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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