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1.  Ginkgo biloba for Preventing Cognitive Decline in Older Adults 
The herbal product Ginkgo biloba is taken frequently with the intention of improving cognitive health in aging. However, evidence from adequately powered clinical trials is lacking regarding its effect on long-term cognitive functioning.
To determine whether G biloba slows the rates of global or domain-specific cognitive decline in older adults.
Design, Setting, and Participants
The Ginkgo Evaluation of Memory (GEM) study, a randomized, double-blind, placebo-controlled clinical trial of 3069 community-dwelling participants aged 72 to 96 years, conducted in 6 academic medical centers in the United States between 2000 and 2008, with a median follow-up of 6.1 years.
Twice-daily dose of 120-mg extract of G biloba (n=1545) or identical-appearing placebo (n=1524).
Main Outcome Measures
Rates of change over time in the Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on sums of z scores of individual tests.
Annual rates of decline in z scores did not differ between G biloba and placebo groups in any domains, including memory (0.043; 95% confidence interval [CI], 0.034-0.051 vs 0.041; 95% CI, 0.032-0.050), attention (0.043; 95% CI, 0.037-0.050 vs 0.048; 95% CI, 0.041-0.054), visuospatial abilities (0.107; 95% CI, 0.097-0.117 vs 0.118; 95% CI, 0.108-0.128), language (0.045; 95% CI, 0.037-0.054 vs 0.041; 95% CI, 0.033-0.048), and executive functions (0.092; 95% CI, 0.086-0.099 vs 0.089; 95% CI, 0.082-0.096). For the 3MSE and ADAS-Cog, rates of change varied by baseline cognitive status (mild cognitive impairment), but there were no differences in rates of change between treatment groups (for 3MSE, P=.71; for ADAS-Cog, P=.97). There was no significant effect modification of treatment on rate of decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive impairment (P>.05).
Compared with placebo, the use of G biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment.
Trial Registration Identifier: NCT00010803
PMCID: PMC2832285  PMID: 20040554
2.  Effects of Ginkgo biloba in dementia: systematic review and meta-analysis 
BMC Geriatrics  2010;10:14.
The benefit of Ginkgo biloba has been discussed controversially. The aim of this review was to assess the effects of Ginkgo biloba in Alzheimer's disease as well as vascular and mixed dementia covering a variety of outcome domains.
We searched MEDLINE, EMBASE, the Cochrane databases, CINAHL and PsycINFO for controlled trials of ginkgo for Alzheimer's, vascular or mixed dementia. Studies had to be of a minimum of 12 weeks duration with at least ten participants per group. Clinical characteristics and outcomes were extracted. Meta-analysis results were expressed as risk ratios or standardized mean differences (SMD) in scores.
Nine trials using the standardized extract EGb761® met our inclusion criteria. Trials were of 12 to 52 weeks duration and included 2372 patients in total. In the meta-analysis, the SMDs in change scores for cognition were in favor of ginkgo compared to placebo (-0.58, 95% confidence interval [CI] -1.14; -0.01, p = 0.04), but did not show a statistically significant difference from placebo for activities in daily living (ADLs) (SMD = -0.32, 95% CI -0.66; 0.03, p = 0.08). Heterogeneity among studies was high. For the Alzheimer subgroup, the SMDs for ADLs and cognition outcomes were larger than for the whole group of dementias with statistical superiority for ginkgo also for ADL outcomes (SMD = -0.44, 95% CI -0.77; -0.12, p = 0.008). Drop-out rates and side effects did not differ between ginkgo and placebo. No consistent results were available for quality of life and neuropsychiatric symptoms, possibly due to the heterogeneity of the study populations.
Ginkgo biloba appears more effective than placebo. Effect sizes were moderate, while clinical relevance is, similar to other dementia drugs, difficult to determine.
PMCID: PMC2846949  PMID: 20236541
3.  Investigation of herb-drug interactions with ginkgo biloba in women receiving hormonal treatment for early breast cancer 
SpringerPlus  2013;2:126.
Women receiving treatment for breast cancer commonly ingest herbal medicines. Little is known about the potential for herb-drug interactions in this population. The aim of this study is to investigate the effect of ginkgo biloba co-administration on the pharmacokinetics of tamoxifen, anastrozole and letrozole. This was a prospective open-label cross-over study in 60 women with early stage breast cancer taking either tamoxifen, anastrozole or letrozole (n=20/group). Participants received ginkgo biloba (EGb 761) for 3 weeks (120 mg twice daily). Trough concentrations of drugs were measured before and after ginkgo biloba treatment using LC-MS/MS. Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events. Trough concentrations before and after treatment with ginkgo biloba were not significantly different for tamoxifen (93.5 ± 29.0, 86.5 ± 25.3 ng/mL; p=0.16), letrozole (91.1 ± 50.4, 89.6 ± 52.14 ng/mL; p=0.60) or anastrozole (29.1 ± 8.6, 29.1 ± 7.6 ng/mL; p=0.97). Ginkgo biloba was well tolerated, with no difference in toxicity during ginkgo biloba. Co-administration of ginkgo biloba does not significantly affect the pharmacokinetics of tamoxifen, anastrozole or letrozole. There was no difference in the toxicity profile of hormone therapy with ginkgo biloba use in women with early stage breast cancer.
PMCID: PMC3625417  PMID: 23596562
Anastrozole; Ginkgo biloba; Herb-drug interaction; Letrozole; Tamoxifen
4.  Does Ginkgo biloba reduce risk of cardiovascular events? 
Cardiovascular disease (CVD) was a preplanned secondary outcome of the Ginkgo Evaluation of Memory (GEM) Study. The trial previously reported that Ginkgo biloba (G. biloba) had no effect on the primary outcome, incident dementia.
Methods and Results
The double-blind trial randomized 3069 participants over 75 years of age to 120 mg of G. biloba EGb 761 twice daily or placebo. Mean follow up was 6.1 years. The identification and classification of CVD was based on methods used in the Cardiovascular Health Study. Differences in time to event between G. biloba and placebo were evaluated using Cox proportional hazards regression adjusted for age and gender. There were 355 deaths in the study, 87 due to coronary heart disease with no differences between G. biloba and placebo. There were no differences in incident myocardial infarction (n=164), angina pectoris (n=207) or stroke (151) between G. biloba and placebo. There were 24 hemorrhagic strokes, 16 on G. biloba and 8 on placebo (not significant). There were only 35 peripheral vascular disease (PVD) events, 12 (0.8%) on G. biloba and 23 (1.5%) on placebo (p=0.04 exact test). Most of the PVD cases had either vascular surgery or amputation.
There was no evidence that G. biloba reduced total or CVD mortality or CVD events. There were more PVD events in the placebo arm. G. biloba cannot be recommended for preventing CVD. Further clinical trials of PVD outcomes might be indicated.
PMCID: PMC2858335  PMID: 20123670
anticoagulation; peripheral vascular disease; cardiovascular disease; stroke; trials
5.  Ginkgo biloba for Prevention of Dementia: A Randomized Controlled Trial 
Ginkgo biloba is widely used for its potential effects on memory and cognition. To date, adequately powered clinical trials testing the effect of G biloba on dementia incidence are lacking.
To determine effectiveness of G biloba vs placebo in reducing the incidence of all-cause dementia and Alzheimer disease (AD) in elderly individuals with normal cognition and those with mild cognitive impairment (MCI).
Design, Setting, and Participants
Randomized, double-blind, placebo-controlled clinical trial conducted in 5 academic medical centers in the United States between 2000 and 2008 with a median follow-up of 6.1 years. Three thousand sixty-nine community volunteers aged 75 years or older with normal cognition (n=2587) or MCI (n=482) at study entry were assessed every 6 months for incident dementia.
Twice-daily dose of 120-mg extract of G biloba (n=1545) or placebo (n=1524).
Main Outcome Measures
Incident dementia and AD determined by expert panel consensus.
Five hundred twenty-three individuals developed dementia (246 receiving placebo and 277 receiving G biloba) with 92% of the dementia cases classified as possible or probable AD, or AD with evidence of vascular disease of the brain. Rates of dropout and loss to follow-up were low (6.3%), and the adverse effect profiles were similar for both groups. The overall dementia rate was 3.3 per 100 person-years in participants assigned to G biloba and 2.9 per 100 person-years in the placebo group. The hazard ratio (HR) for G biloba compared with placebo for all-cause dementia was 1.12 (95% confidence interval [CI], 0.94–1.33; P=.21) and for AD, 1.16 (95% CI, 0.97–1.39; P=.11). G biloba also had no effect on the rate of progression to dementia in participants with MCI (HR, 1.13; 95% CI, 0.85–1.50; P=.39).
In this study, G biloba at 120 mg twice a day was not effective in reducing either the overall incidence rate of dementia or AD incidence in elderly individuals with normal cognition or those with MCI.
PMCID: PMC2823569  PMID: 19017911
6.  Randomised, double blind, placebo controlled comparison of ginkgo biloba and acetazolamide for prevention of acute mountain sickness among Himalayan trekkers: the prevention of high altitude illness trial (PHAIT) 
BMJ : British Medical Journal  2004;328(7443):797.
Objective To evaluate the efficacy of ginkgo biloba, acetazolamide, and their combination as prophylaxis against acute mountain sickness.
Design Prospective, double blind, randomised, placebo controlled trial.
Setting Approach to Mount Everest base camp in the Nepal Himalayas at 4280 m or 4358 m and study end point at 4928 m during October and November 2002.
Participants 614 healthy western trekkers (487 completed the trial) assigned to receive ginkgo, acetazolamide, combined acetazolamide and ginkgo, or placebo, initially taking at least three or four doses before continued ascent.
Main outcome measures Incidence measured by Lake Louise acute mountain sickness score ≥ 3 with headache and one other symptom. Secondary outcome measures included blood oxygen content, severity of syndrome (Lake Louise scores ≥ 5), incidence of headache, and severity of headache.
Results Ginkgo was not significantly different from placebo for any outcome; however participants in the acetazolamide group showed significant levels of protection. The incidence of acute mountain sickness was 34% for placebo, 12% for acetazolamide (odds ratio 3.76, 95% confidence interval 1.91 to 7.39, number needed to treat 4), 35% for ginkgo (0.95, 0.56 to 1.62), and 14% for combined ginkgo and acetazolamide (3.04, 1.62 to 5.69). The proportion of patients with increased severity of acute mountain sickness was 18% for placebo, 3% for acetazoalmide (6.46, 2.15 to 19.40, number needed to treat 7), 18% for ginkgo (1, 0.52 to 1.90), and 7% for combined ginkgo and acetazolamide (2.95, 1.30 to 6.70).
Conclusions When compared with placebo, ginkgo is not effective at preventing acute mountain sickness. Acetazolamide 250 mg twice daily afforded robust protection against symptoms of acute mountain sickness.
PMCID: PMC383373  PMID: 15070635
7.  Ginkgo biloba does not improve cognitive function in MS 
Neurology  2012;79(12):1278-1284.
To determine whether Ginkgo biloba extract (ginkgo) improves cognitive function in persons with multiple sclerosis (MS).
Persons with MS from the Seattle and Portland VA clinics and adjacent communities who scored 1 SD or more below the mean on one of 4 neuropsychological tests (Stroop Test, California Verbal Learning Test II [CVLT-II], Controlled Oral Word Association Test [COWAT], and Paced Auditory Serial Addition Task [PASAT]) were randomly assigned to receive either one 120-mg tablet of ginkgo (EGb-761; Willmar Schwabe GmbH & Co, Germany) or one placebo tablet twice a day for 12 weeks. As the primary outcome, we compared the performance of the 2 groups on the 4 tests at exit after adjusting for baseline performance.
Fifty-nine subjects received placebo and 61 received ginkgo; 1 participant receiving placebo and 3 receiving ginkgo were lost to follow-up. Two serious adverse events (AEs) (myocardial infarction and severe depression) believed to be unrelated to the treatment occurred in the ginkgo group; otherwise, there were no significant differences in AEs. The differences (ginkgo − placebo) at exit in the z scores for the cognitive tests were as follows: PASAT −0.2 (95% confidence interval [CI] −0.5 to 0.1); Stroop Test −0.5 (95% CI −0.9 to −0.1); COWAT 0.0 (95% CI −0.2 to 0.3); and CVLT-II 0.0 (95% CI −0.3 to 0.3); none was statistically significant.
Treatment with ginkgo 120 mg twice a day did not improve cognitive performance in persons with MS.
Classification of evidence:
This study provides Class I evidence that treatment with ginkgo 120 mg twice a day for 12 weeks does not improve cognitive performance in people with MS.
PMCID: PMC3440446  PMID: 22955125
8.  The use of Ginkgo biloba for the prevention of chemotherapy-related cognitive dysfunction in women receiving adjuvant treatment for breast cancer, N00C9 
Patients undergoing treatment for cancer often report problems with their cognitive function, which is an essential component of health-related quality of life. Pursuant to this, a two-arm randomized, placebo-controlled, double-blind, phase III clinical trial was conducted to evaluate Ginkgo biloba (EGB 761) for the prevention of chemotherapy-related cognitive dysfunction in patients with breast cancer.
Previously chemotherapy naïve women about to receive adjuvant chemotherapy for breast cancer were randomized to receive 60 mg of EGB 761 or a matching placebo twice daily. The study agent was to begin before their second cycle of chemotherapy and to be taken throughout chemotherapy and 1 month beyond completion. The primary measure for cognitive function was the High Sensitivity Cognitive Screen (HSCS), with a secondary measure being the Trail Making Tests (TMT) A and B. Subjective assessment of cognitive function was evaluated by the cognitive subscale of the Perceived Health Scale (PHS) and the Profile of Mood States (POMS). Data were collected at baseline and at intervals throughout and after chemotherapy, up to 24 months after completion of adjuvant treatment. The primary statistical analysis included normalized area under the curve (AUC) comparisons of the HSCS, between the arms. Secondary analyses included evaluation of the other measures of cognition as well as correlational analyses between self-report and cognitive testing.
One hundred and sixty-six women provided evaluable data. There were no significant differences in AUC up to 12 months on the HSCS between arms at the end of chemotherapy or at any other time point after adjuvant treatment. There were also no significant differences in TMT A or B at any data point. Perceived cognitive functions, as measured by the PHS and confusion/bewilderment subscale of the POMS, were not different between arms at the end of chemotherapy. There was also little correlation between self-reported cognition and cognitive testing. No differences were observed in toxicities per Common Terminology Criteria for Adverse Events (CTCAE) assessment between Ginkgo biloba and placebo throughout the study; however, after chemotherapy, the placebo group reported worse nausea (p = .05).
This study did not provide any support for the notion that Ginkgo biloba, at a dose of 60 mg twice a day, can help prevent cognitive changes from chemotherapy. These analyses do provide data to further support the low associations between patients’ self-report of cognition and cognitive performance, based on more formal testing.
PMCID: PMC3587364  PMID: 23150188
Ginkgo biloba; Chemotherapy-related cognitive dysfunction; Adjuvant treatment; Breast cancer; Dietary supplements
9.  Effectiveness of Ginkgo biloba in treating tinnitus: double blind, placebo controlled trial 
BMJ : British Medical Journal  2001;322(7278):73.
To determine whether Ginkgo biloba is effective in treating tinnitus.
Double blind, placebo controlled trial using postal questionnaires.
1121 healthy people aged between 18 and 70 years with tinnitus that was comparatively stable; 978 participants were matched (489 pairs).
12 weeks' treatment with either 50 mg Ginkgo biloba extract LI 1370 three times daily or placebo.
Main outcome measures
Participants' assessment of tinnitus before, during, and after treatment. Questionnaires included items assessing perception of how loud and how troublesome tinnitus was. Changes in loudness were rated on a six point scale. Changes in how troublesome were rated on a five point scale.
There were no significant differences in primary or secondary outcome measures between the groups. 34 of 360 participants receiving active treatment reported that their tinnitus was less troublesome after 12 weeks of treatment compared with 35 of 360 participants who took placebo.
50 mg Ginkgo biloba extract LI 1370 given 3 times daily for 12 weeks is no more effective than placebo in treating tinnitus.
PMCID: PMC26593  PMID: 11154618
10.  Effect of Ginkgo Biloba (EGb 761) on Treadmill Walking Time Among Adults with Peripheral Artery Disease: A Randomized Clinical Trial 
Medical therapies for treatment of peripheral artery disease (PAD) are limited. Ginkgo biloba has been reported to increase maximal and pain-free walking distance among patients with (PAD); however, the evidence is inconsistent. The objective of this study was to compare the effects of 300 mg/d of Ginkgo biloba (EGb 761) vs. placebo on treadmill walking time and related cardiovascular measures among subjects with PAD.
A double-blind, placebo-controlled, parallel design trial with a 4 month duration was employed. Subjects were 62 adults, age 70 ± 8 years (mean, SD), with claudication symptoms of PAD. The primary study outcomes were maximal and pain free walking time on a treadmill. Secondary outcomes included flow mediated vasodilation (FMVD), a measure of antioxidant status as assessed by determining antibody levels to epitopes of oxidized LDL, and questionnaires addressing walking impairment and quality of life.
Maximal treadmill walking time increased by 20±80s and 91±242s in the placebo and EGb 761 groups, respectively (P=0.12). Pain-free walking time increased by 15±31s and 21±43s, respectively (P=0.28). No significant differences were detected between groups for any of the secondary outcomes.
In older adults with PAD, Ginkgo biloba produced a modest but insignificant increase in maximal treadmill walking time and flow-mediated vasodilation. These data do not support the use of Ginkgo biloba as an effective therapy for PAD, although a longer duration of use should be considered in any future trials.
PMCID: PMC2748261  PMID: 18628657
Ginkgo biloba; peripheral artery disease; claudication; treadmill time
11.  Ginkgo biloba and risk of cancer: Secondary Analysis of the Ginkgo Evaluation of Memory (GEM) Study 
Evidence from in vitro and in vivo studies suggests that Ginkgo biloba has cancer chemopreventive properties, but epidemiological evidence is sparse. We analyzed cancer as a secondary endpoint in the Ginkgo Evaluation of Memory (GEM) Study, the largest randomized, double-blind, placebo-controlled clinical trial of Ginkgo supplementation to date.
A total of 3,069 GEM participants 75+ years of age were randomized to twice-daily doses of either 120mg Ginkgo extract (EGb 761) or placebo and followed for a median 6.1 years. We identified hospitalizations for invasive cancer by reviewing hospital admission and discharge records for all reported hospitalizations over follow-up. Using an intention-to-treat approach, we compared the risk of cancer hospitalization between participants assigned to treatment and those assigned to placebo.
During the intervention, there were 148 cancer hospitalizations in the placebo group and 162 in the EGb 761 group (Hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.87–1.36; p=0.46). Among the site-specific cancers analyzed, we observed an increased risk of breast (HR, 2.15; 95% CI, 0.97–4.80; p=0.06) and colorectal (HR, 1.62; 95% CI, 0.92–2.87; p=0.10) cancer, and a reduced risk of prostate cancer (HR, 0.71; 95% CI, 0.43–1.17; p=0.18).
Overall, these results do not support the hypothesis that regular use of Ginkgo biloba reduces the risk of cancer.
PMCID: PMC2917376  PMID: 20582906
Ginkgo biloba; randomized controlled trial; breast cancer; prostate cancer; complimentary and alternative medicine
12.  Effect of Acetazolamide and Gingko Biloba on the Human Pulmonary Vascular Response to an Acute Altitude Ascent 
High Altitude Medicine & Biology  2013;14(2):162-167.
Ke, Tao, Jiye Wang, Erik R. Swenson, Xiangnan Zhang, Yunlong Hu, Yaoming Chen, Mingchao Liu, Wenbin Zhang, Feng Zhao, Xuefeng Shen, Qun Yang, Jingyuan Chen, and Wenjing Luo. Effect of acetazolamide and gingko biloba on the human pulmonary vascular response to an acute altitude ascent. High Alt Med Biol 14:162–167, 2013.—Acetazolamide and gingko biloba are the two most investigated drugs for the prevention of acute mountain sickness (AMS). Evidence suggests that they may also reduce pulmonary artery systolic pressure (PASP). To investigate whether these two drugs for AMS prevention also reduce PASP with rapid airlift ascent to high altitude, a randomized controlled trial was conducted on 28 healthy young men with acetazolamide (125 mg bid), gingko biloba (120 mg bid), or placebo for 3 days prior to airlift ascent (397 m) and for the first 3 days at high altitude (3658 m). PASP, AMS, arterial oxygen saturation (Sao2), mean arterial pressure (MAP), heart rate (HR), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF) were assessed both at 397 m and 3658 m. HR, PEF, and PASP increased with altitude exposure (p<0.05), and SaO2 decreased (p<0.05). PASP with acetazolamide (mean at 3658 m, 26.2 mm Hg; incremental change, 4.7 mm Hg, 95% CI., 2.6–6.9 mm Hg) was lower than that with ginkgo biloba (mean at 3658 m, 33.7 mm Hg, p=0.001; incremental change, 13.1 mm Hg, 95%CI., 9.6–16.5 mm Hg, p=0.002), and with placebo (mean at 3658 m, 34.7 mm Hg, p<0.001; 14.4 mm Hg, 95% CI., 8.8–20.0 mm Hg, p=0.001). The data show that a low prophylactic dosage of acetazolamide, but not gingko biloba, mitigates the early increase of PASP in a quick ascent profile.
PMCID: PMC3694514  PMID: 23795737
acetazolamide; gingko Biloba; pulmonary artery systolic pressure; acute mountain sickness; randomized controlled trial
13.  Ginkgo biloba Extract for Patients with Early Diabetic Nephropathy: A Systematic Review 
Objectives. To evaluate the effectiveness and safety of a Ginkgo biloba extract for patients with early diabetic nephropathy. Methods. Randomised controlled trials (RCTs) conducted on adults with early diabetic nephropathy which used Gingko biloba extract were included. The major databases were searched, and manufacturers of Gingko biloba products were contacted for information on any published or unpublished studies. Two authors independently extracted the data from the included studies. Data analysis was conducted using Review Manager 5.0 software. Results. Sixteen RCTs were included. Ginkgo biloba extract decreased the urinary albumin excretion rate (UAER), fasting blood glucose (FBG), serum creatinine (SCR), and blood urea nitrogen (BUN). The extract also improved hemorheology. The methodological quality in the included studies was low. The explicit generation of the allocation sequence was described in only 6 trials. None of the included trials were confirmed to use blinding. Three studies had observed adverse events. One study using angiotensin-converting enzyme inhibitor (ACEi) reported mild cough in both groups. No serious adverse effects were reported. Conclusions. Gingko biloba extract is a valuable drug which has prospect in treating early diabetic nephropathy, especially with high UAER baseline level. The safety for early diabetic nephropathy is uncertain. Long-term, double-blinded RCTs with large sample sizes are still needed to provide stronger evidence.
PMCID: PMC3595672  PMID: 23533513
14.  Adjunctive treatment with oral AKL1, a botanical nutraceutical, in chronic obstructive pulmonary disease 
The objective of this pilot trial was to evaluate the safety and efficacy of AKL1, a patented botanical formulation containing extracts of Picrorhiza kurroa, Ginkgo biloba, and Zingiber officinale, as add-on therapy for patients with chronic obstructive pulmonary disease (COPD) and chronic cough.
Patients and methods
This randomized, double-blind, placebo-controlled trial enrolled male and female patients >18 years old with COPD and Leicester Cough Questionnaire (LCQ) score of <18. The 10-week study period comprised a 2-week single-blind placebo run-in period followed by add-on treatment with AKL1 or placebo twice daily for 8 weeks. The primary study endpoint was the change from week 0 to week 8 in cough-related health status, as assessed by the LCQ.
Of 33 patients enrolled, 20 were randomized to AKL1 and 13 to placebo. Patients included 19 (58%) men and 14 (42%) women of mean (standard deviation [SD]) age of 67 (9.4) years; 15 (45%) patients were smokers and 16 (49%) were ex-smokers. The mean (SD) change from baseline in LCQ score at 8 weeks was 2.3 (4.9) in the AKL1 group and 0.6 (3.7) in the placebo group, with mean difference in change of 1.8 (95% confidence interval: −1.5 to 5.1; P=0.28). The St George’s Respiratory Questionnaire score improved substantially in the AKL1 treatment group by a mean (SD) of −7.7 (11.7) versus worsening in the placebo group (+1.5 [9.3]), with mean difference in change of −9.2 (95% confidence interval: −19.0 to 0.6; P=0.064). There were no significant differences between treatment groups in change from baseline to week 8 in other patient-reported measures, lung function, or the 6-minute walk distance.
Further study is needed with a larger patient population and over a longer duration to better assess the effects of add-on therapy with AKL1 in COPD.
PMCID: PMC4096458  PMID: 25031533
Leicester Cough Questionnaire; anti-inflammatory; Picrorhiza kurroa; Ginkgo biloba; Zingiber officinale
15.  The Hawthorne Effect: a randomised, controlled trial 
The 'Hawthorne Effect' may be an important factor affecting the generalisability of clinical research to routine practice, but has been little studied. Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge, no attempt has been made to quantify them. Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia.
Participants in a dementia trial were randomised to intensive follow-up (with comprehensive assessment visits at baseline and two, four and six months post randomisation) or minimal follow-up (with an abbreviated assessment at baseline and a full assessment at six months). Our primary outcomes were cognitive functioning (ADAS-Cog) and participant and carer-rated quality of life (QOL-AD).
We recruited 176 participants, mainly through general practices. The main analysis was based on Intention to treat (ITT), with available data. In the ANCOVA model with baseline score as a co-variate, follow-up group had a significant effect on outcome at six months on the ADAS-Cog score (n = 140; mean difference = -2.018; 95%CI -3.914, -0.121; p = 0.037 favouring the intensive follow-up group), and on participant-rated quality of life score (n = 142; mean difference = -1.382; 95%CI -2.642, -0.122; p = 0.032 favouring minimal follow-up group). There was no significant difference on carer quality of life.
We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia resulted in a better outcome than minimal follow-up, as measured by their cognitive functioning.
Trial registration
Current controlled trials: ISRCTN45577048
PMCID: PMC1936999  PMID: 17608932
16.  A double-blind, randomized clinical trial of dietary supplementation on cognitive and immune functioning in healthy older adults 
Declining cognitive function is relatively common and increasingly prevalent. Studies have shown that different nutrients (e.g., Ginkgo biloba and vitamin E) appear to be effective at improving memory and concentration, while less is known about their effect on immunity.
This study investigated the effect of Ginkgo Synergy® plus Choline (n = 33) and OPC Synergy® plus Catalyn® (n = 31) versus placebo (n = 33) in a 6-month, randomized, double-blind trial on cognitive and immune functioning among English-speaking, non-smoking, healthy older adults. The Stroop Color and Word Test, Trail Making Test A and B, Controlled Oral Word Association, Hopkins Verbal Learning, Mini-Mental State Exam, and Digit Symbol were administered at baseline and 3 and 6 months follow-up to assess cognitive functioning. Cytokines and growth factors were measured at baseline and 6 months to assess inflammation and immune functioning. Data were analyzed with linear mixed modeling.
No serious adverse events were noted in this study. According to time on the Trail Making Test-B, the Ginkgo Synergy® plus Choline arm showed improvement from baseline to 3 months follow-up (mean difference = 24.2; SE = 6.4; 95% CI: 8.6, 39.7; p = 0.01). On the Controlled Oral Word Association Trial-S, the scores significantly increased for the Ginkgo Synergy® plus Choline arm from baseline to 6 months follow-up (mean difference = 2.1; SE = 0.8; 95% CI: 0.2, 3.9; p < 0.05) and for the OPC Synergy® plus Catalyn® arm from baseline to 3 months follow-up (mean difference = 2.1; SE = 0.8; 95% CI: 0.2, 4.0; p < 0.05). Epidermal growth factor significantly decreased from baseline to 6 months follow-up for the Ginkgo Synergy® plus Choline arm (mean difference = 120.7; SE = 28.4; 95% CI: 62.6, 178.8; p < 0.001).
Our study showed isolated and modest effects of a Ginkgo biloba plus choline-based formula on cognitive and immune functioning among healthy older adults with no history of significant cognitive deficits. Our trial was registered with (ID: NCT01672359). This study was supported by a grant from Standard Process, Inc.
PMCID: PMC3916807  PMID: 24495355
Cognitive functioning; Immune functioning; Ginkgo biloba; Choline; Dietary supplement; Older adults; Trail making test; Controlled oral word association; Epidermal growth factor
17.  Effect of Ginkgo Biloba on the Pharmacokinetics of Raltegravir in Healthy Volunteers 
Antimicrobial Agents and Chemotherapy  2012;56(10):5070-5075.
Medicinal herbs may cause clinically relevant drug interactions with antiretroviral agents. Ginkgo biloba extract is a popular herbal product among HIV-infected patients because of its positive effects on cognitive function. Raltegravir, an HIV integrase inhibitor, is increasingly being used as part of combined antiretroviral therapy. Clinical data on the potential inhibitory or inductive effect of ginkgo biloba on the pharmacokinetics of raltegravir were lacking, and concomitant use was not recommended. We studied the effect of ginkgo biloba extract on the pharmacokinetics of raltegravir in an open-label, randomized, two-period, crossover phase I trial in 18 healthy volunteers. Subjects were randomly assigned to a regimen of 120 mg of ginkgo biloba twice daily for 15 days plus a single dose of raltegravir (400 mg) on day 15, a washout period, and 400 mg of raltegravir on day 36 or the test and reference treatments in reverse order. Pharmacokinetic sampling of raltegravir was performed up to 12 h after intake on an empty stomach. All subjects (9 male) completed the trial, and no serious adverse events were reported. Geometric mean ratios (90% confidence intervals) of the area under the plasma concentration-time curve from dosing to infinity (AUC0-∞) and the maximum plasma concentration (Cmax) of raltegravir with ginkgo biloba versus raltegravir alone were 1.21 (0.93 to 1.58) and 1.44 (1.03 to 2.02). Ginkgo biloba did not reduce raltegravir exposure. The potential increase in the Cmax of raltegravir is probably of minor importance, given the large intersubject variability of raltegravir pharmacokinetics and its reported safety profile.
PMCID: PMC3457394  PMID: 22802250
18.  Phase II Study of Ginkgo Biloba in Irradiated Brain Tumor Patients: Effect on Cognitive Function, Quality of Life, and Mood 
Journal of neuro-oncology  2012;109(2):357-363.
Ginkgo biloba has been reported to improve cognitive function in older adults and patients with Alzheimer’s disease and multi-infarct dementia. We conducted an open-label phase II study of this botanical product in symptomatic irradiated brain tumor survivors.
Eligibility criteria included: life expectancy ≥ 30 weeks, partial or whole brain radiation ≥ 6 months before enrollment, no imaging evidence of tumor progression in previous 3 months, or stable or decreasing steroid dose, and no brain tumor treatment planned while on study. The ginkgo biloba dose was 120 mg/day (40 mg t.i.d.) for 24 weeks followed by a 6-week washout period. Assessments performed at baseline, 12, 24 (end of treatment), and 30 weeks (end of washout) included KPS, Functional Assessment of Cancer Therapy-Brain (FACT-Br), Profile of Mood States (POMS), Mini-Mental Status Exam (MMSE), Trail Making Test Parts A (TMT-A) and B (TMT-B), Digit Span Test (DST), Modified Rey Osterrieth Complex Figure (ROCF), California Verbal Learning Test Part II (CVLT-II), and the F-A-S Test.
Of the 34 patients enrolled on study, 23 (68%) completed 12 weeks of treatment and 19 (56%) completed 24 weeks of treatment. There were significant improvements at 24 weeks in: executive function (TMT-B) (p=0.007), attention/concentration (TMT-A) (p=0.002), and non-verbal memory (ROCF – immediate/delayed recall) (p=0.001/0.002), mood (p=.002), FACT brain subscale (p=0.001), and the FACT physical subscale (p=.003).
Some improvement in quality of life and cognitive function were noted with ginkgo biloba. However, treatment with ginkgo biloba was associated with a high dropout rate.
PMCID: PMC3752650  PMID: 22700031
ginkgo biloba; radiation; cognitive function; quality of life; brain tumors
19.  Assessment of health claims, content, and safety of herbal supplements containing Ginkgo biloba  
Food & Nutrition Research  2010;54:10.3402/fnr.v54i0.5221.
European Regulation 1924/2006 states that all health claims made on foods need to be substantiated scientifically.
To apply the PASSCLAIM criteria for the scientific substantiation of health claims on foods to herbal supplements containing Ginkgo biloba. Evaluation of three selected claimed health effects for G. biloba (improvement of blood circulation, improvement of symptoms of old age, and improvement of memory) was achieved through review of publicly available scientific data. A total of 35 human intervention studies were evaluated. Commercially available products claimed to contain mainly G. biloba (N=29) were randomly sampled in the Netherlands and analyzed for their content on ginkgo extract. Also, a toxicological risk assessment was performed.
The three selected health claims investigated could not be substantiated. This was mainly because of a lack of data from studies in healthy volunteers. In most studies results performed with a 24% standardized G. biloba extract were described. However, our chemical analysis showed that 25 of the 29 sampled products did not contain the required minimum 24% standardized extract. Moreover, in most preparations the content of substances typical for G. biloba did not conform to what was declared on the label. Since toxicity data for G. biloba are very limited, a safety limit could not be established.
Evidence is lacking for three health claims of herbal products with G. biloba. Neither safety nor efficacy can be guaranteed at the recommended daily dose. The multidisciplinary approach described in this paper provides good insight into issues that are relevant for the evaluation of health claims for herbal food supplements.
PMCID: PMC2950792  PMID: 20927202
Ginkgo biloba; health claims; substantiation; botanicals; content; safety
20.  Efficacy and tolerability of Ginkgo biloba extract EGb 761® in dementia: a systematic review and meta-analysis of randomized placebo-controlled trials 
The objective of this systematic review was to evaluate current evidence for the efficacy of Ginkgo biloba extract EGb 761® in dementia. Seven of 15 randomized, placebocontrolled trials in patients with dementia identified by database searches met all our selection criteria and were included in the meta-analysis. In these trials, patients were treated with 120 mg or 240 mg per day of the defined extract EGb 761 or placebo. Efficacy was assessed using validated tests and rating scales for the cognitive domain, the functional domain (activities of daily living), and global assessment. Tolerability was evaluated by risk differences based on incidences of adverse events and premature discontinuation rates. Of 2,684 outpatients randomized to receive treatment for 22–26 weeks, 2,625 represented the full analysis sets (1,396 for EGb 761 and 1,229 for placebo). Standardized mean differences for change in cognition (−0.52; 95% confidence interval [CI] −0.98, −0.05; P=0.03), activities of daily living (−0.44; 95% CI −0.68, −0.19; P<0.001), and global rating (−0.52; 95% CI −0.92, −0.12; P=0.01) significantly favored EGb 761 compared with placebo. Statistically significant superiority of EGb 761 over placebo was confirmed by responder analyses as well as for patients suffering from dementia with neuropsychiatric symptoms. Treatment-associated risks in terms of relative risks of adverse events and premature withdrawal rates did not differ noticeably between the two treatment groups. In conclusion, meta-analyses confirmed the efficacy and good tolerability of Ginkgo biloba extract EGb 761 in patients with dementia.
PMCID: PMC4259871  PMID: 25506211
Alzheimer’s disease; vascular dementia; mixed dementia; efficacy; safety
21.  Alcohol Intake and Blood Pressure: A Systematic Review Implementing a Mendelian Randomization Approach 
PLoS Medicine  2008;5(3):e52.
Alcohol has been reported to be a common and modifiable risk factor for hypertension. However, observational studies are subject to confounding by other behavioural and sociodemographic factors, while clinical trials are difficult to implement and have limited follow-up time. Mendelian randomization can provide robust evidence on the nature of this association by use of a common polymorphism in aldehyde dehydrogenase 2 (ALDH2) as a surrogate for measuring alcohol consumption. ALDH2 encodes a major enzyme involved in alcohol metabolism. Individuals homozygous for the null variant (*2*2) experience adverse symptoms when drinking alcohol and consequently drink considerably less alcohol than wild-type homozygotes (*1*1) or heterozygotes. We hypothesise that this polymorphism may influence the risk of hypertension by affecting alcohol drinking behaviour.
Methods and Findings
We carried out fixed effect meta-analyses of the ALDH2 genotype with blood pressure (five studies, n = 7,658) and hypertension (three studies, n = 4,219) using studies identified via systematic review. In males, we obtained an overall odds ratio of 2.42 (95% confidence interval [CI] 1.66–3.55, p = 4.8 × 10−6) for hypertension comparing *1*1 with *2*2 homozygotes and an odds ratio of 1.72 (95% CI 1.17–2.52, p = 0.006) comparing heterozygotes (surrogate for moderate drinkers) with *2*2 homozygotes. Systolic blood pressure was 7.44 mmHg (95% CI 5.39–9.49, p = 1.1 × 10−12) greater among *1*1 than among *2*2 homozygotes, and 4.24 mmHg (95% CI 2.18–6.31, p = 0.00005) greater among heterozygotes than among *2*2 homozygotes.
These findings support the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.
Using a mendelian randomization approach Sarah Lewis and colleagues find strong support for the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.
Editors' Summary
High blood pressure (hypertension) is a common medical condition that affects nearly a third of US and UK adults. Hypertension has no symptoms but can lead to heart attacks or strokes. It is diagnosed by measuring blood pressure—the force that blood moving around the body exerts on the inside of large blood vessels. Blood pressure is highest when the heart is pumping out blood (systolic pressure) and lowest when it is filling up with blood (diastolic pressure). Normal blood pressure is defined as a systolic pressure of less than 130 millimeters of mercury (mmHg) and a diastolic pressure of less than 85 mmHg (a blood pressure of 130/85). A reading of more than 140/90 indicates hypertension. Many factors affect blood pressure, but overweight people and individuals who eat too much salty or fatty foods are at high risk of developing hypertension. Mild hypertension can often be corrected by lifestyle changes, but many people also take antihypertensive drugs to reduce their blood pressure.
Why Was This Study Done?
Another modifiable lifestyle factor thought to affect blood pressure is alcohol intake. Observational studies that ask people about their drinking habits and measure their blood pressure suggest that alcohol intake correlates with blood pressure, but they cannot prove a causal link because of “confounding”—other risk factors associated with alcohol drinking, such as diet, might also affect the study participant's blood pressures. A trial that randomly assigns people to different alcohol intakes could provide this proof of causality, but such a trial is impractical. In this study, therefore, the researchers have used “Mendelian randomization” to investigate whether alcohol intake affects blood pressure. An inactive variant of aldehyde dehydrogenase 2 (ALDH2; the enzyme that removes alcohol from the body) has been identified. People who inherit the variant form of this gene from both parents have an ALDH2 *2*2 genotype (genetic makeup) and become flushed and nauseated after drinking. Consequently, they drink less than people with a *1*2 genotype and much less than those with a *1*1 genotype. Because inheritance of these genetic variants does not affect lifestyle factors other than alcohol intake, an association between ALDH2 genotypes and blood pressure would indicate that alcohol intake has an effect on blood pressure without any confounding.
What Did the Researchers Do and Find?
The researchers identified ten published studies (mainly done in Japan where the ALDH2 gene variant is common) on associations between ALDH2 genotype and blood pressure or hypertension using a detailed search protocol (a “systematic review”). A meta-analysis (a statistical method for combining the results of independent studies) of the studies that had investigated the association between ALDH2 genotype and hypertension showed that men with the *1*1 genotype (highest alcohol intake) and those with the *1*2 genotype (intermediate alcohol intake) were 2.42 and 1.72 times more likely, respectively, to have hypertension than those with the *2*2 genotype (lowest alcohol intake). There was no association between ALDH2 genotype and hypertension among the women in these studies because they drank very little. Systolic and diastolic blood pressures showed a similar relationship to ALDH2 genotype in a second meta-analysis of relevant studies. Finally, the researchers estimated that for men the lifetime effect of drinking 1 g of alcohol a day (one unit of alcohol contains 8 g of alcohol in the UK and 14 g in the US; recommended daily limits in these countries are 3–4 and 1–2 units, respectively) would be an increase in systolic blood pressure of 0.24 mmHg.
What Do These Findings Mean?
These findings support the suggestion that alcohol has a marked effect on blood pressure and hypertension. Consequently, some cases of hypertension could be prevented by encouraging people to reduce their daily alcohol intake. Although the Mendelian randomization approach avoids most of the confounding intrinsic to observational studies, it is possible that a gene near ALDH2 that has no effect on alcohol intake affects blood pressure, since genes are often inherited in blocks. Alternatively, ALDH2 could affect blood pressure independent of alcohol intake. The possibility that ALDH2 could effect blood pressure independently of alcohol is intake made unlikely by the fact that no effect of genotype on blood pressure is seen among women who drink very little. Additional large-scale studies are needed to address these possibilities, to confirm the current finding in more people, and to improve the estimates of the effect that alcohol intake has on blood pressure.
Additional Information.
Please access these Web sites via the online version of this summary at
The MedlinePlus encyclopedia has a page on hypertension (in English and Spanish)
The American Heart Association provides information for patients and health professionals about hypertension
The UK Blood Pressure Association provides information for patients and health professionals on all aspects of hypertension, including information about alcohol affects blood pressure
The Explore@Bristol science center (a UK charity) provides an alcohol unit calculator and information on the effects of alcohol
The International Center for Alcohol Policies provides drinking guidelines for countries around the world
PMCID: PMC2265305  PMID: 18318597
22.  Effect of Memo®, a natural formula combination, on Mini-Mental State Examination scores in patients with mild cognitive impairment 
Mild cognitive impairment encompasses the clinical continuum between physiologic age-related cognitive changes and dementia. A variety of medications, including herbal preparations (in particular Ginkgo biloba and Panax ginseng), have been advocated as treatments for cognitive impairment in the elderly. In this study, we investigated the effect of an already marketed dietary supplement (Memo®) combining 750 mg of lyophilized royal jelly with standardized extracts of G. biloba 120 mg and P. ginseng 150 mg on Mini-Mental State Examination (MMSE) scores in patients with mild cognitive impairment.
Sixty-six subjects presenting with forgetfulness and satisfying the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) clinical criteria for mild cognitive impairment were randomly divided into an experimental group treated with one Memo capsule before breakfast daily for 4 weeks and a control group who took placebo. The mean change in MMSE score from baseline and reported adverse effects were compared between the two groups.
The mean change in MMSE score in the group treated with Memo for 4 weeks was significantly greater than in the control group (+2.07 versus +0.13, respectively) by the Student’s t-test (t = 6.485, P < 0.0001). This was also true after adjusting for age as a covariate and educational level as a factor nested within the treatment groups in a general linear model (analysis of covariance, F = 9.675 [corrected model], P < 0.0001).
This combined triple formula may be beneficial in treating the cognitive decline that occurs during the aging process as well as in the early phases of pathologic cognitive impairment typical of insidious-onset vascular dementia and in the early stages of Alzheimer’s disease. Larger-sized studies with longer treatment durations are needed to confirm this.
Video abstract
PMCID: PMC3740822  PMID: 23950642
mild cognitive impairment; Alzheimer’s disease; vascular dementia; Mini-Mental State Examination
23.  Permian ginkgophyte fossils from the Dolomites resemble extant O-ha-tsuki aberrant leaf-like fructifications of Ginkgo biloba L 
Structural elucidation and analysis of fructifications of plants is fundamental for understanding their evolution. In case of Ginkgo biloba, attention was drawn by Fujii in 1896 to aberrant fructifications of Ginkgo biloba whose seeds are attached to leaves, called O-ha-tsuki in Japan. This well-known phenomenon was now interpreted by Fujii as being homologous to ancestral sporophylls. The common fructification of Ginkgo biloba consists of 1-2 (rarely more) ovules on a dichotomously divided stalk, the ovules on top of short stalklets, with collars supporting the ovules. There is essentially no disagreement that either the whole stalk with its stalklets, collars and ovules is homologous to a sporophyll, or, alternatively, just one stalklet, collar and ovule each correspond to a sporophyll. For the transition of an ancestral sporophyll resembling extant O-ha-tsuki aberrant leaves into the common fructification with stalklet/collar/ovule, evolutionary reduction of the leaf lamina of such ancestral sporophylls has to be assumed. Furthermore, such ancestral sporophylls would be expected in the fossil record of ginkgophytes.
From the Upper Permian of the Bletterbach gorge (Dolomites, South Tyrol, Italy) ginkgophyte leaves of the genus Sphenobaiera were discovered. Among several specimens, one shows putatively attached seeds, while other specimens, depending on their state of preservation, show seeds in positions strongly suggesting such attachment. Morphology and results of a cuticular analysis are in agreement with an affiliation of the fossil to the ginkgophytes and the cuticle of the seed is comparable to that of Triassic and Jurassic ones and to those of extant Ginkgo biloba. The Sphenobaiera leaves with putatively attached seeds closely resemble seed-bearing O-ha-tsuki leaves of extant Ginkgo biloba. This leads to the hypothesis that, at least for some groups of ginkgophytes represented by extant Ginkgo biloba, such sporophylls represent the ancestral state of fructifications.
Some evidence is provided for the existence of ancestral laminar ginkgophyte sporophylls. Homology of the newly found fossil ginkgophyte fructifications with the aberrant O-ha-tsuki fructifications of Ginkgo biloba is proposed. This would support the interpretation of the apical part of the common Ginkgo biloba fructification (stalklet/collar/ovule) as a sporophyll with reduced leaf lamina.
PMCID: PMC3087549  PMID: 21044353
24.  Treatment with ginkgo biloba extract protects rats against acute pancreatitis-associated lung injury by modulating alveolar macrophage 
Acute pancreatitis (AP) protease release induces lung parenchymal destruction via inflammatory mediators. Ginkgo biloba has been reported to have anti-inflammatory effects.
To evaluate the effect of ginkgo biloba extract on experimental acute pancreatitis-associated lung injury in the rat and to investigate the underlying mechanisms.
Material and methods
Acute pancreatitis was induced in rats by injection of 5% sodium taurocholate into the biliary pancreatic duct. Ginkgo biloba extract (GBE) was administered and pancreas and lung injury were assessed by histological examination. Alveolar macrophages were harvested by bronchoalveolar lavage. Specificity fluorescent probe DAF-FM-DA was applied to observe nitric oxide (NO) bioavailability in alveolar macrophage. The expression of tumour necrosis factor α (TNF-α) and macrophage migration inhibitory factor (MIF) protein in alveolar macrophage was studied by ELISA.
In sodium taurocholate-induced acute pancreatitis, treatment with GBE significantly protected rats against lung injury associated with pancreatitis in histological sections. Ginkgo biloba extract had a tendency to down-regulate NO bioavailability compared with the AP group, but without statistical significance. Moreover, TNF-α and MIF at protein levels in alveolar macrophage with GBE treatment were decreased compared with the AP group.
These results suggest that GBE could effectively protect rats against acute pancreatitis-associated lung injury. The GBE may inhibit excessive activation of alveolar macrophages from acute pancreatitis-associated lung injury through down-regulation of generation of NO, TNF-α and MIF. These findings suggest that ginkgo biloba extract is a suitable candidate as an effective strategy against acute pancreatitis-associated lung injury.
PMCID: PMC4027842  PMID: 24868298
ginkgo biloba extract; acute pancreatitis; lung injury; alveolar macrophage
25.  EST analysis in Ginkgo biloba: an assessment of conserved developmental regulators and gymnosperm specific genes 
BMC Genomics  2005;6:143.
Ginkgo biloba L. is the only surviving member of one of the oldest living seed plant groups with medicinal, spiritual and horticultural importance worldwide. As an evolutionary relic, it displays many characters found in the early, extinct seed plants and extant cycads. To establish a molecular base to understand the evolution of seeds and pollen, we created a cDNA library and EST dataset from the reproductive structures of male (microsporangiate), female (megasporangiate), and vegetative organs (leaves) of Ginkgo biloba.
RNA from newly emerged male and female reproductive organs and immature leaves was used to create three distinct cDNA libraries from which 6,434 ESTs were generated. These 6,434 ESTs from Ginkgo biloba were clustered into 3,830 unigenes. A comparison of our Ginkgo unigene set against the fully annotated genomes of rice and Arabidopsis, and all available ESTs in Genbank revealed that 256 Ginkgo unigenes match only genes among the gymnosperms and non-seed plants – many with multiple matches to genes in non-angiosperm plants. Conversely, another group of unigenes in Gingko had highly significant homology to transcription factors in angiosperms involved in development, including MADS box genes as well as post-transcriptional regulators. Several of the conserved developmental genes found in Ginkgo had top BLAST homology to cycad genes. We also note here the presence of ESTs in G. biloba similar to genes that to date have only been found in gymnosperms and an additional 22 Ginkgo genes common only to genes from cycads.
Our analysis of an EST dataset from G. biloba revealed genes potentially unique to gymnosperms. Many of these genes showed homology to fully sequenced clones from our cycad EST dataset found in common only with gymnosperms. Other Ginkgo ESTs are similar to developmental regulators in higher plants. This work sets the stage for future studies on Ginkgo to better understand seed and pollen evolution, and to resolve the ambiguous phylogenetic relationship of G. biloba among the gymnosperms.
PMCID: PMC1285361  PMID: 16225698

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