Ginkgo Extract EGb Research Articles

The Protective Effect of Egb 761 Against 3-Nitropropionic Acid-Induced Hearing Loss: The Role of Sirtuin 1.

Objectives Local administration of 3-nitropropionic acid (3-NP) to the inner ear induces sensorineural hearing loss. Several studies have shown the otoprotective effects of ginkgo biloba extract EGb 761. Moreover, EGb 761 has been reported to activate Sirtuin 1 (SIRT1). The present study was designed to investigate whether EGb 761 prevents 3-NP-induced sensorineural hearing loss and determine its effects on the expression of SIRT1.MethodsSprague Dawley rats were divided into four experimental groups: control group receiving vehicle of 3-NP, EGb group receiving EGb 761, 3-NP group receiving 3-NP, and EGb+3-NP group receiving EGb 761 and 3-NP. EGb 761 was given orally for 5 days. The 3-NP solution was injected into the tympanum 3 days after the start of EGb 761 administration. The auditory brainstem response was recorded before and after the injection. At 4 weeks after the administration of 3-NP or vehicle of 3-NP, cochleae were harvested, and hematoxylin and eosin staining and immunohistochemistry for SIRT1 antibody were performed.ResultsEGb+3-NP group showed significantly lower threshold shifts than 3-NP group. There was a significant preservation of type II fibrocytes and spiral ganglion cells in EGb+3-NP group than in 3-NP group. In EGb+3-NP group, there was a significantly greater number of SIRT1 immunopositive type II fibrocytes and spiral ganglion cells than in 3-NP group. Calculating the percentage of SIRT1 immunoreactive type II fibrocytes and spiral ganglion cells in viable type II fibrocytes and spiral ganglion cells, respectively, EGb+3-NP group showed significantly higher SIRT1 immunoreactive cells than 3-NP group.Conclusion These results suggest that EGb 761 may prevent hearing loss induced by 3-NP in an acute ototoxic animal model, which appears to be related with SIRT1 expression.

Effect of Ginkgo biloba extract EGb761 on apoptosis of K-ras mutational human colon cancer cells DLD1 and its mechanism

Objective To explore the effect of Ginkgo biloba extract (EGb761) on apoptosis of K-ras mutational human colon cancer cells DLD1 (DLD1/G13D) and its mechanism. Methods Human colon cancer cell lines DLD1/G13D and DLD1 with K-ras wild type (DLD1/WT) were cultured in vitro, the cell proliferation and apoptosis after 24 h of EGb761 were measured. Proteins involved in related signal pathway were detected by Western blot or ELISA. Results EGb761 reduced cell proliferation and induced cell apoptosis in a concentration-dependent manner in DLD1/WT and DLD1/G13D cells. EGb761 downregulated the expression of RIP1, impaired the phosphorylation of IκB and decreased the level of NF-κB in DLD1/WT and DLD1/G13D cells [DLD1/G13D: (24 ± 4)%, DLD1/WT: (29 ± 9)% (P < 0.05). Conclusion EGb761 restrains the proliferation and induces the apoptosis of DLD1/WT and DLD1/G13D cells. The mechanism may be related to the degradation of RIP-1 and inhibition of activation of NF-κB signaling pathway. Key words: Colonic neoplasms; Ginkgo biloba extract; Mutation; Apoptosis; NF-κB signaling pathway

Ginkgo biloba extract EGb 761-induced upregulation of LincRNA-p21 inhibits colorectal cancer metastasis by associating with EZH2.

EGb 761, the standard ginkgo biloba extract, is frequently prescribed in traditional Chinese medicine. Currently, there is no research focusing on its role in human colorectal cancer progression. In our study, we determined the anti-metastatic effect of EGb 761 on colorectal cancer cells and further explored the potential underlying regulatory mechanism. The cell migration and invasion assay indicated that EGb 761 treatment of colorectal cancer cells induced inhibition of cell migration and invasion ability in a concentration-dependent manner. To further explore the underlying regulatory mechanisms that may account for these findings, we performed quantitative real-time PCR (RT-qPCR), western blotting and immunoprecipitation analysis. The results showed that EGb 761 induced upregulation of LincRNA-p21 expression in a dose- and time-dependent manner. Overexpression of LincRNA-p21 also suppressed colorectal cancer cell metastasis. Furthermore, EGb 761 as well as LincRNA-p21 inhibited the expression of extracellular matrix protein, fibronectin. More importantly, RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays showed that LincRNA-p21 directly interacted with EZH2, and this interaction suppressed the expression of fibronectin. Finally, the gain and loss function assay revealed that EGb 761 inhibited migration, invasion and fibronctin expression by the LincRNA-p21/EZH2 pathway in colorectal cancer cells. Hence, EGb 761 may be a promising treatment regimen for colorectal cancer and restoration of LincRNA-p21 levels may be helpful for enhancing the anti-cancer effect of EGb 761.

Treatment effects of Ginkgo biloba extract EGb 761® on the spectrum of behavioral and psychological symptoms of dementia: meta-analysis of randomized controlled trials.

To assess the effects of EGb 761® on specific BPSD, we analyzed data from all randomized, placebo-controlled, at least 20-week, trials of EGb 761® enrolling patients with dementia (probable Alzheimer's disease (AD), probable vascular dementia or probable AD with cerebrovascular disease) who had clinically significant BPSD (Neuropsychiatric Inventory (NPI) total score at least 6). Data were pooled and joint analyses of NPI single item composite and caregiver distress scores were performed by meta-analysis with a fixed effects model. Four trials involving 1628 patients (EGb 761®, 814; placebo, 814) were identified; treatment duration was 22 or 24 weeks; the daily dose of EGb 761® was 240 mg in all trials. Pooled analyses including data from the full analysis sets of all trials (EGb 761®, 796 patients; placebo, 802 patients) revealed significant superiority of EGb 761® over placebo in total scores and 10 single symptom scores. Regarding caregiver distress scores, EGb 761®-treated patients improved significantly more than those receiving placebo in all symptoms except delusions, hallucinations, and elation/euphoria. The benefit of EGb 761® mainly consists of improvement in symptoms present at baseline, but the incidence of some symptoms was also decreased. Twenty two- to twenty four-week treatment with Ginkgo biloba extract EGb 761® improved BPSD (except psychotic-like features) and caregiver distress caused by such symptoms.

Ginkgo biloba extract EGb761 attenuates brain death-induced renal injury by inhibiting pro-inflammatory cytokines and the SAPK and JAK-STAT signalings

This study aimed to investigate the protective effects of EGb761, a Ginkgo Biloba extract, against brain death-induced kidney injury. Sixty male Sprague Dawley rats were randomly divided into six groups: sham, brain-death (BD), BD + EGb b48h (48 hours before BD), BD + EGb 2 h (2 hours after BD), BD + EGb 1 h, and BD + EGb 0.5 h. Six hours after BD, serum sample and kidney tissues were collected for analyses. The levels of blood urea nitrogen (BUN) and serum creatinine significantly elevated in the BD group than in sham group. In all the EGb761-treated BD animals except for the BD + Gb 2 h group, the levels of BUN and serum creatinine significantly reduced (all P < 0.01). EGb761 attenuated tubular injury and lowered the histological score. In addition, the longer duration of drug treatment was, the better protective efficacy could be observed. EGb761 significantly reduced IL-1β, IL-6, TNF-α, MCP-1, IP-10 mRNA expression and macrophage infiltration in the kidney. EGb761 treatment at 48 hour before brain death significantly attenuate the levels of p-JNK-MAPK, p-p38-MAPK, and p-STAT3 proteins (all P < 0.05, compared to BD group). In summary, our data showed that EGb761 treatment protected donor kidney from BD-induced damages by blocking SAPK and JAK-STAT signalings. Early administration of EGb761 can provide better protective efficacy.

Commentary: A retrospective classification of diagnoses in terms of DSM-5 for patients included in randomized controlled trials of Ginkgo biloba extract EGb 761®

Commentary: A retrospective classification of diagnoses in terms of DSM-5 for patients included in randomized controlled trials of Ginkgo biloba extract EGb 761®

Long-term pre-treatment of antioxidant Ginkgo biloba extract EGb-761 attenuates cerebral-ischemia-induced neuronal damage in aged mice

Antioxidant activity has been attributed to the neuroprotective effects of Ginkgo biloba extract EGb-761 on brain disorders including ischemic stroke. It is suggested that oxidative stress implicates in neuron injuries during aging. However, whether or not EGb-761 could be used to treat age-related cerebral ischemia is unclear. In the present study, we directly studied the protective effects of EGb-761 in brain ischemia in the mice with different age. As expected, the recovery from brain damages was impaired in aged mice (24 months) in an animal model of middle cerebral artery occlusion (MCAO). Notably, a 12-month pretreatment of EGb-761 significantly ameliorated the ischemic injury of aged mice in a dose-dependent manner. The decreased stroke severity by EGb-761 was suggested by the reduced infarct volumes and brain edema, accompanied by alleviated oxidative stress. Additionally, we further explored the potential involvement of extra-cellular signal-regulated kinase (ERK) activation by MCAO in aged mice. ERK activation after MCAO was diminished by EGb-761, and this reduction may be mediated through an upregulation of phosphatase PP2A by EGb-761. These observations collectively support that natural antioxidant EGb-761 could be potentially exploited as an effective approach in treating neurological injury during aging.

Cognitive impairment in diabetes mellitus and hypertension, a possibility of correction

Objective: to evaluate cognitive functions in patients with type 2 diabetes mellitus (DM2) and hypertension and the efficacy of Ginkgo biloba extract Egb 761®. Patients and methods. 120 patients with DM2 and 50 hypertensive patients with no complications or a history of stroke and/or myocardial infarction, without active complaints of hypomnesia and other cognitive functions were examined. The exclusion criteria were prior stroke and/or myocardial infarction; clinically significant diseases of the peripheral arteries and major arteries of the head; DM2 decompensation; glomerular filtration rate <60 ml/min; proliferative retinopathy; and other endocrine diseases. The investigators used the following methods for the evaluation of cognitive functions: the Mini-Mental State Examination, the Montreal Cognitive Assessment, and the hand- eye coordination test (Parts A and B). Results and discussion. 85% of the patients with DM2 were found to have cognitive impairments (CI): disorders of attention, short-term memory, and thinking speed. Out of them, 82.5% had moderate CI and 2.5% had dementia. 30% of the hypertensive patients were diagnosed as having moderate CIs and 10% had dementia. At the same time, the degree of CI was higher in the patients with MD2 than in those with hypertension. The use of Egb 761® 240 mg/day for 3 months had a statistically significant positive impact on cognitive functions (improvements in short-term memory, concentration, and thinking speed) and everyday activity. Conclusion. The authors consider that CIs are the first sign of encephalopathy in DM2. It is also noted that DM2 has a more pronounced impact on cognitive functions than hypertension. Egb 761® can be used as an effective drug to treat CI in these diseases.

Effects of Ginkgo Biloba Extract EGb-761 on Neuropathic Pain in Mice: Involvement of Opioid System.

Neuropathic pain is considered as one of the most difficult types of pain to manage with conventional analgesics. EGb-761 is extracted from leaves of Ginkgo biloba and has analgesia and anti-inflammatory properties. This study aimed to examine the effect of EGb-761 on chronic constriction injury (CCI)-induced neuropathic pain behaviors, including thermal hyperalgesia and mechanical allodynia, and to explore the possible mechanisms underlying this action. To this end, CCI mice were intraperitoneally injected with EGb-761 (10, 20, 40, and 80 mg/kg), and thermal hyperalgesia, mechanical allodynia, cytokines, and mu-opioid receptor expression were measured. Results showed that EGb-761 attenuated thermal hyperalgesia and mechanical allodynia dose-dependently and the best delivery time window was from day 7 to day 14 after CCI. Additionally, EGb-761 treatment significantly decreased pro-inflammatory cytokines and enhanced mu opioid receptor (MOR) expression in the sciatic nerve. Moreover, the opioid antagonist naloxone prevented the effect of EGb-761 on thermal hyperalgesia and mechanical allodynia but did not influence the effect of EGb-761 on inflammatory cytokines. In conclusion, this study suggests that the potential of EGb-761 as a new analgesic for neuropathic pain treatment, and opioid system may be involved in the EGb-761-induced attenuation of thermal hyperalgesia and mechanical allodynia. Copyright © 2016 John Wiley & Sons, Ltd.

Therapeutic Value of Ginkgo biloba Extract EGb 761® in an Animal Model (Meriones unguiculatus) for Noise Trauma Induced Hearing Loss and Tinnitus.

Noise induced hearing loss (NIHL) is a common disease in modern societies and may lead to maladaptations within the auditory system that finally result in subjective tinnitus. Available therapies may only alleviate the symptoms rather than restore normal hearing. In a previous study we demonstrated that the prophylactic application of Ginkgo biloba extract EGb 761® significantly reduces NIHL and tinnitus development in our Mongolian gerbil (Meriones unguiculatus) animal model. Here, we tested whether the application of EGb 761® has beneficial effects after the formation of permanent NIHL and tinnitus. To this end we monitored the therapeutic effects of EGb 761® on noise trauma-induced changes in signal processing within the auditory system of our animal model by behavioral (acoustic startle response, ASR) and electrophysiological approaches (auditory brainstem responses, ABR). We found that–in contrast to vehicle–three weeks of daily oral EGb 761® treatment (100 mg/kg body weight) led to a restoration of hearing thresholds back to pre-trauma conditions. In addition, all 9 animals that displayed behavioral signs of subjective tinnitus showed improvement, with 7 of them showing complete relief of tinnitus symptoms during the time of EGb 761® treatment. After discontinuation of EGb 761® treatment, tinnitus related behavior reappeared in all but one of these animals while auditory thresholds remained restored. A detailed analysis of ABR waves revealed that EGb 761® treatment did not simply change auditory processing back to pre-trauma conditions, but led to subtle changes of ABR wave amplitude and latency at different levels of the auditory pathway, with an overall increase of response to low stimulus intensities and a decrease at high intensities. The functional relevance of these changes may be the observed improvement of hearing thresholds while at the same time suppression of responses to high stimulus intensities may point to a global inhibitory mechanism that counteracts tinnitus.

EGb761 improves cognitive function and regulates inflammatory responses in the APP/PS1 mouse

There is accumulating evidence that the Ginkgo biloba extract EGb761 may help to prevent Alzheimer's disease (AD). However, the underlying mechanism of its action remains to be elaborated. In this study, we examined the effects of EGb761 using the APP/PS1 transgenic mouse model of AD. Two-month-old APP/PS1 mice were supplemented with EGb761 daily for 6months. We found that this chronic treatment with EGb761 improved the cognitive function of these mice and also significantly alleviated amyloid plaque deposition. Although the level of insoluble amyloid beta (Aβ) was decreased, the soluble content of Aβ was not changed after administration of EGb761. We then determined the changes in central inflammation and observed that the activated microglia around amyloid plaque was increased in these treated mice. We also found that chronic EGb761 treatment downregulated pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS), and upregulated anti-inflammatory cytokines and Arginase-1 (Arg-1), suggesting that EGb761 regulated the phenotype of activated microglia in the APP/PS1 mouse brain. In support of this, pretreatment of the BV2 microglial cell line with EGb761 inhibited the inflammatory reaction to Aβ. Furthermore, the addition of conditioned media derived from BV2 cells that were co-treated with Aβ and EGb761, protected neurons against treatment of Aβ and inhibited apoptotic damage. Taken together, our results demonstrated that EGb761 provided a protective effect in APP/PS1 mouse. This protection was correlated with an inhibition of the pro-inflammatory effects of microglia and an induction of anti-inflammatory effects. These results strongly suggest that EGb761 provides a protective effect in APP/PS1 mouse via regulation of inflammation in the brain.

Effects of Ginkgo biloba extract EGb 761® on cognitive control functions, mental activity of the prefrontal cortex and stress reactivity in elderly adults with subjective memory impairment - a randomized double-blind placebo-controlled trial.

ObjectiveCognitive control as well as stress reactivity is assumed to depend on prefrontal dopamine and decline with age. Because Ginkgo biloba extract EGb761® increases prefrontal dopamine in animals, we assessed its effects on cognitive functions related to prefrontal dopamine.MethodsEffects of 240‐mg EGb761® daily on task‐set‐switching, response‐inhibition, delayed response, prospective‐memory, task‐related fMRI‐BOLD‐signals and the Trier Social Stress‐Test were explored in a randomized, placebo‐controlled, double‐blind pilot‐trial in 61 elderly volunteers with subjective memory impairment.† ResultsBaseline‐fMRI‐data showed BOLD‐responses in regions commonly activated by the specific tasks. Task‐switch‐costs decreased with EGb761® compared to placebo (ANOVA‐interaction: Group × Time × Switch‐Costs p = 0.018, multiple tests uncorrected), indicating improved cognitive flexibility. Go–NoGo‐task reaction‐times corrected for error‐rates indicated a trend for improved response inhibition. No treatment effects were found for the delayed response and prospective‐memory tasks and fMRI‐data. A non‐significant trend indicated a potentially accelerated endocrine stress‐recovery. EGb761® was safe and well tolerated.ConclusionWe observed indications for improved cognitive flexibility without changes in brain activation, suggesting increased processing efficiency with EGb761®. Together with a trend for improved response inhibition results are compatible with mild enhancement of prefrontal dopamine. These conclusions on potential beneficial effect of EGb761® on prefrontal dopaminergic functions should be confirmed by direct measurements. © 2016 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons, Ltd.

EGb761 attenuates depressive-like behaviours induced by long-term light deprivation in C57BL/6J mice through inhibition of NF-κB-IL-6 signalling pathway.

Our previous investigation found that Ginkgo extract EGb761 could attenuate the depressive-like behaviours induced by a single injection of lipopolysaccharide in mice. However, it has not been investigated whether EGb761 is effective on depressive-like behaviours induced by long-term light deprivation and whether its effects are associated with the inhibition of NF-κB-IL-6 signalling pathway. In this study, three groups (vehicle group, EGb761 low-dose group, and EGb761 high-dose group) of C57BL/6J male mice were exposed to constant darkness for four weeks. The control mice remained on a 12 : 12 light-dark cycle. Depressive-like behaviours were evaluated by tail suspension test (TST), forced swim test (FST), and sucrose preference test (SPT). Spontaneous locomotor activity was evaluated by open field test (OFT). Levels of IL-6, IL-6 mRNA, NF-κB p65, phospho-NF-κB p65, IκBα, and phospho-IκBα were measured using Elisa, western blotting, or PCR assays. NF-κB p65 DNA binding activity was evaluated using Chemi Transcription Factor Assay Kit. Results showed long-term light deprivation prolonged the immobile time in TST and FST, shortened the latency to immobility in FST, reduced spontaneous locomotor activity in OFT, decreased sucrose preference in SPT, and increased levels of IL-6, IL-6 mRNA, NF-κB p65, phospho-NF-κB p65, and phospho-IκBα in hippocampal tissue. EGb761 dose-dependently reversed the changes of the above parameters induced by long-term light deprivation, without affecting spontaneous locomotor activity. We conclude that EGb761 could attenuate the depressive-like behaviours and inhibit the NF-κB-IL-6 signalling pathway in a light-deprivation-induced mouse model of depression.

Neuropsychiatric symptoms in dementia and the effects of Ginkgo biloba extract EGb 761&amp;reg; treatment: additional results from a 24-week randomized, placebo-controlled trial

Neuropsychiatric symptoms in dementia and the effects of Ginkgo biloba extract EGb 761® treatment: additional results from a 24-week randomized, placebo-controlled trial Anatol Nacu,1 Robert Hoerr21Clinical Psychiatry Hospital, State University of Medicine and Pharmacy Nicolae Testemiţanu, Chişinău, Republic of Moldova; 2Clinical Research Department, Dr Willmar Schwabe GmbH and Co. KG, Karlsruhe, GermanyBackground: In randomized controlled trials, Ginkgo biloba extract EGb 761® has proven to be effective in the treatment of dementia.Trial registration: Clinical-Trials.ru 390378.Patients and methods: In pre-specified descriptive analyses of data from a recently published trial, we examined the effects of EGb 761® on specific neuropsychiatric symptoms. In a 24-week, double-blind, multi-center trial, 410 outpatients with mild to moderate dementia and clinically significant neuropsychiatric symptoms were enrolled and randomized to receive 240 mg/day EGb 761® or placebo. The Neuropsychiatric Inventory composite score and the SKT short cognitive performance test were prospectively defined as co-primary outcomes; caregiver distress scores and single item scores were prospectively defined as secondary outcomes.Results: Post-baseline efficacy data were available for 402 patients included in the full analysis set. Neuropsychiatric Inventory composite and caregiver distress scores improved significantly more under EGb 761® treatment than under placebo (P

Ginkgo biloba extract EGb 761-mediated inhibition of aromatase for the treatment of hormone-dependent breast cancer

Ginkgo biloba has been used in herbal medicines for thousands of years. Although a standard G. biloba extract, EGb 761 has been used to improve cognition in breast cancer patients, its effects on breast cancer are unknown. Therefore, we investigated the antitumorigenic effects of EGb 761 using an in vitro cell model and an in vivo xenograft model. EGb 761 significantly inhibited aromatase activity in aromatase over-expressing MCF-7 cells (MCF-7 AROM). In addition, EGb 761 exposure reduced cytochrome p450 aromatase (CYP19) mRNA and protein expression; CYP19 promoter I.3 and PII expression particularly decreased. These inhibitory effects on aromatase were accompanied by reduced 17β-estradiol levels in MCF-7 AROM cells. For elucidating antitumorigenic effects, MCF-7 AROM cells were implanted in BALB/c nude mice prior to oral EGb 761 treatment for 3 weeks. EGb 761 reduced the tumor size and significantly reduced tumor CYP19 mRNA expression. Taken together, our results indicated that EGb 761 inhibited aromatase and exerted antitumor effects on breast cancer cells both in vitro and in vivo. These findings suggest that EGb761 may be a useful aromatase inhibitor for the treatment for estrogen-sensitive breast cancer.

Principal component analysis of production batches of the Ginkgo biloba extract EGb 761® over a period of 10 years on the basis of routine quality control parameters

Principal component analysis of production batches of the Ginkgo biloba extract EGb 761® over a period of 10 years on the basis of routine quality control parameters

Effects of Ginkgo biloba Extract EGb 761, Donepezil and their Combination on Central Cholinergic Function in Aged Rats

Ginkgo extract EGb 761 and cholinesterase inhibitors have been shown to be effective in the treatment of dementia patients. In addition to neuroprotective effects, Ginkgo extract EGb 761 has been reported to elevate brain levels of certain neurotransmitters such as dopamine, noradrenaline, and acetylcholine. In the present study, we investigated the impact of EGb 761, donepezil and the combination of both drugs on the central cholinergic system in aged rats. 24 month old rats received EGb 761 (100 mg/kg/day), donepezil (1.5 mg/kg/day), the combination of both drugs or vehicle control by oral gavage for 14 days. We used microdialysis in rat hippocampus to monitor extracellular concentrations of acetylcholine (ACh), choline, glucose and lactate. Brain homogenates were prepared to measure activities of acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and high affinity choline uptake (HACU). While EGb 761 alone had no effect, donepezil and the combination of donepezil and EGb 761 increased basal ACh levels by 2- to 3-fold. Concomitantly, significant reductions of AChE and HACU were measured in both groups. No differences were seen between donepezil and the combination in these parameters. Treatment with EGb 761 decreased extracellular choline release and showed a tendency to moderately elevate ChAT activity. We found that donepezil and EGb 761 do not display a pharmacological interaction when given together. Adding EGb 761 did not modify the effects of donepezil on the hippocampal cholinergic system. Reduced choline levels indicate neuroprotective properties of EGb 761. Therefore, the combination of EGb 761 and donepezil may be beneficial in the treatment of Alzheimer's disease (AD). This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

A retrospective classification of diagnoses in terms of DSM-5 for patients included in randomized controlled trials of Ginkgo biloba extract EGb 761(®).

When the early trials of Ginkgo biloba extract EGb 761® were conducted, different terms were used to denote ageing-associated neurocognitive disorders. With the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), a taxonomy covering dementia and pre-dementia stages of such disorders became available. DSM-5 diagnostic criteria for neurocognitive disorders (NCDs) were applied to patients with any type of ageing-associated cognitive impairment, including dementia, enrolled in randomized controlled clinical trials of EGb 761®, taking into account the reported inclusion and exclusion criteria and patient characteristics at baseline. For 23 of 31 trials (74 %), the inclusion diagnoses could be classified as NCD in accordance with DSM-5. Thirteen trials enrolled patients with major NCD, four trials enrolled patients with mild NCD and six trials enrolled patients with NCD, who could not be classified unambiguously as having mild or major NCD. Although various terms were formerly used for neurocognitive disorders, the patients enrolled in the majority of clinical trials with EGb 761® could be classified retrospectively using modern DSM-5 diagnostic criteria.Electronic supplementary materialThe online version of this article (doi:10.1007/s00406-015-0632-y) contains supplementary material, which is available to authorized users.

Efficacy of Ginkgo biloba extract EGb 761® in dementia with behavioural and psychological symptoms: A systematic review

Objectives. To review current evidence of efficacy of Ginkgo biloba extract EGb 761® in dementia with behavioural and psychological symptoms (BPSD). Methods. Randomized, placebo-controlled trials assessing the effects of EGb 761® in dementia patients with BPSD were included if the diagnosis was made in accordance with internationally accepted criteria, the treatment period was at least 22 weeks, outcome measures covered BPSD and at least two of the following domains of assessment, i.e. cognition, activities of daily living and clinical global assessment, and methodological quality was adequate. An analysis of covariance (ANCOVA) model was used to calculate the pooled effect estimates and to compare effects of EGb 761® and placebo; furthermore, combined risk differences of response rates were calculated. Results. Four published trials were identified, involving altogether 1,628 outpatients with mild to moderate dementia. Least-square mean differences for change from baseline in cognition, BPSD (including caregiver distress rating), activities of daily living, clinical global impression, and quality of life favoured EGb 761® (P < 0.001 for all comparisons). Conclusions. The pooled analyses provide evidence of efficacy of EGb 761® at a daily dose of 240 mg in the treatment of out-patients suffering from Alzheimer's, vascular or mixed dementia with BPSD.

Long-term treatment with Ginkgo biloba extract EGb 761 improves symptoms and pathology in a transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by extracellular deposits of amyloid β peptide (Aβ) and microglia-dominated neuroinflammation. The therapeutic options for AD are currently limited. In this study, we investigated the antiinflammatory effects and the underlying molecular mechanisms of Ginkgo biloba extract EGb 761 when administered to TgCRND8 AD mice, which overexpress human Alzheimer's amyloid precursor protein (APP) specifically in neurons. We gave APP-transgenic mice EGb 761 as a dietary supplement for 2 or 5months. Plasma concentrations of EGb 761 components in mice were in the same range as such concentrations in humans taking EGb 761 at the recommended dose (240mg daily). Treatment with EGb 761 for 5months significantly improved the cognitive function of the mice as measured by the Barnes Maze test. It also attenuated the loss of synaptic structure proteins, such as PSD-95, Munc18-1, and SNAP25. Treatment with EGb 761 for 5months inhibited microglial inflammatory activation in the brain. The effects of treatment with EGb 761 for 2months were weak and not statistically significant. Moreover, EGb 761 activated autophagy in microglia. Treatment with EGb 761 decreased Aβ-induced microglial secretion of TNF-α and IL-1β and activation of caspase-1, both of which were abolished by the inhibition of autophagy. Treatment with EGb 761 also reduced the concentrations of NLRP3 protein that colocalized with LC3-positive autophagosomes or autolysosomes in microglia. Additionally, long-term treatment with EGb 761 may reduce cerebral Aβ pathology by inhibiting β-secretase activity and Aβ aggregation. Therefore, long-term treatment with G. biloba extract EGb 761, a clinically available and well-tolerated herbal medication, ameliorates AD pathology by antiinflammatory and Aβ-directed mechanisms.