and executive function in healthy university students. METHODS: Using a placebo-controlled double-blind design, in experiment 1, 52 students were randomly allocated to receive a single dose of ginkgo (120 mg, n=26) or placebo (n=26), and were tested 4 h later. In experiment 2, 40 students were randomly allocated to receive ginkgo (120 mg/day; n=20) or placebo (n=20) for a 6-week period and were tested at baseline and after 6 weeks of treatment. In both experiments, participants underwent tests of sustained attention, episodic and working memory, mental flexibility and planning, and completed mood rating scales. RESULTS: The acute dose of ginkgo significantly improved performance on the sustained-attention task and pattern-recognition memory task; however, there were no effects on working memory, planning, mental flexibility or mood. After 6 weeks of treatment, there were no significant effects of ginkgo on mood or any of the cognitive tests. CONCLUSIONS: In line with the literature, after acute administration ginkgo improved performance in tests of attention and memory. However, there were no effects after 6 weeks, suggesting that tolerance develops to the effects in young, healthy participants.

Adolescent↗

Ginkgo biloba for tinnitus.

BACKGROUND: Tinnitus can be described as the perception of sound in the absence of external acoustic stimulation. At present no specific therapy for tinnitus is acknowledged to be satisfactory in all patients. There are a number of reports in the literature suggesting that Ginkgo biloba may be effective in the management of tinnitus. However, there also appears to be a strong placebo effect in tinnitus management. OBJECTIVES: To assess the effect of Ginkgo biloba in patients who are troubled by tinnitus. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 4 2003), MEDLINE (1966 - 2003), EMBASE (1974 - 2003), and reference lists of identified publications. Date of the most recent search was December 2003. SELECTION CRITERIA: Adults (18 years and over) complaining of tinnitus. Adults with a primary complaint of cerebral insufficiency where tinnitus forms part of the syndrome. DATA COLLECTION AND ANALYSIS: Both reviewers independently extracted data and assessed trials for quality. MAIN RESULTS: Twelve trials were identified from the search as being relevant to the review. Ten trials were excluded on methodological grounds. No trials of tinnitus in cerebral insufficiency reached a satisfactory standard for inclusion in the review. There was no evidence that Ginkgo biloba was effective for the primary complaint of tinnitus. The incidence of side effects was small. REVIEWERS' CONCLUSIONS: The limited evidence did not demonstrate that Ginkgo biloba was effective for tinnitus which is a primary complaint. There was no reliable evidence to address the question of Ginkgo biloba for tinnitus associated with cerebral insufficiency.

Adult↗

Evaluation of commercial ginkgo and echinacea dietary supplements for colchicine using liquid chromatography-tandem mass spectrometry.

In response to concerns that commercial dietary supplements containing Ginkgo biloba (ginkgo) and Echinacea purpurea, Echinacea angustifolia, or Echinacea pallida (echinacea) might be contaminated with colchicine, a highly selective and sensitive assay was developed for colchicine that is based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS-MS). The method utilizes reversed-phase HPLC separation of compounds in a methanolic extract of the dietary supplement or botanical sample followed by positive ion electrospray ionization with collision-induced dissociation and multiple reaction monitoring of three characteristic fragmentation pathways of the protonated molecule of colchicine, m/z 400 --> 358, 400 --> 326, and 400 --> 310. The minimal detectable concentration of colchicine using this assay was 10 pg on-column, which is equivalent to 20 ppb colchicine in a 0.5 g ginkgo leaf sample. The method was validated by analyzing 0.5 g samples spiked with colchicine and determining the recovery. A total of 26 commercial ginkgo and echinacea dietary supplements were purchased from pharmacies in Chicago, IL, and analyzed for colchicine. In contrast to a recent report, no colchicine was detected in any of the samples. In addition, authenticated ginkgo leaves were collected, assayed, and found to contain no colchicine, which is consistent with the botanical literature. On the basis of the results obtained using this new LC-MS-MS assay, which is more sensitive and more selective than previously published methods for colchicine, we find no cause for concern regarding colchicine contamination of ginkgo or echinacea dietary supplements.

Chromatography, High Pressure Liquid↗

Medicinal herbs: NTP extracts the facts.

The National Toxicology Program (NTP) has announced that it will design and initiate studies to identify and characterize possible adverse health effects that may be associated with prolonged use or higher doses of some of the most popular medicinal herbs, including Ginkgo biloba, Echinacea angustifolia, and Panax quinquefolius (American ginseng). The NTP studies a large variety of substances to which the population may be exposed in the environment, occupationally, in the food supply, or elsewhere.

Animals↗

[Oral anticoagulants and medicinal plants. An emerging interaction].

The consumption of herbal medicines is increasing steadily throughout the world, although to our knowledge there are neither studies on their effectiveness nor controls over the quality and safety of these preparations. Considered "food integrators", these preparations are marketed without restriction. It is a common notion that natural therapy has neither side nor toxic effects: allergic reactions, direct toxic effects or those due to contamination, carcinogenicity, mutagenicity, and heavy metal toxicity have been reported as adverse events caused by herbs. Rather than replacing traditional therapy, most herbal medical treatment is used in conjunction with it. Also, the attending physician is generally not informed that the patient is using herbs. Because Passionflower, hydroalcoholic extracts, Juniper and Verbena officinalis supply variable quantities of vitamin K, they can lessen the effect of oral anticoagulant therapy. Ganoderma Japonicum, Papaw, Salvia miltiorrhiza, Ginseng, Devil's claw, Garlic, Quinine, Ginkgo, Ginger, Red Clover and Horse-Chestnut reinforce warfarin action by heterogeneous mechanisms. They should thus not be used in patients on oral anticoagulant and/or antiplatelet therapy. The scientific community must take into account the adverse events caused by interaction between herbal medicine and conventional therapy, and patients must be informed of the dangers of these preparations. If a bleeding event occurs or the quality of anticoagulant therapy is poor, the clinician should consider the possibility of interaction between conventional therapy and herbal medicine that the patient has neglected to mention he is taking.

Administration, Oral↗

Systematic reviews of herbal medicines--an annotated bibliography.

OBJECTIVE: To provide a comprehensive collection and a summary of systematic reviews of clinical trials on herbal medicines. METHODS: Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of herbal medicines; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pretested form and summarized descriptively. RESULTS: From a total of 79 potentially relevant reviews preselected in the screening process 58 met the inclusion criteria. 30 of the reports reviewed ginkgo (for dementia, intermittent claudication, tinnitus, and macular degeneration), hypericum (for depression) or garlic preparations (for cardiovascular risk factors and lower limb atherosclerosis). The quality of primary studies was criticized in the majority of the reviews. Most reviews judged the available evidence as promising but definitive conclusions were rarely possible. CONCLUSIONS: Systematic reviews are available on a broad range of herbal preparations prescribed for defined conditions. There is very little evidence on the effectiveness of herbalism as practiced by specialist herbalists who combine herbs and use unconventional diagnosis.

Clinical Trials as Topic↗

Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach.

Systematic evidence regarding herb-drug interactions is lacking. This study investigated herb-drug interactions with warfarin. S-warfarin concentration and response (prothrombin complex activity) data from healthy subjects (n = 24) who received a single warfarin dose (25 mg) and either St John's wort, Asian ginseng, Ginkgo biloba, or ginger were analyzed using a population pharmacokinetic-pharmacodynamic modeling approach. The ratio of S-warfarin apparent clearance (CL/F) compared to control was 1.39 +/- 0.06 and 1.14 +/- 0.04 after St John's wort and Asian ginseng pretreatment, respectively. Other pharmacokinetic and pharmacodynamic parameters were unaffected. Coadministration of St John's wort significantly increased S-warfarin CL/F, whereas treatment with Asian ginseng produced only a moderate increase in CL/F. Ginkgo and ginger did not affect the pharmacokinetics of warfarin in healthy subjects. None of the herbs studied had a direct effect on warfarin pharmacodynamics. Studies in anticoagulated patients are warranted to assess the clinical significance of these herb-drug interactions.

Adult↗

Effect of nitric oxide and plant antioxidants on microsomal content of lipid radicals.

The antioxidant ability of nitric oxide (NO) generated by a chemical donor and of commercially available antioxidant preparations was assayed. SNAP (S-Nitroso-N-acetylpenicilamine) was used as the NO donor, and Ginkgo biloba, wheat and alfalfa preparations were tested. Lipid peroxidation was assayed by EPR employing a reaction system consisting of rat liver microsomes, ADP, FeCl3, NADPH and POBN in phosphate buffer, pH=7.4. In vitro NO exposure decreased microsomal lipid peroxidation in a dose-dependent manner. The dose responsible for inhibiting the microsomal content of lipid radical adducts by 50% (LD50) for SNAP was 550 microM (NO generation rate 0.1 microM/min). The addition of 50 microM hemoglobin to the incubation media prevented NO effect on lipid peroxidation. The addition of an amount of the antioxidant preparations equivalent to the LD50 doses inhibited lipid peroxidation by 21, 15, and 33% for wheat, alfalfa, ginkgo biloba preparations respectively in the presence of 550 microM SNAP. We detected a decrease in the content of lipid radical adducts after simultaneous supplementation, although it was less than 50%, even when LD50 doses of the products were added. This suggests that NO and the natural antioxidants inhibit lipid peroxidation by a mechanism that has both common and non-shared features.

Animals↗