Biloba Extract Research Articles

Metal ion and antioxidant alterations in leaves between different sexes of Ginkgo biloba L.

A comparative study was carried out to determine some valuable phytochemical components, macro- and microelement and redox parameters in leaves of male and female Ginkgo biloba trees and in extracts made from them. G. biloba extracts have become more popular as a therapeutic agent in the modern pharmacology in neurodegenerative diseases, in which increased brain metal levels can be observed and free radical reactions are involved. Macro- and microelement components, total phenol content, H-donating activity and reducing power as well as total scavenger capacity were determined in the samples. Well detectable differences were obtained for micro- and macroelement contents between male and female samples, but no toxic elements could be detected in the extracts. Male extracts contained more hazardous metals (e.g. Fe) compared to the female ones, while extracts from female leaves had higher levels of ions, which are known to have beneficial effects in neurodegenerative diseases. The ethanolic extracts of male leaves showed the highest H-donating activity, reducing power and total phenol content, as well as the best total scavenger activity. Ginkgo extracts due to the antioxidant properties may have favourable effects as dietary supplements in several neurodegenerative diseases, but this study draws the attention that critical evaluation is required in view of the potential hazard induced by their metal ion constitution. Our results lead us to the conclusion that although the aqueous extracts of female leaves are characterized by relatively lower antioxidant properties, they may be more eligible for these purposes due to their favourable metal ion constitution.

Immunohistological evidences ofGinkgo biloba extract altering Bax to Bcl-2 expression ratio in the hippocampus and motor cortex of senescence accelerated mice

Ginkgo biloba extract 761 appears to display neuroprotective effect in many nervous diseases and aging. Deterioration of mental functions during aging is always accompanied by loss of neurons, presumably through apoptosis. Here, we studied the effect of G. biloba extract in the expression of Bax/Bcl-2 ratio, an important apoptotic index, in the hippocampus and motor cortex of the aging brain. Bax and Bcl-2 expressions were examined with immunohistochemical methods. Senescence Accelerated Mice Prone Strain 8 was used because the aging process was accelerated with neuropathological alterations similar to those found in the aging human brain. The mice were fed with either G. biloba extract or sucrose from the age of 3 weeks until sacrifice at 3 or 9 months old. In the hippocampus of G. biloba fed 9-month-old mice, the ratio of Bax positive cell to Bcl-2 positive cell (Bax/Bcl-2 expression ratio) was 11.43 +/- 3.11 (mean +/- SD); significantly lower (P < 0.05) than the Bax/Bcl-2 expression ratio of 20.99 +/- 5.34 in the sucrose fed mice. The Bax/Bcl-2 expression cell ratios, however, in the motor cortex were not significantly different between the two groups (2.22 +/- 1.35 versus 2.27 +/- 2.02 for the G. biloba and the sucrose fed mice, respectively). The decrease in the Bax/Bcl-2 expression cell ratio following G. biloba treatment might hence be able to protect the aging hippocampus from moving further down the apoptotic pathway. Western blotting confirmed the decrease of Bax in the brain even after a short term and high dose Ginkgo treatment. It is speculated that the G. biloba extract may be a potential neuroprotective agent against apoptosis through the differential expressions of the Bax and Bcl-2 in the hippocampus.

DISTINCT ROLE OF BILOBALIDE AND GINKGOLIDE A IN THE MODULATION OF RAT CYP2B1 AND CYP3A23 GENE EXPRESSION BY GINKGO BILOBA EXTRACT IN CULTURED HEPATOCYTES

In the present study, primary cultures of rat hepatocytes were treated for 48 h with one of several extracts of Ginkgo biloba (10, 100, or 1000 microg/ml). Maximal increase in CYP2B1 and CYP3A23 mRNA levels was obtained at 100 microg/ml. This concentration of G. biloba extract also increased CYP3A2 and CYP3A18 mRNA expression in addition to CYP2B-mediated 7-benzyloxyresorufin O-dealkylation (BROD) and CYP3A-mediated testosterone 6beta-hydroxylation. In other experiments, cultured hepatocytes were treated for 48 h with bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, kaempferol, quercetin, isorhamnetin, or a flavonol diglycoside at a concentration that represented the level present in a 100 microg/ml concentration of an extract. Only bilobalide (2.8 microg/ml) increased CYP2B1 mRNA expression, and the -fold increase (7.9 +/- 0.5; mean +/- S.E.M.) was similar to that (8.3 +/- 1.7) by the extract. By comparison, only ginkgolide A (1.1 microg/ml) increased CYP3A23 mRNA expression, but the extent (2.6 +/- 0.5-fold) was less than the 5.3 +/- 1.7-fold increase by the extract. A greater concentration (5 microg/ml) of ginkgolide A was required to elevate CYP3A2 and CYP3A18 mRNA expression. Over the range of 1 to 5 microg/ml, bilobalide increased CYP2B1 mRNA and BROD, but not CYP3A23 mRNA or testosterone 6beta-hydroxylation, whereas ginkgolide A increased CYP3A23 mRNA and testosterone 6beta-hydroxylation, but not CYP2B1 mRNA or BROD. Overall, our novel results indicate a distinct role of bilobalide and ginkgolide A in the modulation of CYP2B1 and CYP3A23 gene expression and enzyme activities by G. biloba extract in primary cultures of rat hepatocytes.

Effect of Ginkgo biloba extract on procarcinogen-bioactivating human CYP1 enzymes: Identification of isorhamnetin, kaempferol, and quercetin as potent inhibitors of CYP1B1

In the present study, we investigated the effect of Ginkgo biloba extracts and some of its individual constituents on the catalytic activity of human cytochrome P450 enzymes CYP1B1, CYP1A1, and CYP1A2. G. biloba extract of known abundance of terpene trilactones and flavonol glycosides inhibited 7-ethoxyresorufin O-dealkylation catalyzed by human recombinant CYP1B1, CYP1A1, and CYP1A2, and human liver microsomes, with apparent Ki values of 2 +/- 0.3, 5 +/- 0.5, 16 +/- 1.4, and 39 +/- 1.2 microg/ml (mean +/- SE), respectively. In each case, the mode of inhibition was of the mixed type. Bilobalide, ginkgolides A, B, C, and J, quercetin 3-O-rutinoside, kaempferol 3-O-rutinoside, and isorhamentin 3-O-rutinoside were not responsible for the inhibition of CYP1 enzymes by G. biloba extract, as determined by experiments with these individual chemicals at the levels present in the extract. In contrast, the aglycones of quercetin, kaempferol, and isorhamentin inhibited CYP1B1, CYP1A1, and CYP1A2. Among the three flavonol aglycones, isorhamentin was the most potent in inhibiting CYP1B1 (apparent Ki = 3 +/- 0.1 nM), whereas quercetin was the least potent in inhibiting CYP1A2 (apparent Ki = 418 +/- 50 nM). The mode of inhibition was competitive, noncompetitive, or mixed, depending on the enzyme and the flavonol. G. biloba extract also reduced benzo[a]pyrene hydroxylation, and the effect was greater with CYP1B1 than with CYP1A1 as the catalyst. Overall, our novel findings indicate that G. biloba extract and the flavonol aglycones isorhamnetin, kaempferol, and quercetin preferentially inhibit the in vitro catalytic activity of human CYP1B1.

Isolation of Ginkgolides A, B, C, J and Bilobalide from G. biloba Extracts.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Isolation of ginkgolides A, B, C, J and bilobalide from G. biloba extracts

Ginkgolides A, B, C and J, together with bilobalide, are unique terpenoid components of the Ginkgo biloba tree. Due to similar chemical properties, their separation is quite tedious. We have developed an efficient and rapid protocol for separation of individual ginkgolides and bilobalide from G. biloba extracts. The procedure takes advantage of enhanced susceptibility of ginkgolides B and C to benzylation and the ease of separation of these products from ginkgolides A and J which do not react. The protocol is applicable to the previously reported enriched extracts prepared from G. biloba leaves. A single chromatographic step prior to benzylation provides bilobalide and mixture of ginkgolides A, B, C, and J. After benzylation, the individual ginkgolides are separated by chromatography.

Cover Picture: Chemistry and Biology of Terpene Trilactones from Ginkgo Biloba (Angew. Chem. Int. Ed. 13/2004)

Terpene trilactones from the ginkgo tree (Ginkgo biloba) are at least partly responsible for the neuromodulatory effects of G. biloba extracts. The cover picture shows a young ginkgo tree, with its characteristic fan‐shaped leaves, growing out of a human brain. Superimposed are the X‐ray crystal structures of bilobalide and ginkgolide B. K. Strømgaard and K. Nakanishi discuss the current status of bilobalide and ginkgolides in their Review on page 1640 ff., with a particular focus on chemical and biological studies.

LiteratureWatch

Alternative and Complementary TherapiesVol. 10, No. 1 LiteratureWatchLiteratureWatchPublished Online:5 Jul 2004https://doi.org/10.1089/107628004772830429AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "LiteratureWatch." , 10(1), pp. 52–53FiguresReferencesRelatedDetailsCited byUnderstanding the Attitudes of Patients with Cancer Toward Complementary and Alternative Therapies Gil Bar-Sela, Sara Danos, Bella Visel, and Inbal Mitnik3 May 2016 | Journal of Palliative Medicine, Vol. 19, No. 5Complementary and Alternative Medicine Use and Breast Cancer Prognosis: A Pooled Analysis of Four Population-Based Studies of Breast Cancer Survivors Rayna Kim Matsuno, Ian S. Pagano, Gertraud Maskarinec, Brian F. Issell, and Carolyn C. Gotay4 December 2012 | Journal of Women's Health, Vol. 21, No. 12Use of Complementary and Alternative Medicine Among Patients: Classification Criteria Determine Level of Use Agnete Egilsdatter Kristoffersen, Vinjar Fønnebø, and Arne Johan Norheim6 November 2008 | The Journal of Alternative and Complementary Medicine, Vol. 14, No. 8Experience of Proximate Spiritual Healing in Women with Breast Cancer, Who Are Receiving Long-Term Hormonal Therapy Fiona Barlow, George T. Lewith, and Jan Walker9 April 2008 | The Journal of Alternative and Complementary Medicine, Vol. 14, No. 3Ginkgo biloba is not a smart drug: an updated systematic review of randomised clinical trials testing the nootropic effects ofG. biloba extracts in healthy people1 January 2007 | Human Psychopharmacology: Clinical and Experimental, Vol. 22, No. 5Complementary and Alternative Medicine Use Among Breast Cancer Survivors Alicia K. Matthews, Sarah A. Sellergren, Dezheng Huo, Marcy List, and Gini Fleming29 June 2007 | The Journal of Alternative and Complementary Medicine, Vol. 13, No. 5Modifiable Risk Factors for Breast Cancer Recurrence: What Can We Tell Survivors? Sandra A. Norman, Sheryl L. Potashnik, Mary Lou Galantino, Angela M. De Michele, Lauren House, and A. Russell Localio27 March 2007 | Journal of Women's Health, Vol. 16, No. 2Acupuncture Use in the United States: Findings from the National Health Interview Survey Adam Burke, Dawn M. Upchurch, Claire Dye, and Laura Chyu13 September 2006 | The Journal of Alternative and Complementary Medicine, Vol. 12, No. 7Levels of Commitment: Exploring Complementary Therapy Use by Women with Breast Cancer Lynda G. Balneaves, Joan L. Bottorff, T. Gregory Hislop, and Carol Herbert30 June 2006 | The Journal of Alternative and Complementary Medicine, Vol. 12, No. 5Coping in Women with Breast Cancer in Complementary and Conventional Care Over 5 Years Measured by the Mental Adjustment to Cancer Scale Marianne Carlsson, Maria Arman, Marie Backman, and Elisabeth Hamrin1 July 2005 | The Journal of Alternative and Complementary Medicine, Vol. 11, No. 3 Volume 10Issue 1Feb 2004 To cite this article:LiteratureWatch.Alternative and Complementary Therapies.Feb 2004.52-53.http://doi.org/10.1089/107628004772830429Published in Volume: 10 Issue 1: July 5, 2004PDF download

Liquid chromatography/electrospray mass spectrometry of bioactive terpenoids inGinkgo biloba L.

Standardized extracts of Ginkgo biloba leaves are mainly used in the treatment of peripheral and celebral circulation disorders, and also as a remedy against asthma, coughs, bladder inflammation, blenorrhagia and alcohol abuse. The leaf extracts contain biflavones, flavonol glycosides and terpene lactones. This paper reports a method based on liquid chromatography coupled with electrospray mass spectrometry for the analysis of terpenoids in G. biloba extracts. This method allows the rapid isocratic separation of underivatized ginkgolides (GA, GB, GC and GJ) and bilobalide at very low levels (10 pg on the column) and their quantitative detection by external standardization with relative standard deviations of 3 and 5% for intra- and inter-day analyses, respectively.

The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease.

To determine the effect of treatment with Ginkgo biloba extract on objective measures of cognitive function in patients with Alzheimer disease (AD) based on formal review of the current literature. An attempt was made to identify all English and non-English-language articles in which G. biloba extract was given to subjects with dementia or cognitive impairment. Inclusion criteria for the meta-analysis were (1) sufficiently characterized patients such that it was clearly stated there was a diagnosis of AD by either Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, or National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, or there was enough clinical detail to determine this by our review; (2) clearly stated study exclusion criteria, ie, those studies that did not have stated exclusions for depression, other neurologic disease, and central nervous system-active medications were excluded; (3) use of standardized ginkgo extract in any stated dose; (4) randomized, placebo-controlled and double-blind study design; (5) at least 1 outcome measure was an objective assessment of cognitive function; and (6) sufficient statistical information to allow for meta-analysis. Of more than 50 articles identified, the overwhelming majority did not meet inclusion criteria, primarily because of lack of clear diagnoses of dementia and AD. Only 4 studies met all inclusion criteria. In total there were 212 subjects in each of the placebo and ginkgo treatment groups. Overall there was a significant effect size of 0.40 (P<.0001). This modest effect size translated into a 3% difference in the Alzheimer Disease Assessment Scale-cognitive subtest. Based on a quantitative analysis of the literature there is a small but significant effect of 3- to 6-month treatment with 120 to 240 mg of G. biloba extract on objective measures of cognitive function in AD. The drug has not had significant adverse effects in formal clinical trials but there are 2 case reports of bleeding complications. In AD, there are limited and inconsistent data that preclude determining if there are effects on noncognitive behavioral and functional measures as well as on clinician's global rating scales. Further research in the area will need to determine if there are functional improvements and to determine the best dosage. Additional research will be needed to define which ingredients in the ginkgo extract are producing its effect in individuals with AD.

Ginkgo bilobaExtract Prevents Mucosal Damage Associated with Small-Intestinal Ischaemia

We have examined how a Ginkgo biloba extract influences the damaging effects of ischaemia in the small-intestinal mucosa. We used a rat experimental model in which a ligated loop of the distal ileum was subjected to ischaemia and revascularization, and the ensuing mucosal damage assessed by lysosomal enzyme release and intestinal permeability measurements. We also determined the mucosal content of malondialdehyde, a lipid peroxidation product, and the mucosal activity of myeloperoxidase, a neutrophil granulocyte marker. Ischaemia and revascularization alone caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-beta-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content in the mucosa, and increased myeloperoxidase activity in the mucosa. Intravenous injection of G. biloba extract caused a dose-dependent attenuation of all these effects of ischaemia. It is suggested, therefore, that G. biloba extract may protect the intestinal mucosa against ischaemic damage by reducing neutrophil infiltration and lipid peroxidation.