Use Of EGb Research Articles

Ginkgo biloba in the management of the COVID-19 severity.

The severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection is linked with inflammatory disorders and the development of oxidative stress in extreme cases. Therefore, anti‐inflammatory and antioxidant drugs may alleviate these complications. Ginkgo biloba L. folium extract (EGb) is a herbal medicine containing various active constituents. This review aims to provide a critical discussion on the potential role of EGb in the management of coronavirus disease 2019 (COVID‐19). The antiviral effect of EGb is mediated by different mechanisms, including blocking SARS‐CoV‐2 3‐chymotrypsin‐like protease that provides trans‐variant effectiveness. Moreover, EGb impedes the development of pulmonary inflammatory disorders through the diminution of neutrophil elastase activity, the release of proinflammatory cytokines, platelet aggregation, and thrombosis. Thus, EGb can attenuate the acute lung injury and acute respiratory distress syndrome in COVID‐19. In conclusion, EGb offers the potential of being used as adjuvant antiviral and symptomatic therapy. Nanosystems enabling targeted delivery, personalization, and booster of effects provide the opportunity for the use of EGb in modern phytotherapy.

Benefits of Treatment with Ginkgo Biloba Extract EGb 761 Alone or Combined with Acetylcholinesterase Inhibitors in Vascular Dementia.

BackgroundVascular dementia (VaD) is the most severe manifestation of cognitive impairment caused by cerebrovascular disease. There are currently no specific drug treatments approved for VaD, with cholinesterase inhibitors (AChEI) being frequently used in VaD. However, the benefits they provide are small and short-lived. The standardized extract of Ginkgo biloba EGb 761 has demonstrated protective properties against neuronal and vascular damage and has been used as a pharmacological treatment for VaD.ObjectivesThis study aims to study the efficacy of EGb 761 alone and in combination with AChEI in a real-life setting. We carried out a retrospective analysis of data over a 12-month period in a sample of people suffering from VaD.MethodsWe retrospectively identified 77 patients with a diagnosis of VaD who had received treatment with any of the following drugs: Ginkgo biloba extract EGb 761 (240 mg daily), donepezil (10 mg daily), galantamine (16 or 24 mg daily), or rivastigmine patch (9.5 or 13.3 mg daily). Subjects were divided into three groups according to the treatment they had received: EGb 761 alone (n = 25), AChEI alone (n = 26), and EGb 761+AChEI (n = 26). Cognitive functioning was assessed by Mini-Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), Symbol Digit Modalities Test (SDMT), Boston Naming Test (BNT), Trail Making Test forms A (TMTA) and B (TMTB), Letter (LFT) and Category Fluency Test (CFT); neuropsychiatric symptoms were assessed by the Neuropsychiatric Inventory (NPI); functional capacity was assessed by Interview for Deterioration in Daily Living (IDDD).ResultsA statistically significant improvement was observed in the EGb 761 group versus the AChEI group at 12 months’ follow-up in CFT (+1.74, p < 0.001), TMTA (−17.91, p = 0.031) and NPI (−5.89, p < 0.001). With regard to the combined treatment, a statistically significant improvement was shown in the EGb 761 plus AChEI treatment group versus AChEI group at the 12-month follow-up in MMSE (+2.0, p = 0.001), RAVLT (+2.23, p = 0.007), CFT (+1.15, p = 0.013), TMTA (−19.92, p = 0.012), TMTB (−46.50, p < 0.001) and NPI (−6.77, p < 0.001). In the same line, a statistically significant improvement was observed in the EGb 761 plus AChEI treatment group versus EGb 761 at 12-month follow-up regarding MMSE (+2.11, p = 0.001), RAVLT (+2.35, p = 0.004) and TMTB (−25.25, p = 0.015).ConclusionAfter 12 months of treatment EGb 761 alone or combined with AChEI showed cognitive and behavioral benefits in patients suffering from VaD. This study thus provides additional real-world evidence for the combined use of EGb 761 and anti-dementia drugs in VaD patients.

Combined treatment with Ginkgo biloba extract EGb 761 plus acetylcholinesterase inhibitors improved cognitive function and neuropsychiatric symptoms in patients with mild cognitive impairment.

IntroductionMild cognitive impairment (MCI) is a neurocognitive state between normal aging and dementia. There is currently no approved treatment for MCI, with acetylcholinesterase inhibitors (AChEI) being the commonly prescribed drugs. The Ginkgo biloba extract EGb 761 is an herbal remedy used for cognitive disorders, including dementia. This study aims to explore the potential synergistic effect of combination therapy with EGb 761 plus AChEI in patients with amnestic MCI in a real‐life setting.MethodsWe retrospectively identified 133 patients with amnestic MCI who were attending a memory clinic. Patients had received treatment with any of the following drugs: G. biloba extract EGb 761, donepezil, galantamine, or rivastigmine at their standard doses. Subjects were divided into three treatment groups: EGb 761, AChEI, and EGb 761+AChEI. Patients were assessed by Mini‐Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), Symbol Digit Modalities Test, Boston Naming Test, Trail Making Test (TMT Parts A and B), Letter and Category Fluency Test (LFT, CFT), Neuropsychiatric Inventory (NPI), and Interview for Deterioration in Daily Living. Mixed‐effects model analysis was carried out to evaluate changes in cognitive, functional, and behavioral outcomes over a 12‐month follow‐up.ResultsAfter 12 months, EGb 761+AChEI showed significant improvement in MMSE, RAVLT, CFT, TMT A‐B, and NPI compared to AChEI and in MMSE and RAVLT compared to EGb 761. At 12 months, EGb 761 was superior to AChEI on the CFT, TMT A‐B, and NPI.DiscussionOur findings suggest that combined therapy with EGb 761 plus AChEI may provide added cognitive and functional benefits in patients with MCI and provides additional real‐world evidence for the combined use of EGb 761 and anti‐dementia drugs in patients with MCI. This study can serve as a model for the design of clinical trials that help to support the combined use of EGb 761 and anti‐dementia drugs in patients with MCI.

The effect of Ginkgo biloba EGb 761 on intestinal anastomotic healing in rats with ischemia-reperfusion induced in the lower extremities

Background/Aim: Remote ischemia-reperfusion (I-R) injury for anastomotic healing is a newly identified risk factor and there is a wide array of studies being conducted. This study aimed to reveal the negative effects of lower I-R on the colonic anastomotic healing process and examine the effects of Ginkgo biloba EGb 761 treatment, a platelet activating factor (PAF) antagonist, on anastomotic healing through the inhibition of pathological mechanisms of mediators causing these negative effects. Methods: Thirty-six Wistar-Albino rats were divided into sham, I-R and I-R+EGb 761 groups, each consisting of 12 rats. In the subjects in the sham group, an end-to-end anastomosis was performed by transecting the descending colon following midline laparotomy. In the I-R group, unilateral lower extremity ischemia was created by occluding the femoral artery and collaterals using a tourniquet from the most proximal segment of the left extremity. Then, the descending colon was transected, anastomosis was performed, and reperfusion was created by a tourniquet application at the 30th minute of ischemia. Different from the I-R (control) group, the subjects in the I-R+EGb 761 group were given two equal doses of 64 mg/kg/d Ginkgo biloba EGb 761 by the orogastric route until 10 days after surgery. After all subjects were sacrificed on the 10th day of surgery, the descending colon segment containing the anastomosis area was resected and samples were taken for bursting pressure and hydroxyproline measurements. Results: In the I-R group, anastomotic bursting pressure and perianastomotic hydroxyproline values were significantly lower compared to the sham group and the I-R+EGb 761 group. However, there was no statistically significant difference in these parameters between the sham and the I-R+EGb 761 groups. Conclusion: Colonic anastomotic bursting pressure and peri-anastomotic hydroxyproline values in the sham group were significantly decreased by lower extremity I-R, and this change was prevented with the use of EGb 761.

Ginkgo biloba extract improves brain uptake of ginsenosides by increasing blood-brain barrier permeability via activating A1 adenosine receptor signaling pathway.

Ginkgo biloba leaves and Panax ginseng are Chinese medicine commonly used in combination for cerebral disease. To investigate the effect of standard extract of Ginkgo biloba leaves (EGb) on facilitating brain uptake of ginsenoside and its underlying mechanisms. The increasing uptake of ginsenosides in the brain of rats by EGb were detected by LC-MS/MS analysis. Evans blue and FITC-dextran leakage were determined to evaluate blood-brain barrier (BBB) permeability in vivo. Transendothelial electrical resistance (TEER) and Na-F penetration rate were measured with a co-culture of the human cerebral microvascular endothelial cell line (hCMEC/D3) and human normal glial cell line (HEB) in vitro BBB model. WB were used to analyzed the expression of BBB tight junctions (TJs) related protein (ZO-1, Occludin, Claudin-3, p-ERM, and p-MLC), ultrastructure of TJs was determined by transmission electron microscope. LC-MS/MS analysis demonstrated that EGb could improve brain uptake of ginsenoside Rg1, Re, Rd and Rb1. In vivo study showed that, BBB permeability was significantly increased after EGb administration, evidenced by the markedly increased penetration of FITC-dextran and Evans Blue into the mice brain parenchyma. In the in vitro BBB model, reduced TEER and increased Na-F penetration rate was observed in EGb group, which was associated with alteration of TJs ultrastructure. Furthermore, the expression of p-ERM and p-MLC in hCMEC/D3 as well as mice brain microvessels were significantly upregulated, but no significant change on the expression of TJs proteins (ZO-1, Occludin and Claudin-3). Moreover, the effect of EGb on in vitro BBB permeability and ERM, MLC phosphorylation was counteracted by DPCPX, an A1 adenosine receptor (A1R) antagonist. EGb might induce ERM/MLC phosphorylation and increase the cell-cell junction gaps to cause a reversible increase of the BBB permeability via A1R signaling pathway. Our results may contribute to better use of EGb in the treatment of brain diseases.

Treatment of dementia and mild cognitive impairment with or without cerebrovascular disease: Expert consensus on the use of Ginkgo biloba extract, EGb 761®.

BackgroundThe Ginkgo biloba special extract, EGb 761® has been widely used in the treatment of neuropsychiatric disorders, including Alzheimer’s disease (AD).MethodsTo guide clinical practice in the Asian region, the Asian Clinical Expert Group on Neurocognitive Disorders compiled evidence‐based consensus recommendations regarding the use of EGb 761® in neurocognitive disorders with/without cerebrovascular disease.ResultsKey randomized trials and robust meta‐analyses have demonstrated significant improvement in cognitive function, neuropsychiatric symptoms, activities of daily living (ADL) and quality of life with EGb 761®versus placebo in patients with mild‐to‐moderate dementia. In those with mild cognitive impairment (MCI), EGb 761® has also demonstrated significant symptomatic improvement versus placebo. World Federation of Societies of Biological Psychiatry guidelines list EGb 761® with the same strength of evidence as acetylcholinesterase inhibitors and N‐methyl‐D‐aspartate (NMDA) antagonists e.g. memantine (Grade 3 recommendation; Level B evidence). Only EGb 761® had Level B evidence in improving cognition, behaviour, and ADL in both AD and vascular dementia patients. Safety analyses show EGb 761® to have a positive risk‐benefit profile. While concerns have been raised regarding a possible increased bleeding risk, several randomized trials and two meta‐analyses have not supported this association.ConclusionsThe Expert Group foresee an important role for EGb 761®, used alone or as an add‐on therapy, in the treatment of MCI and dementias, particularly when patients do not derive benefit from acetylcholinesterase inhibitors or NMDA antagonists. EGb 761® should be used in alignment with local clinical practice guidelines.

Cognitive complaints and cognitive impairment in patients with chronic daily headache

Comorbidities in chronic daily headache (CDH) include emotional disorders (depression, anxiety), insomnia, and musculoskeletal pain at other sites. In CDH, the most common type is a subjective (according to patients themselves) and/or objective (based on the results of cognitive tests) reduction in cognitive functions, which can be caused by emotional disorders, insomnia and/or brain diseases, and a negative effect of chronic pain on cognitive functions. Objective : to analyze cognitive complaints and their changes in patients with CDH. Patients and methods. Subjective complaints and cognitive functions were evaluated in 90 patients (76 women and 14 men) aged 23 to 78 years (mean age, 46.7±12.0 years) with primary forms of CDH according to the Montreal Cognitive Assessment (MCA) for 12 months. The majority (68.9%) of patients with CHD complained of diminished memory; however, its mild disorders (25– 26 MCA scores) were found in only a small proportion (23.3%). All patients with subjective diminished memory were ascertained to have neurotic disorders (depression, anxiety disorder) and/or insomnia or a concurrence of mental disorder and insomnia. Results and discussion. All the patients received treatment options, including optimal pharmacotherapy for headache and concomitant diseases, an educational conversation, cognitive- behavioral therapy, and therapeutic exercises. In cognitive impairment (CI), cognitive training was used and Ginkgo biloba extract (EGb 761®) prescribed; in sleep disorders, sleep hygiene rules were explained. Therapy declined the mean number of headache days a month from 29.1±2.03 (at baseline) to 9.3±9.35 (at 12-month follow-up) (p=0.002); while the subjective complaints regressed in the majority of patients; mild MCA changes persisted only in 6.7% of the patients. Management tactics for CHD patients having mild CI and cardiovascular risk factors and the use of EGb 761® to improve cognitive functions were considered. Conclusion. It has been ascertained that in many cases, CI is associated with emotional disorders and insomnia, as well as with pathophysiological mechanisms of chronic pain itself; CI in some patients has a vascular origin. The use of combined treatment programs can promptly and effectively reduce the frequency of headache and improve cognitive functions. EGb 761® (Tanakan®) has a beneficial effect on subjective CI and mild CI.

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.

Ginkgo biloba Extract 761: A Review of Basic Studies and Potential Clinical Use in Psychiatric Disorders.

Ginkgo biloba extract 761 (EGb 761) is a well-defined extract obtained from Ginkgo biloba leaves according to a standardized method. It has been used extensively for the treatment of diseases related to the central nervous system including neurosensory disturbances, cerebrovascular insufficiency, peripheral vascular disturbances, and degenerative dementia. The potential use of EGb 761 has also been suggested for the treatment of psychiatric disorders such as anxiety and depression, which is discussed in the current review. These disorders constitute a global epidemic with serious economic and social consequences. Current available treatments with synthetic drugs may have some disadvantages and undesired side effects. There are diverse natural extracts that have been used for the treatment of psychiatric disorders due to their therapeutic action and low rate of side effects, such as EGb 761. EGb 761 has the ability to produce neuroprotection due to its chemical composition and the synergy of its components. We describe several neuroprotective mechanisms of action of EGb 761 such as antioxidant effects, modulation of neurotransmission, neuroendocrine regulation, and upregulation of neurotrophic factors, which underlie its potential therapeutic effect on psychiatric disorders. Furthermore, we discuss the therapeutic effects of EGb 761 both in animal models of psychiatric disorders and in clinical studies that include these pathologies. We focus on depression, anxiety, and schizophrenia, as well as the therapeutic action of EGb 761 on dementia in comorbidity with psychiatric disorders. In the current review, we propose thef potential use of EGb 761, alone or combined with current medication treatment, for psychiatric disorders.

Sleep and cognitive dysfunctions. Therapeutic approach

This review focuses on the possible mechanisms of sleep disorders in patients with cognitive impairment (CI) of different severity. The interrelation between CI, emotional disorders and insomnia, as well as the dependence of CI severity on the degree of sleep disorders, are discussed. The issues related to treatment of sleep disorders in patients with CI, the advantages and disadvantages of modern somnogenic medications are studied. Recommendations on management of patients with a combination of sleep disorders and CI are provided. Data on the use of Egb 761 to treat CI no dementia and melatonin-based drugs to treat sleep disorders in patients with CI are presented.

The Ginkgo biloba Extract EGb 761 Modulates Proteasome Activity and Polyglutamine Protein Aggregation.

The standardized Ginkgo biloba extract EGb 761 has well-described antioxidative activities and effects on different cytoprotective signaling pathways. Consequently, a potential use of EGb 761 in neurodegenerative diseases has been proposed. A common characteristic feature of a variety of such disorders is the pathologic formation of protein aggregates, suggesting a crucial role for protein homeostasis. In this study, we show that EGb 761 increased the catalytic activity of the proteasome and enhanced protein degradation in cultured cells. We further investigated this effect in a cellular model of Huntington's disease (HD) by employing cells expressing pathologic variants of a polyglutamine protein (polyQ protein). We show that EGb 761 affected these cells by (i) increasing proteasome activity and (ii) inducing a more efficient degradation of aggregation-prone proteins. These results demonstrate a novel activity of EGb 761 on protein aggregates by enhancing proteasomal protein degradation, suggesting a therapeutic use in neurodegenerative disorders with a disturbed protein homeostasis.

&lt;emph type="ital"&gt;Ginkgo biloba&lt;/emph&gt; Extract and Preventing Alzheimer Disease

GINKGO BILOBA LEAVES AND EXTRACTS ARE WIDELY used over-the-counter preparations marketed in the United States as food supplements or nutraceuticals, and as such, explicit health claims are not listed in their labeling. In other countries and in the popular press, G biloba is advocated for the treatment of a broad and seemingly ever-increasing range of medical conditions. The extract used in the Ginkgo Evaluation of Memory (GEM) study reported in this issue of JAMA by DeKosky and colleagues and in many other clinical and preclinical studies is Ginkgo extract EGb 761 (Schwabe Pharmaceuticals, Karlsruhe, Germany). The extract is standardized to contain 2 major constituents: 22% to 27% flavonoids and 5% to 7% terpene lactones (ginkgolides and bilobalide). Unique to G biloba trees, the terpene lactones consist of several ginkgolides and bilobalide. The flavonoids and ginkgolides have protean biological activity in preclinical research. The flavonoids are active as antioxidants and appear neuroprotective. Ginkgolide B is a potent antagonist of the platelet activating factor receptor. Ginkgolides A and J variously inhibit hippocampal neuron dysfunction and neuronal cell death caused by amyloid beta protein-42 (A 42). Ginkgolides A and J decrease A 42-induced pathological behaviors, enhance neurogenesis in animal models of Alzheimer disease, and inhibit A aggregation, providing considerable rationale for G biloba extracts as potential treatments for Alzheimer disease. Some of the components of G biloba extract are as active in preclinical models of neurodegeneration and Alzheimer disease as new drug candidates being developed by pharmaceutical companies and some research universities. The GEM trial involved 3069 participants who were not cognitively impaired or had mild cognitive impairment and were randomized to receive EGb 761 (120 mg twice daily) or identically appearing and tasting placebo and were followed up for the onset of dementia. The main results were that use of EGb 761 over the median follow-up period of 6.1 years did not delay the onset of dementia due to any cause including Alzheimer disease specifically. The hazard ratios for all-cause dementia (1.12 [95% confidence interval {CI}, 0.94-1.33]) and for Alzheimer disease (1.16 [95% CI, 0.971.39]) numerically favored placebo and the lower limits of the 95% CIs were not compatible with any potentially meaningful level of dementia risk reduction. The investigators also found no favorable effects of EGb 761 for reducing cardiovascular serious adverse events or total mortality, 2 of 4 secondary outcomes. The relationship of ginkgo extract use and cardiovascular disease is potentially more complex, however, in that the 25% of participants with cardiovascular disease prior to randomized treatment showed increased risk for developing dementia with EGb 761 treatment (hazard ratio, 1.56 [95% CI, 1.14-2.15], P=.006). Moreover, the infrequently occurring serious adverse events of hemorrhagic stroke favored placebo—8 events with placebo vs 16 events with EGb 761—although the difference was not statistically significant. Furthermore, this difference appeared inconsistent with the similarly infrequent incidence of vascular dementia (by definition dementia subsequent to stroke) that favored EGb 761, 17 placebo cases vs 7 with EGb 761 (hazard ratio,0.41 [95% CI, 0.17-0.98], P=.05). These 2 latter observations may be the result of chance, often seen in post hoc analyses of very few events. The former observation, however, suggests that at least in patients aged 75 years or older with cardiovascular disease, G biloba may have risks and the decision to use this agent should be carefully considered. Although DeKosky and colleagues do not report results of their 2 other secondary outcomes—overall cognitive decline and functional disability—it is unlikely that a trial with no difference in dementia outcomes would yield significant benefits in the cognitive and functional impairments that define the dementia outcomes. Nevertheless, the effects of EGb 761 on actual cognitive test scores and daily function ratings are important because individuals without cognitive impairment who use G biloba may expect it to noticeably improve their intellectual function over the short term but not necessarily to prevent Alzheimer disease or other dementia over the long term.

Ginkgo biloba extract EGb 761 has anti-inflammatory properties and ameliorates colitis in mice by driving effector T cell apoptosis

Ulcerative colitis is a dynamic, chronic inflammatory condition of the colon associated with an increased colon cancer risk. Ginkgo biloba is a putative antioxidant and has been used for thousands of years to treat a variety of ailments. The aim of this study was to test whether the standardized G.biloba extract, EGb 761, is an antioxidant that can be used to prevent and treat colitis in mice. Here, we show that EGb 761 suppresses the activation of macrophages and can be used to both prevent and treat mouse colitis. Markers of inflammation (iNOS, Cox-2 and tumor necrosis factor-alpha) and inflammatory stress (p53 and p53-phospho-serine 15) are also downregulated by EGb 761. Furthermore, we show that EGb 761 reduces the numbers of CD4+/CD25-/Foxp3- effector T cells in the colon. Interestingly, EGb 761 drives CD4+ effector T cell apoptosis in vitro and in vivo, providing a mechanistic explanation to the reduction in numbers of this cell type in the colon. This current study is in agreement with previous studies supporting a use of EGb 761 as a complementary and alternative strategy to abate colitis and associated colon cancer.

Protection against Human Immunodeficiency Virus Type 1 Tat Neurotoxicity by Ginkgo biloba Extract EGb 761 Involving Glial Fibrillary Acidic Protein

Human immunodeficiency virus (HIV)-1 Tat protein is an important pathogenic factor in HIV-associated neuropathogenesis. Despite recent progress, the molecular mechanisms underlying Tat neurotoxicity are still not completely understood. However, few therapeutics have been developed to specifically target HIV infection in the brain. Recent development of an inducible brain-specific Tat transgenic mouse model has made it possible to define the mechanisms of Tat neurotoxicity and evaluate anti-neuroAIDS therapeutic candidates in the context of a whole organism. Herein, we demonstrate that administration of EGb 761, a standardized formulation of Ginkgo biloba extract, markedly protected Tat transgenic mice from Tat-induced developmental retardation, inflammation, death, astrocytosis, and neuron loss. EGb 761 directly down-regulated glial fibrillary acidic protein (GFAP) expression at both protein and mRNA levels. This down-regulation was, at least in part, attributable to direct effects of EGb 761 on the interactions of the AP1 and NF-kappaB transcription factors with the GFAP promoter. Most strikingly, Tat-induced neuropathological phenotypes including macrophage/microglia activation, central nervous system infiltration of T lymphocytes, and oxidative stress were significantly alleviated in GFAP-null/Tat transgenic mice. Taken together, these results provide the first evidence to support the potential for clinical use of EGb 761 to treat HIV-associated neurological diseases. Moreover, these findings suggest for the first time that GFAP activation is directly involved in Tat neurotoxicity, supporting the notion that astrocyte activation or astrocytosis may directly contribute to HIV-associated neurological disorders.

Ginkgo biloba extract EGb 761 increases endothelial nitric oxide production in vitro and in vivo.

Beneficial effects of Ginkgo biloba on peripheral arterial occlusive disease have been repeatedly shown in clinical trials, especially after use of EGb 761, a standardized special extract. Since the underlying mechanisms are widely unknown, we aimed to elucidate the molecular basis on which EGb 761 protects against endothelial dysfunction in vitro and in vivo. Application of therapeutically feasible doses of EGb 761 for 48 h caused endothelial nitric oxide (NO) production by increasing endothelial nitric oxide synthase (eNOS) promoter activity and eNOS expression in vitro. Phosphorylation of eNOS at a site typical for Akt (Ser 1177) was acutely enhanced by treatment with EGb 761, as was Akt phosphorylation at Ser 478. Furthermore, the extract caused acute relaxation of isolated aortic rings and NO-dependent reduction of blood pressure in vivo in rats. These influences on eNOS represent a putative molecular basis for the protective cardiovascular properties of EGb 761.

Experimental study on inhibition of neuronal toxical effect of levodopa by ginkgo biloba extract on Parkinson disease in rats.

In order to observe neuronal toxical effect of Levodopa and investigate if using Levodopa together with Ginkgo Bilobar Extract (EGb) would be an workable method to treat Parkinson disease, rat models of Parkinson disease (PD) were made by injecting 6-OHDA stereotaxically to right side of the mesencephic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Rotational behavioral observation, TUNEL, immunocytochemistry, Nissl's body staining were performed to measure the difference between group treated by Levodopa (50 mg/kg every day for 3 days, 5 days, 7 days, L-dopa group) and group treated by Levodopa combined with EGb (100 mg/kg every day, E-D group). The results showed that in the L-dopa group, the numbers of apoptosis of substantial nigra, rings of rotational behavior were more than those in the E-D group (P < 0.05). The numbers of Nissl's cells in L-dopa group were fewer than in E-D group (P < 0.05). The results suggested that Levodopa had neur toxic effect and EGb may decrease the toxicity of levodopa. The combined use of EGb with Levodopa may be a workable method to treat PD and may be better than using Levodopa alone.

Effects of L-Carnitine and Ginkgo Biloba Extract (EG b 761) in Experimental Bleomycin-Induced Lung Fibrosis

The effects of Ginkgo biloba extract (EGb 761) and l -carnitine on bleomycin (BLM)-induced lung fibrosis were studied in rats. BLM (cumulative dose of 180 mgkg−1) was given intraperitoneally (i.p.) three times weekly for 4 consecutive weeks. Treatment with BLM enhanced the responsiveness of isolated pulmonary arterial rings to serotonin (5-HT), significantly increased the normal serum level of tumour necrosis factor (TNF- α) by ∼105% and markedly elevated the level of lipid peroxide (LPO) and collagen content in the lung homogenates by 34 and 83%, respectively. EGb 761 (100mgkg−1 ), given in drinking water for the whole study period, totally abolished the BLM-induced alterations in the measured biochemical and pharmacological parameters. Meanwhile, l -carnitine (500 mg kg−1 ), administered in drinking water, significantly decreased the BLM-induced elevations of serum TNF-α , LPO level in lung tissues and the enhanced responsiveness of pulmonary arterial rings to 5-HT. However,l -carnitine did not reduce the increase in the collagen content produced by BLM. The results of the present study indicate the beneficial effects of EGb 761 and l -carnitine against lung toxicity induced by BLM treatment. Furthermore, the present data shows the advantageous use of EGb 761 as a protective agent in BLM-induced lung fibrosis under the experimental circumstances.

Effects of repeated treatments with an extract of Ginkgo biloba (EGb 761) on cerebral glucose utilization in the rat: an autoradiographic study

1. l. The autoradiographic method based on 2-deoxy- d[1- 14C]glucose ([ 14C]DG) was used to determine glucose utilization in 49 discrete structures of rat brain under control conditions and after the animals had received repeated treatment with an extract of Ginkgo biloba (EGb 761). 2. 2. Oral administration of EGb 761 (50 or 150 mg/kg/day) to adult male rats for 15 days did not modify body weight, mean arterial blood pressure, the concentrations of glucose or hemoglobin in blood, blood gases or arterial pH. 3. 3. EGb 761 treatments produced only slight-to-moderate changes in glucose utilization in the various brain structures; i.e. decreases to an extent not exceeding 18.4% at the 50 mg/kg dose or 11.7% at the 150 mg/kg dose. 4. 4. Glucose utilization was significantly decreased only in the frontoparietal somatosensory cortex, nucleus accumbens, cerebellar cortex and pons and only with the 50 mg/kg dose of EGb 761. 5. 5. Although the four brain structures affected by EGb 761 treatment do not, in themselves, constitute a specific functional system of the CNS, these effects appear useful in explaining mechanisms underlying the clinical use of EGb 761 in treating problems associated with deficient somatosensory processing (e.g. impairment of “vigilance”) and vestibular mechanisms (e.g. vertiginous syndromes).

Effects of a Ginkgo biloba extract on two models of cortical hemiplegia in rats

To screen drugs potentially useful in the pharmacological treatment of subjects with brain lesions, we studied the effects of chronic (7 and 30 days) treatments with a Ginkgo biloba extract (EGb761-IPSEN; EGb) in two animal models of cortical hemiplegia: one induced by motor cortex aspiration and another using a reversible inactivation of the motor cortex through chronic, localized infusion of y-aminobutyric acid (GABA), via osmotic minipumps. The elevated beam test was used in water-deprived animals trained to drink saccharin-sweetened solutions (with or without EGb) and to perform to criteria before the surgical procedures. From the day after surgery, the rats were administered 100 mg/kg of EGb daily for 7 or 30 days. In all groups with motor impairment in which the extract was administered, a faster and more complete recovery was observed, which was significantly different from that of rats which received only saccharin solutions. The salutary effect of EGb was more marked in ablation-induced hemiplegia than in the GABA-treated group. In the former injury model, EGb-treated animals had smaller ventricular diameters than non-treated rats. No differences concerning sensory deficits were detected among groups. EGb was also acutely administered during the epileptic syndrome that follows interruption of chronic GABA infusions (the GABA-withdrawal syndrome). No anticonvulsant effects of EGb were observed. These results suggest a potential use of EGb in brain-injured patients as this product shows little toxicity in animals and man after chronic administration. The active principles among terpenes (ginkgolides, bilobalides and flavonolheterosides present in the EGb) and the mechanisms for this beneficial effects remain to be elucidated.