GINKGO BILOBA
Ginkgo biloba extract protects against mercury(II)-induced oxidative tissue damage in rats
1: Food Chem Toxicol. 2007 Apr;45(4):543-50. Epub 2006 Aug 30.
Ginkgo biloba extract protects against mercury(II)-induced oxidative tissue damage in rats.
Marmara University, School of Pharmacy, Department of Pharmacology, Istanbul, Turkey.
Mercury(II) is a highly toxic metal which induces oxidative stress in the body. In this study we aimed to investigate the possible protective effect of Ginkgo biloba (EGb), an antioxidant agent, against experimental mercury toxicity in rat model. Following a single dose of 5mg/kg mercuric chloride (HgCl(2); Hg group) either saline or EGb (150mg/kg) was administered for 5days. After decapitation of the rats trunk blood was obtained and the tissue samples from the brain, lung, liver, and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Formation of reactive oxygen species in the tissue samples was monitored by chemiluminescence (CL) technique. BUN, creatinin, ALT, and AST levels and tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) activity were assayed in serum samples. The results revealed that HgCl(2) induced oxidative damage caused significant decrease in GSH level, significant increase in MDA level, MPO activity and collagen content of the tissues. Treatment of rats with EGb significantly increased the GSH level and decreased the MDA level, MPO activity, and collagen contents. Similarly, serum ALT, AST and BUN levels, as well as LDH and TNF-alpha, were elevated in the Hg group as compared to control group. On the other hand, EGb treatment reversed all these biochemical indices. Our results implicate that mercury-induced oxidative damage in brain, lung, liver, and kidney tissues protected by G. biloba extract, with its antioxidant effects.
PMID: 17267089 [PubMed - in process]
Effect of Ginkgo biloba extract on the rat heart mitochondrial function
1: J Ethnopharmacol. 2006 Dec 28; [Epub ahead of print]
Effect of Ginkgo biloba extract on the rat heart mitochondrial function.
Institute for Biomedical Research, Kaunas University of Medicine, Eiveniu Street 4, LT-50009 Kaunas-7, Lithuania.
Ginkgo biloba L. (Ginkgoaceae) originated from China, first introduced to Europe in the 18th century, it is now distributed all over the world. The leaves of Ginkgo biloba include a rich complex of active compounds responsible for various pharmacological properties. Ginkgo biloba extract improves blood circulation, protects against oxidative cell damage, blocks platelet aggregation that could be important for prevention of cardiovascular diseases. Therefore the fluid extract from Ginkgo biloba leaves was prepared and tested for it is effect on rat mitochondrial function. Our data showed that 0.5mul/ml of GE (containing 0.57ng/ml of rutin, 0.23ng/ml of quercitrin, 0.105ng/ml of hyperosid and 0.02ng/ml of quercetin) had no effect on the State 2 respiration rate of mitochondria with all used substrates: pyruvate+malate, succinate and palmitoyl-l-carnitine. Further increase in GE concentration (2 and 4mul/ml), increased the State 2 respiration rate with all respiratory substrates in a dose-dependent manner (by 35-116%). The State 3 respiration rate was not affected by GE. In order to identify which compounds of GE could be responsible for the observed effects, we measured the effect of pure flavonoids: rutin, quercetin, hyperosid and quercitrin on mitochondrial respiration. All flavonoids (except of hyperosid) at maximal used concentration, comparable/identical to that in GE, stimulated the State 2 respiration rate only by 8-20%, i.e. less effectively as compared to GE. Therefore, for the explanation of the GE-induced uncoupling of oxidative phosphorylation, other biologically active compounds of GE have to be taken into account in future studies.
PMID: 17258877 [PubMed - as supplied by publisher]
Ginkgo biloba for cognitive impairment and dementia.
1: Cochrane Database Syst Rev. 2002;(4):CD003120.
Ginkgo biloba for cognitive impairment and dementia.
Department of Clinical Geratology, University of Oxford, Oxford, UK, OX2 6HE. jacqueline.birks@geratology.ox.ac.uk
BACKGROUND: Extracts of the leaves of the maidenhair tree, Ginkgo biloba, have long been used in China as a traditional medicine for various disorders of health. A standardized extract is widely prescribed in Germany and France for the treatment of a range of conditions including memory and concentration problems, confusion, depression, anxiety, dizziness, tinnitus and headache. The mechanisms of action are thought to reflect the action of several components of the extract and include increasing blood supply by dilating blood vessels, reducing blood viscosity, modification of neurotransmitter systems, and reducing the density of oxygen free radicals. OBJECTIVES: The aim of the review is to assess the efficacy and safety of Ginkgo biloba for the treatment of patients with dementia or cognitive decline. SEARCH STRATEGY: Trials were identified on 26 June 2002 through a search of the CDCIG Specialized Register which contains records from all main medical databases (MEDLINE, EMBASE, CINAHL, PsycINFO, SIGLE,LILACS), from ongoing trials databases such as Clinicaltrials.gov and Current Controlled Trials and many other sources. The search terms used were ginkgo*, tanakan, EGB-761, EGB761 and "EGB 761". SELECTION CRITERIA: All relevant, unconfounded, randomized, double-blind controlled studies, in which extracts of Ginkgo biloba at any strength and over any period were compared with placebo for their effects on people with acquired cognitive impairment, including dementia, of any degree of severity. DATA COLLECTION AND ANALYSIS: Data for the meta-analyses are based on reported summary statistics for each study. For the intention-to-treat analyses we sought data for each outcome measure on every patient randomized, irrespective of compliance. For the analyses of completers we sought data on every patient who completed the study on treatment. For continuous or ordinal variables, such as psychometric test scores, clinical global impression scales, and quality of life scales, there are two possible approaches. If ordinal scale data appear to be approximately normally distributed, or if the analyses reported by the investigators suggest that parametric methods and a normal approximation are appropriate, then the outcome measures will be treated as continuous variables. The second approach, which may not exclude the first, is to concatenate the data into two categories which best represent the contrasting states of interest, and to treat the outcome measure as binary. For binary outcomes, the endpoint itself is of interest and the Peto method of the typical odds ratio is used. MAIN RESULTS: Overall, there are no significant differences between Ginkgo and placebo in the proportion of participants experiencing adverse events. Most studies report the analyses of data from participants who completed the treatment, there are few attempts at ITT analyses. Therefore we report completers analyses only. The CGI scale, measuring clinical global improvement as assessed by the physician, was dichotomized between participants who showed improvement and those who were unchanged or worse. There are benefits associated with Ginkgo (dose less than 200mg/day) compared with placebo at less than 12 weeks (54/63 showed improvement compared with 20/63, OR 15.32, 95% CI 5.90 to 39.80, P=<.0001), and Ginkgo (dose greater than 200mg/day) at 24 weeks (57/79 compared with 42/77, OR 2.16, 95% CI 1.11 to 4.20, P=.02). Cognition shows benefit for Ginkgo (dose less than 200mg/day) compared with placebo at 12 weeks (SMD -0.57, 95% CI -1.09, -0.05, P=0.03, random effects model), Ginkgo (greater than 200 mg/day) at 12 weeks (SMD -0.56, 95% CI -1.12 to -0.0, P=0.05), at 12 weeks (Ginkgo any dose) (SMD -0.71, 95% CI -1.23 to -0.19 P=0.008, random effects model) at 24 weeks (Ginkgo any dose) (SMD -0.17, 95% CI -0.32 to -0.02 P=0.03) and at 52 weeks (Ginkgo less than 200 mg/day) (SMD -0.41, 95% CI -0.71 to -0.11, P=<.01). Activities of Daily Living (ADL) shows benefit for Ginkgo (dose less than 200mg/day) compared with placebo at 12 weeks (SMD -1.10, 95% CI -1.79, -0.41, P=0mg/day) compared with placebo at 12 weeks (SMD -1.10, 95% CI -1.79, -0.41, P=<.01), Ginkgo (dose less than 200 mg/day ) at 24 weeks (SMD -0.25, 95% CI -0.49 to -0.00, P=.05), and at 52 weeks (Ginkgo less than 200 mg/day) (SMD -0.41, 95% CI -0.71 to -0.11, P=<.01). Measures of mood and emotional function show benefit for Ginkgo (dose less than 200 mg/day) compared with placebo at less than 12 weeks (SMD -0.51, 95% CI -0.99 to -0.03, P=.04) and Ginkgo (dose less than 200mg/day) at 12 weeks (SMD -1.94, 95% CIs -2.73, -1.15 P=<.0001). There are no significant differences between Ginkgo and placebo in the proportion of participants experiencing adverse events. There are no data available on Quality of Life, measures of depression or dependency. REVIEWER'S CONCLUSIONS: Ginkgo biloba appears to be safe in use with no excess side effects compared with placebo. Many of the early trials used unsatisfactory methods, were small, and we cannot exclude publication bias. Overall there is promising evidence of improvement in cognition and function associated with Ginkgo. However, the three more modern trials show inconsistent results. Our view is that there is need for a large trial using modern methodology and permitting an intention-to-treat analysis to provide robust estimates of the size and mechanism of any treatment effects.
PMID: 12519586 [PubMed - indexed for MEDLINE]
Ginkgo biloba and ovarian cancer prevention: Epidemiological and biological evidence
1: Cancer Lett. 2006 Dec 26; [Epub ahead of print]
Ginkgo biloba and ovarian cancer prevention: Epidemiological and biological evidence.
Laboratory of Gynecologic Oncology and Epidemiology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Dana-Farber Cancer Center, USA.
There is considerable interest in herbal therapies for cancer prevention but often with little scientific evidence to support their use. In this study, we examined epidemiological data regarding effects of commonly used herbal supplements on risk for ovarian cancer and sought supporting biological evidence. 4.2% of 721 controls compared to 1.6% of 668 cases regularly used Ginkgo biloba for an estimated relative risk (and 95% confidence interval) of 0.41 (0.20,0.84) (p=0.01); and the effect was most apparent in women with non-mucinous types of ovarian cancer, RR=0.33 (0.15,0.74) (p=0.007). In vitro experiments with normal and ovarian cancer cells showed that Ginkgo extract and its components, quercetin and ginkgolide A and B, have significant anti-proliferative effects ( approximately 40%) in serous ovarian cancer cells, but little effect in mucinous (RMUG-L) cells. For the ginkgolides, the inhibitory effect appeared to be cell cycle blockage at G0/G1 to S phase. This combined epidemiological and biological data provide supportive evidence for further studies of the chemopreventive or therapeutic effects of Ginkgo and ginkgolides on ovarian cancer.
PMID: 17194528 [PubMed - as supplied by publisher]
Pharmacological Studies Supporting the Therapeutic Use of Ginkgo biloba Extract for Alzheimer’s Disease
Pharmacological Studies Supporting the Therapeutic Use of Ginkgo biloba Extract for Alzheimer’s Disease
B. Ahlemeyer1, J. Krieglstein1
1 Institute for Pharmacology und Toxicology, Department of Pharmacy, Philipps University of Marburg, Germany
The standardized Ginkgo biloba extract EGb 761® (definition see editorial) has been shown to produce neuroprotective effects in different in vivo and in vitro models. Since EGb 761® is a complex mixture containing flavonoid glycosides, terpene lactones (non-flavone fraction) and various other constituents, the question arises as to which of these compounds mediates the protective activity of EGb 761®. Previous studies have demonstrated that the non-flavone fraction was responsible for the antihypoxic activity of EGb 761®. Thus, we examined the neuroprotective and anti-apoptotic ability of the main constituents of the non-flavone fraction, the ginkgolides A, B, C, J and bilobalide. In focal cerebral ischemia models, the administration of bilobalide (5 - 20 mg/kg, s. c.) 60 min before ischemia dose-dependently reduced the infarct area in mouse brain and the infarct volume in rat brain 2 days after the onset of the injury. 30 minutes of pretreatment with ginkgolide A (50 mg/kg, s. c.) and ginkgolide B (100 mg/kg, s. c.) reduced the infarct area in the mouse model of focal ischemia. In primary cultures of hippocampal neurons and astrocytes from neonatal rats, ginkgolide B (1 μM) and bilobalide (10 μM) protected the neurons against damage caused by glutamate (1 mM, 1 h) as evaluated by trypan blue staining. In addition, bilobalide (0.1 μM) was able to increase the viability of cultured neurons from chick embryo telencepalon when exposed to cyanide (1 mM, 1h). Furthermore, we attempted to find out whether ginkgolides A, B, and J and bilobalide were also able to inhibit neuronal apoptosis (determined by nuclear staining with Hoechst 33 258 and TUNEL-staining). Ginkgolide B (10 μM), ginkgolide J (100 μM) and bilobalide (1 μM) reduced the apoptotic damage induced by serum deprivation (24h) or treatment with staurosporine (200 nM, 24h) in cultured chick embryonic neurons. Bilobalide (100 μM) rescued cultured rat hippocampal neurons from apoptosis caused by serum deprivation (24h), whereas ginkgolide B (100 μM) and bilobalide (100 μM) reduced apoptotic damage induced by staurosporine (300 nM, 24h). Ginkgolide A failed to affect apoptotic damage neither in serum-deprived nor in staurosporine-treated neurons. The results suggest that some of the constituents of the non-flavone fraction of EGb 761® possess neuroprotective and anti-apoptotic capacity, and that bilobalide is the most potent one. In contrast, ginkgolic acids (100 - 500 μM) induced neuronal death, which showed features of apoptosis as well as of necrosis, but these constituents were removed from EGb 761® below an amount of 0.0005 %. Taking together, there is experimental evidence for a neuroprotective effect of EGb 761® that agrees with clinical studies showing the efficacy of an oral treatment in patients with mild and moderate dementia.
http://www.thieme-connect.com/DOI/DOI?10.1055/s-2003-40454
Cognitive Performance, SPECT, and Blood Viscosity in Elderly Non-demented People Using Ginkgo Biloba
Cognitive Performance, SPECT, and Blood Viscosity in Elderly Non-demented People Using Ginkgo Biloba
R. F. Santos1, J. C. F. Galduróz1, A. Barbieri2, M. L. V. Castiglioni2, L. Y. Ytaya3, O. F. A. Bueno1
Department of Psychobiology, Universidade Federal de São Paulo-Escola Paulista de Medicina
2 Imaging Diagnostics/Nuclear Medicine Department, Universidade Federal de São Paulo - Escola Paulista de Medicina
3 Nuclear Medicine Service, Hospital Israelita Albert Einstein, Brazil
The aging process is associated with several cognitive alterations. This study looks at the effects of taking dried extract of Ginkgo biloba, which has been used in several countries in an attempt to minimize these effects. The subjects were 48 men aged 60 - 70 matched between control and experimental groups for educational level. Evaluation was based on a number of neuropsychological tests in an attempt to cover the largest possible number of functions including Single Photon Emission Computer Tomography (SPECT) and measures of blood viscosity. The study was run on a double-blind basis with placebo and Ginkgo biloba groups evaluated over a period of 8 months. After treatment, the experimental group showed a reduction in blood viscosity, improved cerebral perfusion in specific areas and improved global cognitive functioning. The control group showed the opposite - higher blood viscosity, a reduction in cerebral perfusion (in specific areas), and cognitive deterioration in different functions. Although the mechanisms by which Ginkgo biloba may contribute to overall enhancement of the parameters evaluated have not been specified, this plant extract certainly appears to be effective in the treatment of cognitive deficits in older people. Further research into its use is called for on the basis of the results obtained here.
http://www.thieme-connect.com/ejournals/abstract/pharmaco/doi/10.1055/s-2003-41197
