An Updated Review of Randomized Clinical Trials Testing the Improvement of Cognitive Function of Ginkgo biloba Extract in Healthy People and Alzheimer's Patients.
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SUBMITTER: Liu H
PROVIDER: S-EPMC7047126 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
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An Updated Review of Randomized Clinical Trials Testing the Improvement of Cognitive Function of <i>Ginkgo biloba</i> Extract in Healthy People and Alzheimer's Patients.
Liu Haolong H Ye Min M Guo Hongzhu H
Frontiers in pharmacology 20200221
Alzheimer's disease (AD) is a common neurodegenerative disease, mainly manifested by cognitive dysfunction. It seriously reduces the quality of life, and there is no ideal treatment strategy in clinical practice. Clinical studies on the treatment of AD with <i>Ginkgo biloba</i> L. leaf extract (EGb) have been reported since 1980s, and many clinical studies have been carried out during the following 30 years. However, the benefits of EGb on the treatment of AD are still controversial. In this rev ...[more]
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Project description:BackgroundTo investigate the ameliorated effects of an extract of Ginkgo biloba extract (GBE) on experimental cardiac remodeling in rats induced by acute cardiac infarction, and further explore the mechanism concentrated on myocardial type I collagen, transforming growth factor beta 1 (TGF-β1), matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9), and provide the experimental data for clinical application of GBE.MethodsRats were divided into five groups (n = 20) as following: sham operation group (group A), acute myocardial infarction model group (group B), acute myocardial infarction model + aspirin (10 mg/kg) treatment group (group C), acute myocardial infarction model + captopril (20 mg/kg) treatment group (group D) and acute myocardial infarction model + Ginkgo biloba extract (100 mg/kg) treatment group (group E). The rat acute myocardial infarction model was reproduced by ligaturing the left anterior descending artery excluding the sham operation group which did not ligation only completed the operational process. Each group was further subdivided into treatment regimens lasting 4 weeks and 8 weeks. Immunohistochemistry and real-time polymerase chain reaction (PCR) methods were used to detect the protein expression and mRNA transcriptional levels of rat myocardial TGF-β1, type I collagen, MMP-2 and MMP-9.ResultsCompared with group B, regardless of the length of treatment (4 or 8 weeks), the TGF-β1, MMP-2 and MMP-9 mRNA transcriptional levels, and the protein expression levels of type I collagen, MMP-2 and MMP-9 in groups D, C and E were significantly decreased (P < 0.01). Furthermore, the mRNA expression levels of TGF-β1 in groups D, C and E were significantly lower after 8 weeks compared to after 4 weeks (P < 0.01), as were the expression levels of type I collagen in groups D, C and E (P < 0.05). There was no statistically significant difference in the protein expression levels of MMP-2 and MMP-9 between groups E and C.ConclusionsGBE could inhibit experimental rat myocardial remodeling after acute myocardial infarction via reduced transcription of TGF-β1, MMP-2 and MMP-9 genes and by the decreased expression of type I collagen, MMP-2 and MMP-9 proteins in myocardial cells.
| S-EPMC4534054 | biostudies-literature
Project description:Alzheimer's disease (AD) is a complex neurodegenerative disease. Numerous investigations have demonstrated that medications that regulate the "brain-gut" axis can ameliorate disease symptoms of AD. Studies have shown that Ginkgo biloba extract (EGb) is involved in intestinal metabolism to meet the goal of illness treatment. EGb is currently utilized extensively in the clinical prevention and treatment of cardiovascular and cerebrovascular diseases. However, the regulatory effect of EGb on intestinal flora and its metabolites in AD pathology remains largely speculative. In this study, the Morris water maze test showed a significant improvement of spatial memory in the AD mouse model (APP/PS1 mice) after EGb treatment. We next confirmed the positive effects of EGb on the gut flora and metabolites of APP/PS1 mice and further showed that EGb treatment reshaped the disturbed gut microbiome, in particular by reducing the Firmicutes/Bacteroides ratio and increasing the abundance of Bacteroidetes, Uroviricota, Streptophyta, and Spirochaetes. Meanwhile, a non-targeted metabolomics analysis showed that EGb treatment significantly reversed the dysfunction of the microbial metabolic phenotype by altering Limosilactobacillus and Parvibacte, with 300 differential metabolites modulated (131 up-regulated, 169 down-regulated). Our findings highlight the significant regulatory impact of EGb on intestinal microflora and microbial metabolism in AD mice models and provide a potential therapeutic strategy for AD.
| S-EPMC10747232 | biostudies-literature
Project description:OBJECTIVE:Trials of ginkgo biloba extract (GBE) for the prevention of acute mountain sickness (AMS) have been published since 1996. Because of their conflicting results, the efficacy of GBE remains unclear. We performed a systematic review and meta-analysis to assess whether GBE prevents AMS. METHODS:The Cochrane Library, EMBASE, Google Scholar and PubMed databases were searched for articles published up to 20 May 2017. Only randomised controlled trials were included. AMS was defined as an Environmental Symptom Questionnaire Acute Mountain Sickness-Cerebral score ≥0.7 or Lake Louise Score ≥3 with headache. The main outcome measure was the relative risk (RR) of AMS in participants receiving GBE for prophylaxis. Meta-analyses were conducted using random-effects models. Sensitivity analyses, subgroup analyses and tests for publication bias were conducted. RESULTS:Seven study groups in six published articles met all eligibility criteria, including the article published by Leadbetter et al, where two randomised controlled trials were conducted. Overall, 451 participants were enrolled. In the primary meta-analysis of all seven study groups, GBE showed trend of AMS prophylaxis, but it is not statistically significant (RR=0.68; 95% CI 0.45 to 1.04; p=0.08). The I2 statistic was 58.7% (p=0.02), indicating substantial heterogeneity. The pooled risk difference (RD) revealed a significant risk reduction in participants who use GBE (RD=-25%; 95% CI, from a reduction of 45% to 6%; p=0.011) The results of subgroup analyses of studies with low risk of bias, low starting altitude (<2500 m), number of treatment days before ascending and dosage of GBE are not statistically significant. CONCLUSION:The currently available data suggest that although GBE may tend towards AMS prophylaxis, there are not enough data to show the statistically significant effect of GBE on preventing AMS. Further large randomised controlled studies are warranted.
| S-EPMC6104799 | biostudies-literature
Project description:BackgroundEnergy deficiency and mitochondrial failure have been recognized as a prominent, early event in Alzheimer's disease (AD). Recently, we demonstrated that chronic exposure to amyloid-beta (Abeta) in human neuroblastoma cells over-expressing human wild-type amyloid precursor protein (APP) resulted in (i) activity changes of complexes III and IV of the oxidative phosphorylation system (OXPHOS) and in (ii) a drop of ATP levels which may finally instigate loss of synapses and neuronal cell death in AD. Therefore, the aim of the present study was to investigate whether standardized Ginkgo biloba extract LI 1370 (GBE) is able to rescue Abeta-induced defects in energy metabolism.Methodology/principal findingsWe used a high-resolution respiratory protocol to evaluate OXPHOS respiratory capacity under physiological condition in control (stably transfected with the empty vector) and APP cells after treatment with GBE. In addition, oxygen consumption of isolated mitochondria, activities of mitochondrial respiratory enzymes, ATP and reactive oxygen species (ROS) levels as well as mitochondrial membrane mass and mitochondrial DNA content were determined. We observed a general antioxidant effect of GBE leading to an increase of the coupling state of mitochondria as well as energy homeostasis and a reduction of ROS levels in control cells and in APP cells. GBE effect on OXPHOS was even preserved in mitochondria after isolation from treated cells. Moreover, these functional data were paralleled by an up-regulation of mitochondrial DNA. Improvement of the OXPHOS efficiency was stronger in APP cells than in control cells. In APP cells, the GBE-induced amelioration of oxygen consumption most likely arose from the modulation and respective normalization of the Abeta-induced disturbance in the activity of mitochondrial complexes III and IV restoring impaired ATP levels possibly through decreasing Abeta and oxidative stress level.Conclusions/significanceAlthough the underlying molecular mechanisms of the mode of action of GBE remain to be determined, our study clearly highlights the beneficial effect of GBE on the cellular OXPHOS performance and restoration of Abeta-induced mitochondrial dysfunction.
| S-EPMC2927422 | biostudies-literature
Project description:Ginkgo biloba has been used for many thousand years as a traditional herbal remedy and its extract has been consumed for many decades as a dietary supplement. Ginkgo biloba leaf extract is a complex mixture with many constituents, including flavonol glycosides and terpene lactones. The National Toxicology Program 2-year cancer bioassay found that G. biloba leaf extract targets the liver, thyroid gland, and nose of rodents; however, the mechanism of G. biloba leaf extract-associated carcinogenicity remains unclear. In the current study, the in vitro genotoxicity of G. biloba leaf extract and its eight constituents was evaluated using the mouse lymphoma assay (MLA) and Comet assay. The underlying mechanisms of G. biloba leaf extract-associated genotoxicity were explored. Ginkgo biloba leaf extract, quercetin, and kaempferol resulted in a dose-dependent increase in the mutant frequency and DNA double-strand breaks (DSBs). Western blot analysis confirmed that G. biloba leaf extract, quercetin, and kaempferol activated the DNA damage signaling pathway with increased expression of γ-H2AX and phosphorylated Chk2 and Chk1. In addition, G. biloba leaf extract produced reactive oxygen species and decreased glutathione levels in L5178Y cells. Loss of heterozygosity analysis of mutants indicated that G. biloba leaf extract, quercetin, and kaempferol treatments resulted in extensive chromosomal damage. These results indicate that G. biloba leaf extract and its two constituents, quercetin and kaempferol, are mutagenic to the mouse L5178Y cells and induce DSBs. Quercetin and kaempferol likely are major contributors to G. biloba leaf extract-induced genotoxicity.
| S-EPMC8142259 | biostudies-literature
Project description:BackgroundStandardized Ginkgo biloba extract (GBE) has demonstrated efficacy in the cognitive functional neuropsychiatric symptoms of patients with Alzheimer's disease (AD). With regard to its underlying molecular mode of action, first evidence was provided that GBE was able to modulate neuronal outgrowth in vitro, but the mechanisms underlying GBE effects on neuroplasticity remain unclear.Methodology/principal findingsIn this study, we investigated the effect of GBE on neurite outgrowth using SH-SY5Y neuroblastoma cells in a 2D and 3D surface culture. The effects of the GBE LI1370 on neuroplasticity and neurite outgrowth were compared to those of nerve growth factor (NGF, 50 ng/ml) which was used as a positive control. We evaluated several parameters of neurite outgrowth such as the neurite number, total neurite length and extend of branching. Our findings showed that GBE (10 and 100 μg/ml) significantly increased neurite outgrowth in the 2D as well as 3D culture model after 3 days of treatment with a comparable effect than that NGF. The use of the 3D cell culture allowed us to better reproduce the in vivo neuronal microenvironment for the evaluation the neurite formation after GBE treatment. In addition, we assessed the effects of GBE on the Akt/mTOR pathway, which is known to promote neuroplasticity induced by nerve growth factors. We showed that GBE treatment induced an increase of phosphorylated IGF1R (Tyr1135/Tyr1136), Akt (Ser473), TSC2 (Ser939), mTOR (Ser2448), PTEN (Ser380) and GSK3β (Ser9).ConclusionTogether, these findings indicate that GBE promotes neurite growth and activates the PI3K/Akt/mTOR pathway suggesting that this plant extract supports neuronal plasticity.
| S-EPMC6886765 | biostudies-literature
Project description:The prevalence of degenerative disorders in public health has promoted in-depth investigations of the underlying pathogenesis and the development of new treatment drugs. Ginkgo biloba leaves extract (EGb) is obtained from Ginkgo biloba leaves and has been used for thousands of years. In recent decades, both basic and clinical studies have established the effects of EGb. It is widely used in various degenerative diseases such as cerebrovascular disease, Alzheimer's disease, macroangiopathy and more. Here, we reviewed several pharmacological mechanisms of EGb, including its antioxidant properties, prevention of mitochondrial dysfunctions, and effect on apoptosis. We also described some clinical applications of EGb, such as its effect on neuro and cardiovascular protection, and anticancer properties. The above biological functions of EGb are mainly focused on aging-related disorders, but its effect on other diseases remains unclear. Thus, through this review, we aim to encourage further studies on EGb and discover more potential applications.
| S-EPMC5758353 | biostudies-literature
Project description:Background: Balance training with vibrotactile neurofeedback (VNF) can improve balance and subjective impairment in age-related vertigo and dizziness. Ginkgo biloba dry extract EGb 761 has been shown to improve subjective impairment in chronic vertigo and the efficacy of conventional balance training. The combination was expected to work synergistically in this difficult-to-treat population. Objectives: To demonstrate the efficacy of VNF added to EGb 761 for age-related vertigo and dizziness. Design: Multicenter, prospective, controlled, randomized, single-blind, two-arm trial (German Clinical Trials Register https://www.drks.de No. DRKS00007633). Setting: Specialist offices and tertiary care outpatient department. Participants: One hundred and twenty subjects aged 60+ years with chronic dizziness for over 3 months, a Dizziness Handicap Inventory (DHI) Sum Score >25 and fall risk in balance-related situations as measured by the geriatric Standard Balance Deficit Test Composite Score (gSBDT-CS)>40. Patients with other distinct vestibular pathology (e.g., Meniére's disease, stroke, BPPV) were excluded. Intervention: EGb 761 (80 mg twice daily for 12 weeks) plus 10 days of individually adapted balance training with VNF, randomized 1:1 to sensitive (active) or non-sensitive (sham) neurofeedback. Measurements: The change in gSBDT-CS after 6 weeks (primary), other gSBDT outcomes, DHI, cognition, hearing, and safety. Results: One hundred nine of 120 enrolled subjects received both treatments at least once. Over 12 weeks, the gSBDT-CS improved by 6.7 (active) vs. 4.5 (sham). There was a difference in favor of the active treatment of -2.4 (95% CI -5.4; 0.6) after 6 weeks. Under active treatment, more pronounced effects occurred in all secondary analyses and in nearly all secondary endpoints. The DHI sum score decreased from 44.1 to 31.1 in the total sample with a treatment group difference after 6 weeks of -3.1, 95% CI (-7.1; 0.9). No safety issues were reported. Conclusion: Over 12 weeks, the combination of balance training with VNF and Ginkgo biloba dry extract EGb 761 reached a clinically relevant improvement of age-related vertigo and dizziness with a good pharmacological safety profile.
| S-EPMC8669892 | biostudies-literature
Project description:PurposeWe assessed the human in vivo metabolic drug interaction profile of Ginkgo biloba extract EGb 761® with respect to the activities of major cytochrome P450 (CYP) enzymes.MethodsA single-center, open-label, randomized, three-fold crossover, cocktail phenotyping design was applied. In random order, the following treatments were administered to 18 healthy men and women for 8 days each: placebo twice daily, EGb 761® 120 mg twice daily, and EGb 761® 240 mg in the morning and placebo in the evening. In the morning of day 8, administration was performed together with the orally administered phenotyping cocktail (enzyme, metric): 150 mg caffeine (CYP1A2, paraxanthine/caffeine plasma ratio 6-h postdose), 125 mg tolbutamide (CYP2C9, plasma concentration 24-h postdose), 20 mg omeprazole (CYP2C19, omeprazole/5-hydroxy omeprazole plasma ratio 3-h postdose), 30 mg dextromethorphan (CYP2D6, dextromethorphan/dextrorphan plasma ratio 3-h postdose), and 2 mg of midazolam (CYP3A, plasma concentration 6-h postdose). Formally, absence of a relevant interaction was assumed if the 90% confidence intervals (CIs) for EGb 761®/placebo ratios of the metrics were within the 0.70-1.43 range.ResultsEGb 761®/placebo ratios for phenotyping metrics were close to unity for all CYPs. Furthermore, respective CIs were within the specified margins for all ratios except CYP2C19 for EGb 761® 120 mg twice daily (90% CI 0.681-1.122) and for CYP2D6 for EGb 761® 240 mg once daily (90% CI 0.667-1.281). These findings were attributed to the intraindividual variability of the metrics used. All treatments were well tolerated.ConclusionEGb 761® has no relevant effect on the in vivo activity of the major CYP enzymes in humans and therefore has no relevant potential to cause respective metabolic drug-drug interactions.
| S-EPMC3332346 | biostudies-literature
Project description: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 (AUC(0-?)) and the maximum plasma concentration (C(max)) 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 C(max) of raltegravir is probably of minor importance, given the large intersubject variability of raltegravir pharmacokinetics and its reported safety profile.
| S-EPMC3457394 | biostudies-literature