Alesse online || DreamPharm
Research Abstracts and Links to Original Sources
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12597260&dopt=Abstract Ref: Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12597260&dopt=Abstract
Ginkgo biloba for the prevention and treatment of cardiovascular disease: a review of the literature.
Mahady GB.
Department of Pharmacy Practice, UIC/NIH Center for Botanical Dietary Supplements, Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA.
Results from clinical trials demonstrate that standardized leaf extracts of Ginkgo biloba (SGB extract) reduce the symptoms of age-associated memory impairment and dementia, including Alzheimer's disease, and may be of benefit in treating intermittent claudication. In addition, preliminary results suggest that SGB extract may be useful in preventing and treating cardiovascular disease (CVD). particularly ischemic cardiac syndrome. Since many patients with cardiovascular disease are already taking anticoagulants and antiplatelet drugs, self-medication with SGB extract is not recommended without the advice of their physician. Although SGB extracts look promising for preventing and treating CVD, well-controlled clinical trials are needed before clinical recommendations can be made.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12590952&dopt=Abstract Ref: Thromb Res 2002 Nov 1;108(2-3):151-160
Effect of the ingestion of Ginkgo biloba extract on platelet aggregation and urinary prostanoid excretion in healthy and Type 2 diabetic subjects.
Kudolo GB, Dorsey S, Blodgett J.
Department of Clinical Laboratory Sciences, MSC 6246, School of Allied Health Sciences, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, 78229-3900, San Antonio, TX, USA
Enhanced platelet function, particularly in response to collagen, is a common occurrence in diabetes that increases the risk of cardiovascular disease. Ginkgo biloba extract is ingested primarily to improve mental focus but it possesses a blood-thinning potential, which has not been well characterized. This study was designed to compare the effect of ingesting G. biloba extract on platelet aggregation in platelet-rich plasma (PRP) and prostanoid urinary excretion in healthy volunteers and subjects with Type 2 diabetes mellitus (T2DM). Before and after ingesting 120 mg of standardized G. biloba extract for 3 months, platelet aggregation was studied in PRP and urinary metabolites of thromboxane B(2) (TXB(2)) and prostacyclin (PGI(2)) were measured. In healthy volunteers (age, 42+/-11 years; BMI, 28.4+/-4.8 kg/m(2); n=28), the ingestion of G. biloba extract significantly increased fasting insulin and C-peptide (10+/-4 vs. 12+/-6 &mgr;U/ml, p<0.007 and 1.3+/-0.8 vs. 2.1+/-1.1 ng/ml, p<0.001, respectively) and significantly reduced collagen but not PAF-mediated platelet aggregation, converting 21 of 28 subjects with [COL+/EPI+] platelets to the [COL-/EPI+] phenotype. This was accompanied by a reduction of 11-dehydro-TXB(2) from 12.4+/-6.1 to 10.3+/-6.1 ng/mg Cr (p<0.04) and PGI(2) metabolites (2,3-dinor-6-keto-PGF(1alpha) and 6-keto-PGF(1alpha)) from 2.2+/-0.8 to 1.8+/-0.8 ng/mg Cr (p<0.05). In the T2DM subjects (age, 54+/-8; BMI, 36.6+/-7.9 kg/m(2); n=19), G. biloba ingestion did not affect pancreatic beta-cell function but significantly reduced platelet aggregation, converting 16 of 19 [COL+/EPI+] platelets to the [COL-/EPI+] phenotype. Unlike the healthy volunteers, this was not accompanied by a reduced urinary prostanoid excretion. G. biloba-induced reduction of both classes of prostanoid metabolites in healthy volunteers, but not in T2DM subjects, may suggest a nonselective inhibition of COX-1-mediated TXA(2) in platelets and COX-2-mediated PGI(2) production by the endothelial cells and perhaps platelet-enriched levels of arachidonic acid or COX-1 activity, or both, in T2DM subjects.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12587812&dopt=Abstract Ref: Pharmacotherapy 2003 Feb;23(2):222-30
A survey of herbal use in children with attention-deficit-hyperactivity disorder or depression.
Cala S, Crismon ML, Baumgartner J.
Kaiser Permanente, Denver, Colorado, USA.
OBJECTIVE: To examine whether herbal medicines were given to children or adolescents receiving care for attention-deficit-hyperactivity disorder or depression. METHODS: Between October 2000 and July 2001, a 23-item questionnaire was administered in five community mental health centers in Texas. Parents or primary caregivers of children who received a psychiatric assessment were sought for participation. One hundred seventeen caregivers completed a questionnaire. The main outcome measure was primary caregivers' self-report of the use of herbal therapy in their children. RESULTS: The lifetime prevalence of herbal therapy in patients was 20% (23 patients). Eighteen patients (15%) had taken herbal medicines during the past year. Recommendations from a friend or relative resulted in the administration of herbal medicines by 61% of 23 caregivers. Herbal medicines were given most frequently for a behavioral condition, with ginkgo biloba, echinacea, and St. John's wort most prevalent. Almost 83% of caregivers gave herbal medicines alone, whereas 13% gave herbal medicines with prescription drugs. Most caregivers (78%) supervised the administration of herbal therapy in their children; the children's psychiatrists (70%), pediatricians (56%), or pharmacists (74%) typically were not aware of the use. CONCLUSIONS: Most caregivers supervised herbal therapy in their children, without communication with a health professional. A need exists for better communication between health professionals and caregivers regarding the use of herbal therapy
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12585329&dopt=Abstract Ref: J Chromatogr A 2003 Jan 31;986(1):121-7
Development and validation of a gas chromatographic-mass spectrometric method for simultaneous identification and quantification of marker compounds including bilobalide, ginkgolides and flavonoids in Ginkgo biloba L. extract and pharmaceutical preparations.
Deng F, Zito SW.
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. Johns University, 8000 Utopia Parkway, Jamaica, NY 11439, USA.
A gas chromatography-mass spectrometry (GC-MS) method was developed and validated for the simultaneous determination of seven major chemical markers (bilobalide, ginkgolides A, B, C, kaempferol, quercetin and isorhamnetin) in phytopharmaceuticals of Ginkgo biloba L. The intra-day relative standard deviations (RSD) and inter-day RSD's were based on the analysis of the standardized Ginkgo biloba L. extract on the same day and on the following 3 consecutive days. The intra-day RSD's ranged from 1.21% (bilobalide) to 6.20% (kaempferol). The inter-day RSD's ranged from 2.10% (bilobalide) to 10.42% (isorhamnetin). Mean recoveries ranged from a low of 63.0 +/- 5.3% (isorhamnetin) to a maximum of 103.5 +/- 6.0% (ginkgolide A). Calibration curves were linear in ranges between 2.73 and 36.36 microg/ml for the markers. Limits of detection ranged from a low of 0.5 microg/ml (bilobalide) to a high of 2.5 microg/ml (quercetin). The limits of quantitation were a low of 1.1 microg/ml (gingkolides A, B, C) to a high of 7.5 microg/ml (kaempferol). The method was applied to a standard extract (>6% total terpenoids and >24% total flavonoids) and six ginkgo capsule phytopharmaceuticals.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12580507&dopt=Abstract Ref: J Chromatogr A 2003 Jan 24;985(1-2):387-94
Ginkgo biloba extract preserves pyruvate and enhances ascorbate in the cortex of gerbils during focal cerebral ischemia. A microdialysis-liquid chromatography study.
Lee MS, Yang DY, Cheng CL, Liang YJ, Yang LL, Cheng FC.
Department of Medical Laboratory, Taichung Veterans General Hospital, Taichung 40705, Taiwan.
The aim of this study was to evaluate dynamic changes in energy-related metabolites in the cortex of gerbils subjected to focal cerebral ischemia after pretreatment with Ginkgo biloba extract. Focal cerebral ischemia was induced by occlusion of the right common carotid artery and the right middle cerebral artery for 60 min in anesthetized gerbils. A microdialysis probe was inserted into the cortex to monitor extracellular lactate. pyruvate and ascorbate during ischemia and reperfusion. The present study demonstrated a dynamic decrease in pyruvate (25% of baseline) and increases in lactate (160% of baseline) and asorbate (300% of baseline) and a 5-fold increase in the lactate:pyruvate (L:P) ratio during cerebral ischemia in the control group. However. pyruvate levels were preserved and ascorbate levels were enhanced with a chronic pretreatment of Ginkgo biloba extract for 8 days (i.p., 100 mg kg(-1) day(-1)). Preservation of pyruvate and enhancement of ascorbate observed in this study may be associated with the neuroprotective effects of Ginkgo biloba extract.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12579948&dopt=Abstract Ref: Yao Xue Xue Bao 2002 Feb;37(2):86-9
Expression of vascular endothelial growth factor in U937 foam cells and the inhibitory effect of drugs
[Article in Chinese]
Yang PY, Rui YC, Zhang L, Li TJ, Qiu Y, Wang JS, Zhang WD.
Department of Pharmacology, Second Military Medical University, Shanghai 200433, China.
AIM: To study the expression of vascular endothelial growth factor (VEGF) in U937 foam cells and the inhibitory effect of salvianolic acid B and Ginkgo biloba extract in vitro. METHODS: U937 cells were incubated with 80 mg.L-1 oxidized low density lipoprotein (OX-LDL) for 48 h and a macrophage-derived foam cell model was established. The VEGF concentration in the media was determined by ELISA; the VEGF protein expression in cells was measured with immunohistochemistry; the VEGF mRNA level in cells was measured by in situ hybridization; the positive ratio detected by a morphometrical analysis system was used as the amount of the VEGF protein expression and the mRNA level. RESULTS: After U937 cells were incubated with OX-LDL, VEGF expression level increased greatly both in the cells and in the media. Salvianolic acid B and Ginkgo biloba extract were shown to remarkably inhibit the increase of VEGF. After treated with 10 micrograms/L-1 salvianolic acid B and Ginkgo biloba extract, the VEGF protein concentration in the media and positive ratio in the cells decreased compared with foam cells. After treated with 10 micrograms.L-1 salvianolic acid B and 100 micrograms.L-1 Ginkgo biloba extract, the VEGF mRNA level decreased measured by in situ hybridization. CONCLUSION: A high VEGF expression level was determined in U937 foam cells. Salvianolic acid B and Ginkgo biloba extract were found to inhibit VEGF expression significantly in U937 foam cells in vitro.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12579940&dopt=Abstract Ref: Yao Xue Xue Bao 2001 Aug;36(8):609-12
Separation and quantitative analysis of ginkgolic acids from Ginkgo biloba leaves by reverse phase argentation high performance liquid chromatography]
[Article in Chinese]
He JR, Xie BJ.
Research Laboratory of Natural Product Chemistry, Food Science Department of Huazhong Agricultural University, Wuhan 430070, China.
AIM: To develop a reverse phase argentation high performance liquid chromatographic (RP-AHPLC) method for the separation and determination of ginkgolic acids. METHODS: Liquid chromatography-electrospray ionization mass spectrometry (LC/ESI-MS) was applied to identify ginkgolic acids from Ginkgo biloba leaves and four ginkgolic acids of the samples were separated and quantified by RP-AHPLC. Leaves were extracted with ethanol and analytes were extracted with hexane after addition of acid/salt solution and adsorbent to matrix solution. Ginkgolic acids were separated and determined within 30 minutes by RP-AHPLC under optimum chromatographic conditions. Methanol and 5% aqueous acetic acid (90:10) containing 0.03 mol.L-1 silver ion was used as mobile phase, column temperature was selected at 30 degrees C, flow rate was 1.0 mL.min-1, UV detection wavelength was at 310 nm. The spectra analysis and purity identification of chromatographic peaks of ginkgolic acids were further confirmed by means of diode array detection. RESULTS: Four ginkgolic acids were baseline separated from each other and from other interfering components. The average recovery and relative standard deviation of the method were 97.3% and 1.6%, respectively. CONCLUSION: RP-AHPLC was an excellent method for separation of homologous with different carbon atom numbers and double bond. The method is useful for the quality control of extract of Ginkgo biloba leaves.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12579453&dopt=Abstract Ref: J Plant Res 2002 Dec;115(6):491-4
The microtubule cycle during successive mitotic waves in the syncytial female gametophyte of ginkgo.
Brown RC, Lemmon B, Nguyen H.
Department of Biology, University of Louisiana at Lafayette, Lafayette, LA 70504-2451, USA,
Plant morphogenesis is driven by a surprising number of microtubule arrays. The four arrays of vegetative tissues are hoop-like cortical, preprophase band (PPB), spindle, and phragmoplast. When syncytia occur during the reproductive phase of the plant life cycle, neither hoop-like corticals nor PPBs are present, and functional phragmoplasts fail to form following the proliferative mitoses that give rise to the multinucleate cytoplasm. Instead, the interphase microtubules are radial microtubule systems (RMSs) that emanate from the nuclei. These RMSs organize the cytoplasm into nascent cells and ultimately trigger phragmoplast formation at their boundaries. During investigations of the syncytial stage that initiates development of the female gametophyte in gymnosperms, we studied the large (3-4 mm) female gametophyte of Ginkgo biloba. Here we describe the microtubule cycle correlated with successive mitotic waves and discuss the importance of this system in studying the acentrosomal nucleation and organization of cycling microtubule arrays.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12578781&dopt=Abstract Ref: Ophthalmology 2003 Feb;110(2):359-62
Effect of Ginkgo biloba extract on preexisting visual field damage in normal tension glaucoma.
Quaranta L, Bettelli S, Uva MG, Semeraro F, Turano R, Gandolfo E.
Centro Glaucoma, Clinica Oculistica Universita di Brescia, Brescia, Italy. Clinica Oculistica, Universita di Catania, Catania, Italy.
OBJECTIVE: To evaluate the effect of Ginkgo biloba extract (GBE) on preexisting visual field damage in patients with normal tension glaucoma (NTG). DESIGN: Prospective, randomized, placebo-controlled, double-masked cross-over trial. PARTICIPANTS: Twenty-seven patients with bilateral visual field damage resulting from NTG. INTERVENTION: Patients received 40 mg GBE, administered orally, three times daily for 4 weeks, followed by a wash-out period of 8 weeks, then 4 weeks of placebo treatment (identical capsules filled with 40 mg fructose). Other patients underwent the same regimen, but took the placebo first and the GBE last. Visual field tests, performed at baseline and at the end of each phase of the study, were evaluated for changes. MAIN OUTCOME MEASURES: Change in visual field and any ocular or systemic complications. RESULTS: After GBE treatment, a significant improvement in visual fields indices was recorded: mean deviation (MD) at baseline versus MD after GBE treatment, 11.40 +/- 3.27 dB versus 8.78 +/- 2.56 dB (t = 8.86, P = 0.0001, chi-square test); corrected pattern standard deviation (CPSD) at baseline versus CPSD after GBE treatment, 10.93 +/- 2.12 dB versus 8.13 +/- 2.12 dB (t = 9.89, P = 0.0001, chi-square test). No significant changes were found in intraocular pressure, blood pressure, or heart rate after placebo or GBE treatment. Any ocular and systemic side effects were recorded for the duration of the trial. CONCLUSIONS: Ginkgo biloba extract administration appears to improve preexisting visual field damage in some patients with NTG.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12576648&dopt=Abstract Ref: Chem Pharm Bull (Tokyo) 2003 Feb;51(2):158-61
Quantitative analysis of bilobalide and ginkgolides from Ginkgo biloba leaves and Ginkgo products using (1)H-NMR.
Choi YH, Choi HK, Hazekamp A, Bermejo P, Schilder Y, Erkelens C, Verpoorte R.
Division of Pharmacognosy, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, The Netherlands.
1H-NMR spectrometry was applied to the quantitative analysis of the bilobalide, ginkgolides A, B, and C in Ginkgo biloba leaves and six kinds of commercial Ginkgo products without any chromatographic purification. The experiment was performed by the analysis of each singlet H-12, which were well separated in the range of delta 6.0-7.0 in the (1)H-NMR spectrum. However, the H-12 protons of bilobalide and ginkgolides may have overlapped with H-6 or H-8 protons of the Ginkgo flavonoids. Therefore, the optimum (1)H-NMR solvent for the analysis of the compound was selected through the evaluation of solvent effects on the resolution of these signals from the compounds. Acetone-d(6)-benzene-d(6) (50 : 50) was found to be the best one among the solvents evaluated. The quantity of the compounds was calculated by the relative ratio of the intensity of each compound to the known amount of internal standard (25 microgram), phloroglucinol. This method allows rapid and simple quantitation of underivatized bilobalide and ginkgolides in 5 min without any pre-purification steps.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12575271&dopt=Abstract Ref: Zhong Yao Cai 2000 Dec;23(12):764-6
Effects of an extract of Ginkgo biloba on the blood flow of brains and back legs of dogs
[Article in Chinese]
Shen M, Lu Z, Ye Q.
Dept. of Pharmacology, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing 210028.
After injecting the injection of an extract of Ginkgo biloba, the cerebral blood flow of dogs wrer increased (P < 0.05-0.001). So were the back legs. And the cerebrovascular resistance was decreased (P < 0.05-0.001).
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12572425&dopt=Abstract Ref: Zhong Yao Cai 1997 Sep;20(9):461-3
Component analysis on polysaccharides in exocarp of Ginkgo biloba
[Article in Chinese]
Song G, Xu A, Chen H, Wang X.
Medical College of Yangzhou University, Yangzhou 225001.
This paper reports the content and component analysis on polysaccharides in exocarp of Ginkgo biloba. The results show that the content of total saccharides is 89.7%; content of polysaccharides is 84.6%; content of reductic saccharides is 5.1%; the polysaccharides are composed of glucose, fructose, galactose and rhamnose.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12570381&dopt=Abstract Ref: J Med Chem 2003 Feb 13;46(4):601-8
Preparation of 7-substituted ginkgolide derivatives: potent platelet activating factor (PAF) receptor antagonists.
Vogensen SB, Stromgaard K, Shindou H, Jaracz S, Suehiro M, Ishii S, Shimizu T, Nakanishi K.
Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, USA.
Ginkgolides are structurally unique constituents of Ginkgo biloba extracts and are known antagonists of the platelet-activating factor (PAF) receptor. Ginkgolide C is 25-fold less potent than ginkgolide B as a PAF receptor antagonist, due to the presence of the 7beta-OH. Recently, we found that 7alpha-fluoro ginkgolide B was equipotent to ginkgolide B underlining the critical importance of the 7-position of ginkgolides for PAF receptor activity. Herein we describe the synthesis of a series of ginkgolide B derivatives with modifications at the 7-position and the pharmacological evaluation of these derivatives as assayed by cloned PAF receptors. In two cases nucleophilic attack on a 7beta-O-triflate ginkgolide B did not lead to the expected products, but gave rise to two unprecedented ginkgolide derivatives, one with a novel rearranged skeleton. Furthermore, standard reduction of 7alpha-azido ginkgolide B did not give the expected primary amine, but instead yielded alkylated amines depending on the solvent employed. Pharmacological testing with cloned PAF receptors showed that ginkgolides with 7alpha-substitutents had increased affinity compared to 7beta-substituents, in particular 7alpha-chloro ginkgolide B, the most potent nonaromatic ginkgolide derivative described to date with a K(i) value of 110 nM.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12566565&dopt=Abstract Ref: Proc Natl Acad Sci U S A 2003 Feb 18;100(4):1580-1585
Short-term administration of omega 3 fatty acids from fish oil results in increased transthyretin transcription in old rat hippocampus.
Puskas LG, Kitajka K, Nyakas C, Barcelo-Coblijn G, Farkas T.
Laboratory of Functional Genomics, Biological Research Center, and Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, P.O. Box 521, H-6701, Szeged, Hungary; and Department of Clinical and Experimental Laboratory Medicine, Semmelweis University, H-1123, Budapest, Hungary.
Reduced brain levels of long chain polyunsaturated fatty acids [arachidonic acid and docosahexanoic acid (DHA)] are observed in elderly subjects and patients with Alzheimer's disease. To determine the effects of n-3 fatty acids on aged rat brain, 2-year-old rats were fed fish oil (27% DHA content) for 1 month, and gene expression analysis and fatty acid and molecular species composition of the major phospholipid species were assessed. No significant alteration could be observed in the fatty acid composition of ethanolamine phosphoglycerides and phosphatidylserines with the exception of DHA, which was slightly higher in brains of rats receiving fish oil. However, a drastic reduction in arachidonic acid in phosphatidylinositoles was observed. The expression of 23 genes was altered in response to fish oil feeding in the hippocampus. The transcription of transthyretin (TTR) was induced by 10-fold as evidenced by microarray analysis and confirmed by real-time quantitative RT-PCR. Expression of IL-1 and NO synthase, which has been implicated in the prevention of neurological diseases, was unaltered. TTR is an amyloid beta protein scavenger, so an increase in its expression could prevent amyloid aggregate formation. We believe the beneficial effects of fish oil might be common to other agents, i.e., induce TTR expression, like nicotine and Ginkgo biloba extract.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12566224&dopt=Abstract Ref: Biol Cell 2002 Nov;94(7-8):511-8
Lacandonia granules are present in Ginkgo biloba cell nuclei.
Jimenez-Ramirez J, Agredano-Moreno LT, Segura-Valdez Md Mde L, Jimenez-Garcia LF.
Herbarium, Department of Comparative Biology, Faculty of Sciences, UNAM, Mexico City 04510, Mexico
Lacandonia schismatica is a rare flowering plant with the sex organs spatially inverted. Several aspects of its cell biology are now known. Interestingly, within the cell nucleus, the chromatin is reticulated and it is associated to a novel structure named Lacandonia granules, a very abundant ribonucleoprotein particle showing similarities to perichromatin and Balbiani ring granules, which are involved in nuclear mRNA metabolism. To see whether these particles are present in other plants, we study the nucleus of Ginkgo biloba, a non-flowering plant. Light, electron and atomic force microscopy show that the cell nuclei of G. biloba are reticulated. Ultrastructural analysis showed that in the nucleoplasm, abundant intranuclear particles 32 nm in diameter are present. The EDTA regressive staining suggested that they contain RNA. Ultrastructural in situ hybridization confirmed the presence of RNA in these particles. Therefore, we conclude that the nuclei of G. biloba are reticulated and contain Lacandonia granules. We suggest that these particles may also be present in other plants.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12562054&dopt=Abstract Ref: Dis Mon 2002 Oct;48(10):671-96
Herbs commonly used by women: an evidence-based review.
Tesch BJ.
OBJECTIVE: To review the evidence of herbs commonly used by women. DATA SOURCES: Articles were located by searching Medline, Cochrane Database of Systemic Reviews, and the Combined Health Information Database and by hand searching the reference lists of recent systematic reviews. The databases were searched in January 2000 and October 2000 by using the Latin and common name of each herb. METHODS OF STUDY SELECTION: Preference was given to randomized, placebo-controlled trials. When available, English language studies were reviewed. If not, data are presented from review articles that summarize the foreign study. RESULTS: Many women use herbal therapies. In the United States, herbs are considered dietary supplements. The Food and Drug Administration (FDA) cannot remove them from the market unless they are proven unsafe. The herb industry plans to improve monitoring. Many prospective randomized controlled trials are being funded. Gingko biloba seems to slow the progression of dementia but increases the risk of bleeding. St John's Wort is efficacious for treating mild to moderate depression but has many drug interactions. Ginseng seems to improve well being in perimenopausal women, but it is often impure and has side effects and drug interactions. Garlic slightly lowers blood pressure and lipids. Echinacea slightly decreases the duration of colds but does not prevent them. Valerian is beneficial for insomnia, but there is no long-term safety data. Black cohosh may help the symptoms of perimenopause, and chasteberry may improve premenstrual syndrome. More study is needed on both herbs. CONCLUSION: Some herbs are medically useful, but the American public would benefit from increased regulation. Manufacturers should be able to ensure that herbs contain pure ingredients. Side effects and drug interactions should be listed. Well-designed studies are being conducted. The results will be helpful to physicians and patients when the clinical evidence becomes available.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12561480&dopt=Abstract Ref: Yi Chuan Xue Bao 2002 Oct;29(10):928-35
Quantitative genetic analysis and multiple trait selection of pharmaceutical composition on Ginkgo biloba L. leaves
[Article in Chinese]
Xing SY, Wu DJ, Xing LF, You XL, Zhang YP, Sun X, Liu YQ.
Forest Department, Forest College, Shandong Agricultural University, Taian 271018, China.
The China possesses more than 70% Ginkgo resources in the world. The purposes of this research are to collect fine seedling and grafting clones in China, to probe genetic law on flavone glycosides and terpenes on Ginkgo leaves, and select leaf-used cultivars of high-pharmaceutical composition. In this research, we have collected 87 clones from 13 provenances and have carried out randomized block experiment at Tancheng, Laizhou and Yaoxiang in Shandong Province. Flavone glycosides and terpenes were determined through HPLC method from an improved Van Beek (1991) techniques and Shimadzu Lc-10 AD (Japan). Data and breeding analyses were carried out through IBMPC and SPQG30 software. The results of variance analyses show that there are significant differences to flavone glycosides, terpenes in clones, and the law of genetic parameters on heritability (h2) and genetic variability coefficient (Gcv), is clone > sex > provenance to flavone glycosides in ginkgo leaves. The sigma g2, h2, Gcv and delta G' in male tree clone leaves are higher than female clone leaves on flavone glycosides. We have found that there is a maximum flavone content clone among males and a maximum terpene clone among females. The results of Q-cluster analyses are consistent with R-factor analyses of twenty higher terpenes clones. The results of index selection show that the ri.Y2, E(I) and CGS' of multiple traits selection including (gamma) trait are higher than single trait and multiple traits selection excluding gamma. The direct or index selection is more suited to leaf-used cultivars of Ginkgo. The genetic stability of each clone was appraised by Wricke's ecovalence method and Nassar & Huhu noparameter method. Flavone glycosides and terpenes are more than 2.09%-2.57% and 0.33%-0.41%, respectively, and we have selected four clones.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12553715&dopt=Abstract Ref: Acta Histochem 2002;104(4):427-30
NADPH-diaphorase activity in the spinal cord after ischemic injury and the effects of pretreatment with Ginkgo biloba extract (EGb 761).
Mechirova E, Domorakova I.
Faculty of Medicine, P.J. Safarik University, Department of Histology and Embryology, Kosice, Slovakia.
Histochemical analysis of NADPH-diaphorase (NADPH-d) activity was performed on segments of the lumbar spinal cord in rabbit after 7 days pretreatment with the Ginkgo biloba extract Tanakan, and 30 min of ischemia followed by 24 h of reperfusion. In sections of the L5 segment of the spinal cord of untreated controls, NADPH-d-positive neurons were identified in the dorsal horns, in the pericentral region and occasionally in the ventral horns. The rabbits were completely paraplegic after 30 min of ischemia and 24 h of reperfusion. High NADPH-d activity was found in the wall of blood vessels in sections of the L5 segment and the numbers of NADPH-d-positive neurons in all sites was moderately elevated. After 7 days of Tanakan pretreatment, 30 min of ischemia and 24 h of reperfusion, the animals did not show paraplegia. Only a light tremor of the hind limbs was observed. NADPH-d activity in blood vessels and neurons was similar to that in controls. In the dorsal horns, NADPH-d positivity in neurons and fibres was increased. Our results indicate that Tanakan can scavenge free radicals produced during ischemia/reperfusion and may reduce reperfusion damage.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12552165&dopt=Abstract Ref: Medicina (Kaunas) 2002;38(12):1220-3
Technology and analysis of Ginkgo tincture
[Article in Lithuanian]
Bernatoniene J, Savickas A, Malinauskas F, Bernatoniene R.
Faculty of Pharmacy, Kaunas University of Medicine, A. Mickeviciaus 9, Lithuania.
The article deals with the production of the tincture of Ginkgo leaves while selecting extractant, the size of particles in a raw material, and the method of extraction. The optimal concentration of the extract was established by experiment and was the following: ethanol of 70 percent (V/V), the particles size 2-3 mm, the production method percolation, and the flow speed of tincture 0.5 ml/min. The tinctura was analyzed at determination of the sum of flavonoids in terms of quercetin, dry residue, the concentration of ethanol, density, refraction index, heavy metals and microbe pollution. The stability of the tincture and its expiry date were fixed.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12551745&dopt=Abstract Ref: Life Sci 2003 Feb 21;72(14):1563-71
The collagenolytic effects of the traditional Chinese medicine preparation, Han-Dan-Gan-Le, contribute to reversal of chemical-induced liver fibrosis in rats.
Li C, Luo J, Li L, Cheng M, Huang N, Liu J, Waalkes MP.
Department of Pharmacology, Guiyang Medical College, China
Han-Dan-Gan-Le (HDGL), a Chinese herb preparation composed of Stephaniat tetrandra, Salvia miltorrhiza, Radix paeoniae, Astragalus membranaceus, and Ginkgo biloba, has been used to treat human liver fibrosis. This study was designed to examine the therapeutic effect of HDGL on chemical-induced liver fibrosis in adult Wistar rats. Liver fibrosis was produced in rats by carbon tetrachloride (1.2 ml CCl(4)/kg, 2 times/week, after an initial dose of 5.0 ml CCl(4)/kg, sc), plus a diet of 20% fat, 0.05% cholesterol (continuous) and 30% alcohol in the drinking water ad libitum (every other day) for 8 weeks. HDGL (0.5 and 1.0 g/kg, ig, daily for 6 weeks) was administered to rats 72 hrs after the last dose of CCl(4) to examine its therapeutic effects on chemical-induced liver fibrosis. Upon pathological examination, the HDGL treatment had significantly reversed chemical-induced liver fibrosis and other hepatic lesions. Hepatic collagen accumulation induced by CCl(4) was markedly reduced by HDGL treatment, as evidenced by hepatic collagen content and by immunohistochemical analysis of type-I collagen in liver. HDGL appeared to stimulate the collagenolytic process in the liver, as a 30-50% increase in urinary excretion of hydroxyproline was observed with HDGL treatment as compared to rats only given CCl(4). In conclusion, HDGL can effectively reverse chemically induced liver fibrosis, and this appears to be due, at least in part, to the stimulation of hepatic collagenolysis, resulting in a resolution of hepatic fibrosis.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12546724&dopt=Abstract Ref: Acta Pharmacol Sin 2003 Feb;24(2):157-62
Effect of Ginkgo biloba leaf extract on electroencephalography of rat with cerebral ischemia and reperfusion.
Zhang YY, Li PF, Li D.
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 200032, China.
AIM: To test the effect of Ginkgo biloba leaf extract on electroencephalography (EEG) during cerebral ischemia and reperfusion. METHODS: Based on the quantitative analysis of EEG using the fast Fourier transform (FFT), the effect of Ginkgo biloba extract (GbE) on rat EEG was surveyed in the model of middle cerebral artery (MCA) occlusion and global cerebral ischemia. RESULTS: In the global cerebral ischemia, GbE 8 and 16 mg/kg could accelerate the recovery of EEG after reperfusion, and GbE 4 mg/kg had the same effect but much weaker. In the MCA occlusion model, GbE 16 and 32 mg/kg greatly suppressed the drop of power spectrum of EEG. CONCLUSION: GbE could mitigate the cerebral damage caused by ischemia.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12546723&dopt=Abstract Ref: Acta Pharmacol Sin 2003 Feb;24(2):152-6
Ginkgo biloba leaf extract enhances levels of caspase-3 and amyloid precursor protein in normal rat hippocampus.
Luo C, Wu Q, Huang XN, Sun AS, Shi JS.
Department of Pharmacology, Zunyi Medical College, Zunyi 563003, China.
AIM: To explore the effect of Ginkgo biloba extract (GbE) on the levels of caspase-3 and amyloid precursor protein (APP) in normal rats' hippocampus. METHODS: Immunohistochemistry method was used for qualitative analysis of the expressions of caspase-3 and APP, and an image analysis method was used for the quantification of the levels of caspase-3 and APP after GbE was administered to rats of different ages for 14 d. RESULTS: The mean absorbance of staining of caspase-3 and APP was markedly higher in GbE group than that in control groups. The expressions of caspase-3 and APP were intensified in the hippocampus of rats after GbE administration. CONCLUSION: GbE can raise the levels of caspase-3 and APP in the hippocampus of normal rats.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12538036&dopt=Abstract Ref: Int Immunopharmacol 2003 Jan;3(1):75-80
Effect of Ginkgo biloba extract, EGb 761, on the cellular immune response in a hypothalamic-pituitary-adrenal axis activation model in the rat.
Puebla-Perez AM, Lozoya X, Villasenor-Garci;a MM.
Laboratorio de Inmunofarmacologi;a de Productos Naturales, Centro de Investigacion Biomedica de Occidente, Mexico
We evaluated the effects of Ginkgo biloba extract (EGb 761) on the cellular immune response of rats with immunosuppression induced by activation of the hypothalamic-pituitary-adrenal (HPA) axis. Groups of five rats were subjected to chronic stress by the application of daily electric shocks (ES) over 7 days. This stress produced a significant decrement in the delayed-type hypersensitivity response (DTH) to dinitrofluorobenzene (DNFB), and a decrease in the proliferation index of splenocytes. Treatment with oral doses of the phytopharmaceutical EGb 761 (100 mg/kg per day over 7 days) restored both the DTH response to DNFB and the proliferation index. EGb 761 has stress-alleviating properties through its moderation of corticosterone levels. It also possesses antioxidant activity that may contribute to its effects on the immune response. Our observations indicate that the phytopharmaceutical EGb 761 possesses immunostimulatory properties.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12536727&dopt=Abstract Ref: Hunan Yi Ke Da Xue Xue Bao 2001 Aug 28;26(4):335-6
Analysis of amino acids and vitamins in ginkgo biloba leaves]
[Article in Chinese]
Chen GH, Den FL, Liu JP.
Analytical Testing Center, Xiangya School of Medicine, Central South University, Changsha 410078, China.
The contents of amino acids and 10 kinds of vitamins in ginkgo biloba leaves were analyzed via HPLC. The results shows that it contains 92.26 mg amino acids per gram leaves the rate of essential amino acids amount to total amino acids amount is 46.9% and the contents of Vc, Vpp, VE, VB6, PGA is 81.47 mg, 9.43 mg, 4.09 mg, 2.90 mg, 1.69 mg per gram leaves respectively. The present effective data will be helpful for further research in its chemical composition and comprehensive utilization.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12532704&dopt=Abstract Ref: Medicina (Kaunas) 2002;38(10):970-5
Importance of biologically active components and plants in the prevention of complications of diabetes mellitus
[Article in Lithuanian]
Savickiene N, Dagilyte A, Lukosius A, Zitkevicius V.
Kauno medicinos universiteto Farmacines chemijos ir farmakognozijos katedra, A. Mickeviciaus 9, 3000 Kaunas.
Diabetes complications, especially late (chronic) ones, are the main reasons of invalidity and early mortality. The most threatening diabetes complications are vascular and metabolic complications (diabetic neuropathy, angiopathy, cataract, glaucoma, optic neuropathy, retinopathy, diabetic nephropathy). Good diabetes control is very important, because in early stages these changes are reversible. In order to decrease the number of diabetes complications and to postpone their development, the use of biologic active components and plants is recommended. The most important biologic active substances for this purpose are vitamins and minerals, proteins, polysaccharides, lectins, saponins and flavonoids. According the scientific data, the mostly used plants are: Ginkgo biloba, Allium sativum, Silybum marianum, Panax Ginseng, Carica papaya, Vaccinium myrtillus, Phaseolus vulgaris. Some of them are proposed for treatment of symptoms related to venous and lymphatic vessel insufficiency, for the prophylaxis and treatment of liver damage caused by metabolic toxins, in chronic degenerative liver conditions, for the therapy of digestive disorders, to increase in the unspecific way the resistance of the organism to various environmental influences, and to stabilize membranes through antioxidant and radical scavenging actions.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12528524&dopt=Abstract Ref: Zhongguo Zhong Yao Za Zhi 2001 May;26(5):329-32
Effects of ginkgo biloba extract on somatosensory evoked potential and nitric oxide after subarachnoid hemorrhage
[Article in Chinese]
Sun BL, Xia ZL, Yang MF, Qiu PM.
Department of Neurology, Affiliated Hospital of Taishan Medical College, Taian 271000, Shandong, China.
OBJECTIVE: To observe the changes of somatosensory evoked potential(SEP) and nitric oxide (NO) after subarachnoid hemorrhage(SAH), and the influence of Ginkgo biloba extract (EGb). METHOD: Rats in sham-operated group, SAH model group and EGb-treated group underwent measurement of dynamic changes of regional cerebral blood flow(rCBF), SEP and NO levels both in serum and in brain tissue within 24 h after operation. RESULT: In SAH group, rCBF decreased immediately after operation, with no tendency to recover within 24 h. The latency of SEP delayed progressively from 1 h to 24 h after SAH. NO levels in serum and in brain tissue decreased and increased respectively from 1 h to 24 h after SAH. EGb effectively antagonized the changes of above parameters. CONCLUSION: SEP is helpful in the judgement on brain ischemic damage after SAH. Decrease of NO in serum and increase of that in brain tissue may lead to cerebral vasospasm and ischemic brain damage respectively after SAH. EGb relieves SAH-induced brain ischemic damage by reversing the pathological alterations of NO.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12519586&dopt=Abstract Ref: Cochrane Database Syst Rev 2002;(4):CD003120
Ginkgo biloba for cognitive impairment and dementia.
Birks J, Grimley EV, Van Dongen M.
Department of Clinical Geratology, University of Oxford, Oxford, UK, OX2 6HE.
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.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12546724&dopt=Abstract Ref: Acta Pharmacol Sin 2003 Feb;24(2):157-62
Effect of Ginkgo biloba leaf extract on electroencephalography of rat with cerebral ischemia and reperfusion.
Zhang YY, Li PF, Li D.
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 200032, China.
AIM: To test the effect of Ginkgo biloba leaf extract on electroencephalography (EEG) during cerebral ischemia and reperfusion. METHODS: Based on the quantitative analysis of EEG using the fast Fourier transform (FFT), the effect of Ginkgo biloba extract (GbE) on rat EEG was surveyed in the model of middle cerebral artery (MCA) occlusion and global cerebral ischemia. RESULTS: In the global cerebral ischemia, GbE 8 and 16 mg/kg could accelerate the recovery of EEG after reperfusion, and GbE 4 mg/kg had the same effect but much weaker. In the MCA occlusion model, GbE 16 and 32 mg/kg greatly suppressed the drop of power spectrum of EEG. CONCLUSION: GbE could mitigate the cerebral damage caused by ischemia.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12600688&dopt=Abstract Ref: Eur J Pharmacol 2003 Mar 7;464(1):1-8
Bilobalide, a sesquiterpene trilactone from Ginkgo biloba, is an antagonist at recombinant alpha(1)beta(2)gamma(2L) GABA(A) receptors.
Huang SH, Duke RK, Chebib M, Sasaki K, Wada K, Johnston GA.
Adrien Albert Laboratory of Medicinal Chemistry, Department of Pharmacology, Faculty of Medicine, University of Sydney, NSW 2006, Sydney, Australia
The sesquiterpene trilactone bilobalide is one of the active constituents of the 50:1 Ginkgo biloba leaf extract widely used to enhance memory and learning. Bilobalide was found to antagonise the direct action of gamma-aminobutyric acid (GABA) on recombinant alpha(1)beta(2)gamma(2L) GABA(A) receptors. The effect of bilobalide on the direct action of GABA at alpha(1)beta(2)gamma(2L) GABA(A) receptors expressed in Xenopus laevis oocytes using two-electrode voltage-clamp method was evaluated and compared with the effects of the classical GABA(A) receptor competitive antagonist bicuculline and noncompetitive antagonist picrotoxinin. Bilobalide (IC(50)=4.6+/-0.5 &mgr;M) was almost as potent as bicuculline and pictrotoxinin (IC(50)=2.0+/-0.1 and 2.4+/-0.5 &mgr;M, respectively) at alpha(1)beta(2)gamma(2L) GABA(A) receptors against 40 &mgr;M GABA (GABA EC(50)). While bilobalide and picrotoxinin were clearly noncompetitive antagonists, the potency of bilobalide decreased at high GABA concentrations suggesting a component of competitive antagonism.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12515221&dopt=Abstract Ref: Zhongguo Zhong Yao Za Zhi 2000 Jul;25(7):408-10
Determination of flavonoids in Ginkgo biloba L. leaves from different producing areas
[Article in Chinese]
Wang H, Zhao GB, Liu SQ, Zheng JH.
School of Pharmaceutical Sciences, Beijing Medical University, Beijing 100083, China.
OBJECTIVE: To compare the contents of flavonoids in the leaves of Ginkgo biloba gathered from 35 producing areas. METHODS: Separating and determining 3 flavonoid aglycones, quercetin, kaempferol and isorhamnetin, by high performance liquid chromatography, and there by calculating the total contents of flavonoids. RESULTS: The contents of flavonoids in the leaves of G. biloba gathered from different producing areas are different, but in those gathered from Pizhou, Zheng'an Xing'an, Anlu, etc. appear higher.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12506530&dopt=Abstract Ref: Ital Heart J 2002 Nov;3(11):689-91
Ginkgo biloba-induced frequent ventricular arrhythmia.
Cianfrocca C, Pelliccia F, Auriti A, Santini M.
Department of Cardiac Diseases, San Filippo Neri Hospital, Rome, Italy.
The use of herbal medications is becoming ever more widespread, but data for them are not yet as robust as for conventional drugs. The available safety information indicates that potential side effects of such use can be due to allergic reactions and bleeding. In this report, a case of frequent ventricular arrhythmias probably due to Ginkgo biloba is presented. The patient complained of palpitations twice in a month and on both occasions symptoms and electrocardiographic evidence of ventricular arrhythmias resolved with discontinuation of Ginkgo biloba. This case underlines that continuing research is needed to elucidate the pharmacological activities of the many herbal remedies now being used.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12501011&dopt=Abstract Ref: Jpn J Pharmacol 2002 Dec;90(4):345-51
Ginkgo biloba Extract Markedly Induces Pentoxyresorufin O-Dealkylase Activity in Rats.
Umegaki K, Saito K, Kubota Y, Sanada H, Yamada K, Shinozuka K.
National Institute of Health and Nutrition.
We examined the effect of Ginkgo biloba extract (GBE) on hepatic drug-metabolizing enzymes, particularly cytochrome P450 (CYP), in rats. Rats were fed a GBE-containing diet or received GBE by intragastric gavage. The concentration of CYP and activity of various CYP enzymes in the liver were increased in a dose- and time-dependent manner. Significant increases in the concentration and activities of CYP enzymes were detected on day 1 of feeding of a 0.5% GBE diet and after administration of 10 mg GBE/kg body weight for 5 days by intragastric gavage. Among the CYP enzymes, the activity of pentoxyresorufin O-dealkylase (PROD), a CYP2B enzyme, was especially markedly increased. The induction of CYP2B enzyme by GBE was confirmed by Western blot analysis. Addition of GBE to a CYP assay system in vitro caused concentration-dependent inhibition of various CYP enzyme activities. The inhibition was more marked for the microsomal enzymes from GBE-treated rats than for those from control rats and more marked against PROD activity among the CYP enzymes tested. When the inhibition of various CYP enzymes activities by GBE in vitro was compared, no marked difference was observed between rat and human hepatic microsomal enzymes. These results indicate that excess intake of GBE induces CYP enzymes, particularly PROD, and may modify the efficacy of drugs taken simultaneously.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12500491&dopt=Abstract Ref: Indian J Physiol Pharmacol 2002 Apr;46(2):167-74
Evaluation of hepatoprotective activity of Ginkgo biloba in rats.
Shenoy KA, Somayaji SN, Bairy KL.
Department of Pharmacology, Kasturba Medical College, Mangalore-575 001.
The mechanism of hepatoprotective effects of Ginkgo biloba (GB), an herbal preparation with wide variety of therapeutic application, on paracetamol (Pcml) induced hepatic damage in rats has been investigated. GB treatment restored the marker enzyme levels indicating the in vivo protective effects against Pcml induced liver damage both in preventive and curative aspects. GB also reversed the increased TBARS levels, and elevated the GSH content of the liver. The results obtained from the study indicate hepatoprotective nature of GB, which might be due to its ability to prevent lipid peroxidation and replenishing the gllutathione level. The effects of GB were comparable to that of silymarin.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12495553&dopt=Abstract Ref: J Pharm Pharmacol 2002 Nov;54(11):1507-14
Influence of pharmaceutical quality on the bioavailability of active components from Ginkgo biloba preparations.
Kressmann S, Biber A, Wonnemann M, Schug B, Blume HH, Muller WE.
Department of Pharmacology, University of Frankfurt, Marie-Curie-Str. 9, 60439 Frankfurt/Main, Germany.
To be effective, herbal medicinal products are expected to meet comparable standards concerning the assessment of efficacy, safety and biopharmaceutical quality as chemically defined synthetic drugs as food supplements. However, these requirements are often not fulfilled, particularly regarding the characterization of biopharmaceutical properties such as in-vitro dissolution and in-vivo bioavailability. With respect to the relevance of biopharmaceutical quality of herbal medicinal products, two different Ginkgo biloba brands (test product: Ginkgo biloba capsules; reference product: Ginkgold) were analysed for dissolution rates and bioavailability of the most relevant active ingredients. Dissolution rates at pH 1 and 4.5 were determined according to the USP 23. The relative bioavailability of ginkgolide A, ginkgolide B and bilobalide was investigated after single oral administration of 120 mg Ginkgo biloba extract as tablets or capsules. Bioavailability data (area under the curve and peak concentration in plasma) were clearly different and did not show bioequivalence of test and reference products. The slow in-vitro dissolution of the test product resulted in a large decrease in bioavailability. These results indicate for the first time that the pharmaceutical properties of a herbal medicinal product have a significant impact on the rate and extent of drug absorption, and very likely on efficacy in humans.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12494270&dopt=Abstract Ref: Basic Res Cardiol 2003 Jan;98(1):59-68
Ginkgo biloba extract EGb 761 attenuates myocardial stunning in the pig heart.
Rioufol G, Pietri S, Culcasi M, Loufoua J, Staat P, Pop C, Drieu K, Ovize M.
Hopital L. Pradel Lyon, France.
Myocardial stunning, a transient contractile dysfunction that appears following a brief period of ischemia, is at least partly due to the production of oxygen-derived free radicals. The objective of the present study was to determine whether the Ginkgo biloba extract EGb761, which has antioxidant properties in vitro, can attenuate myocardial stunning in vivo. Forty-seven anesthetized open-chest farm pigs underwent 10 min of occlusion of the left anterior descending coronary artery (LAD), followed by 3 hours of reperfusion. They were pretreated with either physiological saline, 100 mg or 300 mg of EGb 761 (Protocol I) or 3 mg or 9 mg of ginkgolide B (GkB) (Protocol II). Contractile function was assessed by sonomicrometry. Both doses of EGb 761 significantly improved recovery of contractile function in the reperfused myocardium with segment shortening averaging 23 +/- 5 % of baseline values at 3 hours post-reflow in controls versus 81 +/- 10 % and 57 +/- 12 % in the EGb100 and EGb300 groups, respectively (p < 0.05 vs control in both cases). In contrast, neither dose of GkB improved functional recovery during reperfusion. ESR experiments revealed that EGb761 resulted in a 59 % decrease in myocardial spin-adduct release during reperfusion (p < 0.05 versus control and GkB groups). A significant 28 % decrease (p < 0.05 vs control group) was also obtained in GkB-treated animals.These results indicate that EGb 761 can attenuate myocardial stunning following a brief ischemic insult in the in situ pig heart by an effect that involves a decrease in the formation of free radicals. As the effect of EGb 761 on functional recovery cannot be explained by the presence of GkB, the beneficial action of the extract on myocardial stunning likely involves complementary effects of both its non-ginkgolide and ginkgolide constituents.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12491037&dopt=Abstract Ref: Arch Toxicol 2003 Jan;77(1):22-9
Standardized extracts of flavonoids increase the viability of PC12 cells treated with hydrogen peroxide: effects on oxidative injury.
Horakova L, Licht A, Sandig G, Jakstadt M, Durackova Z, Grune T.
Neuroscience Research Center, Medical Faculty (Charite), Humboldt University Berlin, Schumannstr. 20/21, 10098 Berlin, Germany.
Oxidative stress plays an important role in cell death associated with many diseases. In the present study, concentration-dependence of hydrogen peroxide on rat pheochromocytoma (PC12) cell viability was studied. Preventive effects of antioxidants on the viability of these cells treated with 2 mM hydrogen peroxide were compared. Trolox and Stobadine, as chain-breaking antioxidants were studied in comparison with standardized extracts of flavonoids of Ginkgo biloba and Pycnogenol, known as agents effective in several diseases. All antioxidants increased the viability of hydrogen peroxide-treated PC12 cells. Flavonoid extracts were more effective than Trolox and Stobadine. Antioxidants were most effective if present after the oxidative treatment. As expected, the preloading with antioxidants was without effect on cell viability. Correlations between viability increase induced by antioxidants, and content of oxidation products of proteins and lipids were studied at concentrations of antioxidants mostly effective in preventing cell death: Trolox (10 micro M), Stobadine (30 micro M), Ginkgo biloba (160 micro g/ml), Pycnogenol (100 micro g/ml). In these concentrations, antioxidants did not statistically significantly decrease the content of protein carbonyls, with exception of Stobadine, which had no effect. Ginkgo biloba, Trolox and Stobadine intensively decreased the content of malondialdehyde, a product of lipid peroxidation. Pycnogenol was without any preventive effect. Concentrations of antioxidants with a large effect on viability of PC12 cells were not effective in preventing oxygen radical-induced injury of proteins. Antioxidants prevented the oxidative injury of lipids more effectively than that of proteins.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12473969&dopt=Abstract Ref: Psychopharmacol Bull 2002 Summer;36(3):108-23
Ginkgo biloba: a smart drug? A systematic review of controlled trials of the cognitive effects of ginkgo biloba extracts in healthy people.
Canter PH, Ernst E.
Department of Complementary Medicine, University of Exeter, United Kingdom.
Extracts of Ginkgo biloba are widely used to alleviate or delay the progress of age-related cognitive impairment. Its use as a "smart" drug by healthy individuals has also been commercially promoted. The aim of this study was to systematically review and critically evaluate the trial data to test whether Ginkgo biloba enhances cognitive function in healthy subjects. Literatures searches of 6 computerised databases were made for placebo-controlled, double-blind trials of the effect of standardized Ginkgo biloba extracts on cognitive function in healthy subjects. Trials published in any language were included and data were extracted independently by the authors following a standardized protocol. Nine trials were identified, and these were mainly short term. The longest had a treatment period of 30 days. Trials were mostly of good intrinsic methodological quality, but certain aspects of methodology were inadequately reported by all trials. Taken together, these studies indicate no marked or consistent positive effects of Ginkgo biloba on any particular objective measure of cognitive function. A positive subjective effect was reported only in the longest trial. It is concluded that a positive effect of Ginkgo biloba on cognitive function is not proven by data from rigorous clinical trials. The use of Ginkgo biloba as a "smart" drug cannot be recommended on the basis of the evidence available to date, and there is a particular need for further long-term trials with healthy subjects.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12464140&dopt=Abstract Ref: Clin Physiol Funct Imaging 2002 Nov;22(6):375-8
Effects of a Ginkgo biloba extract on forearm haemodynamics in healthy volunteers.
Mehlsen J, Drabaek H, Wiinberg N, Winther K.
Department of Clinical Physiology and Nuclear Medicine, Frederiksberg Hospital, Denmark.
The aim was to validate possible vasodilating effects of a Ginkgo biloba extract with a secondary aim of finding a pharmacodynamic signal relating to the active component of these extracts. We studied the effect of G. biloba extract on forearm haemodynamics in 16 healthy subjects (nine females, seven males) with a median age of 32 years (range: 21-47). The study was conducted as a randomized, double-blinded cross-over design using oral treatment with G. biloba extract (Gibidyl Forte(R) t.i.d. or placebo for 6 weeks. Forearm blood flow and venous capacity were measured by strain-gauge plethysmography. Blood pressure was measured by standard sphygmomanometry, and forearm vascular resistance (FVR) was derived. Measurements were made at baseline and after 3, 6, 9 and 12 weeks of treatment. Forearm blood flow was significantly higher during active treatment after 3 and 6 weeks as compared with placebo treatment for 3 and 6 weeks (P<0.05). Mean arterial blood pressure was unchanged, making the calculated FVR significantly lower during active treatment (P<0.02). It is concluded that oral treatment with a G. biloba extract (Gibidyl Forte(R)) is able to dilate forearm blood vessels causing increments in regional blood flow without changing blood pressure levels in healthy subjects. The increments in blood flow may be used as a biological signal for pharmacokinetic studies.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12457632&dopt=Abstract Ref: Pharmacol Res 2002 Dec;46(6):565-568
BILOBALIDE AND NEUROPROTECTION.
DEFEUDIS FV.
Institute for BioScience, 153 West Main Street, 01581, Westboro, MA, USA
In vivo studies have indicated that systemically administered bilobalide, a sesquiterpene trilactone constituent of Ginkgo biloba leaf extracts, can reduce cerebral edema produced by triethyltin, decrease cortical infarct volume in certain stroke models, and reduce cerebral ischemia. In vitro and ex vivo studies indicate that bilobalide has multiple mechanisms of action that may be associated with neuroprotection, including its preservation of mitochondrial ATP synthesis, its inhibition of apoptotic damage induced by staurosporine or by serum-free medium, its suppression of hypoxia-induced membrane deterioration in the brain, and its actions of increasing the expression of the mitochondrial DNA-encoded COX III subunit of cytochrome c oxidase and the ND1 subunit of NADH dehydrogenase. As multiple modes of action may apply to bilobalide, it could be useful in developing therapy for disorders involving cerebral ischemia and neurodegeneration.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12451978&dopt=Abstract Ref: Zhong Yao Cai 2002 Sep;25(9):651-3
Study on the antibacterial activity of ginkgolic acids
[Article in Chinese]
Yang X, Chen J, Qian Z, Guo T.
Jiangsu University, Zhenjiang 212013.
In this article we studied the anti-bacterial activity of the extract from testa of Ginkgo biloba and ginkgolic acids. They can inhibit the growth of Staphylocococus aureus, Escherichia coli, Bacillus subtilis, B. cereus and MRSA. Ginkgolic acids combined with peniciline can enhance their inhibitory activity to MRSA.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12451313&dopt=Abstract Ref: J Cardiovasc Pharmacol 2002 Dec;40(6):809-14
Protective effect of ginkgo biloba extract on endothelial cell against damage induced by oxidative stress.
Ren de C, Du GH, Zhang JT.
The viability of bovine aortic endothelial cells (BAECs) treated with 0.1 m H O was decreased by 39.8%, and 100 mg/l EGb761 increased the viability by 20.6%. Exposure BAECs to H O for 6 min resulted in a significant elevation in the intracellular free Ca. Pretreatment of BAECs with 10 mg/l and 100 mg/l EGb761 for 10 min showed a decrease in the intracellular free Ca, 4.5% and 20.6%, respectively. The apoptotic rate of BAECs measured by propidium iodide (PI) staining was (38.1 +/- 2%) after 18 h of treatment with H O. Pretreatment of BAECs with 100 mg/l EGb761 for 1 h reduced the apoptotic rate to 27 +/- 1%. In addition, there were about 5-7% of cells stained positive measured by TUNEL assay. When BAECs were exposed to 0.1 m H O for 18 h, the number of TUNEL-positive cells increased to 37-44%. When 10 mg/l EGb761 and 100 mg/l EGb761 were used, the TUNEL-positive cells decreased to 26.5 +/- 3.1% and 17.5 +/- 1.7%, respectively. Furthermore, EGb761 also inhibited caspase-3 activity induced by H O. It is concluded that EGb761 has protective effect on bovine vascular endothelial cells against damage induced by H O. Further studies are needed to clarify the mechanisms of action of EGb761.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12421115&dopt=Abstract Ref: CNS Drugs 2002;16(12):811-24
Non-cholinergic strategies for treating and preventing Alzheimer's disease.
Doraiswamy PM.
Departments of Psychiatry and Medicine, Duke University Medical Center, Durham, North Carolina, USA.
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.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12411102&dopt=Abstract Ref: Chin Med J (Engl) 2002 Sep;115(9):1316-20
Protective effects of Ginkgo biloba extract on rats during cerebral ischemia/reperfusion.
Hu B, Sun S, Mei G, Chen L, Tong E.
Neurology Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
OBJECTIVE: To study the effect of Ginkgo biloba extract on rats during ischemia/reperfusion and its influence on intracellular calcium in hippocampal neurons. METHODS: Model of intraluminal occlusion of the middle cerebral artery (MCAO) was used to prepare the ischemia/reperfusion cortex tissue. Concentration of MDA was determined by measuring thiobarbituric acid-reactive substance. GSH-PX was quantified using the thiobarbituric acid (TBA) technique. SOD was assayed througha xanthine method. Endogenous amino acids were quantified by high performance liquid chromatographic (HPLC) analysis. Primary culturs of hippocampal neurons were prepared for a free intracellular calcium ([Ca(2+)]I) assay by Fura-2 based single cell microfluoremetric technique. RESULTS: Comparing control and treatment groups, the concentration of SOD and GSH-PX were higher, whereas that of MDA was much lower; the concentration of glutamate and aspartate decreased and that of GABA increased markedly at all time point (P < 0.01), Gly also decreased at some time points (P < 0.05). The differences were significant between the groups of 10 mg/kg, 15 mg/kg and the groups of 5 mg/kg. When 1 x 10(-5) mol/L glutamate was applied with 25 micro g/ml ginkgo biloba extract to cultured neurons, the increase in [Ca(2+)]I was lower than that caused by applying glutamate alone. Its peak value was much lower and increased phase was longer, its declining phase was shorter. After returning to baseline, the application of 1 x 10(-5) mol/L glutamate could induce the reaction to recover. CONCLUSIONS: Ginkgo biloba extract could protect damaged neurons by keeping the balance of inhibitory/excitatory aminoacids, enhancing the free radical scavengers system, and inhibiting the effect of glutamate on [Ca(2+)]I.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12404706&dopt=Abstract Ref: Hum Psychopharmacol 2002 Jan;17(1):45-9
The acute nootropic effects of Ginkgo biloba in healthy older human subjects: a preliminary investigation.
Nathan PJ, Ricketts E, Wesnes K, Mrazek L, Greville W, Stough C.
Neuropharmacology Laboratory, Brain Sciences Institute, Swinburne University of Technology, Australia.
Ginkgo biloba has been shown to have chronic memory enhancing effects in healthy subjects and patients with dementia. There is limited research on the acute nootropic effects of Ginkgo biloba in humans. The current study aimed to examine the acute effects of Ginkgo biloba (120 mg) on memory functioning in healthy older volunteers using the cognitive drug research (CDR) battery of memory tests and the Rey auditory verbal learning task (AVLT). The study was a double-blind placebo-controlled design, with each participant tested under both placebo and Ginkgo biloba treatment conditions. Testing was conducted pre- and 90 min post-drug administration for each treatment condition. Treatment conditions were separated by a 7 day wash out period. No acute effects of Ginkgo biloba were found for any of the memory tests examined. The findings suggest that 120 mg of Ginkgo biloba has no acute nootropic effects in healthy older humans.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12404705&dopt=Abstract Ref: Hum Psychopharmacol 2002 Jan;17(1):35-44
Acute, dose-dependent cognitive effects of Ginkgo biloba, Panax ginseng and their combination in healthy young volunteers: differential interactions with cognitive demand.
Scholey AB, Kennedy DO.
Human Cognitive Neuroscience Unit, Division of Psychology, University of Northumbria, Newcastle upon Tyne NE1 8ST, UK.
The present paper describes three studies examining the acute effects of single doses of Ginkgo biloba (GK501), Ginseng (G115) and their combination (Ginkoba M/E, Pharmaton SA) on the performance of healthy young adults (mean age 21 years) during serial arithmetic tasks with differing cognitive load. In each double-blind, placebo-controlled study three different treatment doses and a placebo were administered, according to a balanced crossover design, with a 7-day washout period between each dose. Participants' scores on two computerised serial subtraction tasks (Serial Threes and Serial Sevens) were assessed pre-dosing and at 1, 2.5, 4 and 6 h thereafter. A number of significant time, dose and task-specific effects were associated with each treatment. There was a dose-dependent improvement in speed of responding during Serial Threes following Ginkgo biloba. Different doses of Ginseng improved accuracy and slowed responses during Serial Sevens. The most striking result, however, was a highly significant and sustained increase in the number of Serial Sevens responses following 320 mg of the Ginkgo-Ginseng combination at all post-treatment testing times. This was accompanied by improved accuracy during Serial Sevens and Serial Threes following the 640 mg and the 960 mg dose, respectively. The paper concludes with speculation into the possible mechanisms underlying these effects.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12404672&dopt=Abstract Ref: Hum Psychopharmacol 2002 Aug;17(6):279-84
A placebo-controlled, double-blind trial of Ginkgo biloba for antidepressant-induced sexual dysfunction.
Kang BJ, Lee SJ, Kim MD, Cho MJ.
Department of Psychiatry, School of Medicine, Kyungpook National University, Taegu, South Korea.
The aim of this study was to examine the effect of Ginkgo biloba on antidepressant-induced sexual dysfunction. The Ginkgo biloba (n=19) and the placebo groups (n=18) were divided; each to be administered with Ginkgo biloba and placebo respectively for 2 months by means of a randomized placebo-controlled, double-blind study. The results of this 2 month trial were: (1) there was no statistical significant difference from the placebo at weeks 2, 4 and 8 after medication; (2) in comparison with baseline, both the Ginkgo biloba group and the placebo group showed improvement in some part of the sexual function, which is suggestive of the importance of the placebo effect in assessing sexual function. This study did not replicate a prior positive finding supporting the use of Ginkgo biloba for antidepressant, especially SSRI, induced sexual dysfunction.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12404671&dopt=Abstract Ref: Hum Psychopharmacol 2002 Aug;17(6):267-77
A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761(R) in a sample of cognitively intact older adults: neuropsychological findings.
Mix JA, David Crews W Jr.
Liberty University, Lynchburg, Virginia, USA.
There appears to be an absence of large-scaled clinical trials that have examined the efficacy of Ginkgo biloba extract on the neuropsychological functioning of cognitively intact older adults. The importance of such clinical research appears paramount in light of the plethora of products containing Ginkgo biloba that are currently being widely marketed to predominantly cognitively intact adults with claims of enhanced cognitive performances. The purpose of this research was to conduct the first known, large-scaled clinical trial of the efficacy of Ginkgo biloba extract (EGb 761(R)) on the neuropsychological functioning of cognitively intact older adults. Two hundred and sixty-two community-dwelling volunteers (both male and female) 60 years of age and older, who reported no history of dementia or significant neurocognitive impairments and obtained Mini-Mental State Examination total scores of at least 26, were examined via a 6-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel-group, clinical trial. Participants were randomly assigned to receive either Ginkgo biloba extract EGb 761(R)(n = 131; 180 mg/day) or placebo (n = 131) for 6 weeks. Efficacy measures consisted of participants' raw change in performance scores from pretreatment baseline to those obtained just prior to termination of treatment on the following standardized neuropsychological measures: Selective Reminding Test (SRT), Wechsler Adult Intelligence Scale-III Block Design (WAIS-III BD) and Digit Symbol-Coding (WAIS-III DS) subtests, and the Wechsler Memory Scale-III Faces I (WMS-III FI) and Faces II (WMS-III FII) subtests. A subjective Follow-up Self-report Questionnaire was also administered to participants just prior to termination of the treatment phase. Analyses of covariance indicated that cognitively intact participants who received 180 mg of EGb 761(R) daily for 6 weeks exhibited significantly more improvement on SRT tasks involving delayed (30 min) free recall (p < 0.04) and recognition (p < 0.01) of noncontextual, auditory-verbal material, compared with the placebo controls. The EGb 761(R) group also demonstrated significantly greater improvement on the WMS-III FII subtest assessing delayed (30 min) recognition (p < 0.025) of visual material (i.e. human faces), compared with the placebo group. However, based on the significant difference (p < 0.03) found between the two groups' pretreatment baseline scores on the WMS-III FII, this result should be interpreted with caution. An examination of the participants' subjective ratings of their overall abilities to remember by treatment end on the Follow-up Self-report Questionnaire also revealed that significantly more (p = 0.05) older adults in the EGb 761(R) group rated their overall abilities to remember by treatment end as 'improved' compared with the placebo controls. Overall, the results from both objective, standardized, neuropsychological tests and a subjective, follow-up self-report questionnaire provided complementary evidence of the potential efficacy of Ginkgo biloba EGb 761(R) in enhancing certain neuropsychological/memory processes of cognitively intact older adults, 60 years of age and over.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12404561&dopt=Abstract Ref: Hum Psychopharmacol 2001 Jul;16(5):409-416
Cognitive effects of a Ginkgo biloba/vinpocetine compound in normal adults: systematic assessment of perception, attention and memory.
Polich J, Gloria R.
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California, USA.
A computerized test battery was used in a double-blind design to assess the cognitive effects of a nutrient compound containing Ginkgo biloba in 24 normal adults. Ten tasks (perceptual, attention and short-term memory) were presented in a standardized manner designed to maximize performance, with substantial pre-test practice employed to minimize response variability. Subjects were given either placebo or Ginkgo biloba extract capsules to consume for 14 days, after which they performed all tasks twice. They then received the other condition, and after 14 days completed the final test session. Response time and error rate stabilized after pre-test practice. A 'working memory capacity' paradigm demonstrated a reliable 50 ms response time decrease between the placebo and Ginkgo biloba testing, suggesting that Ginkgo biloba speeds short-term working memory processing in normal adults.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12404317&dopt=Abstract Ref: Hum Psychopharmacol 2000 Jun;15(4):227-235
The effects of Ginkgo biloba extract (LI 1370) supplementation on activities of daily living in free living older volunteers: a questionnaire survey.
Cockle SM, Kimber S, Hindmarch I.
HPRU Medical Research Centre, University of Surrey, Egerton Road, Guildford, Surrey GU2 5XP, UK.
This survey assessed the impact of four months supplementation with 120 mg/day of the standardized Ginkgo biloba special extract (LI 1370) on activities of daily living and various aspects of mood and sleep in a population of free living older volunteers using both observer- and self-rated scales. 5028 Participants (mean age 68.9 years) were recruited through a magazine editorial. One thousand received Ginkgo biloba extract (GBE) and the remainder were allocated to the Control group. The B-ADL (activities of daily living) Scale was completed at baseline and at the end of month 4 by an informant familiar with the participant, a Self-rating ADL scale and Line Analogue Ratings Scales of mood and sleep were completed by the participants at the end of months 1, 2, 3, and 4. There were significant differences between the GBE and Control groups on all scales at each time point. The GBE group felt better able to cope with their daily activities and showed positive changes in mood and sleep compared to the Control group. These results suggest that GBE supplementation has beneficial effects on areas of functioning that have implications for quality of life in an older population.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12399731&dopt=Abstract Ref: J Fr Ophtalmol 2002 Sep;25(7):731-2
Spontaneous hyphema caused by Ginkgo biloba extract
[Article in French]
Schneider C, Bord C, Misse P, Arnaud B, Schmitt-Bernard CF.
Service d'Ophtalmologie, CMC Gui de Chauliac, C.H.U. de Montpellier, France.
We report the first case of a patient in whom Ginkgo biloba extract proved to be the unique cause of spontaneous hyphema. Extensive ophthalmological and biological investigations were undertaken in order to assess the role of Ginkgo biloba: platelet numbering, hemostasis factors, Willebrand antigen, ristocetin cofactor, platelet glycoprotein immunophenotyping, glycoprotein expression after activation by thrombin, inflammatory markers, B-scan ultrasonography, and fluorescent iridography. No putative causes of hyphema were recorded other than Gingko biloba intake. The bleeding originated from the 12-o'clock position of the iris margin. Anamnesis identified Ginkgo biloba extract ingestion from 2 weeks before the appearance of the patient's visual trouble. Ginkgo biloba intake was stopped and the hemorrhage resolved with no recurrence during the 18 months of follow-up. Ginkgo biloba is known for platelet inhibition and is extensively used in the elderly because of its beneficial effects as a vascular protector. The clinical progression of the present case strongly suggests that Ginkgo biloba may cause hemorrhage and hyphema, even in the absence of any other predisposing factor.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12398553&dopt=Abstract Ref: J Nat Prod 2002 Oct;65(10):1501-4
Efficient extraction of ginkgolides and bilobalide from Ginkgo biloba leaves.
Lichtblau D, Berger JM, Nakanishi K.
Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, USA.
An efficient and rapid protocol has been developed for extracting ginkgolides and bilobalide (terpene trilactones) from Ginkgo biloba leaves. The procedure takes advantage of the extraordinary stability of the terpene trilactone structure to a variety of chemical treatments, especially oxidation, despite the presence of multiple oxygen functions. The protocol involves boiling the aqueous extract of leaves with dilute hydrogen peroxide, extraction with ethyl acetate, washing with basic solutions, and charcoal filtration to yield an off-white powder, terpene trilactone content 60-70%. It is likely that the hydrogen peroxide treatment degrades the undesired leaf constituents that lead to intense emulsification during extractions. Further reversed-phase chromatography of the extracts with polymeric resins removes the undesirable ginkgolic acids to amounts less than 10 ppm. The extracts are suited for pure terpene trilactone preparation, enrichment of terpene trilactone content in nutraceuticals, and preparations of low-flavonoid/high-terpene trilactone controls in medicinal studies. The four ginkgolides (ginkgolides A, B, C, J) and bilobalide isolated from the extract were identical in all respects with authentic specimens.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396085&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):725-31
Ginkgo biloba extract EGb 761 increases stress resistance and extends life span of caenoraibditis elegans.
Wu Z, Smith JV, Paramasivam V, Butko P, Khan I, Cypser JR, Luo Y.
Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg 39406, USA.
EGb 761, a standardized extract of Ginkgo biloba leaves, has been used in clinical trials for its beneficial effects on brain functions. In mammals, EGb 761 has been shown to enhance cognition, stress resistance, and longevity, but its molecular and cellular mechanisms are not known. In the present investigation, we used the model organism Caenorhabditis elegans to evaluate pharmacological effects of EGb 761 on aging. We tested the theory that EGb 761 augments the natural antioxidant system of C elegans, and thus increases stress resistance and longevity. We found that treatment of the wild-type worms with EGb 761 extended their median life span by 8%. Amongst several purified components of EGb 761, the flavonoid tamarixetin showed the most dramatic effect: it extended the median life span by 25%. Furthermore, EGb 761 increased the wild type's resistance to acute oxidative and thermal stress by 33% and 25%, respectively. Treatment of the prematurely aging mutant worms mev-1 with EGb 761 increased their resistance to acute oxidative and thermal stress by 33% and 11%, respectively. It appears that oxidative stress, a major determinant of life span, as well as other types of stress, can be successfully counteracted by the Ginlkgo biloba extract EGb 761.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396084&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):717-23
The Ginkgo biloba extract modulates the balance between proliferation and differentiation in the olfactory epithelium of adult mice following bulbectomy.
Didier A, Jourdan F.
Laboratoire de Neurosciences et Systemes Sensoriels, Universite Claude Bernard Lyon1, CNRS UMR 5020, France.
Abstract - The adult olfactory receptor neurons (ORNs), located in the olfactory epithelium (OE) are permanently renewed thanks to neuronal progenitors present in the deep part of the OE, the globose basal cells (GBCs). Following the ablation of their synaptic target, the olfactory bulb (OB), ORNs degenerate by apoptosis and a wave of neurogenesis, including proliferation of GBCs and neuronal differentiation of their progeny, restores the olfactory function. The Ginkgo biloba extract (EGb 761) (Beaufour Ipsen, France) was administered to adult mice at the doses of 50 or 100 mg/kg, following bilateral bulbectomy and its effects on the expression of PCNA, reflecting the number of proliferating GBCs and on growth associated protein 43 (GAP-43), expressed by differentiating neurons were measured by Western blotting. PCNA expression peaked 9 days post-bulbectomy in untreated animals, but 7 days post-lesion in EGb 761-treated animals. A simultaneous reduction in GAP-43 expression suggested that EGb 761 may temporarily favor the proliferation of GBCs rather than their entry into the differentiation pathway. Probably as a consequence of the earlier onset of the neurogenetic response to bulbectomy, neuronal differentiation was enhanced in the OE, 3 weeks post-bulbectomy. These data suggest that EGb 761 may have beneficial effects upon neurogenesis in the OE through changing the balance between proliferation and differentiation.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396082&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):699-707
Anti-apoptotic properties of Ginkgo biloba extract EGb 761 in differentiated PC12 cells.
Smith JV, Burdick AJ, Golik P, Khan I, Wallace D, Luo Y.
Department of Biological Sciences, University of Southern Mississippi, Hattiesburg 39406-5018, USA.
Standard Ginkgo biloba leaf extract (EGb 761) has been known to have neuroprotective effects ranging from molecular and cellular, to animal and human studies, however, the cellular and molecular mechanisms remain unclear. Using PC 12 cells, a well-established model for studying neuroprotection, we have determined the mechanism of action of EGb 761 on cell survival following apoptosis induced by serum-deprivation or treatment with staurosporine (STS). Our results show that EGb 761 treatments of PC12 cells are able to prevent serum deprivation- and STS-induced mitochondrial damage, attenuate release of cytochrome c and DNA fragmentation. EGb 761, but not vitamin E. inhibited STS-induced activation of the caspase-3 enzyme. Two of the EGb 761 components, bilobalide B and ginkgolide C show more significant inhibition than the EGb 761 extract. Furthermore, DNA microarray assay results indicate that transcription of multiple apoptosis-related genes is either up- or down-regulated in cells treated with EGb 761. These results suggest that inhibition of apoptotic machinery may, at least in part, mediate multiple neuroprotective effects of EGb 761, and that EGb 761 and vitamin E act on different molecular paths to provide neuroprotection.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396080&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):685-92
Ginkgo biloba extract EGb 761 protects against mitochondrial aging in the brain and in the liver.
Sastre J, Lloret A, Borras C, Pereda J, Garcia-Sala D, Droy-Lefaix MT, Pallardo FV, Vina J.
Departamento de Fisiologia, Facultad de Medicina, Universitat de Valencia, Spain.
According to the free radical theory of aging, oxygen-derived free radicals causes the age-associated impairment at the cellular and tissue levels. The mitochondrial theory of aging points to mitochondria, and specially mitochondrial DNA, as the major targets of free radical attack upon aging. Thus, oxidative damage to mtDNA accumulate with age in human and rodent tissues and also is inversely related to maximum life span of mammals. Mitochondrial deficits, such as a decrease in mitochondrial membrane potential, occur upon aging due to oxidative damage. The age-related mitochondrial oxidative stress may be prevented by late onset administration of certain antioxidants, such as Ginkgo biloba extract EGb 761. These antioxidants may also delay the physiological impairment associated with aging.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396079&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):681-4
Effects of chronic administration of bilobalide on amino acid levels in mouse brain.
Sasaki K, Hatta S, Wada K, Itoh M, Yoshimura T, Haga M.
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, lshikari-Tobetsu, Japan.
We have previously demonstrated that 4-day-treatment of mice with bilobalide, a sesquiterpene of Ginkgo biloba L., increases GABA levels in mouse brain, but, effects of chronic treatment with it are not clear. To study effects of chronic treatment of mice with bilobalide on amino acid levels in the brain, we determined the levels of aspartate, glutamate, serine, glutamine, glycine, taurine and GABA in the hippocampus, striatum and cortex. Bilobalide (3 mg/kg/day) was administered orally to 4-week-old mice for 40 days. Bilobalide treatment resulted in a significant increase in the levels of glutamate, aspartate, gamma-aminobutyric acid (GABA), and glycine in the hippocampus of mice compared with the control. An increased level of glycine after bilobalide treatment was also detected in the striatum. In the cortex, bilobalide increased the GABA level, whereas it decreased the level of aspartate. These changes in the levels of various amino acids may be involved in the broad spectrum of pharmacological activities of the extract of Ginkgo biloba on the central nervous system.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396078&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):671-9
Ginkgo biloba extract (EGb 761) protects Na,K-ATPase isoenzymes during cerebral ischemia.
Pierr S, Jamme I, Robert K, Gerbi A, Duran MJ, Sennoune S, Droy-Lefaix MT, Nouvelot A, Maixent JM.
Laboratoire de Recherche Cardiologique, Universite de la Mediterranee, Faculte de Medecine, IFR Jean-Roche, Marseille, France.
Disturbances of Na,K-ATPase activity are implicated in the pathophysiology of cerebral ischemia. Previous experiments have shown that EGb 761 protects NaK-ATPase activity against one hour of cerebral ischemia. In the brain however, the 3 isoenzymes responsible for Na,K-ATPase activity may be differentially affected by various times of ischemia. In the present study, we investigated the effect of a longer period of ischemia, and the protection provided by a pre-treatment with EGb 761 on each of the 3 cerebral NaK-ATPase isoenzymes. In control and EGb 761 pre-treated mice exposed to a 6 hr unilateral occlusion of the middle cerebral artery, Na,K-ATPase activity was decreased by 60% and lipid peroxidation was increased by 40% in the ipsilateral (ischemic) cortex compared to the contralateral one. In parallel, membrane integrity was altered. The alteration of NaK-ATPase activity, as a whole, resulted from a decrease in the activity of the 3 isoenzymes. The two isoenzymes of high ouabain affinity however, had their affinities decreased while the sensitivity of the lowest affinity isoenzyme was increased. Pre-treatment with EGb 761 abolished the differences observed between ipsi- and contralateral cortex, with the exception of the change in ouabain affinity of the low affinity isoenzyme. Ischemia also induced changes in Na,K-ATPase isoenzyme ouabain affinities in the contralateral cortex that where not prevented by EGb 761.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396077&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):663-9
Bilobalide, a component of the Ginkgo biloba extract (EGb 761), protects against neuronal death in global brain ischemia and in glutamate-induced excitotoxicity.
Chandrasekaran K, Mehrabian Z, Spinnewyn B, Chinopoulos C, Drieu K, Fiskum G.
Department of Anesthesiology, University of Maryland School of Medicine, Baltimore 21201, USA.
In this study, the effect of bilobalide, a purified terpene lactone component of the Ginkgo biloba extract (EGb 761), and EGb 761 against ischemic injury and against glutamate-induced excitotoxic neuronal death was compared. In the case of ischemic injury, neuronal loss and the levels of mitochondrial DNA (mtDNA)-encoded cytochrome oxidase (COX) subunit III mRNA in the hippocampal regions of gerbils was measured. A significant increase in neuronal death and a significant decrease in COX III mRNA were observed in the hippocampal CA1 neurons at 7-days of reperfusion after 5 min of transient global forebrain ischemia. Oral administration of EGb 761 at 25, 50 and 100 mg/kg/day and bilobalide at 3 and 6 mg/kg/day for 7 days before ischemia progressively protected hippocampal CA1 neurons against ischemia-induced neuronal death and reductions in COX III mRNA. In rat cerebellar neuronal cultures, addition of bilobalide or EGb 761 protected in a dose-dependent manner against glutamate-induced excitotoxic neuronal death [effective concentration (EC50) = 5 microg/ml (12 microM) forbilobalide and 100 microg/ml for EGb 761]. These results suggest thatboth EGb 761 and bilobalide protect against ischemia-induced neuronal death in vivo and glutamate-induced neuronal death in vitro by synergistic mechanisms involving anti-excitotoxicity, inhibition of free radical generation, scavenging of reactive oxygen species, and regulation of mitochondrial gene expression.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396076&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):655-62
Common gene targets of Ginkgo biloba extract (EGb 761) in human tumor cells: relation to cell growth.
Li W, Pretner E, Shen L, Drieu K, Papadopoulos V.
Department of Cell Biology, Georgetown University Medical Center, Washington, DC 20057 USA.
The standardized extract of Ginkgo biloba leaves (EGb 761) has been shown to inhibit aggressive human breast cancer cell proliferation both in vitro and in vivo. These results were extended to human glioma and hepatoma cells in vitro suggesting that EGb 761 may have a more widespread application for tumor growth control. To understand the mechanism by which EGb 761 acts to inhibit cell proliferation, we investigated the effects of EGb 761 on human breast cancer, glioma and hepatoma cell transcriptomes by means of various large-scale DNA array techniques. The data presented focus on genes regulated by EGb 761 that are common to the three tumor cell types and for which the data were verified by two different types of DNA microarray and/or RNA (Northern) blot analysis and real-time quantitative PCR. These results could therefore help elucidate the mechanism of cytostatic action of EGb 761 and identify genes important for tumor growth.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396075&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):647-53
Induction of heme oxygenase 1 by Ginkgo biloba in neuronal cultures and potential implications in ischemia.
Zhuang H, Pin S, Christen Y, Dore S.
Ginkgo biloba extract (EGb 761) is a standardized extract originating in traditional Chinese medicine. Ginkgo biloba dried leaves have been used for centuries to treat various neurological conditions. The constituents from the extract are likely to have synergistic effects that have been shown to be protective against oxidative stress injury. However, the cellular mechanisms of protection afforded by Ginkgo biloba are still unclear. The cascade leading to neuronal cell death in acute and chronic neurodegenerative conditions, such as cerebral ischemia and Alzheimer's disease, has been postulated to be mediated by free radical damage. We tested the hypothesis that the neuroprotective action of EGb 761 could be due partially to an induction of heme oxygenase I (HO1). We and others have previously reported that modulation of HO total activity may well have direct physiological implications in stroke and in Alzheimer's disease. Heme oxygenase acts as an antioxidant enzyme by degrading heme into iron, carbon monoxide, and biliverdin which is rapidly converted into bilirubin. Through the use of primary neuronal cultures, we demonstrated that EGb 761 induces HO1 in a dose-dependent manner (0, 10, 50, 100 and 500 microg/ml) and time-dependent manner with a maximal induction at 8 hr. We are proposing that several of the protective effects of EGb 761 in ischemia could be mediated through beneficial actions of heme degradation and its metabolites.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396074&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):641-6
The Ginkgo biloba extract EGb 761 increases viability of hnt human neurons in culture and affectsthe expression of genes implicated in the stress response.
Soulie C, Nicole A, Christen Y, Ceballos-Picot I.
INSERM U383, Hjpital Necker, Paris, France.
There are numerous studies describing the neuroprotective effects of Ginkgo biloba extract EGb 761 on patients with disturbances of vigilance, memory and cognitive functions associated with aging and senility. Describing the pattern of gene expression in EGb 761-treated human hNT neurons may elucidate the molecular pathways leading to the neuroprotection. We used cDNA macroarrays including genes implicated in the antioxidant and stress responses to define the transcriptional effects of EGb 761 (250 microg/ml, 24 hr) on human hNT neurons. Seven genes were identified whose expression was strongly modified by the EGb 761 treatment. Three groups are distinguished: genes encoding transcription factors (increase of NF-kappaB p65 subunit and zinc finger protein 91 mRNAs, and decrease of c-myc transcripts), genes involved in antioxidant defenses (increase of the CuZn SOD mRNAs, and decrease of glutathione reductase and glutathione S-transferase pi mRNAs) and genes involved in stress responses (up-regulation of HSP70 transcripts). Consistent with the modulation of mRNAs by EGb 761, the enzymatic activities of glutathione reductase and glutathione S-transferase were decreased. Surprisingly, CuZn SOD activity was decreased despite increased abundance of the mRNAs; furthermore MnSOD activity was unmodified, and thus the effect of EGb 761 was specific to CuZn SOD. These results support the idea that modulation of target genes and transcription factors may be involved in the neuroprotective action of EGb 761.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396073&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):633-9
Use of ginkgolide B and A ginkgolide-activated response element to control gene transcription: example of the adrenocortical peripheral-type benzodiazepine receptor.
Amri H, Drieu K, Papadopoulos V.
Department of Cell Biology, Georgetown University Medical Center, Washington, DC, USA.
Identification of the molecular switch controlling glucocorticoid synthesis might facilitate the development of pharmacological tools to control circulating cortisol levels. The transport of cholesterol from intracellular sources to the inner mitochondrial membrane represents the rate-determining step in the cascade of reactions leading to cortisol synthesis. A key element in this step is the peripheral-type benzodiazepine receptor (PBR). Several studies have indicated the beneficial effects of Ginkgo biloba on memory and stress control. Using pharmacological, biochemical and proteomic methods, we demonstrated that the standardized Ginkgo biloba extract EGb 761 and its isolated component ginkgolide B (GKB) inhibit PBR ligand binding and protein expression, resulting in decreased serum corticosterone levels. We further demonstrated that EGb 761- and GKB-induced inhibition of PBR protein is preceded by a decrease in mRNA-levels due to transcriptional suppression of PBR gene expression. Further studies indicated that the action of GKB is mediated by a transcription factor binding to the PBR gene promoter, thereby regulating PBR gene expression. These data indicate that EGb 761-induced inhibition of glucocorticoid production is due to specific transcriptional suppression of the adrenal PBR gene by GKB, and suggest that EGb 761 and GKB might serve as pharmacological tools to control excess glucocorticoid formation.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396072&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):625-31
Global gene expression analysis identifies cell and tissue specific actions of Ginkgo biloba extract, EGb 761.
Gohil K, Packer L.
University of California, Davis 95616, USA.
Clinical and pre-clinical uses of Ginkgo biloba extract encompass a broad spectrum of pathologies that include peripheral arterial disorders, cardiovascular and neuronal dysfunctions and resolution of ischemia-reperfusion injuries. Many of these pathologies develop over time and recruit multiple cell types and molecular pathways that alter the cellular a nd molecular profiles of the failing targetorgans. Transcriptional processes are important determinants of the pathogenesis of these chronic disease states. Therefore the potential therapeutic and preventive actions of a standardized Ginkgo biloba extract, EGb 761, may be affected through modulation of transcriptional processes. We have used various techniques for large-scale mRNA expression analysis, including differential display of mRNAs, cDNA arrays and high-density oligonucleotide arrays, to evaluate the actions of EGb 761 on the activities of the genomes in vitro and in vivo. The results show broad but cell specific actions of Ginkgo biloba extract that may enhance antioxidant defenses in vitro in cancer cells and modulate neuronal functions in cortex and hippocampus in brain in vivo. The large scale analysis of mRNAs in response to Ginkgo biloba extract in vitro and in vivo show that the standardized extract affects the activities of the mammalian genome. The data provide some support for the concept that the actions of EGb 761 are mediated through it effects on the process of gene transcription which plays a causative role in chronic diseases.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396071&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):613-23
Ginkgo biloba extract: from molecular mechanisms to the treatment of Alzhelmer's disease.
Zimmermann M, Colciaghi F, Cattabeni F, Di Luca M.
Dept of Pharmacological Sciences, University of Milano, Italy.
Ginkgo biloba is registered for the treatment of several diseases and disorders in Europe. In the United States, it is marketed as a dietary supplement; the French and the German agencies consider it to be effective for the treatment of several diseases, and the immense amount of clinical studies concerning Ginkgo biloba makes it worth revising the existing literature about this notable plant. A brief history of the common use of this drug will be followed by a short botanic characterization. The biochemical composition of the original drug, the leaf itself, will be described in detail together with a brief discussion of commercial extracts and the problem of studying Ginkgo biloba clinically to verify the safety and efficacy of its extracts in the treatment of disorders like Alzheimer's diseases. Aspects of molecular mechanisms modifying the efficacy of this drug will be outlined. Several agents like antioxidants, anti-inflammatory drugs, cholinergic agents, estrogens, or neurotrophic factors are in use for the treatment of this neurodegenerative disease, but none can prove fully convincing benefit. In this field, Ginkgo biloba appears as a useful and sensible supplementary medication to treat Alzheimer's disease, as it seems to be a synthesis of all the different profiles of action of the various, commonly used drugs but with less side effects.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396070&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):601-11
What is Ginkgo biloba extract EGb 761? An overview--from molecular biology to clinical medicine.
Christen Y, Maixent JM.
Beaufour-Ipsen, Paris, France.
EGb 761 (extract of Ginkgo biloba 761) comes from a single type of tree, a living fossil, the only remaining representative of its phylum; it contains chemical substances unknown in other living things. The flavonoid fraction accounts for 24% of the extract and terpenes (ginkgolides and bilobalide) for 6%. It acts in many different situations and organs, and exerts protective effect on neurodegenerative, sensory, and vascular diseases. In all of these different domains, it has been shown to act at all levels of the organization of life: molecules, cells, tissue, entire organisms, sometimes in particular situations (related to a particular pathology or to senescence) and in humans. Although many questions remain, what stands out in the literature is the overall consistency of the data. Particularly remarkable is that EGb 761 does not exert a specific unidirectional action (activating or inhibiting) in these various domains of physiology and pathology; rather it is regulatory, helping the organism to adapt to the circumstances in which it finds itself.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12396069&dopt=Abstract Ref: Cell Mol Biol (Noisy-le-grand) 2002 Sep;48(6):593-9
Egb 761 in the postgenomic era: new tools from molecular biology for the study of complex products such as Ginkgo biloba extract.
Christen Y, Olano-Martin E, Packer L.
Beaufour Ipsen, Paris, France.
The decoding of the human genome has completely changed our views on medicine. Beyond sequencing, tools of the postgenomic era may lead to a better understanding of various therapies, especially those with a complex effect on numerous cellular components and functions. The development of high-density oligonucleotide microarrays led to pioneer studies on the multiple gene expression effects exhibited by Ginkgo biloba extract EGb 761, changing traditional pharmacology and medicine concepts. Instead of studying a simple gene or protein, a global investigation of all genes or proteins at once can give insights of the complexity of biological systems.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12392793&dopt=Abstract Ref: Neurobiol Aging 2002 Sep-Oct;23(5):891-97
Natural extracts as possible protective agents of brain aging.
Bastianetto S, Quirion R.
Department of Psychiatry and Pharmacology and Therapeutics, Douglas Hospital Research Centre, McGill University, 6875 LaSalle Boulevard, Verdun, Que, Canada H4H 1R3.
A growing number of studies suggest that natural extracts and phytochemicals have a positive impact on brain aging. We examined the potential of the Ginkgo biloba extract EGb 761 and red wine-derived constituents on cell death produced by beta-amyloid (Abeta) peptides and oxidative stress, with respect to their possible deleterious role in age-related neurological disorders. We found that EGb 761, possibly through the antioxidant properties of its flavonoids, was able to protect hippocampal cells against toxic effects induced by Abeta peptides. Moreover, we showed that an exposure of rat hippocampal cells to the nitric oxide (NO) donor sodium nitroprusside (SNP) resulted in a decrease in cell survival and increase in reactive oxygen species (ROS) accumulation. However, EGb 761 and red wine-derived polyphenols protected against these events, due to their antioxidant activities, and their ability to block SNP-stimulated activity of protein kinase C (PKC). Taken together, these results support the hypothesis that dietary intake of natural substances may be beneficial in normal aging of the brain.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12387790&dopt=Abstract Ref: Exp Eye Res 2002 Oct;75(4):421-30
Molecular and cellular assessment of ginkgo biloba extract as a possible ophthalmic drug.
Thiagarajan G, Chandani S, Harinarayana Rao S, Samuni AM, Chandrasekaran K, Balasubramanian D.
Hyderabad Eye Research Foundation, L. V. Prasad Eye Institute, India.
We have investigated the biochemical and cell biological basis of the reported beneficiary effects of the leaf extracts of the plant Ginkgo biloba, which has been used as a possible ophthalmic drug. The antioxidant, antimicrobial, anti-apoptotic and cytoprotective properties of the standardized extract called EGb761 were assayed. Chemical stresses were induced in cells using alloxan or dexamethasone, and the effect of EGb761 on them was studied using the MTT and TUNEL assays. Its ability to modulate the activities of some antioxidant enzymes was tested in vitro. In addition, cataract was induced in rats through selenite injection, and the effect of EGb761 administration on the progression of cataract was studied using slit lamp examination. Ginkgo biloba was found to be an excellent antioxidant. It readily scavenges reactive oxygen and nitrogen radicals and inhibits oxidative modifications that occur to proteins in vitro. It enters intact cells and protects them from alloxan-mediated and light-mediated stress, and the nuclear DNA from single strand breaks. It also effectively inhibits chemically induced apoptosis. It does not modulate the activities of endogenous antioxidant enzymes, nor does it have any significant antimicrobial activity. Unlike some other plant extracts, it is not phototoxic. In experiments wherein selenite cataract was induced in laboratory rats, treatment with the extract significantly retards the progression of lens opacification in vivo. Ginkgo biloba's inherent antioxidant, antiapoptotic and cytoprotective action and potential anticataract ability appear to be some of the factors responsible for its beneficial effects.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12378625&dopt=Abstract Ref: World J Gastroenterol 2002 Oct;8(5):832-6
Apoptosis of hepatoma cells SMMC-7721 induced by Ginkgo biloba seed polysaccharide.
Chen Q, Yang GW, An LG.
Department of Biology, Shandong Normal University, Jinan 250014, Shandong Province, China.
AIM: To study the apoptosis of hepatoma cells SMMC-7721 induced by polysaccharide isolated from Ginkgo biloba seed. METHODS: Ginkgo biloba seed polysaccharide (GBSP) was isolated by ethanol fractionation of Ginkgo biloba seed and purified by Sephadex G-200 chromatography. The purity of GBSP was verified by reaction with iodine-potassium iodide and ninhydrin and confirmed by UV spectrophotometer, cellulose acetate membrane electrophoresis and Sepharose 4B gel filtration chromatography. The Scanning Electron Microscope (SEM) and Flow Cytometry (FCM) were used to examine the SMMC-7721 cells with and without GBSP treatment at 500 mg/ml for 36 h. RESULTS: GBSP product obtained was of high purity with the average molecular weight of 1.86 X 10(5). Quantitative analysis of SMMC-7721 cells in vitro with FCM showed that the percentages of G(2)-M cells without and with GBSP treatment were 17.01+/-1.28 % and 11.77+/-1.50% (P<0.05), the debris ratio of the cells were 0.46+/-0.12 % and 0.06+/-0.06 % (P<0.01), and the apoptosis ratio of cells was 3.84+/-0.55 % and 9.13+/-1.48 % (P<0.01) respectively. Following GBSP treatment, microvilli of SMMC-7721 cells appeared thinner and the number of spherical cells increased markedly. Most significantly, the apoptosis bodies were formed on and around the spherical cells treated with GBSP. CONCLUSION: GBSP could potentially induce the apoptosis of SMMC-7721 cells.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12378150&dopt=Abstract Ref: Ann Pharm Fr 2002 Jul;60(4):232-6
Protection of synaptosomal polyunsaturated fatty acids from by extract of Ginkgo biloba-EGb 761
[Article in French]
Ramassamy Ch, Nouvelot A, Christen Y, Costentin J.
Universite du Quebec a Trois Rivieres, Dept. Chimie-Biologie CP 500, Trois Rivieres, Canada/G9A 5H7.
Previous studies have demonstrated that ascorbic acid associated with ferrous ions induced deleterious effects on several targets or functions of striatal dopaminergic nerve endings, which were prevented by the Ginkgo biloba extract EGb 761. The present study attempted to assess whether a peroxidation of polyunsaturated fatty acids of their membranes could be associated with (or even responsible for) these alterations. Synaptosomes were prepared from mice striata. Their 1 h incubation with ascorbic acid (0.1 mM) resulted in a marked increase (+300%) of thiobarbituric acid reactive substances, that roughly are considered to correspond to the malondialydehyde level. Under these conditions the level of polyunsaturated fatty acids, measured by gas chromatography, decreased by -23% whereas the level of saturated fatty acids was not modified. Both the increase in thiobarbituric acid reactive substances and the decrease in polyunsaturated fatty acids were prevented by EGb 761 (10 micro g/ml). Similarly, the increase of TBARS was prevented by the vitamin E analogue trolox C (0.1mM) as well as by the ferrous ions chelating agent desferrioxamine (0.1mM). These data suggest that the polyunsaturated fatty acids peroxidation could be the origin of previously reported synaptosomal alterations induced by ascorbic acid/Fe(2 +).
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12377378&dopt=Abstract Ref: Neurosci Lett 2002 Oct 25;332(1):33-6
Effect of quercetine on survival and morphological properties of cultured embryonic rat spinal motoneurones.
Ternaux JP, Portalier P.
Unite de Neurocybernetique Cellulaire, FRE 2102 CNRS, Universite de la Mediterranee, 280 Bd. Sainte Marguerite, 13009 Marseille, France.
Quercetine a flavonoid compound present in many plants and in the extract of Ginkgo biloba was shown to enhance the survival of purified rat spinal embryonic motoneurones, sampled at day embryonic 15 and maintained in culture for several days. Survival of embryonic spinal motoneurones is dose dependent and concentrations of quercetine ranging from 1 to 10 microM increase by 25% the number of living motoneurones in the culture. Excepted a slight significant decrease in the number of branches at day 3 and a small reduction of total neuritic length, no drastic changes in the motoneurones morphologies were observed in presence of quercetine. Results are discussed in term of neuronal protective effect of quercetine.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12370096&dopt=Abstract Ref: Acta Pharmacol Sin 2002 Oct;23(10):919-23
Inhibitory effects of Ginkgo biloba extract on vascular endothelial growth factor in rat aortic endothelial cells.
Zhang L, Rui YC, Yang PY, Qiu Y, Li TJ, Liu HC.
Department of Pharmacology, School of Pharmacy,The Second Military Medical University, Shanghai 200433, China.
AIM: To study the protective effects of Ginkgo biloba extract (GbE) against rat aortic endothelial cells (RAEC) damage induced by lysophosphatidylcholine (LPC). METHODS: Cell injury were determined by MTT assay and LDH release. Vascular endothelial growth factor (VEGF) protein production from RAEC was determined by enzyme-linked immunosorbent assay (ELISA). VEGF mRNA expression was examined by in situ hybridization and dot blot. RESULTS: GbE 0.01-1 microg/L prevented LPC-induced injury in cultured RAEC in a concentration-dependent manner. Cultured RAEC could express VEGF protein and VEGF mRNA was induced by LPC 5 mg/L. GbE could inhibit the expression of VEGF protein and VEGF mRNA in co-cultured RAEC with LPC. CONCLUSION: LPC could induce a strong expression of VEGF in RAEC. GbE could protect RAEC against the LPC-induced damage and downregulate VEGF protein and VEGF mRNA expression in cultured RAEC.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12369732&dopt=Abstract Ref: J Physiol Pharmacol 2002 Sep;53(3):337-48
Reduction of rise in blood pressure and cortisol release during stress by Ginkgo biloba extract (EGb 761) in healthy volunteers.
Jezova D, Duncko R, Lassanova M, Kriska M, Moncek F.
Laboratory of Pharmacological Neuroendocrinology, Slovak Academy of Sciences, Bratislava.
The standardized extract of Ginkgo biloba (EGb 761) was found not only to improve memory and aging associated cognitive deficits but also to exert beneficial effects on mood. An antistress action of the extract has been suggested but not directly proven. The present study was aimed to evaluate the effects of EGb 761 on salivary cortisol and blood pressure responses during stress in healthy young volunteers (n = 70) in a double blind placebo controlled design. A stress model involving a combination of static exercise (handgrip) and mental stimuli was used. Single treatment with EGb 761 (120 mg) reduced stress-induced rise in blood pressure without affecting the heart rate. Salivary cortisol responses showed differences with respect to the gender and the time of day of the stress exposure, with the activation only in male subjects in the afternoon. This activation was absent if they were treated with EGb 761. The performance in a short memory test with higher scores achieved by women remained unaffected by EGb 761 treatment. Thus, this study provides evidence that EGb 761 has an inhibitory action on blood pressure and it may influence cortisol release in response to some stress stimuli.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12366386&dopt=Abstract Ref: Clin Exp Pharmacol Physiol 2002 Nov;29(11):963-7
Effects of Ginkgo biloba extract (EGb 761) on cerebral thrombosis and blood pressure in stroke-prone spontaneously hypertensive rats.
Sasaki Y, Noguchi T, Yamamoto E, Giddings JC, Ikeda K, Yamori Y, Yamamoto J.
Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan.
1. An extract of Ginkgo biloba (EGb 761) has been reported to alleviate cerebrovascular problems. In the present study, we investigated the antithrombotic effects of EGb 761 in cerebral blood vessels of stroke-prone spontaneously hypertensive rats (SHRSP/Izm). 2. In the present study, EGb 761 was administered orally to SHRSP/Izm at 60 and 120 mg/kg each day for 3 weeks from the age of 7 weeks. The age-related increase in blood pressure observed in SHRSP was suppressed significantly by EGb 761 at both doses 3 weeks after treatment. 3. Thrombotic potential was assessed in vivo using a He-Ne laser-induced thrombosis model and was significantly suppressed by EGb 761. 4. The anti-oxidant effects of EGb 761 were determined by measurement of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). At 120 mg/kg, EGb 761 decreased 8-OHdG significantly compared with control animals. 5. Urinary nitrite/nitrate, nitric oxide (NO) metabolites, were increased significantly after administration of EGb 761. Expression of endothelial NO synthase (eNOS) mRNA was measured using a real-time quantitative reverse transcription-polymerase chain reaction method. The expression of eNOS mRNA in the EGb 761 group (120 mg/kg) was significantly higher than in the control group. 6. The results indicate that EGb 761 decreases blood pressure and mediates strong antithrombotic and anti-oxidant effects in SHRSP. These pharmacological activities may contribute to the beneficial properties of EGb 761 observed in clinical practice.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12362826&dopt=Abstract Ref: Ugeskr Laeger 2002 Sep 2;164(36):4161-5
Herbal medicines--evidence and drug interactions in clinical practice
[Article in Danish]
Kistorp TK, Laursen SB.
Amtssygehuset i Gentofte, anaestesiologisk afdeling, H:S Frederiksberg Hospital, anaestesiklinikken. k
We present an evidence-based literature review of five commonly used herbs in Denmark: St John's wort, ginkgo biloba, valerian, garlic, and ginseng. Various drug interactions are associated with the intake of some herbal medicines, and may result in many clinical conditions. We bring this to the attention of clinical practitioners. Attention to clinical practice and recommendations for discontinuation of the five herbs are given before surgery. Physicians should be aware of and report potential drug interactions and adverse effects, so as to throw more light on this subject.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12354581&dopt=Abstract Ref: Life Sci 2002 Oct 18;71(22):2625-31
The effects of melatonin and Ginkgo biloba extract on memory loss and choline acetyltransferase activities in the brain of rats infused intracerebroventricularly with beta-amyloid 1-40.
Tang F, Nag S, Shiu SY, Pang SF.
Department of Physiology, Faculty of Medicine, The University of Hong Kong, China.
Intraventricular infusion of rats with beta-amyloid for 14 days resulted in memory deficit in the water maze as well as decreases in choline acetyltransferase activities and somatostatin levels in the cerebral cortex and hippocampus. These changes were not altered by daily intraperitoneal injection of 20 mg/Kg melatonin. Orally administered Ginkgo biloba extract, however, partially reversed the memory deficit and the decrease in choline actyltransferase activities in the hippocampus. The latter treatment failed to reverse the decrease in somatostatin levels. The results indicate that orally administered Ginkgo biloba extract can protect the brain against beta-amyloid from changes leading to memory deficit through its effect on the cholinergic system.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12269382&dopt=Abstract Ref: Life Sci 2002 Apr 26;70(23):2783-92
Feeding of Ginkgo biloba extract (GBE) enhances gene expression of hepatic cytochrome P-450 and attenuates the hypotensive effect of nicardipine in rats.
Shinozuka K, Umegaki K, Kubota Y, Tanaka N, Mizuno H, Yamauchi J, Nakamura K, Kunitomo M.
Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women s Univ., Nishinomiya, Japan.
Ginkgo biloba extract (GBE) has been used clinically for improving peripheral vascular diseases in France and Germany and is ingested widely as a herbal medicine in some countries. However, accurate information about its safety as an herbal medicine has not been sufficiently established. To address this issue, we examined the effect of GBE on hepatic drug metabolizing enzymes and their influence on hypotensive drug in rats. Male rats were fed either a control diet or diet containing GBE (0.5% w/w) for 4 weeks. The feeding of a GBE diet did not change the serum transaminase activity, but increased the liver weight and the phospholipid concentration in the liver. In addition, the GBE diet markedly increased the content of cytochrome P-450 (CYP), and the activity of glutathione S-transferase in the liver. Furthermore, the GBE diet markedly induced levels of CYP2B1/2, CYP3A1 and CYP3A2 mRNA in the liver. The levels of CYP1A1, CYP1A2, CYP2E1, CYP2C11 and CYP4A1 were unchanged. The feeding of GBE for 4 weeks significantly reduced the hypotensive effect of nicardipine that was reported to be metabolized by CYP3A2 in rats. These findings suggest that GBE reduces the therapeutic potency of the Ca2+ channel blocker, nicardipine, via enhancement of cytochrome P-450 expression.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12244892&dopt=Abstract Ref: Wien Med Wochenschr 2002;152(15-16):427-31
Pharmaco-economic evaluation of Ginkgo special extract EGb 761 for dementias in Austria
[Article in German]
Horr R, Kieser M.
Abteilung Klinische Forschung, Dr. Willmar Schwabe GmbH & Co., Willmar-Schwabe-Strasse 4, D-76227 Karlsruhe, Deutschland.
The aim of the study was to carry out an economic evaluation of the therapeutic effects achievable with ginkgo special extract Egb 761 in dementia in Austria. The care-cost savings that could be achieved with ginkgo special extract Egb 761 therapy were estimated on the basis of the extent to which it delayed growing dependency and an increasing need for care--this being ascertained from the active treatment/placebo differences on GERRI after 6 months of treatment with Egb 761 and evaluated using the rates of the Austrian Federal Care Allowance Law--and compared with the cost of this therapy. The duration of illness, the start and duration of treatment, and the Egb 761 dose were varied in a series of scenarios in a sensitivity analysis. In all the scenarios the care-cost savings exceed the costs of the ginkgo special extract Egb 761 therapy. The cost/savings ratio is most favourable when the treatment is started early and when it is used in patients with dementia of the Alzheimer type. For every month by which the transition from the stage requiring a small to moderate amount of care to the stage requiring considerable or very considerable care can be delayed, one can save 812 [symbol: see text]. Prescribing ginkgo special extract Egb 761 for dementia makes sense from the national economic viewpoint because the product can yield care-cost savings that exceed the cost of the treatment itself.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12244891&dopt=Abstract Ref: Wien Med Wochenschr 2002;152(15-16):423-6
Ginkgo extract in impaired vision--treatment with special extract EGb 761 of impaired vision due to dry senile macular degeneration
[Article in German]
Fies P, Dienel A.
The therapeutic efficacy of Ginkgo special extract Egb 761 was investigated in a controlled, double-blind trial involving 99 patients with impaired vision due to senile, dry macular degeneration. The primary objective target variable was the change in the corrected visual acuity of the more severely impaired eye at baseline, during a six months treatment period with either 240 mg/die (group I = 50 patients) or 60 mg/die (group II = 49 patients) Egb 761. Marked improvement of the study participants' vision was observed in both treatment groups already after four weeks, with more pronounced improvements in group I (acuity increases by 0.13 in group I vs. 0.10 in group II after 24 weeks). The fraction of patients with improvement of visual acuity > or = 0.2 was nearly twice as large in the group treated with 240 mg/die Egb 761 as in patients receiving the lower dosage (p = 0.08). Subjective health impairments, if present, could be improved during treatment as well. The investigator rated a favorable tolerability for both dosages of Egb 761. In conclusion, the results demonstrate the therapeutic efficacy of Egb 761 in patients with senile, dry macular degeneration, with obvious benefits in every-day life.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12244890&dopt=Abstract Ref: Wien Med Wochenschr 2002;152(15-16):418-22
Value of Ginkgo biloba in treatment of Alzheimer dementia
[Article in German]
Loew D.
During the last decade, there has been an explosive growth of research concerning the extract of Ginkgo biloba termed Egb 761. In experimental studies, animal studies and clinical studies Ginkgo biloba has shown a similar pharmacological potency and clinical efficacy like synthetic defined drugs in the therapy of reduced cerebral performance. Ginkgo biloba special extract Egb 761 is a standardized and highly purified extract of Ginkgo leaves. Among the active constituents are the ginkgo-flavone glycosides and the terpene-lactones (ginkgolides, bilobalide). The multifactorial principle of action of Ginkgo biloba is characterized by rheological and blood-flow-promoting properties, protective effects against ischaemia and hypoxia, effects on nerve cell energy metabolism, antioedematous and myelin-protective effects, radical-scavenger activity, effects on various cerebral transmitter and receptor systems. These action principles constitute the rationale for clinical trials in vascular dementia and primary degenerative dementia of the Alzheimer type, and in mixed forms of both. The cerebral bioavailability of Ginkgo biloba extract has been demonstrated by electroencephalography. In clinical trials of different working-groups, effects of Ginkgo biloba on the cognitive performance, global function, and activities of the daily living have been found. Metaanalysis in the indication--demential disorders--comparing Ginkgo biloba versus acetylcholinesterase inhibitors have shown a similar clinical efficacy of both therapy regimens with an additional drug safety benefit for Ginkgo. Due to the clinical efficacy the WHO accepted Ginkgo biloba as an antidementiv drug and add it in January 2000 into the recent ATC-Classification Index. In future antidementive therapy drugs with an different mode of action should be given in combination. Furthermore clinical trials with fixed combinations of acetylcholinesterase inhibitors with Ginkgo biloba extracts in moderate or severe dementia would be necessary.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12242828&dopt=Abstract Ref: Zhongguo Zhong Yao Za Zhi 1998 Dec;23(12):746-7, back cover
Influence of Ginkgo biloba L. exocarp polysaccharides on serum superoxide dismutase activity and malondialdehyde level in mice under different states]
[Article in Chinese]
Xu A, Chen H, Wang L, Wang Q.
Medical College of Yangzhou University, Yangzhou 225002.
OBJECTIVE: To study the influence of Ginkgo biloba exocarp polysaccharides(GBEP) on serum superoxide dismutase(SOD) activity and malondialdehyde(MDA) level in mice under different states. METHOD: GBEP was orally administrated to S180 bearing mice, cyclophosphamide(CTX) intoxicated mice and normal mice. The contents of SOD and MDA in the mice's blood were checked. RESULT: GBEP significantly enhanced SOD activity and decreased MDA content in S180 bearing mice. Similar effects were observed in CTX-intoxicated mice. In normal mice, however, no such effects were observed. CONCLUSION: GBEP may modulate the free radical system in mice under abnormal states.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12222666&dopt=Abstract Ref: Phytomedicine 2002 Jul;9(5):442-6
Evaluation of commercial Ginkgo biloba dietary supplements for the presence of colchicine by high-performance liquid chromatography.
Li W, Fitzloff JF, Farnsworth NR, Fong HH.
Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, 60612, USA.
A high-performance liquid chromatographic method with photodiode array detection was developed for the detection of the presence of colchicine in commercial ginkgo products. The method is based on the baseline separation of constituents in ginkgo samples plus reference colchicine. The minimal detectable concentration of colchicine is 1.0 ng on column in the current assay. By analysis of retention time and UV profile of suspect peaks in the sample with those of reference colchicine, none of the nine commercial ginkgo products analyzed contained colchicine.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12219929&dopt=Abstract Ref: J Chromatogr A 2002 Aug 16;967(1):21-55
Chemical analysis of Ginkgo biloba leaves and extracts.
van Beek TA.
Laboratory of Organic Chemistry, Phytochemical Section, Wageningen University, The Netherlands.
The chemical analysis and quality control of Ginkgo leaves and extracts is reviewed. Important constituents present in the medicinally used leaves are the terpene trilactones, i.e., ginkgolides A, B, C, J and bilobalide, many flavonol glycosides, biflavones, proanthocyanidins, alkylphenols, simple phenolic acids, 6-hydroxykynurenic acid, 4-O-methylpyridoxine and polyprenols. In the commercially important Ginkgo extracts some of these compound classes are no longer present. Many publications deal with the analysis of the unique terpene trilactones. They can be extracted with aqueous acetone or aqueous methanol but also supercritical fluid extraction is possible. Still somewhat problematic is their sample clean-up. Various procedures, not all of them validated, employing partitioning or SPE have been proposed. Some further development in this area can be foreseen. Separation and detection can be routinely carried out by HPLC with RI, ELSD or MS, or with GC-FID after silylation. TLC is another possibility. No quantitative procedure for flavonol glycosides has been published so far due their difficult separation and commercial unavailability. Fingerprint analysis by gradient RP-HPLC is possible. After acidic hydrolysis to the aglycones quercetin, kaempferol and isorhamnetin and separation by HPLC, quantitation is straightforward and yields by recalculation an estimation of the original total flavonol glycoside content. For biflavones, simple phenols, 6-hydroxykynurenic acid, 4-O-methylpyridoxine and polyprenols analytical procedures have been published but not all assays are yet ideal. Lately a there is a lot of interest in the analysis of the undesired alkylphenols and a few validated procedures have been published. The analysis of Ginkgo proanthocyanidins is still in its infancy and no reliable assays exist.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12214044&dopt=Abstract Ref: J Alzheimers Dis 2001 Aug;3(4):401-407
Ginkgo biloba neuroprotection: Therapeutic implications in Alzheimer's disease.
Luo Y.
Department of Biological Sciences, Box 5018, University of Southern Mississippi, Hattiesburg, MS 39406, USA. Tel.: +1 601 266 5417; Fax: +1 601 266 5797;
An extract of Ginkgo biloba leaves, EGb761, is becoming one of the most popular dietary supplements in the United States to enhance memory. In Europe it is a commonly prescribed drug for treatment of age-related deterioration, including degenerative dementias of the Alzheimer type (AD). Substantial experimental evidence indicates that EGb761 has neuroprotective potency under conditions such as ischemia, seizures and peripheral nerve damage. However, the mechanisms of such neuroprotective effects remain unknown, partially because of the complex chemical composition of EGb761 and the resulting so-called "polyvalent" action. This review focuses on cellular and molecular approaches towards understanding the polyvalent action of EGb761 neuroprotective effect. Two potential mechanisms of action, reducing oxidative damage and stimulating cell survival machinery, are discussed. Better understanding of the neuroprotective mechanisms of EGb761 will provide impetus for possible combination therapies and for the design of rational, "mechanism-based" strategies that target age-related neurodegeneration and Alzheimer's disease.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12213959&dopt=Abstract Ref: Proc Natl Acad Sci U S A 2002 Sep 17;99(19):12197-202
Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761.
Luo Y, Smith JV, Paramasivam V, Burdick A, Curry KJ, Buford JP, Khan I, Netzer WJ, Xu H, Butko P.
Departments of Biological Sciences and Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, MS 39406, USA.
Standardized extract from the leaves of the Ginkgo biloba tree, labeled EGb761, has been used in clinical trials for its beneficial effects on brain functions, particularly in connection with age-related dementias and Alzheimer's disease (AD). Substantial experimental evidence indicates that EGb761 protects against neuronal damage from a variety of insults, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing an AD-associated double mutation, we report that EGb761 inhibits formation of amyloid-beta (Abeta) fibrils, which are the diagnostic, and possibly causative, feature of AD. The decreased Abeta fibrillogenesis in the presence of EGb761 was observed both in the conditioned medium of this Abeta-secreting cell line and in solution in vitro. In the cells, EGb761 significantly attenuated mitochondrion-initiated apoptosis and decreased the activity of caspase 3, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that (i) neuronal damage in AD might be due to two factors: a direct Abeta toxicity and the apoptosis initiated by the mitochondria; and (ii) multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of Abeta aggregation, underlie the neuroprotective effects of EGb761.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12213586&dopt=Abstract Ref: Biochem Pharmacol 2002 Sep;64(5-6):913-7
Genomic responses to herbal extracts: lessons from in vitro and in vivo studies with an extract of Ginkgo biloba.
Gohil K.
Department of Internal Medicine, University of California, Davis, CA 95616, USA.
Do herbal extracts offer effective dietary supplements to prevent deregulation of the transcriptome? Can they normalize deregulated transcriptomes of chronic human diseases? Are the effects of herbal extracts targeted to specific molecular pathways in tissue-specific manner? Are the effects of herbal supplements reversible? These questions pose important challenges to the fields of molecular nutrition and medicine, which are committed to understanding the molecular basis of physiology during health and disease. Transcription of the molecular information encoded in the deoxynucleotide sequences of DNA to the nucleotide sequences of RNA play a vital, causative, role in the coordinated adaptation of the organism to its changing environment and its nutritional needs. Pathogenesis is a manifestation of defects in transcription of the genome. Herbal extracts may target these obligatory processes. Increased availability of tools for quantitative and comprehensive analysis of messenger RNAs offer powerful means to understand and identify changes in these fundamental processes. Studies with the extract of Ginkgo biloba leaves show that the extract affects transcription of functionally diverse groups of genes in vitro and in vivo. The observations offer molecular evidence for bioactivity of the extract and offer an analytical strategy to define and predict physiological effects of complex mixtures of phytochemicals.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12213536&dopt=Abstract Ref: Pharmacol Biochem Behav 2002 Nov;73(4):893-900
A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba. Anticholinesterase and cognitive enhancing activities.
Das A, Shanker G, Nath C, Pal R, Singh S, Singh H.
Division of Pharmacology, Central Drug Research Institute, P.O. Box 173, Lucknow, 226 001, India.
Bacopa monniera and Ginkgo biloba are well-known cognitive enhancers in Indian and Chinese traditional medicine systems. Standardized extracts of B. monniera and G. biloba were used to evaluate the antidementic and anticholinesterase activities in adult male Swiss mice. Antidementic activity was tested against scopolamine (3 mg/kg ip)-induced deficits in passive avoidance test. Three different extracts of B. monniera (30 mg/kg) and extract of G. biloba (15, 30 and 60 mg/kg) were administered postoperatively, daily for 7 days and 60 min after the last dose, i.e., on Day 7, first trial was conducted. In passive avoidance test, increased transfer latency time (TLT) and no transfer response (NTR) were taken as criteria for learning. TLT and NTR were significantly increased and decreased in second trial, 24 h after the first trial in control group and scopolamine-dementia group, respectively. The B. monniera- and G. biloba-treated groups produced significant increase in TLT and NTR on second trial (40-80%) after scopolamine treatment, thus, attenuating its antidementic effect. Both the extracts showed a dose (10-1000 microg)-dependent inhibitory effect on acetylcholinesterase (AChE) activity (in vitro), performed spectrophotometrically. IC(50) of G. biloba was 268.33 microg, whereas none of the extracts of B. monniera showed more than 50% inhibition. At a dose concentration of 30 and 60 mg/kg, extracts of G. biloba showed a cognitive enhancing property and, at the same time, a significant decrease in AChE-specific activity in both per se and scopolamine-dementia groups. These extracts possess a significant anticholinesterase and antidementic properties, which may be useful in the treatment of dementia.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12203273&dopt=Abstract Ref: Phytother Res 2002 Aug;16(5):488-90
Effect of Ginkgo biloba extract on beta-adrenergic receptors in different rat brain regions.
Hadjiivanova ChI, Petkov VV.
Department of Chemistry and Biochemistry, Faculty of Ecology, University of Forestry, 10 Kliment Ohridski Avenue, Sofia 1756, Bulgaria.
The effect of oral administration of Ginkgo biloba extract at a dose of 90 mg/kg for 7 consecutive days on rat brain beta-adrenergic receptors in the frontal cortex, hippocampus, striatum and hypothalamus was studied. Ginkgo biloba treatment induced a significant decrease in the density (B(max)) of beta-adrenoreceptors in the frontal cortex and hippocampus. It has been suggested that modulation of the beta-adrenergic system is implicated in the favourable effects of Ginkgo biloba extracts on learning and memory.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12190754&dopt=Abstract Ref: Anaesthesia 2002 Sep;57(9):889-99
The peri-operative implications of herbal medicines.
Hodges PJ, Kam PC.
Department of Anaesthesia and Pain Management, University of Sydney at Royal North Shore Hospital, St Leonard's, NSW 2065, Australia.
An increasing number of patients are taking herbal medicines such as echinacea, garlic, ginkgo biloba, ginseng, St John's Wort, valerian, ephedra, kava, grapefruit juice and ginger. Although these herbal medications are considered 'natural' products that may have some benefits, adverse effects such as increased bleeding tendencies and drug interactions are associated with their use. Surgeons and anaesthetists may be unaware of their patients' use of these medications because it is common for patients not to disclose their use of this form of medication, and both surgeons and anaesthetists often fail to enquire about their use. Anaesthetists and surgeons must be familiar with the effects of herbal medicines and should specifically enquire about the use of herbal medicines during pre-operative assessment. Currently available data suggest that all herbal medicines should be ceased 2 weeks before surgery.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12190325&dopt=Abstract Ref: J Med Chem 2002 Aug 29;45(18):4038-46
Ginkgolide derivatives for photolabeling studies: preparation and pharmacological evaluation.
Stromgaard K, Saito DR, Shindou H, Ishii S, Shimizu T, Nakanishi K.
Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, USA.
The terpene trilactones (TTLs), ginkgolides and bilobalide, are structurally unique constituents of Ginkgo biloba extracts, which exhibit various neuromodulatory properties. Although the TTLs are believed to be responsible for some of these effects, the specific interactions with targets in the central nervous system remain to be elucidated on a molecular level. Ginkgolides are known antagonists of the platelet-activating factor (PAF) receptor. Herein, we describe the first examination of the binding of native TTLs and their derivatives to the cloned PAF receptor, confirming that of the TTLs, ginkgolide B is the most potent PAF receptor antagonist. Ginkgolide derivatives carrying photoactivatable and fluorescent groups for the purpose of performing photolabeling have been prepared and evaluated using the cloned PAF receptor. These studies have shown that ginkgolide derivatives with aromatic photoactivatable substituents are potent PAF receptor antagonists with K(i) values of 0.09-0.79 microM and hence excellent ligands for clarifying the binding of ginkgolides to PAF receptor by photolabeling studies. Ginkgolide derivatives incorporating both fluorescent and photoactivatable groups still retained binding affinity to the PAF receptor and hence should be promising ligands for photolabeling and subsequent sequencing studies.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12186600&dopt=Abstract Ref: JAMA 2002 Aug 21;288(7):835-40
Ginkgo for memory enhancement: a randomized controlled trial.
Solomon PR, Adams F, Silver A, Zimmer J, DeVeaux R.
Bronfman Science Center, Williams College, 33 Hoxsey St, Williamstown, MA 01267, USA.
CONTEXT: Several over-the-counter treatments are marketed as having the ability to improve memory, attention, and related cognitive functions in as little as 4 weeks. These claims, however, are generally not supported by well-controlled clinical studies. OBJECTIVE: To evaluate whether ginkgo, an over-the-counter agent marketed as enhancing memory, improves memory in elderly adults as measured by objective neuropsychological tests and subjective ratings. DESIGN: Six-week randomized, double-blind, placebo-controlled, parallel-group trial. SETTING AND PARTICIPANTS: Community-dwelling volunteer men (n = 98) and women (n = 132) older than 60 years with Mini-Mental State Examination scores greater than 26 and in generally good health were recruited by a US academic center via newspaper advertisements and enrolled over a 26-month period from July 1996 to September 1998. INTERVENTION: Participants were randomly assigned to receive ginkgo, 40 mg 3 times per day (n = 115), or matching placebo (n = 115). MAIN OUTCOME MEASURES: Standardized neuropsychological tests of verbal and nonverbal learning and memory, attention and concentration, naming and expressive language, participant self-report on a memory questionnaire, and caregiver clinical global impression of change as completed by a companion. RESULTS: Two hundred three participants (88%) completed the protocol. Analysis of the modified intent-to-treat population (all 219 participants returning for evaluation) indicated that there were no significant differences between treatment groups on any outcome measure. Analysis of the fully evaluable population (the 203 who complied with treatment and returned for evaluation) also indicated no significant differences for any outcome measure. CONCLUSIONS: The results of this 6-week study indicate that ginkgo did not facilitate performance on standard neuropsychological tests of learning, memory, attention, and concentration or naming and verbal fluency in elderly adults without cognitive impairment. The ginkgo group also did not differ from the control group in terms of self-reported memory function or global rating by spouses, friends, and relatives. These data suggest that when taken following the manufacturer's instructions, ginkgo provides no measurable benefit in memory or related cognitive function to adults with healthy cognitive function.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12169298&dopt=Abstract Ref: Prog Neurobiol 2002 Jun;67(3):235-57
The CNS effects of Ginkgo biloba extracts and ginkgolide B.
Maclennan KM, Darlington CL, Smith PF.
Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.
Ginkgo biloba extracts such as EGb-761 have been suggested to have a multitude of beneficial effects on CNS function, from enhancing cognitive function in dementia to facilitating recovery from acute forms of neural damage such as hypoxia/ischemia. Ginkgolide B, one of the major components of EGb-761, is a potent platelet-activating factor (PAF) receptor antagonist, which is also regarded as having neuroprotective effects in the CNS. The aim of this review is to summarise and to critically evaluate the current evidence on the CNS effects of EGb-761 and ginkgolide B, with particular emphasis on the data relating to their neuroprotective effects.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12164271&dopt=Abstract Ref: Phytother Res 2002 May;16(3):253-5
Comparative study of two Ginkgo biloba extracts on the phagocytic activity and DTH response of healthy mice.
Villaseno-Garcia MM, Puebla-Perez AM, Lozoya X.
Immunopharmacology of Natural Products Laboratory, Biomedical Research Centre in Western Area, IMSS, Guadalajara, Jalisco, Mexico.
The phagocytic activity and delayed-type Hypersensitivity (DTH) response to dinitrofluorobenzene (DNFB) of healthy BALB/c mice treated orally (100 mg/kg/day for 7 days) using two Ginkgo biloba extracts were studied. The phytopharmaceuticals Gb 30 (Alban Muller International, France) and EGb 761 (Schwabe, Germany) administered orally stimulated the phagocytic activity of peritoneal and alveolar macrophages. Likewise, the DTH response was found to be increased only with Gb 30 treatment. These results suggest that Ginkgo biloba possesses immunological activity in addition to the biological activity reported. The different chemical concentration of the components of the Ginkgo biloba extracts mentioned above may be responsible for the differences in the observed findings.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12162946&dopt=Abstract Ref: Pharmacol Res 2002 Jun;45(6):461-7
Effects of L-carnitine and ginkgo biloba extract (EG b 761) in experimental bleomycin-induced lung fibrosis.
Daba MH, Abdel-Aziz AA, Moustafa AM, Al-Majed AA, Al-Shabanah OA, El-Kashef HA.
Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Kingdom of Saudi Arabia.
The effects of Ginkgo biloba extract (EGb 761) and L-carnitine on bleomycin (BLM)-induced lung fibrosis were studied in rats. BLM (cumulative dose of 180 mgkg(-1)) was given intraperitoneally (i.p.) three times weekly for 4 consecutive weeks. Treatment with BLM enhanced the responsiveness of isolated pulmonary arterial rings to serotonin (5-HT), significantly increased the normal serum level of tumour necrosis factor (TNF-alpha) by approximately 105% and markedly elevated the level of lipid peroxide (LPO) and collagen content in the lung homogenates by 34 and 83%, respectively. EGb 761 (100 mgkg(-1) ), given in drinking water for the whole study period, totally abolished the BLM-induced alterations in the measured biochemical and pharmacological parameters. Meanwhile, L-carnitine (500 mg kg(-1) ), administered in drinking water, significantly decreased the BLM-induced elevations of serum TNF-alpha, LPO level in lung tissues and the enhanced responsiveness of pulmonary arterial rings to 5-HT. However,L-carnitine did not reduce the increase in the collagen content produced by BLM. The results of the present study indicate the beneficial effects of EGb 761 and L-carnitine against lung toxicity induced by BLM treatment. Furthermore, the present data shows the advantageous use of EGb 761 as a protective agent in BLM-induced lung fibrosis under the experimental circumstances.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12135620&dopt=Abstract Ref: Toxicology 2002 Aug 15;177(2-3):167-77
In vitro evaluation of the cytotoxic potential of alkylphenols from Ginkgo biloba L.
Hecker H, Johannisson R, Koch E, Siegers CP.
Institute of Experimental and Clinical Pharmacology and Toxicology, Medical University of Lubeck, Ratzeburger Alle 160, Lubeck, Germany.
Extracts from the leaves of Ginkgo biloba L. belong to the most widely used phytopharmaceuticals. In crude Ginkgo extracts, ginkgolic acids (GA) and related alkylphenols (e.g. cardanols and cardols) have been recognized as hazardous compounds with suspected cytotoxic, allergenic, mutagenic and carcinogenic properties. To further assess the cytotoxic potential of GA, their effect on the human keratinocyte cell line HaCaT and the rhesus monkey kidney tubular epithelial cell line LLC-MK(2) was investigated. The action of a defined mixture of GA on cell growth, viability and integrity was evaluated by the neutral red uptake assay as well as the release of lactate dehydrogenase (LDH) and acid phosphatase (ACP). Cell morphology was examined by electron microscopy. For comparison, the effect of the standardized Ginkgo extract EGb 761, which contains less than 5 ppm GA, was also investigated.Following incubation of cells with EGb 761, neutral red uptake was half-maximally inhibited at concentrations of 900 mg/l (HaCaT) and 1480 mg/ml (LLC-MK(2)). The corresponding IC(50)-values for the mixture of GA ranged between 22 mg/l (HaCaT) and 4.6 mg/l (LLC-MK(2)), respectively. In parallel to the inhibition of neutral red uptake, a concentration dependent release of LDH was observed when cells were incubated in the presence of GA (1-100 mg/l). In contrast, even at a concentration of 1800 mg/l EGb 761 did not cause release of LDH above controls. Since GA interacted with the assay for ACP, no index of lysosomal damage could be established by this method. Incubation of HaCaT cells with GA for 18 h increased the proportion of apoptotic cells from about 6% (control) to nearly 80% at concentrations of >or=30 mg/l. Electron microscopic analysis of HaCaT cells revealed a drug induced formation of myelinosomes possibly due to the inhibition of lysosomal enzymes, while morphological evaluation of LLC-MK(2) cells indicated that the cytotoxic activity of GA in these cells is primarily mediated by transformation of mitochondria, which is probably induced by uncoupling of oxidative phosphorylation.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12122516&dopt=Abstract Ref: Transpl Int 2002 Jul;15(7):377-9
Bleeding complications precipitated by unrecognized Gingko biloba use after liver transplantation.
Hauser D, Gayowski T, Singh N.
VA Pittsburgh Healthcare System, Infectious Disease Section, University Drive C, Pittsburgh, PA 15240, USA.
Because of its neurocognitive enhancing effects, Gingko biloba has emerged as amongst the most commonly used herbal products. We report a liver transplant recipient with potentially life-threatening toxicity resulting from Gingko biloba use. Seven days after a second liver transplantation for recurrent hepatitisB virus infection, subphrenic hematoma was documented in a 59-year-old Korean patient. Failure to control bleeding with CT-guided drainage necessitated exploratory laparotomy for the evacuation of a large subphrenic hematoma. Three weeks later, an episode of vitreous hemorrhage was documented. Unbeknownst to his care providers, the patient had been consuming Gingko biloba throughout the postoperative period. No further bleeding episodes occurred after the cessation of Gingko biloba use. Unrecognized use of herbal products may be associated with serious side effects and adverse clinical sequelae in transplant recipients. Given their increasing popularity, the use of herbal products should be routinely sought as part of the history in transplant recipients.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12119881&dopt=Abstract Ref: MMW Fortschr Med 2002 May 16;144(20):36-9
Starting Alzheimer therapy in early stages whenever possible. Activities of daily living remain intact longer
[Article in German]
Fuchsberger T, Padberg F, Faltraco F, Moller HJ, Hampel H.
Alzheimer-Gedachtniszentrum, Psychiatrische Klinik und Poliklinik, LMU Munchen.
In recent years, the efficacy of symptomatic antidementive drugs in the treatment of Alzheimer's disease (AD) has been well documented. A prerequisite for maximally effect antidementive treatment is early diagnosis and a subsequent specific diagnostic clarification. A further essential is early initiation of treatment to delay progression of the disease and thus early loss of daily skills and independence ending in the need for intensive nursing care. Currently, cholinesterase inhibitors, the efficacy of which has been confirmed in placebo-controlled multicenter studies, are recommended for the treatment of mild to moderate AD. Further substances with proven efficacy are memantine, ginkgo biloba extract EGb761 and certain classical nootropics. To treat behavioral and other psychological disturbances, symptom-related substances such as selective serotonin reuptake inhibitors and atypical neuroleptics should be employed. In addition to their positive effect on cognitive disturbances, cholinesterase inhibitors also have an appreciable impact on concomitant psychopathological symptoms.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12112284&dopt=Abstract Ref: Phytother Res 2002 Jun;16(4):312-5
Enhanced conditioned inhibitory avoidance by a combined extract of Zingiber officinale and Ginkgo biloba.
Topic B, Hasenohrl RU, Hacker R, Huston JP.
Institute of Physiological Psychology, Heinrich-Heine-University of Dusseldorf, Universitatsstr. 1, D-40225 Dusseldorf, Germany.
Previous work has shown that intragastric administration of Zingicomb, a preparation consisting of Zingiber officinale and Ginkgo biloba extracts, has anxiolytic-like properties. The aim of the present study was to assess the effects of acute treatment with this preparation on inhibitory avoidance learning. The influence of pre-trial administered Zingicomb (ZC) on inhibitory avoidance conditioning was investigated in adult male Wistar rats, with a one-trial step-through avoidance task. The animals were treated intragastrically with either vehicle, 0.5, 1, 10 or 100 mg/kg ZC 60 min prior to the acquisition trial. When tested 24 h after training, rats which had received 10 mg/kg ZC exhibited significantly longer step-through latencies than vehicle treated animals. This result, thus, demonstrates the beneficial effects of Zingicomb on conditioned inhibitory avoidance. Unlike conventional anxiolytic drugs, such as the benzodiazepines, which tend to have amnesic properties, this phytopharmacon is a potent anxiolytic agent which, additionally, can facilitate performance on a learning task, indicating promising clinical applications.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12094291&dopt=Abstract Ref: Planta Med 2002 Jun;68(6):501-4
Inhibition of intracellular calcium elevation and blunting of vasopressor response due to serotonin by ginkgolide B.
Wang Y, Yu YQ, Xu JG.
Department of Pharmacology, School of Medicine, Nanjing University, Nanjing, PR China.
The vascular effects of each individual composition in the extract of Ginkgo biloba have not been clarified. In this work, we have investigated whether ginkgolide B (GKB), a terpene lactone component from Ginkgo biloba, modulates intracellular calcium ([Ca (2+)] i) of vascular smooth muscle cells (smc) and how it influences the vasopressor response in vitro caused by serotonin (5-HT). GKB (3.2 - 9.6 microM) selectively decreased serotonin-induced [Ca (2+)] i elevations in cultured smc from bovine aorta in dose-dependent manner, while it had no effects on both resting [Ca (2+)] i and potassium-elicited [Ca (2+)] i elevations. On the other hand, GKB in a concentration of 3.2 - 9.6 microM moderately decreased the maximal pressor efficacy of serotonin by 14 - 45 % in rat mesenteric vascular beds, and the EC50 remained unchanged. The comparison study also showed GKB had no effects on noradrenaline-elicited pressor reactions. These results implicate that GKB may selectively inhibit serotonin-mediated [Ca (2+)] i mobilization in vascular smc and non-competitively alleviate the vasopressor effect of serotonin in vitro.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12062581&dopt=Abstract Ref: Pharmacol Biochem Behav 2002 Jul;72(4):913-22
Ginkgo biloba extract: cognitive enhancer or antistress buffer.
Ward CP, Redd K, Williams BM, Caler JR, Luo Y, McCoy JG.
Department of Psychology, The University of Southern Mississippi, Hattiesburg, MS 39406, USA.
Constituents extracted from the leaves of the Ginkgo biloba tree possess beneficial properties that may buffer the aging nervous system from deterioration due to oxidative stress. In the present investigation, a standardized extract of G. biloba (EGb 761) or an equal volume of the vehicle was administered (100 mg/kg/day) to senescent (20-month) C57BL/6 male mice for up to 82 consecutive days. Animals were tested twice in the Morris water maze (MWM) after 28 and 70 days of treatment. No differences were observed in acquisition or retention of performance on the water maze. Elevated-plus maze (EPM) trials were conducted prior to and subsequent to the chronic treatment regimen. Marked baseline differences in plus-maze performance were present in the first experiment. A second experiment used a matched-pairs design to minimize preexisting differences. Results supported the hypothesis that EGb 761 may serve as an antistress buffer, attenuating the increase in anxiety typically observed in animals after cold water exposure. Tissue samples from the hippocampus and cortex were analyzed by Western blot for the transcription factor cyclic-AMP response element binding (CREB) protein. EGb 761 had no significant effect on immunoreactivity to CREB from either the hippocampus or the cerebral cortex.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12053674&dopt=Abstract Ref: Otolaryngol Pol 2002;56(1):83-8
Results of combined treatment for vestibular receptor impairment with physical therapy and Ginkgo biloba extract (Egb 761)]
[Article in Polish]
Orendorz-Fraczkowska K, Pospiech L, Gawron W.
Katedra i Klinika Otolaryngologii AM we Wroclawiu.
Vestibular receptor impairment causes symptoms called vestibular organ peripheral lesion syndrome. Subjective and objective symptoms of vestibular lesion diminish gradually in the process of vestibular compensation. Stimulating a patient to action is a basic factor that influences on the compensation process. The aim of our studies was an evaluation of treatment results in patients with vertigo of peripheral origin with the use of gingko biloba extract together with kinezytherapy. Ginkgo biloba extract shows vasoactive, rheologic, metabolic and neural effects. We have examined 45 persons aged between 35 and 48 years (38 on average, 35 female, 13 male) with clinical symptoms of peripheral vestibular lesion. In each case we performed as follows: ORL physical examination, pure tone audiometry, suprathreshold audiometry, electronystagmography (eyes open and closed nystagmus, cervical tests, caloric tests according to Hallpike), static and dynamic posturography. In all of the cases vestibular rehabilitation originally programmed in our Clinic was applied. N 23 cases (17 female and 6 male) chosen at random, kinezytherapy together with gingko biloba in tablet was applied: 2 tablets twice a day for 3 months. Control examination were performed on 30, 60 and 90 days of treatment. Treatment results evaluation was based on anamnesis, electronystagmography, static and dynamic posturography. CONCLUSIONS: 1. In almost all of the cases with peripheral lesion of vestibular organ, after 30 days of application of gingko biloba extract together with kinezytherapy and without gingko biloba there was vestibular compensation confirmed in electronystagmography but there were disturbances in static and dynamic posturography. 2. Control examination in the course of treatment revealed gradual improvement in vestibular tests in both group (with and without biloba extract). But in patients treated with gingko biloba extract the improvement was more clear and faster an dynamic posturography. It implies central effect of gingko biloba extract that allows to gain full vestibular compensation sooner.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12051570&dopt=Abstract Ref: Int J Clin Pharmacol Ther 2002 May;40(5):188-97
The efficacy of Ginkgo special extract EGb 761 in patients with tinnitus.
Morgenstern C, Biermann E.
Allgemeines Krankenhaus St. Georg. Hamburg, Germany.
OBJECTIVE: The objective of the present study in 60 patients with chronic tinnitus aurium was to confirm the efficacy of oral treatment with 2 x 80 mg Ginkgo special extract EGb 761 per day subsequent to 10-day EGb 761 infusion treatment. METHODS: Patients with chronic tinnitus aurium underwent 10 days of in-patient infusion treatment with 200 mg/day EGb 761, after which they were randomized to double-blind, oral out-patient treatment with either 2 x 80 mg/day EGb 761 or placebo, given over a scheduled treatment period of 12 weeks. The primary outcome measure was the change in tinnitus volume in the more severely affected ear during randomized treatment. RESULTS: Fifty-two of 60 patients (89.7%) completed the infusion treatment; complete sets of data were available for 40 (66.7%), 30 (50.0%) and 22 (36.7%) patients after 4, 8 and 12 weeks of randomized treatment, respectively. For the primary outcome measure, significant superiority of EGb 761 over placebo was demonstrated in the intention-to-treat analysis data set after 4, 8 and 12 weeks of out-patient treatment (p < 0.05, 1-tailed), although the absolute treatment group difference was moderate. The results were supported by the secondary outcome measures for efficacy (e.g. decreased hearing loss, improved self-assessment of subjective impairment). During out-patient treatment, there were no attributable adverse events under EGb 761. CONCLUSIONS: A combination of infusion therapy followed by oral administration of Ginkgo special extract EGb 761 appears to be effective and safe in alleviating the symptoms associated with tinnitus aurium.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12025528&dopt=Abstract Ref: J Int Med Res 2002 Mar-Apr;30(2):195-9
An open, pilot study to evaluate the potential benefits of coenzyme Q10 combined with Ginkgo biloba extract in fibromyalgia syndrome.
Lister RE.
Phylax Ltd, Beaconsfield, UK.
An open, uncontrolled study was undertaken to measure the subjective effects of coenzyme Q10 combined with a Ginkgo biloba extract in volunteer subjects with clinically diagnosed fibromyalgia syndrome. Anecdotal reports from patients with fibromyalgia syndrome have claimed benefits from the use of these supplements. The aim of this study was to determine if these reports could be substantiated in a pilot clinical trial. Patient questioning had determined that poor quality of life was a major factor in the condition and a quality-of-life questionnaire was used to measure potential benefit. Subjects were given oral doses of 200 mg coenzyme Q10 and 200 mg Ginkgo biloba extract daily for 84 days. Quality of life was measured, using the well-validated Dartmouth Primary Care Cooperative Information Project/World Organization of Family Doctors (COOP/WONCA) questionnaire that measures seven different subjective responses, at 0-, 4-, 8-, and 12-week intervals. The subjects were asked for an overall self-rating at the end of the study. A progressive improvement in the quality-of-life scores was observed over the study period and at the end, the scores showed a significant difference from those at the start. This was matched by an improvement in self-rating with 64% claiming to be better and only 9% claiming to feel worse. Adverse effects were minor. A controlled study is now planned.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12016854&dopt=Abstract Ref: Yao Xue Xue Bao 1998 Dec;33(12):901-5
Protective effects of Ginkgo biloba extract on focal cerebral ischemia and thrombogenesis of carotid artery in rats
[Article in Chinese]
Zhang Y, Gu D, Mao S, Chen W.
Shanghai Second Medical University, Ruijin Hospital, Shanghai Hypertensive Institute, Shanghai 200025.
Rat focal cerebral ischemia induced by occlusion and thrombogenesis of middle cerebral artery(MCAO) was used as experimental model to study the effects of extract of Ginkgo biloba (EGb) and the positive control drugs were urokinase and nimodipine on cerebral infarct size and neurological deficits. The results showed that cerebral ischemia and neurological deficits appeared in rat focal cerebral ischemic models, and the degree was of cerebral ischemia larger in occlusion model than in thrombogenesis model. The cerebral infarct size was significantly smaller and neurological deficits greatly improved at large dose of EGb(200 mg.kg-1, i.v.), the preventive effect appeared to be better than the treatment effect. The positive control drugs urokinase and nimodipine were also shown to distinctly decrease the cerebral infarct size and improve the neurological deficits in the models. Small dose of EGb(100 mg.kg-1, i.v.) was found to decrease the cerebral infarct size of thrombogenesis model, and improve neurological deficits of both thrombogenesis and occlusion model. EGb was also shown to inhibit the thrombogensis of rat common carotid artery stimulated by electrical current in dose-dependent manner. This experiment indicates that EGb might have beneficial effects on prevention and treatment of ischemic stroke and thrombogenesis.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12020739&dopt=Abstract Ref: Physiol Behav 2002 Apr 15;75(5):739-51
Modulation of cognition and mood following administration of single doses of Ginkgo biloba, ginseng, and a ginkgo/ginseng combination to healthy young adults.
Kennedy DO, Scholey AB, Wesnes KA.
Human Cognitive Neuroscience Unit, Division of Psychology, University of Northumbria, Newcastle-upon-Tyne NE1 8ST, UK.
It has previously been demonstrated in separate studies that single doses of Ginkgo biloba, Panax ginseng, and a combination of the two extracts can improve different aspects of cognitive performance in healthy young volunteers. The present study directly compared the effects of single doses of G. biloba, ginseng, and a product combining the two on aspects of mood and cognitive performance in the same cohort of healthy, young adult volunteers. The study followed a randomised placebo-controlled, double-blind, balanced, cross-over design. Twenty participants received 360 mg of ginkgo, 400 mg of ginseng, 960 mg of a product combining the two extracts, and a matching placebo. Treatment order was dictated by random allocation to a Latin square, with a 7-day wash-out period between treatments. Cognitive testing comprised completion of the Cognitive Drug Research (CDR) computerised assessment battery and two serial subtraction mental arithmetic tasks. Mood was assessed with Bond-Lader visual analogue scales. Following a baseline cognitive assessment, further test sessions took place 1, 2.5, 4, and 6 h after the day's treatment was taken. The results largely supported previous findings. All three treatments were associated with improved secondary memory performance on the CDR battery, with the ginseng condition evincing some improvement in the speed of performing memory tasks and in the accuracy of attentional tasks. Following ginkgo and the ginkgo/ginseng combination performance of both the Serial Threes and Serial Sevens, subtraction tasks was also improved at the later testing sessions. No modulation of the speed of performing attention tasks was evident. Improvements in self-rated mood was also found following ginkgo and to a lesser extent the combination product.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12009978&dopt=Abstract Ref: J Agric Food Chem 2002 May 22;50(11):3150-5
Biologically active secondary metabolites from Ginkgo biloba.
Bedir E, Tatli II, Khan RA, Zhao J, Takamatsu S, Walker LA, Goldman P, Khan IA.
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, and Department of Pharmacology and Pharmacognosy, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, USA.
Three new compounds, (7E)-2beta,3alpha-dihydroxy-megastigm-7-en-9-one (1), 3-[5,7-dihydroxy-2-(4-methoxyphenyl)-4-oxo-4H-chromen-8-yl]-4-methoxybenzoic acid (2), and 4'-O-methyl myricetin 3-O-(6-O-alpha-L-rhamnopyranosyl)-beta-D-glucopyranoside (3), were isolated from Ginkgo biloba, together with 27 known compounds. The structures of the new compounds were determined primarily from 1D- and 2D-NMR analysis. The 4-O-methylbenzoic acid structural feature at C-8 in 2 is encountered for the first time. The antioxidant activities of 29 compounds isolated from Ginkgo biloba were evaluated on intracellular reactive oxygen species in HL-60 cells. It was found that quercetin, kampferol, and tamarixetin had antioxidant activity that was approximately 3-fold greater than that of their respective glycosides and also approximately 3-fold greater than that of a standard ascorbic acid with an IC(50) at maximum effectiveness.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12006162&dopt=Abstract Ref: High Alt Med Biol 2002 Spring;3(1):29-37
Ginkgo biloba for the prevention of severe acute mountain sickness (AMS) starting one day before rapid ascent.
Gertsch JH, Seto TB, Mor J, Onopa J.
The University of Hawaii, John A. Burns School of Medicine, and the Kapiolani Clinical Research Center, Honolulu, Hawaii 96813, USA.
Previous studies suggest that 5 days of prophylactic ginkgo decreases the incidence of acute mountain sickness (AMS) during gradual ascent. This trial was designed to determine if ginkgo is an effective prophylactic agent if begun 1 day prior to rapid ascent. In this double-blind, randomized, placebo-controlled trial, 26 participants residing at sea level received ginkgo (60 mg TID) or placebo starting 24 h before ascending Mauna Kea, Hawaii. Subjects were transported from sea level to the summit (4205 m) over 3 hours, including 1 hour at 2835 m. The Lake Louise Self-report Questionnaire constituted the primary outcome measure at baseline, 2835 m, and after 4 h at 4205 m. AMS was defined as a Lake Louise Self-report Score (LLSR) >/= 3 with headache. Subjects who developed severe AMS were promptly transported to lower altitude for the remainder of the study. The ginkgo (n = 12) and placebo (n = 14) groups were well matched (58% vs. 50% female; median age 28 yr, range 22-53 vs. 33 yr, range 21-53; 58% vs. 57% Caucasian). Two (17%) subjects on ginkgo and nine (64%) on placebo developed severe AMS and required descent for their safety (p = 0.021); all recovered without sequelae. Median LLSR at 4205 m was significantly lower for ginkgo versus placebo (4, range 1-8 vs. 5, range 2-9, p = 0.03). Ginkgo use did not reach statistical significance for lowering incidence of AMS compared with placebo (ginkgo 7/12, 58.3% vs. placebo 13/14, 92.9%, p = 0.07). Twenty-one of 26 (81%) subjects developed AMS overall. This is the first study to demonstrate that 1 day of pretreatment with ginkgo 60 mg TID may significantly reduce the severity of AMS prior to rapid ascent from sea level to 4205 m.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12005361&dopt=Abstract Ref: J Pharm Pharmacol 2002 May;54(5):661-9
Pharmaceutical quality of different Ginkgo biloba brands.
Kressmann S, Muller WE, Blume HH.
Biocenter Niederursel, Department of Pharmacology, University of Frankfurt, Germany.
Ginkgo biloba-containing brands are one of the top sellers within the growing market for herbal remedies in many European countries as well as in the USA. In the consumers' interest, these brands should feature a certain quality and should be transparent in quality claims. In this investigation, a variety of products on the USA market was studied with respect to pharmaceutical quality, such as quantity of constituents and in-vitro dissolution. In terms of the content of active substances, flavone glycosides ranged from 24% to 36% and terpene lactones from 4% to 11%. With ginkgolic acids, there was a very large range, from < 500 ppm to about 90000 ppm. Comparing the dissolution rates of terpene lactones and flavone glycosides within the single products, most were approximately the same. Thus, terpene lactones and flavone glycosides were released from these products and dissolved at the same rate in most cases. Furthermore, most of the products investigated released more than the required 75% of the content of both components within 30 min. However, several products showed clear and relevant differences in dissolution rates to the rest (e.g. < 75% within 30 min or even less than 25% after 60 min in one case, indicating much poorer pharmaceutical quality). Beside the comparability respectively standardisation of the extracts used, the in-vitro dissolution of the relevant constituents should be similar to other drugs to guarantee comparable in-vivo performance of herbal products. An important step in standardising pharmaceutical quality is the pharmacopoeial monograph for Ginkgo biloba extract in Germany, standardising the content of pharmacologically relevant substances (flavone glycosides 22-27% and terpenlactones 5-7%, 2.8-3.4% ginkgolides A, B, C and 2.6-3.2% bilobalide thereof). Many of the investigated products, which refer to the German Commission E (of the Federal Institute for Drugs and Medicinal Devices) monograph, are not in accordance with this specification. Thus, they can not be considered to be pharmaceutically equivalent.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12002672&dopt=Abstract Ref: J Ocul Pharmacol Ther 2002 Apr;18(2):197-202
Pharmacokinetics and bioavailability of a Ginkgo biloba extract.
Drago F, Floriddia ML, Cro M, Giuffrida S.
Institute of Ocular Pharmacology, Faculty of Medicine, University of Catania, Italy.
The aim of the present study was to assess the bioavailability of the main active ingredient in Ginkgo biloba extract, ginkgolid B. The study also focused on the pharmacokinetics of two different dosage regimens for orally administered Gingko biloba extract, 80 mg once daily and 40 mg twice daily for 7 days. Twelve healthy volunteers took part in the study. They were randomly assigned to one of the two treatment groups: 40 mg twice daily or 80 mg once daily, with an interval of 21 days between cycles. Statistical analysis was used to assess the main pharmacokinetic parameters. The results show that a dosage of 40 mg twice daily (every 12 hrs) is accompanied by a significantly longer half-life (t1/2) and mean residence time (MRT) than a single 80 mg dose, even though the latter causes a higher concentration peak (Cmax). The maximum concentration time (Tmax) is 2.3 hrs after administration in both treatments.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11991253&dopt=Abstract Ref: Life Sci 2002 Feb 22;70(14):1657-67
Effects of extract of Ginkgo biloba leaves and its constituents on carcinogen-metabolizing enzyme activities and glutathione levels in mouse liver.
Sasaki K, Hatta S, Wada K, Ueda N, Yoshimura T, Endo T, Sakata M, Tanaka T, Haga M.
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.
The effects of a standardized extract of Ginkgo biloba L. leaves (EGb) and its terpene constituents, bilobalide and ginkgolides, on the activities of detoxification enzymes, i.e., glutathione S-transferases (GSTs) and DT-diaphorase, and glutathione contents, were investigated in the mouse liver. Oral treatment with EGb (100-1,000 mg/kg) and bilobalide (10-30 mg/kg) once a day for 4 days caused a dose-dependent elevation in GST activity. Ginkgolide A (30 mg/kg, for 4 days) also significantly elevated GST activity, whereas ginkgolide B and ginkgolide C at the same dose had no effects. EGb significantly increased the protein level of GST pi, and bilobalide significantly increased those of GST alpha and GST mu Moreover, EGb-treatment and bilobalide-treatment caused significant elevations in DT-diaphorase activity and in hepatic glutathione contents.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11989597&dopt=Abstract Ref: Tumori 2001 Nov-Dec;87(6):417-22
Ginkgo biloba extract (EGb 761) modulates bleomycin-induced acute lung injury in rats.
El-Khatib AS, Moustafa AM, Abdel-Aziz AA, Al-Shabanah OA, El-Kashef HA.
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
The effect of Ginkgo biloba extract (EGb 761) on bleomycin (BLM)-induced acute lung injury was studied in rats. The responsiveness of isolated pulmonary arterial rings to 5-hydroxytryptamine (5-HT) as well as the levels of some relevant biochemical markers in the lung tissue were taken as evidence for the acute lung injury. BLM was given intraperitoneally at a dose of 15 mg/kg/day for five consecutive days. It was found that BLM treatment attenuated the vasoconstrictor effect of 5-HT on the isolated pulmonary arteries. In lung tissues BLM also elevated the level of lipid peroxides and enhanced the activity of glutathione peroxidase. On the other hand, the level of glutathione and the activity of alkaline phosphatase were reduced. Body weight, lung weight and tissue glutathione-S-transferase activity were, however, not altered. Oral administration of EGb 761 at a dose of 100 mg/kg/day for five consecutive days did not alter any of the chosen biochemical parameters in the lung tissue except for a slight reduction in alkaline phosphatase activity. However, treatment with EGb 761 reduced the responsiveness of the pulmonary artery to 5-HT. Administration of EGb 761 (100 mg/kg/day; po) two hours prior to BLM (15 mg/kg/day; ip), for five consecutive days blunted the occurrence of further reduction in the vasoconstrictor response of the pulmonary artery to 5-HT. Furthermore, EGb 761 tended to normalize BLM-induced alterations in the measured biochemical markers in the lung tissue. The apparent modulatory influence of EGb 761 on BLM-induced acute lung injury stems, at least in part, from its beneficial free radical scavenging properties that provide the extract with antioxidant activity.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11988854&dopt=Abstract Ref: Planta Med 2002 Apr;68(4):316-21
Kwak WJ, Han CK, Son KH, Chang HW, Kang SS, Park BK, Kim HP.
SK Chemicals Ltd., Suwon, Korea.
Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a phospholipase A2 inhibitor and this compound showed the potent antiarthritic activity in rat adjuvant-induced arthritis as well as analgesic activity. This investigation was carried out to find effects on cyclooxygenase (COX)-1 and -2 including an in vivo effect. Ginkgetin (1 - 10 microM) and the biflavonoid mixture (10 - 50 microg/ml), mainly a 1 : 1 mixture of ginkgetin and isoginkgetin, from Ginkgo biloba leaves, inhibited production of prostaglandin E2 from lipopolysaccharide-induced RAW 264.7 cells. This inhibition was mediated, at least in part, by down-regulation of COX-2 expression, but not by direct inhibition of COX-1 or COX-2 activity. Down-regulation of COX-2 by ginkgetin was also proved in the dorsal skin of ICR mouse treated by 12-O-tetradecanoylphorbol 13-acetate (TPA). At total doses of 1,000 microg/site on the dorsal skin (15 mm x 15 mm), ginkgetin inhibited prostaglandin E2 production by 65.6 % along with a marked suppression of COX-2 induction. In addition, ginkgetin and the biflavonoid mixture (100 - 1,000 microg/ear) dose-dependently inhibited skin inflammation of croton oil induced ear edema in mice by topical application. The present study suggests that ginkgetin from Ginkgo biloba leaves down-regulates COX-2 induction in vivo and this down-regulating potential is associated with an anti-inflammatory activity against skin inflammatory responses.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11976546&dopt=Abstract Ref: Ann Pharm Fr 2002 Jan;60(1):22-7
Plant biotechnology: an avant-garde research for an ancestral tree, the Ginkgo biloba
[Article in French]
Sohier C.
Institut Henri Beaufour, c/o Centre de Recherche Nestle Tours, Notre Dame D'Oe, B.P. 9716, F 37097 Tours Cedex 2.
A biotechnology program on Ginkgo biloba was implemented in early 80's, in order to improve the biosynthesis in the whole plant and in cell cultures of therapeutically active substances, mainly terpenes like ginkgolides. This program led to very interesting results in various directions In addition, by the mean of in vitro culture, metabolic studies have given some pertinent fundamental results adding to the basic understanding of Ginkgo biloba: ginkgolides and bilobalide are biosynthesized in the roots of the plant and then translocated to the leaves. Two separate and independent metabolic pathways have been underlined for the formation of isopentenylpyrophosphate (IPP), the fundamental unit involved both in the biosynthesis of the sitosterol and the ginkgolides. The possibilities offered by plant biotechnology allowed the implementation of new tools for propagation and improvement of the Ginkgo biloba and have enriched the knowledge of the biosynthesis of active principles.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11967997&dopt=Abstract Ref: J Cell Biochem 2002;85(3):572-82
Effects of Ginkgo biloba extract on the proliferation of vascular smooth muscle cells in vitro and on intimal thickening and interleukin-1beta expression after balloon injury in cholesterol-fed rabbits in vivo.
Lin SJ, Yang TH, Chen YH, Chen JW, Kwok CF, Shiao MS, Chen YL.
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Restenosis may develop in response to cytokine activation and smooth muscle cell proliferation. Ginkgo biloba extract (EGb) has been used to treat cardiovascular and cerebrovascular diseases. In the present study, the effects of EGb on the growth of cultured vascular smooth muscle cells (VSMC), as well as on the expression of interleukin-1beta (IL-1beta) and the intimal response in balloon-injured arteries of cholesterol-fed rabbits, were investigated. Using bromodeoxyuridine incorporation as an index of cell proliferation, EGb was found to inhibit serum-induced mitogenesis of cultured rat aorta VSMC in a dose-dependent manner. In vivo, EGb and probucol ( positive control) reduced the atheroma area in thoracic aortas of male New Zealand white rabbits fed a 2% cholesterol diet for 6 weeks with balloon denudation of the abdominal aorta being performed at the end of the third week. Intimal hyperplasia, expressed as the intimal/medial area ratio, in the abdominal aortas was significantly inhibited in the both the EGb group (0.61 +/- 0.06) and the probucol group (0.55 +/- 0.03) compared to the C group (0.87 +/- 0.02). In the balloon-injured abdominal aorta, both EGb and probucol significantly reduced IL-1beta mRNA and protein expression and the percentage of proliferating cells. The inhibitory effects of EGb on the intimal response might be attributed to its antioxidant capacity. EGb may have therapeutic potential for the prevention of restenosis after angioplasty.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11960600&dopt=Abstract Ref: Biochem Pharmacol 2002 Apr 1;63(7):1241-9
Sensitization of human neutrophil defense activities through activation of platelet-activating factor receptors by ginkgolide B, a bioactive component of the Ginkgo biloba extract EGB 761.
Lenoir M, Pedruzzi E, Rais S, Drieu K, Perianin A.
CNRS UPRES-A 8068, Departement de Biologie Cellulaire, ICGM, Hopital Cochin, 27 rue du Faubourg St. Jacques, 75679 Paris Cedex 14, France.
Ginkgolide B (GKB, BN 52021) was described as a platelet-activating factor (Paf) receptor antagonist. However, it is not known whether all GKB biological effects are mediated through Paf receptor antagonism only. To gain insight into the drug mode of action, we investigated here the effects of GKB per se on functional and signaling activities in human polymorphonuclear leukocytes (PMN). Treatment of PMN with GKB (0.5-12 microM) stimulates a rapid and weak production of reactive oxygen species determined by chemiluminescence. ROS production required the activation of protein kinase C (PKC), tyrosine kinases and p38 mitogen-activated protein kinase as indicated by inhibitory effects of, respectively, GF 109203X (IC(50) of 0.5 microM), genistein (IC(50) of 0.5 microM) and SB 203580 (IC(50) of 0.2 microM) or SB 202190 (IC(50) of 1.1 microM). GKB stimulated a Pertussis toxin-sensitive PLD activity assessed by the formation of tritiated phosphatidic acid and choline. By contrast, GKB did prevent the Paf-mediated PLD activity and CL response (IC(50) of 2 microM). Interestingly, both GKB and Paf-induced CL response were prevented by selective Paf antagonists such as CV 6209 or WEB 2086 indicating that GKB may directly activate Paf receptors. Finally, GKB potentiated the CL response induced by fMet-Leu-Phe and zymosan. These results show that GKB is the first partial agonist of the Paf receptor described so far capable of priming the polymorphonuclear leukocyte function.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11958534&dopt=Abstract Ref: Neurochem Res 2002 Apr;27(4):319-23
Ginkgo biloba extracts EGb 761 and bilobalide increase NADH dehydrogenase mRNA level and mitochondrial respiratory control ratio in PC12 cells.
Tendi EA, Bosetti F, Dasgupta SF, Stella AM, Drieu K, Rapoport SI.
Brain Physiology and Metabolism Section, National Institute on Aging. National Institutes of Health. Bethesda, MD 20892, USA.
In the present study, we investigated the effect of Ginkgo biloba extract, EGb 761, and one of its components, bilobalide, on gene expression of subunit 1 of mitochondrial NADH dehydrogenase (ND1) in PC12 cells. By Northern blot analysis we found a approximately 2-fold significant increase in NDI mRNA level, after 48 and 72 h exposure to 100 microg/ml EGb 761 and to 10 microg/ml bilobalide. We also evaluated, by oxygraphy measurements, mitochondrial respiration during state 3 and state 4. In cells treated with EGb 761 and bilobalide for 48 and 72 h, state 4 respiration was significantly decreased, and the respiratory control ratio was increased. These results provide evidence that EGb 761 and bilobalide exert their protective effects by up-regulating mitochondrial ND1 gene expression and by decreasing state 4 respiration, whose increase is thought to be responsible for oxidative damage.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11941954&dopt=Abstract Ref: Hepatogastroenterology 2002 Jan-Feb;49(43):201-4
An assessment of the effect of Ginkgo Biloba EGb 761 on ischemia reperfusion injury of intestine.
Pehlivan M, Dalbeler Y, Hazinedaroglu S, Arikan Y, Erkek AB, Gunal O, Turkcapar N, Turkcapar AG.
Department of General Surgery, Abant Izzet Baysal University, Duzce School of Medicine, 14450 Konuralp, Duzce, Turkey.
BACKGROUND/AIMS: The aim of this study was to determine the effect of Ginkgo Biloba (EGb 761) on reperfusion injury of the small bowel. METHODOLOGY: Forty-eight male 200-250 g Spraque-Dawley rats in six groups were used to determine the biochemical and histopathological changes after a 30-min ischemia and 30-min reperfusion. Pre-treatment with 50 mg/kg EGb 761 (Tebofortan, Karlsruhe-Germany) or 10-mL/kg saline was administered intravenously in the treatment and control groups. The superior mesenteric artery was occluded distal to the right colic artery and collateral arcades were ligated to provide complete ischemia. Ischemia was determined by the existence of pulseless or pale color of the small intestine. The return of the pulses and the reestablishment of the pink color were assumed to be the reperfusion of the intestine. Rats that were administered Egb 761 and saline were subjected to laparotomy, ischemia, or ischemia-reperfusion procedures. Mucosal lesions were graded from 0 to 5 in histopathological examination. Malondialdehyde and myeloperoxidase levels of the intestinal mucosa were measured. RESULTS: No significant difference was noted between the control and treatment groups regarding the histopathological changes. Although malonyldialdehyde and myeloperoxidase levels of the reperfusion + EGb 761 group were slightly higher than the laparotomy + saline group, they were significantly lower than the reperfusion + saline group. CONCLUSIONS: We concluded that EGb 761 pre-treatment before ischemia-reperfusion decreased malondialdehyde and myeloperoxidase levels and attenuated the mucosal damage.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11938864&dopt=Abstract Ref: Zhongguo Zhong Xi Yi Jie He Za Zhi 2000 Dec;20(12):917-9
Experimental study on suppressive effect of ginkgo extract on adhesion of vascular endothelial cell to monocyte induced by minimally modified low density lipoprotein
[Article in Chinese]
Liu C, Qian G, Liu H.
Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin 300020.
OBJECTIVE: To observe the effect of Ginkgo extract on the interaction between minimally modified low density lipoprotein (MM-LDL) induced human umbilical vein endothelial cell (HUVEC) and U937 monocyte-like cell line. METHODS: The adhesive percentage between HUVEC and U937 by counting and the expression of VCAM-1, ICAM-1, P-selectin by ELISA. RESULTS: Treatment of HUVEC with MM-LDL (75 micrograms/ml) for 4 hrs could significantly increase the adhesion of U937 to HUVEC (P < 0.01) and Ginkgo extract could suppress the adhesion in dose-dependent manner. The surface expression of VCAM-1, ICAM-1, P-selectin was not induced by MM-LDL, while recombination tumor necrosis factor-alpha 5.0 ng/ml, as a positive control, could do. CONCLUSION: Ginkgo extract afforded protection against HUVEC damage induced by MM-LDL and the adhesion of monocytes to endothelial cells induced by MM-LDL is not mediated by VCAM-1, ICAM-1 and P-selectin.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11925776&dopt=Abstract Ref: Wien Med Wochenschr 2002;152(3-4):77-80
Symptomatic therapy of Alzheimer dementia
[Article in German]
Forstl H.
Klinik und Poliklinik fur Psychiatrie und Psychotherapie der Technischen Universitat Munchen, Ismaninger Strasse 22, D-81672 Munchen, Deutschland.
No causal treatment or highly effective preventive strategies are available for Alzheimer's disease to date. Symptomatic measures are still essential to improve cognitive and behavioural deficits. Acetylcholinesterase inhibitors, the NMDA-antagonist memantine and the phytopharmaco ginkgo biloba are currently the substances most extensively studied and most widely used to improve cognition and activities of daily living. Behavioural disturbances oftentimes respond to antidementia drugs, but may demand specific treatment with neuroleptics, antidepressants, stabilizers and other substances.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11908671&dopt=Abstract Ref: Genome 2002 Feb;45(1):8-12
DNA polymorphism in the living fossil Ginkgo biloba from the eastern United States.
Kuddus RH, Kuddus NN, Dvorchik I.
Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, PA 15213, USA.
Random amplified polymorphic DNA (RAPD) analysis is a valuable tool in studying inter- and intra-specific genetic variations, patterns of gene expression, and for the identification of specific genes using nearly isogenic variants. Here we used RAPD analysis to study the genetic variation in Ginkgo biloba grown in the eastern United States. Our results support the evidence that Southern blot hybridization of RAPD using probes made from cloned DNA fragments allows a more accurate analysis of the RAPD pattern than dye-stained gels or Southern blot hybridization of RAPD blots using probes made from purified PCR products. Using these techniques, we observed a high degree of relatedness among plants grown in certain localities although significant genetic variation may exist in the species, and could be a possible explanation for the observed variations in the efficacy of medications derived from Ginkgo biloba extract.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11902921&dopt=Abstract Ref: J Agric Food Chem 2002 Mar 27;50(7):1840-4
Selective responses of three Ginkgo biloba leaf-derived constituents on human intestinal bacteria.
Lee HS, Kim MJ.
Research Center for Industrial Development of Biofood Materials and Institute of Agricultural Science & Technology, College of Agriculture, Chonbuk National University, Chonju 561-756, Korea.
The selective responses of Ginkgo biloba leaf-derived materials against six intestinal bacteria was examined using an impregnated paper disk method and compared with that of bilobalide, ginkgolides A and B, kaempferol, and quercetin. The components of G. biloba leaves were characterized as kaempferol 3-O-alpha-(6' "-p-coumaroylglucosyl-beta-1,4-rhamnoside), kaempferol 3-O-(2' '-O-beta-D-glucopyranosyl)-alpha-L-rhamnopyranoside, and quercetin 3-O-alpha-(6' "-p-coumaroylglucosyl-beta-1,4-rhamnoside) by spectroscopic analysis. The growth responses varied with each bacterial strain tested. At 2 mg/disk, kaempferol 3-O-alpha-(6' "-p-coumaroylglucosyl-beta-1,4-rhamnoside) and quercetin 3-O-alpha-(6' "-p-coumaroylglucosyl-beta-1,4-rhamnoside) revealed potent inhibition against Clostridium perfringens, and kaempferol 3-O-(2' '-O-beta-D-glucopyranosyl)-alpha-L-rhamnopyranoside showed a clear inhibitory effect on Escherichia coli. At 0.5 mg/disk, quercetin 3-O-alpha-(6' "-p-coumaroylglucosyl-beta-1,4-rhamnoside) showed a strong activity against C. perfringens, but weak activity was exhibited by kaempferol 3-O-alpha-(6' "-p-coumaroylglucosyl-beta-1,4-rhamnoside) against C. perfringens and kaempferol 3-O-(2' '-O-beta-D-glucopyranosyl)-alpha-L-rhamnopyranoside against E. coli. No inhibition was observed from treatments conducted with bilobalide, ginkgolides A and B, kaempferol, or quercetin. Furthermore, these isolated compounds did not inhibit Bifidobacterium bifidum, B. longum, B. adolescentis, or Lactobacillus acidophilus.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11870327&dopt=Abstract Ref: Acta Crystallogr C 2002 Mar;58(Pt 3):o195-8
Three ginkgolide hydrates from Ginkgo biloba L.: ginkgolide A monohydrate, ginkgolide C sesquihydrate and ginkgolide J dihydrate, all determined at 120 K.
Zhao J, Muhammad I, Dunbar DC, Khan IA, Fischer NH, Fronczek FR.
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
A low-temperature structure of ginkgolide A monohydrate, (1R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11aS)-3-(1,1-dimethylethyl)-hexahydro-4,7b-dihydroxy-8-methyl-9H-1,7a-epoxymethano-1H,6aH-cyclopenta[c]furo[2,3-b]furo[3',2':3,4]cyclopenta[1,2-d]furan-5,9,12(4H)-trione monohydrate, C(20)H(24)O(9) x H(2)O, obtained from Mo K alpha data, is a factor of three more precise than the previous room-temperature determination. A refinement of the ginkgolide A monohydrate structure with Cu K alpha data has allowed the assignment of the absolute configuration of the series of compounds. Ginkgolide C sesquihydrate, (1S,2R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11S,11aR)-3-(1,1-dimethylethyl)-hexahydro-2,4,7b,11-tetrahydroxy-8-methyl-9H-1,7a-epoxymethano-1H,6aH-cyclopenta[c]furo[2,3-b]furo[3',2':3,4]cyclopenta[1,2-d]furan-5,9,12(4H)-trione sesquihydrate, C(20)H(24)O(11) x 1.5H(2)O, has two independent diterpene molecules, both of which exhibit intramolecular hydrogen bonding between OH groups. Ginkgolide J dihydrate, (1S,2R,3S,3aS,4R,6aR,7aR,7bR,8S,10aS,11aS)-3-(1,1-dimethylethyl)-hexahydro-2,4,7b-trihydroxy-8-methyl-9H-1,7a-epoxymethano-1H,6aH-cyclopenta[c]furo[2,3-b]furo[3',2':3,4]cyclopenta[1,2-d]furan-5,9,12(4H)-trione dihydrate, C(20)H(24)O(10) x 2H(2)O, has the same basic skeleton as the other ginkgolides, with its three OH groups having the same configurations as those in ginkgolide C. The conformations of the six five-membered rings are quite similar across ginkgolides A-C and J, except for the A and F rings of ginkgolide A.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11856998&dopt=Abstract Ref: Am J Ther 1996 Jan;3(1):63-73
Central Nervous System Effects of Ginkgo Biloba, a Plant Extract.
Itil TM, Eralp E, Tsambis E, Itil KZ, Stein U.
New York Institute for Medical Research, Tarrytown, NY, USA.
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.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11853165&dopt=Abstract Ref: Biol Pharm Bull 2002 Feb;25(2):197-200
Safety of dietary supplements: chronotropic and inotropic effects on isolated rat atria.
Kubota Y, Umegaki K, Tanaka N, Mizuno H, Nakamura K, Kunitomo M, Shinozuka K.
School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
We investigated the effects of dietary supplements on atria isolated from male Wistar rats. The examined supplements, which are increasingly used in Japan, those were Ginkgo biloba extract (GBE), catechins, isoflavones, sodium iron chlorophyllin and sodium copper chlorophyllin. GBE at 100-1000 microg/ml significantly increased the beat rate and the contractile force. Catechins at 1-100 microg/ml significantly potentiated the contractile force but did not effect the beat rates. However, isoflavones, sodium iron and sodium copper chlorophyllins did not change the contractile force or the beat rates. To identify the active ingredient of GBE, ginkgolide B, quercetin and amentoflavone on the atria were tested. Ginkgolide B weakened the contractile force. Quercetin potentiated the contractile force at only 30 microg/ml. Amentoflavone significantly increased the beat rate. From these findings, amentoflavone and quercetin were considered to be the principal ingredients of GBE producing the positive chronotropic and inotropic actions, respectively. In the case of catechins, (-)-epigallocatechin gallate (EGCg), one of the principal ingredients, produced inotropic actions. These findings suggest that there are some dietary supplements which affect cardiac function, such GBE and catechins.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11842916&dopt=Abstract Ref: Nutr Neurosci 2001;4(5):399-412
Differential, dose dependent changes in cognitive performance following acute administration of a Ginkgo biloba/Panax ginseng combination to healthy young volunteers.
Kennedy DO, Scholey AB, Wesnes KA.
Division of Psychology, University of Northumbria, Newcastle upon Tyne, UK.
We have previously shown differential cognitive improvements following single doses of Ginkgo biloba and of Ginseng. There is also evidence that chronic administration of a combination of standardised extracts of Ginkgo biloba and Panax ginseng may improve aspects of cognitive performance both in pathological populations and the healthy middle aged. No investigation has thus far looked either at the cognitive effects of single doses of such a combination, nor the effects of the combination on healthy young volunteers. The present study investigated whether acute administration of a combination of standardised extracts of Ginkgo biloba (GK501, Pharmaton SA) and Ginseng (G115, Pharmaton SA) had any consistent effect on mood and aspects of cognitive performance ("quality of memory", "secondary memory", "working memory", "speed of memory", "quality of attention" and "speed of attention") that can be derived by factor analysis of the cognitive drug research computerised assessment battery. The study followed a placebo-controlled, double blind, balanced, crossover design. Twenty healthy young adult volunteers received 320, 640, and 960 mg of the combination, and a matching placebo, in an order dictated by random allocation to a Latin square, and with a seven-day wash-out period between treatments. Following a baseline cognitive assessment, further test sessions took place 1, 2.5,4 and 6 h after the day's treatment. The most striking result was a dose-dependent improvement in performance on the "quality of memory" factor for the highest dose. Further analysis revealed that this effect was differentially targeted at the secondary memory rather than the working memory component. There was also a dose dependent decrement in performance of the "speed of attention" factor for both the 320 and 640 mg doses. These results are discussed in the context of previous findings within this series of studies.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11842336&dopt=Abstract Ref: Planta Med 2002 Jan;68(1):76-9
Biflavones of Ginkgo biloba stimulate lipolysis in 3T3-L1 adipocytes.
Dell'Agli M, Bosisio E.
Department of Pharmacological Sciences, Faculty of Pharmacy, University of Milan, Milan, Italy.
Ginkgo biloba L. biflavones were shown to increase cAMP phosphodiesterase activity and to stimulate skin microcirculation. The aim of this study was to investigate whether biflavones were able to stimulate lipolysis in adipocytes. Lipolysis was assayed in fully differentiated 3T3-L1 fat cells in the presence of biflavones at 0.005 - 100 microM. Cell viability was evaluated at 0.5 -100 microM. Theophylline and caffeine were used as reference compounds. Lipolytic activity in untreated cells was 0.62 +/- 0.15 micromoles glycerol/mg DNA/h. All biflavones except sciadopitysin stimulated lipolysis in a concentration-dependent fashion. Maximal stimulation was observed at 0.1 - 0.5 microM. At higher concentrations the effect diminished progressively and was lost at 100 microM. Only a partial loss of cell viability was observed with biflavones at 10 - 100 microM.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11829655&dopt=Abstract Ref: J Agric Food Chem 2002 Feb 13;50(4):846-9
Extraction of pharmaceutical components from Ginkgo biloba leaves using supercritical carbon dioxide.
Yang C, Xu YR, Yao WX.
Laboratory of Environmental-Analytical Chemistry and Ecological Toxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
Ginkgo biloba extract (GBE) has many remarkable pharmacological and clinical effects, and it is the most frequently used product as a phytomedicine in many countries. The combination of primary extraction with 70% ethanol followed by extraction using supercritical carbon dioxide provides an efficient and economical means for obtaining flavonoids and terpenoids from Ginkgo biloba leaves. The supercritical fluid extraction (SFE) is affected by pressure, temperature, and the concentration of modifier in the extractant. At the most favorable experimental conditions of 300 MPa, 60 degrees C, and carbon dioxide containing 5% ethanol as modifier, the yield of GBE powder is 2.1% (based on the air-dry weight of Ginkgo biloba leaves) compared to a yield of only 1.8% by conventional solvent extraction. The contents of flavonoids and terpenoids in SFE products are 35.9% and 7.3%, respectively, which are significantly higher than the general standards of 24% and 6%, respectively.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11810408&dopt=Abstract Ref: J Neural Transm 2001;108(12):1457-74
Effect of Ginkgo biloba extract (EGb761) on glucose metabolism-related markers in streptozotocin-damaged rat brain.
Loffler T, Lee SK, Noldner M, Chatterjee SS, Hoyer S, Schliebs R.
Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Federal Republic of Germany.
To reveal whether an extract of Ginkgo biloba (EGb761) may affect streptozotocin (STZ)-induced impairments in brain glucose metabolism, autoradiographies of [3H]cytochalasin-B binding to the total population of glucose transporters, [125I]insulin binding to insulin receptors, [3H]glyburide binding to sulfonylurea receptors, and radioactive in situ hybridization for GLUT3 mRNA were carried out in hippocampal brain sections of adult rats that have additionally been divided into good performers (GP) and poor performers (PP) by behavioural tests before the experiments. The STZ-induced increases in hippocampal [3H]cytochalasin-B binding to (total) glucose transporters returned to almost normal values following EGb761 treatment, regardless of the experimental animal group (GP or PP) tested. Similarly, the STZ-mediated enhancements in hippocampal insulin receptor binding of GP rats were partially compensated by the treatment with EGb761. The data suggest beneficial effects of EGb671 on impaired brain glucose metabolism, at least under the experimental conditions used in the study presented.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11806299&dopt=Abstract Ref: Therapie 2001 Sep-Oct;56(5):595-600
Protective effects of a Ginkgo biloba extract (EGb 761) on ischemia-reperfusion injury
[Article in French]
Clostre F.
EGb 761 is a standardized extract of dried leaves of Ginkgo biloba. EGb 761 is a neuroprotective and anti-ischaemic drug. Its broad spectrum of pharmacological activities allows it to be adequate to the numerous pathological requirements--haemodynamic, haemorrheological, metabolic--which occur in cerebral, retinal, cochleovestibular, cardiac or peripheral ischaemia. Moreover, EGb 761 has direct effects in retinal and myocardial ischaemia and reperfusion injuries. EGb 761 improves retinal microcirculation, reduces oedema of the retinal inner layer and protects chemoreceptors against free-radical injuries. On myocardial ischaemia-reperfusion models, EGb 761 improves myocardial functional recovery, and reduces the number of ventricular extrasytoles and the duration of ventricular tachycardia induced by reperfusion. EGb 761 protects the retina and the heart against ischaemia-reperfusion damage via its free radical-scavenging and anti-lipoperoxidative properties and its regulation of mitochondrial respiratory function.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11803237&dopt=Abstract Ref: Neuropsychobiology 2002;45(1):19-26
Influence of the severity of cognitive impairment on the effect of the Ginkgo biloba extract EGb 761 in Alzheimer's disease.
Le Bars PL, Velasco FM, Ferguson JM, Dessain EC, Kieser M, Hoerr R.
New York University Medical Center and Memory Centers of America, New York, NY, USA.
OBJECTIVE: To explore the treatment effect of EGb 761((R)) (EGb) in Alzheimer's disease depending on baseline severity. METHODS: We applied stratification to the intent-to-treat data set collected during a 52-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study with 120 mg of EGb, using cutoff points of 23 and 14 for the Mini-Mental State Examination (MMSE) score. Outcome measures used were the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) and the Geriatric Evaluation by Relative's Rating Instrument (GERRI). RESULTS: In the severity stratum 1 (MMSE >23), the placebo group did not show significant changes, while the EGb group improved significantly by 1.7 points on the ADAS-Cog and by 0.09 points on the GERRI. In the severity stratum 2 (MMSE <24), the placebo group worsened by 4.1 points on the ADAS-Cog and 0.18 points on the GERRI, whereas the EGb group showed 60% less decline on the ADAS-Cog (treatment difference of 2.5 points) and no change on the GERRI (treatment difference of 0.25 points). The most severely impaired subgroup (MMSE <15) showed slightly more pronounced worsening for both treatment groups. However, in comparison to placebo, EGb induced virtually the same magnitude of effect as was observed in the entire stratum 2. CONCLUSIONS: The results of this retrospective analysis indicated that a treatment effect favorable to EGb could be observed with respect to cognitive performance (p = 0.02) and social functioning (p = 0.001) regardless of the stage of dementia, whether mild or moderately severe. However, the relative changes from baseline measured at endpoint depended heavily on the severity at baseline. Improvement was observed in the group of patients with very mild to mild cognitive impairment, while in more severe dementia, the mean EGb effect should be considered more in terms of stabilization or slowing down of worsening, as compared to the greater deterioration observed with placebo.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11775047&dopt=Abstract Ref: J Clin Psychiatry 2001 Nov;62(11):878-83
A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia.
Zhang XY, Zhou DF, Zhang PY, Wu GY, Su JM, Cao LY.
Yale University School of Medicine, Neuropsychopharmacology Lab, New Haven, CT 06520-8066, USA.
BACKGROUND: Many studies have indicated that excess free radical formation may be involved in the pathogenesis of patients with schizophrenia. Some investigators suggested that the use of free radical scavengers might provide improvement in schizophrenia. The aim of this study was to determine the effectiveness and to evaluate the side effects of extract of Ginkgo biloba (EGb) plus haloperidol in chronic, treatment-resistant inpatients with schizophrenia. METHOD: One hundred nine patients meeting DSM-III-R criteria for schizophrenia completed a double-blind, placebo-controlled, parallel-group study of EGb plus haloperidol. Fifty-six of the patients were randomly assigned to receive a fixed dose of 360 mg/day of EGb plus a stable dose of haloperidol, 0.25 mg/kg/day, and 53 were assigned to receive placebo plus the same dose of haloperidol for 12 weeks. Patients were assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Scale for the Assessment of Positive Symptoms (SAPS) at baseline, week 6, and week 12 and the Treatment Emergent Symptom Scale (TESS) for side effects at week 12. RESULTS: There was a significant reduction in both groups in BPRS total score after 12 weeks of treatment (p < .05). However, a significant reduction in total SAPS and SANS scores was noted in the EGb group (p < .05), but not in the placebo group. There was a lower SAPS total score in the EGb group than in the placebo group at the end of 12 weeks of treatment (p < .05). Of those treated with EGb plus haloperidol, 57.1% were rated as responders as compared with only 37.7% of those receiving placebo plus haloperidol when assessed by the SAPS (chi2 = 4. 111, p = .043). After 12 weeks of treatment, TESS subscore 1 (behavioral toxicity) and subscore 3 (symptoms of nerve system) were significantly decreased in the EGb group compared with the placebo group (p < .05). CONCLUSION: EGb treatment may enhance the effectiveness of antipsychotic drugs and reduce their extrapyramidal side effects.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11749805&dopt=Abstract Ref: Acta Pharmacol Sin 2001 Dec;22(12):1089-93
Protective effect and mechanism of Ginkgo biloba leaf extracts for Parkinson disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Yang SF, Wu Q, Sun AS, Huang XN, Shi JS.
Department of Pharmacology, Zunyi Medical College, Zunyi 563003, China.
AIM: To observe the effects of extracts of Ginkgo biloba leaves (EGb) on the Parkinson disease (PD) models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its ion 1-methyl-4-phenylpyridinium (MPP+). METHODS: MPTP was microinjected into substantia nigra of rats to induce a behavior change of rotation. EGb (ip, 50 or 100 mg.kg(1 . d-1) was pretreated consecutively for 19 d before MPTP administered and 1 d after MPTP administered. The contents of malondialdehyde (MDA), superoxide dismutase (SOD), and dopamine (DA) in substantia nigra of model rats were determined. Apoptosis of PC12 cells was induced by MPP+, and the protective effect of EGb (25, 50, and 100 mg/L) was also observed. The cells of apoptosis were observed under a microscope and counted under a fluoroscope after stained with AO/EB. RESULTS: EGb (100 mg . kg-1 . d-1) decreased the duration and frequency of the rotation of rats (P < 0.05, n = 10 ) while EGb (50 or 100 mg/L)inhibited the decreases of DA and SOD and the increase of MDA induced by MPTP, (P < 0.05 or P < 0.01, n = 10). MPP+ (10 micromol/L) induced the apoptosis of PC12 cells, and EGb (50 or 100 mg/L) prevented cells from apoptosis at 6 h, 12 h, and 24 h (P < 0.05 or P < 0.01, n = 3). CONCLUSION: EGb possesses protective effect on the PD models in vivo and in vitro. The anti-oxidation and anti-apoptosis may be one of the mechanisms underlying the neuroprotective effect of EGb.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11743961&dopt=Abstract Ref: Brain Res 2001 Dec 20;922(2):282-92
Neuroprotective effects of bilobalide, a component of the Ginkgo biloba extract (EGb 761), in gerbil global brain ischemia.
Chandrasekaran K, Mehrabian Z, Spinnewyn B, Drieu K, Fiskum G.
Department of Anesthesiology, University of Maryland School of Medicine, MSTF 5-34, 685 West Baltimore St., Baltimore, MD 21201, USA.
The neuroprotective effect of Ginkgo biloba extract (EGb 761) against ischemic injury has been demonstrated in animal models. In this study, we compared the protective effect of bilobalide, a purified terpene lactone from EGb 761, and EGb 761 against ischemic injury. We measured neuronal loss and the levels of mitochondrial DNA (mtDNA)-encoded cytochrome oxidase (COX) subunit III mRNA in vulnerable hippocampal regions of gerbils. At 7 days of reperfusion after 5 min of transient global forebrain ischemia, a significant increase in neuronal death and a significant decrease in COX III mRNA were observed in the hippocampal CA1 neurons. Oral administration of EGb 761 at 25, 50 and 100 mg/kg/day and bilobalide at 3 and 6 mg/kg/day for 7 days before ischemia progressively protected CA1 neurons from death and from ischemia-induced reductions in COX III mRNA. In addition, both bilobalide and EGb 761 protected against ischemia-induced reductions in COX III mRNA in CA1 neurons prior to their death, at 1 day of reperfusion. These results suggest that oral administration of bilobalide and EGb 761 protect against ischemia-induced neuron death and reductions in mitochondrial gene expression.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11742783&dopt=Abstract Ref: Age Ageing 2001 Nov;30(6):523-5
Ginkgo biloba precipitating epileptic seizures.
Granger AS.
Health Care of the Elderly, Queen's Medical Centre, Nottingham, UK.
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.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11738417&dopt=Abstract Ref: Phytochemistry 2001 Dec;58(8):1251-6
Coumaroyl flavonol glycosides from the leaves of Ginkgo biloba.
Tang Y, Lou F, Wang J, Li Y, Zhuang S.
Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210038, PR China.
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.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11673643&dopt=Abstract Ref: Biofactors 2001;15(1):39-52
Induction of glutathione synthesis in human keratinocytes by Ginkgo biloba extract (EGb761).
Rimbach G, Gohil K, Matsugo S, Moini H, Saliou C, Virgili F, Weber SU, Packer L.
Department of Molecular and Cell Biology, University of California, Berkeley, USA.
The objective of the present study was to characterize the action of Ginkgo biloba extract (EGb761) and its sub-fractions on glutathione homeostasis in a human keratinocyte cell culture model. Cells were incubated with EGb761, its purified flavonoid (quercetin, kaempferol, rutin) or terpenoids (gingkolides A, B, C, J, bilobalide) constituents or the vehicle for up to 72 hours. Incubation of keratinocytes with the purified flavonoids or terpenoids did not affect cellular GSH levels. However, EGb761 treatment (up to 200 microg/ml) resulted in a dose-dependent increase of cellular GSH. Western blot analysis of extracts from cells treated with EGb761 revealed increased levels of the catalytic subunit of gamma-glutamylcysteinyl synthetase (gamma-GCS), the rate-limiting enzyme in GSH synthesis. The abundance of mRNA for the catalytic subunit (assayed by RT-PCR) was also increased by the treatment with EGb761. Increased levels of cellular GSH by EGb761 were also observed in other cell lines including those from human bladder and liver as well as in murine macrophages indicating that the induction of gamma-GCS mRNA, protein and GSH may be an ubiquitous effect of EGb761 in mammalian cells.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11716149&dopt=Abstract Ref: J Neural Transm 2001;108(8-9):969-78
Age-related increase of oxidative stress-induced apoptosis in mice prevention by Ginkgo biloba extract (EGb761).
Schindowski K, Leutner S, Kressmann S, Eckert A, Muller WE.
Department of Pharmacology, Biocenter, Johann Wolfgang Goethe-University, Frankfurt am Main, Federal Republic of Germany.
Enhanced apoptosis and elevated levels of reactive oxygen species (ROS) play a major role in aging. In addition, several neurodegenerative diseases are associated with increased oxidative stress and apoptosis in neuronal tissue. Antioxidative treatment has neuro-protective effects. The aim of the present study was to evaluate changes of susceptibility to apoptotic cell death by oxidative stress in aging and its inhibition by the antioxidant Ginkgo biloba extract EGb761. We investigated basal and ROS-induced levels of apoptotic lymphocytes derived from the spleen in young (3 months) and old (24 months) mice. ROS were induced by 2-deoxy-D-ribose (dRib) that depletes the intracellular pool of reduced glutathione. Lymphocytes from aged mice accumulate apoptotic cells to a significantly higher extent under basal conditions compared to cells from young mice. Treatment with dRib enhanced this difference, implicating a higher sensitivity to ROS in aging. Apoptosis can be reduced in vitro by treatment with EGb761. In addition, mice were treated daily with 100 mg/kg EGb761 per os over a period of two weeks. ROS-induced apoptosis was significantly reduced in the EGb761 group. Interestingly, this effect seemed to be more pronounced in old mice.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11603292&dopt=Abstract Ref: Acta Pharmacol Sin 2000 Dec;21(12):1153-6
Protective effects of Ginkgo biloba extract on gastric mucosa.
Wang Q, Zhao WZ, Ma CG.
Department of Pharmacology, Anhui Medical University, Hefei 230032, China.
AIM: To study the protective effects of Ginkgo biloba extract (GbE) on gastric mucosa. METHODS: By means of restaint-cold stress (RCS) in rats and 100% ethanol gavage in mice, the index of gastric mucosal injury was evaluated. The gastric juice was collected using pyloric ligation, and the volume and acidity of juice, and activity of pepsin were determined. The content of malondialdehyde (MDA) was measured by thiobarbituric acid (TBA) method. RESULTS: GbE (25, 50, and 100 mg/kg, bid x 5 d, ig) inhibited dose-dependently the gastric mucosal injury induced by RCS and 100% ethanol gavage. The index of gastric mucosal injury after RCS in groups pretreated with GbE was 58%, 43%, and 31% of control group respectively. The index of gastric mucosal injury induced by ethanol in groups pretreated with GbE was 62%, 36%, and 26% of the control group, respectively. And GbE enhanced the protective effects of cimetidine (Cim) on gastric mucosa. But it did not obviously influence the volume and acidity of gastric juice as well as the activity of pepsin. One hour after the administration of ig 100% ethanol, the contents of MDA in gastric mucosa and serum in mice increased (P < 0.01) vs the control group. But pretreatment with GbE (25, 50, and 100 mg/kg, ig) could inhibit this increase of MDA both in gastric mucosa and in serum. CONCLUSION: GbE had protective effects on gastric mucosa and GbE plus Cim possessed the synergism in the treatment of acute gastric mucosal lesions.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11565403&dopt=Abstract Ref: Altern Ther Health Med 2001 Sep-Oct;7(5):70-86, 88-90
Efficacy, safety, and use of ginkgo biloba in clinical and preclinical applications.
McKenna DJ, Jones K, Hughes K.
Institute for Natural Products Research, St. Croix, Minn., USA.
Ginkgo biloba is a dioecious tree with a history of use in traditional Chinese medicine. Although the seeds are most commonly employed in traditional Chinese medicine, in recent years standardized extracts of the leaves have been widely sold as a phytomedicine in Europe and as a dietary supplement in the United States. The primary active constituents of the leaves include flavonoid glycosides and unique diterpenes known as ginkgolides; the latter are potent inhibitors of platelet activating factor. Clinical studies have shown that ginkgo extracts exhibit therapeutic activity in a variety of disorders including Alzheimer's disease, failing memory, age-related dementias, poor cerebral and ocular blood flow, congestive symptoms of premenstrual syndrome, and the prevention of altitude sickness. Due in part to its potent antioxidant properties and ability to enhance peripheral and cerebral circulation, ginkgo's primary application lies in the treatment of cerebrovascular dysfunctions and peripheral vascular disorders.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11583389&dopt=Abstract Ref: Acta Otolaryngol 2001 Jul;121(5):579-84
Ginkgo biloba extract EGb 761 or pentoxifylline for the treatment of sudden deafness: a randomized, reference-controlled, double-blind study.
Reisser CH, Weidauer H.
Department of Otolaryngology, University of Heidelberg, Germany.
In a randomized, prospective, double-blind study involving 72 patients, the therapeutic efficacy of ginkgo extract EGb 761 (n = 37) was compared to that of pentoxifylline (n = 35) for the treatment of sudden deafness. The two therapeutic schedules were equally well tolerated and showed a statistically significant equivalence in improvement or in return to normal of the auditory thresholds in the two patient groups. Furthermore, no differences were found between the treatment groups with regard to the criteria for a return to normal of speech discrimination and reduction of the tinnitus which arose at the same time as the sudden hearing loss. The patient's subjective assessment of the treatment with regard to improvement in hearing and reduction in tinnitus suggested that Ginkgo biloba extract was more beneficial than pentoxifylline. In summary, it was shown that treatment of sudden deafness with ginkgo special extract EGb 761 was as effective as treatment with pentoxifylline.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11571835&dopt=Abstract Ref: Wien Klin Wochenschr 2001 Aug 16;113(15-16):580-7
Evaluation of the allergenic potential of Ginkgo biloba extracts.
Mossabeb R, Kraft D, Valenta R.
Department of Pathophysiology, University of Vienna, Austria.
Ginkgo biloba extracts are used for the treatment of central and peripheral malperfusion, cerebral insufficiency and dementia. Between 1996 and 1998, several patients in Austria who had received parenteral Ginkgo extracts were reported to have developed allergy-like symptoms. The aim of the present study was to determine whether Ginkgo biloba extracts contain type I allergens. The protein content of Ginkgo biloba extracts was determined by BCA protein determination and SDS-PAGE. We used sera from 95 polysensitized plant-allergic patients (the sera contained IgE antibodies against most plant allergens), and rabbit antisera raised against defined recombinant plant allergens. The presence of allergens in Ginkgo extracts was determined by dot-blotting and Wester blot. Neither rabbit antisera nor IgE antibodies of patients reacted to the Ginkgo extracts. In addition, it was shown that prick testing of the skin could be conveniently used to study Gingko extracts for allergenic activity. In conclusion, no evidence for the presence of type I allergens in Ginkgo extracts was found. We recommend serological and/or skin testing to exclude sensitisation to components of Ginkgo biloba extracts.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11548897&dopt=Abstract Ref: Eur Arch Otorhinolaryngol 2001 Jul;258(5):213-9
Effect of treatment with Ginkgo biloba extract EGb 761 (oral) on unilateral idiopathic sudden hearing loss in a prospective randomized double-blind study of 106 outpatients.
Burschka MA, Hassan HA, Reineke T, van Bebber L, Caird DM, Mosges R.
Institut fur Medizinische Statistik, Informatik und Epidemiologie der Medizinischen Einrichtungen der Universitat Koln, Germany.
OBJECTIVE: Test of dose-response relationship for Ginkgo biloba extract EGb 761 (oral) in outpatients with acute idiopathic sudden sensorineural hearing loss (ISSHL) of at least 15 dB at one frequency within the speech range occurring less than 10 days before study inclusion. DESIGN: Multicentre, randomized, double-blind phase III study comparing dosages of 120 mg twice daily and 12 mg twice daily over 8 weeks. MAIN ENDPOINT: Recovery (in dB) of the auditory threshold from the initial measurement to the value on the last day of treatment, averaged over those frequencies from 0.25, 0.5, 1, 2, and 3 kHz for which the initial hearing loss amounted to 15 dB or more compared to the level on the opposite side. PATIENTS: 106 patients with an average age of 44+/-16 years and with hearing loss at affected frequencies 26 dB +/- 9 dB included between December 1995 and July 1997. RESULTS: Large majorities of both treatment groups recovered completely. In exploratory analyses of the 96 patients included according to the protocol, patients given the higher dose had less risk of not recovering well (< or =10 dB residual hearing loss) (one-sided Fisher test: P = 0.0061), especially if they had no tinnitus (n = 44, P = 0.00702). CONCLUSION: A higher dosage of EGb 761 (oral) appears to speed up and secure the recovery of ISSHL patients, with a good chance that they will recover completely, even with little treatment. This was already observed after one week of treatment. We find it justified to treat patients who have unilateral ISSHL of less than 75 dB and neither tinnitus nor vertigo with 120 mg oral EGb 761 twice daily.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11543732&dopt=Abstract Ref: Biochem Pharmacol 2001 Oct 1;62(7):963-74
Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced signaling pathways involved in the release of tumor necrosis factor-alpha.
Wadsworth TL, McDonald TL, Koop DR.
Department of Physiology and Pharmacology, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098, USA.
Administration of bacterial lipopolysaccharide (LPS) to laboratory animals and cultured macrophages induces tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine. Pretreatment with Ginkgo biloba extract (EGb 761) inhibited the in vivo production of TNF-alpha (measured by ELISA) after challenge with LPS. To begin to understand the mechanism of this inhibition, we evaluated the in vitro effects of EGb 761 and its flavonoid component, quercetin, on LPS-treated RAW 264.7 macrophages. Pretreatment with EGb 761 or quercetin concentration-dependently inhibited TNF-alpha release, as measured by the L929 fibroblast assay. Northern blotting demonstrated that quercetin inhibited LPS-induced TNF-alpha mRNA, but did not alter its half-life. Activation of mitogen-activated protein kinases (MAPKs) and the redox-sensitive transcription factors, nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1), are key events in the signal transduction pathways mediating TNF-alpha induction. Phosphorylation of extracellular signal-related kinases 1 and 2 (ERK 1/2), p38 MAPK, and Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), members of the MAPK family, was analyzed by western blotting. Our results suggest that quercetin is unique in its ability to inhibit TNF-alpha transcription by inhibiting the phosphorylation and activation of JNK/SAPK and, therefore, suppressing AP-1-DNA binding [assessed by electrophoretic mobility shift analysis (EMSA)]. Results from western analysis, EMSA, and transient transfections suggest that EGb 761 diminishes LPS-induced NF-kappaB but has no effect on LPS-induced TNF-alpha transcription. Both EGb 761 and quercetin inhibited ERK1/2 phosphorylation and p38 MAPK activity, which are important in the post-transcriptional regulation of TNF-alpha mRNA.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11525790&dopt=Abstract Ref: Surv Ophthalmol 2001 Jul-Aug;46(1):43-55
Complementary and alternative medicine for glaucoma.
Rhee DJ, Katz LJ, Spaeth GL, Myers JS.
Glaucoma Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Given the recent interest in complementary and alternative medicine (CAM), some patients may seek such treatments to supplement their traditional glaucoma management. The prevalence of CAM use for glaucoma is approximately 5%. We reviewed the literature to determine the potential benefit of various alternative treatments. Aside from a temporary osmotic effect from high dose intravenous ascorbic acid, there is no evidence that megavitamin supplementation has a beneficial effect on glaucoma. During exercise, autoregulation in healthy eyes seems to maintain a consistent blood flow rate to the optic nerve despite fluctuations in intraocular pressure (IOP). In a glaucomatous eye, the very modest IOP-lowering that follows exercise may be offset by the initial elevation in IOP that occurs when one first initiates exercise. At this time, there is no evidence to encourage or discourage the use of special diets, acupuncture, relaxation techniques, or therapeutic touch specifically for the treatment of glaucoma. Very little research has been done on the majority of herbal remedies with regard to their treatment of glaucoma. Marijuana can cause a profound lowering of IOP, but the high nonresponse rate, short half life, and significant toxicity are strong indicators that it is not an appropriate therapeutic agent. Ginkgo biloba and some other Chinese herbal remedies do not affect IOP, but may improve blood flow to the optic nerve and, as such, may have a beneficial effect on glaucoma. These agents have recognized toxicities. Although there are some well-designed studies of alternative treatments, many of the recommendations for using alternative treatments are currently unsupported by the data provided.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11518563&dopt=Abstract Ref: Chem Biol Interact 2001 Jul 31;137(1):43-58
Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced release of nitric oxide.
Wadsworth TL, Koop DR.
Department of Physiology and Pharmacology, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098, USA.
Administration of bacterial lipopolysaccharide (LPS) to laboratory animals and cultured macrophages is known to induce the production of nitric oxide (NO) from inducible nitric oxide synthase (iNOS). Here we show that pre-treatment with Ginkgo biloba extract (EGb 761) suppresses the in vivo production of NO (measured by the Griess reaction) after challenge with LPS. In order to begin to understand the mechanism of this inhibition, we evaluated in vitro effects of EGb 761 and its flavonoid component, quercetin, on LPS-treated RAW 264.7 macrophages. Pre-treatment with EGb 761 or quercetin dose-dependently inhibited NO release. Both substances scavenged NO generated from the decomposition of sodium nitroprusside. Western analysis showed that EGb 761 and quercetin inhibited LPS-induced levels of iNOS protein. Northern blotting demonstrated that EGb 761 and quercetin decreased LPS-induced iNOS mRNA levels without altering the half-life. Activation of mitogen activated protein kinases (MAPKs) and the redox-sensitive transcription factors, nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) are key events in the signal transduction pathways mediating iNOS induction. In our studies, both EGb 761 and quercetin inhibited p38 MAPK activity, which is necessary for iNOS expression in LPS-stimulated RAW 264.7 macrophages. However, differences in the response of NF-kappaB, AP-1, and Jun N-terminal kinase/stress activated protein kinase (JNK/SAPK) and its downstream substrates to EGb 761 and quercetin suggest that quercetin is not the sole component responsible for the in vivo inhibition of LPS-induced iNOS activation by EGb 761.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11509191&dopt=Abstract Ref: Pharmacol Biochem Behav 2001 Jul-Aug;69(3-4):351-8
Effect of the Ginkgo biloba extract, EGb 761, on memory formation in day-old chicks.
Rickard NS, Kowadlo N, Gibbs ME.
Psychology Department, Monash University, Caulfield, Victoria 3145, Australia.
Previous studies indicate that the Ginkgo biloba extract, EGb 761, has a facilitative effect on deficient memory. The temporal parameters of this effect, however, have not been clearly defined or distinguished from the effect on normal memory. The aim in the current study was to investigate the effects of EGb 761 on memory using a well-controlled animal model. Day-old chicks were trained on either a weakly or strongly reinforced version of a passive avoidance task. Long-term memory formation of the weakly reinforced version of the task was improved significantly by EGb 761 (3 mg/ml) when administered between 10 and 30 min after training. However, the same dose of EGb 761 impaired retention when administered prior to strongly reinforced training. These data provide convincing evidence that posttraining administration of EGb 761 initiates long-term memory in chicks with only short-term memory, but that the same dose-administered pretraining can be deleterious for normal retention. This dual effect has important implications for the clinical use of Ginkgo biloba extracts.
Ginkgo biloba and Alzheimer's disease
Ginkgo story
About Ginkgo biloba
Ginseng and Ginkgo: ginkgo and ginseng together.
DreamPharm Ginkgo biloba
Ginkgo biloba research abstract and source links
Paxil online || Buy Celexa Online