Ginkgo Extract EGb Research Articles

Ginkgo Extract EGb761 Confers Neuroprotection by Reduction of Glutamate Release in Ischemic Brain

Ginkgo extract EGb761 has shown anti-edema and anti-ischemic effects in various experimental models. In the present study, we demonstrate neuroprotective effects of EGb761 in experimental stroke while monitoring brain metabolism by microdialysis. We have used oxygen-glucose deprivation in brain slices in vitro and middle cerebral artery occlusion (MCAO) in vivo to induce ischemia in mouse brain. We used microdialysis in mouse striatum to monitor extracellular concentrations of glucose and glutamate. In vitro, EGb761 reduced ischemia-induced cell swelling in hippocampal slices by 60%. In vivo, administration of EGb761 (300 mg/kg) reduced cell degeneration and edema formation after MCAO by 35-50%. Immediately following MCAO, striatal glucose levels dropped to 25% of controls, and this reduction was not significantly affected by EGb761. Striatal glutamate levels, in contrast, increased 15-fold after MCAO; after pretreatment with EGb761, glutamate levels only increased by 4-5fold. We show that pretreatment with EGb761 strongly reduces cellular edema formation and neurodegeneration under conditions of ischemia. The mechanism of action seems to be related to a reduction of excitotoxicity, because ischemia-induced release of glutamate was strongly suppressed. Ginkgo extracts such as EGb761 may be valuable to prevent ischemia-induced damage in stroke-prone patients.

Ginkgo biloba extract EGB761 protects against aging-associated diastolic dysfunction in cardiomyocytes of D-galactose-induced aging rat.

The aim of the present study was to make use of the artificially induced aging model cardiomyocytes to further investigate potential anti-aging-associated cellular diastolic dysfunction effects of EGB761 and explore underlying molecular mechanisms. Cultured rat primary cardiomyocytes were treated with either D-galactose or D-galactose combined with EGB761 for 48 h. After treatment, the percentage of cells positive for SA-β-gal, AGEs production, cardiac sarcoplasmic reticulum calcium pump (SERCA) activity, the myocardial sarcoplasmic reticulum calcium uptake, and relative protein levels were measured. Our results demonstrated that in vitro stimulation with D-galactose induced AGEs production. The addition of EGB761 significantly decreased the number of cells positive for SA-β-gal. Furthermore, decreased diastolic [Ca2+]i, curtailment of the time from the maximum concentration of Ca2+ to the baseline level and increased reuptake of Ca2+ stores in the SR were also observed. In addition, the level of p-Ser16-PLN protein as well as SERCA was markedly increased. The study indicated that EGb761 alleviates formation of AGEs products on SERCA2a in order to mitigate myocardial stiffness on one hand; on other hand, improve SERCA2a function through increase the amount of Ser16 sites PLN phosphorylation, which two hands finally led to ameliorate diastolic dysfunction of aging cardiomyocytes.

Placental Extract Improves Hippocampal Neuronal Loss and Fear Memory Impairment Resulting From Chronic Restraint Stress in Ovariectomized Mice

We have recently found that combination of ovariectomy (OVX) and chronic restraint stress causes cognitive dysfunction and reduces hippocampal CA3 neurons in female rats and mice and that estrogen replacement and chronic treatment with Ginkgo biloba extract EGb 761 suppress the OVX/stress-induced behavioral and morphological changes. In this study, we examined the effect of placental extract on the memory impairment and neuromorphological change in OVX/stress-subjected mice. Female Slc:ICR strain mice were randomly divided into four groups: vehicle-treated OVX, porcine placental extract (120 and 2160 mg/kg)-treated OVX, and sham-operated control groups. Two weeks after surgical operation, OVX mice underwent restraint stress for 21 days (6 h/day), and all animals were then subjected to a contextual fear conditioning test followed by morphological examination by Nissl staining. Placental extract was orally administered once daily until the behavioral analysis was carried out. Chronic treatment with both doses of placental extract improved the OVX/stress-induced fear memory impairment and Nissl-positive cell loss of the hippocampal CA3 region, although it did not affect the loss of bone mineral density and increase in body weight after OVX. These results have important implications for the neuroprotective and cognition-enhancing effects of placental extract in postmenopausal women.

Effect of Ginkgo biloba special extract EGb 761® on human cytochrome P450 activity: a cocktail interaction study in healthy volunteers

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.

The Effect of 2,5-hexanedione on Myelin Protein Zero Expression, and Its Mitigation Using Ginkgo Biloba Extract

Objective To investigate the role of myelin protein zero (P 0) in 2,5-hexanedione (2,5-HD)-induced peripheral nerve injury, and the protective effect of Ginkgo biloba extract (Egb761) on 2,5-HD-induced toxic peripheral neuropathy. Methods After 4 weeks of treatment with 2,5-HD at different doses (50, 100, 200, 400 mg/kg) in rats, changes in the levels of P 0 in rat sciatic nerves was investigated, and the effect of Egb761 on 2,5-HD-induced toxic peripheral neuropathy was studied. Results The blood-nerve barrier (BNB) permeability of the sciatic nerve increased, and the expression of P 0 mRNA and P 0 protein decreased in a dose-dependent manner after treatment with 2,5-HD for 4 weeks. Pretreatment with Egb761 protected against BNB interruption, and inhibited P 0 mRNA and protein reduction during 2,5-HD treatment. Pretreatment with Egb761 significantly reduced loss of body weight ( P<0.01) and mitigated gait abnormalities (2.85±0.22) induced by 400 mg/kg 2,5-HD ( P<0.01). It also reduced the signs of neurotoxicity induced by 2,5-HD. Conclusion 2,5-HD inhibited the expression of P 0 in a dose-dependent manner, and this may be an important mechanism by which toxic peripheral neuropathy is induced by 2,5-HD. Egb761 has a protective effect against 2,5-HD-induced peripheral neurotoxicity in rats.

Efficacy and Tolerability of a Once Daily Formulation of Ginkgo biloba Extract EGb 761® in Alzheimer's Disease and Vascular Dementia: Results from a Randomised Controlled Trial

A 24-week randomised controlled trial was conducted to assess the efficacy of a 240 mg once-daily preparation of Ginkgo biloba extract EGb 761® in 404 outpatients ≥ 50 years diagnosed with mild to moderate dementia (SKT 9-23), Alzheimer's disease (AD) or vascular dementia (VaD), with neuropsychiatric features (NPI total score ≥ 5). Separate analyses were performed for diagnostic subgroups (probable or possible AD; VaD). 333 patients were diagnosed with AD and 71 with VaD. EGb 761® treatment was superior to placebo with respect to the SKT total score (drug-placebo differences: 1.7 for AD, p<0.001, and 1.4 for VaD, p<0.05) and the NPI total score (drug-placebo differences: 3.1 for AD, p<0.001 and 3.2 for VaD, p<0.05). Significant drug-placebo differences were found for most secondary outcome variables with no major differences between AD and VaD subgroups. Rates of adverse events in EGb 761® and placebo groups were essentially similar. EGb 761® improved cognitive functioning, neuropsychiatric symptoms and functional abilities in both types of dementia.

Experimental evidence of Ginkgo biloba extract EGB as a neuroprotective agent in ischemia stroke rats

EGb761 is a standard extract of Ginkgo biloba, which is a kind of traditional Chinese herbs that has widely used in clinic treatment of stroke in China. However, its effects against ischemic stroke have not been evaluated comprehensively and its neuroprotective mechanism has not really been explored. In the present study, magnetic resonance diffusion-weighted imaging (DWI), neurological behavior and TTC staining were used to evaluate the therapeutic effect of EGb761 in rat ischemic models. Additionally, Western blot and immunohistochemistry were performed to measure the phosphorylations of cAMP response element binding protein (CREB) and Akt as well as the expression of brain-derived neurotrophic factor (BDNF) in rat brains. The results showed that Ginkgo biloba extract injection significantly increased the apparent diffusion coefficient (ADC) value and average diffusion coefficient (DCavg) value both in the peripheral zone and central zone, improved behavior scores, as well as enhanced the phosphorylations of AKT, CREB and the expression of BDNF in the brains. All these data demonstrate that EGb761 had significant therapeutic effects on ischemic stroke and it perhaps worked through activating the Akt-CREB-BDNF pathway.

Specific memory effects of Ginkgo biloba extract EGb 761 in middle-aged healthy volunteers

Introduction Recent reviews showed that Ginkgo biloba extract EGb 761 1 1 Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany. is effective to enhance performance in patients with cognitive impairment (e.g., dementia). The aim of this study was to investigate the effects of EGb 761 on memory and the specificity of such effects on distinct memory functions in middle-aged healthy volunteers. Methods A total of 188 healthy subjects aged 45–56 years were randomised to receive EGb 761 (240 mg once daily) or placebo for 6 weeks. Outcome measures were the change in memory performance in a demanding standardised free recall paradigm (list of appointments) and a less demanding standardised recognition test (driving-route). Based on previous findings we predicted superiority of EGb 761 in recall testing. Specificity in effects was assessed by separating immediate vs. delayed and quantitative vs. qualitative free recall measures. Results After 6 weeks, EGb 761-treated subjects improved significantly in quantity of recall, i.e., the number of correctly recalled appointments (drug–placebo differences: p = 0.038 for immediate and p = 0.008 for delayed recall). Effects on qualitative recall performance (ratio of false to correct items) were similar (drug–placebo differences: p = 0.092 for immediate and p = 0.010 for delayed recall). No superiority of Ginkgo was evident in another everyday memory test which asked for recognition of a driving route (drug–placebo differences: p > 0.10). The incidence of adverse events was low and not significantly different between treatment groups. Discussion EGb 761 (240 mg once daily) improves free recall of appointments in middle-aged healthy volunteers, which requires high demands on self-initiated retrieval of learned material. This function is known to be sensitive to normal aging, i.e., reduced in healthy middle-aged subjects. No effects are seen in a less demanding everyday memory task which does not tap this critical function. This ties in with previous studies which found specific patterns of benefit from EGb 761 in demanding cognitive tasks.

P4‐231: Neuropsychiatric symptoms of dementia and related caregiver distress: Effects of treatment by a once‐daily formulation of Ginkgo biloba Extract EGb 761®

P4‐231: Neuropsychiatric symptoms of dementia and related caregiver distress: Effects of treatment by a once‐daily formulation of Ginkgo biloba Extract EGb 761®

Comprehensive evaluation of neuroprotective effects of Ginkgo biloba extract EGB against ischemic stroke

EGb761 is a standard extract of Ginkgo biloba, which is a kind of traditional Chinese herbs that has widely used in clinic treatment of stroke in China. However, its effects against ischemic stroke have not been evaluated comprehensively and its neuroprotective mechanism has not really been explored. In the present study, magnetic resonance diffusion-weighted imaging (DWI), neurological behavior and TTC staining were used to evaluate the therapeutic effect of EGb761 in rat ischemic models. Additionally, Western blot and immunohistochemistry were performed to measure the phosphorylations of cAMP response element binding protein (CREB) and Akt as well as the expression of brain-derived neurotrophic factor (BDNF) in rat brains. The results showed that Ginkgo biloba extract injection significantly increased the apparent diffusion coefficient (ADC) value and average diffusion coefficient (DCavg) value both in the peripheral zone and central zone, improved behavior scores, as well as enhanced the phosphorylations of AKT, CREB and the expression of BDNF in the brains. All these data demonstrate that EGb761 had significant therapeutic effects on ischemic stroke and it perhaps worked through activating the Akt-CREB-BDNF pathway.

Ginkgo extract EGb 761® shields from slowly accumulating neurodegenerative-like changes in a newly developed cell culture model induced by the combined action of low doses of antimycin A1 and 2-deoxy-d-glucose

Different cell culture models were already used to analyze the molecular base of the neuroprotective activities of the Ginkgo biloba extract EGb 761(®) after a single or short-term application. In these previous studies cells were severely injured with agents that promptly induce fatal cellular damage, like vast oxidative stress or mitochondrial dysfunction, and the protective effects of EGb 761(®) on such acute damage were evaluated. Our present study aimed to test EGb 761(®) action in cell cultures, where cellular functions are only moderately impaired by a longer lasting, but relatively modest oxidative stress, reduction of mitochondrial function and reduced intracellular energy levels, thereby causing only slow occurence of cellular damage over a time period of 2weeks. To this end we used neuroblastoma cells (SK-N-MC) that were treated with low doses of a combination of antimycin A1 and 2-deoxy-D: -glucose. Addition of EGb 761(®) to the culture medium efficiently shielded the cells from progressing injury by reduced ATP-levels, oxidized redox state, lipid peroxidation damage and oxidative damage of mitochondrial DNA. As a result the cells were protected from apoptotic death that was observed in cultures without EGb 761(®) after 2weeks of damage occurence. This cell culture system characterizing moderate cellular stress will be applied in future studies to further investigate the mode of action of single EGb 761(®) compounds.

Central and Local Administration of Gingko Biloba Extract EGb 761® Inhibits Thermal Hyperalgesia and Inflammation in the Rat Carrageenan Model

Oral administration of the standardized Ginkgo biloba extract EGb 761® has been shown to inhibit thermal hyperalgesia in rodent models of inflammatory and postsurgical pain, but the mechanism underlying these effects is not known. We sought to determine the site of action of EGb 761 by investigating the antihyperalgesic and antiinflammatory properties of EGb 761 after local and central drug administration in the rat carrageenan model of inflammation. Adult male Wistar rats received an intraplantar injection of carrageenan (3%) or saline into the left hindpaw followed 3 hours later by an intraplantar injection of EGb 761 (30, 100, or 300 μg) or vehicle into the left paw; or intrathecal injection of EGb 761 (0.5, 1, 3, 10, or 100 μg) or vehicle into the lumbar spinal cord region. Diclofenac (100 μg) was administered as a positive control. Hindpaw withdrawal latency (in seconds) to thermal stimulation, response threshold (in grams) to mechanical stimulation, and paw volume were measured at 0, 2, 4, 6, and 24 hours after carrageenan injection. Both intraplantar (30, 100, and 300 μg) and intrathecal (0.5 and 1 μg) EGb 761 significantly inhibited carrageenan-induced thermal hyperalgesia and were equally as effective as diclofenac, but had no effect on mechanical hypersenitivity. Application ≥3 μg EGb 761 to the spinal cord induced adverse behavioral effects, which precluded further nociceptive testing. Intraplantar (300 μg) and intrathecal (1 μg) EGb 761 also significantly reduced paw edema. These studies show that EGb 761 acts both at the site of inflammation and centrally at the spinal cord level to inhibit inflammation and thermal hyperalgesia, and may be useful in the treatment of inflammatory pain.

Effects of Ginkgo Biloba Special Extract EGb 761&amp;#174; in Very Mild Cognitive Impairment (vMCI)

Objective: To assess effects of EGb 761® on cognition and quality of life in subjects with very mild cognitive impair-ment. Methods: We randomized 300 subjects aged 45 to 65 with cognitive complaints and low functioning (more than one standard deviation below appropriate norm) in at least one cognitive test to double-blind treatment with once daily 240 mg EGb 761® or placebo for 12 weeks. Results: The exploratory intention-to-treat analysis showed significant im-provement (p < 0.025, one-sided) beyond practice effects for EGb 761® in a measure of attention (Vienna Test System - Work Performance Series) and trends in favour of EGb 761® in measures of memory (Wechsler Memory Scale III - Faces I, Appointments Test – delayed recall), and perceived physical health (SF36 - factor score Physical Health). Cognitive effects were more pronounced and more consistent (p < 0.025 in 4 of 5 tests) in subjects with lower memory function at baseline. Specifically, practice effects in the more demanding tests were attenuated or absent in these sub-jects. Conclusion: Ginkgo biloba extract EGb 761® improved cognitive functioning and aspects of quality of life in sub-jects with very mild cognitive impairment.

Alleviating neuropsychiatric symptoms in dementia: the effects of Ginkgo biloba extract EGb 761&amp;reg;. Findings from a randomized controlled trial

Purpose:To examine the effects of Ginkgo biloba extract EGb 761® on neuropsychiatric symptoms of dementia.Patients and methods:Randomized, controlled, double-blind, multicenter clinical trial involving 410 outpatients with mild to moderate dementia (Alzheimer’s disease with or without cerebrovascular disease, vascular dementia), scoring at least 5 on the Neuropsychiatric Inventory (NPI), with at least one item score of 3 or more. Total scores on the SKT cognitive test battery (Erzigkeit’s short syndrome test) were between 9 and 23. After random allocation, the patients took 240 mg of EGb 761® or placebo once daily for a period of 24 weeks. Changes from baseline to week 24 in the NPI composite and in the SKT total score were the primary outcomes. The NPI distress score was chosen as a secondary outcome measure to evaluate caregivers’ distress.Results:The NPI composite score improved by −3.2 (95% confidence interval −4.0 to −2.3) in patients taking EGb 761® (n = 202), but did not change (−0.9; 0.9) in those receiving placebo (n = 202), which resulted in a statistically significant difference in favor of EGb 761® (P < 0.001). Treatment with EGb 761® was significantly superior to placebo for the symptoms apathy/indifference, sleep/night-time behavior, irritability/lability, depression/dysphoria, and aberrant motor behavior. Caregivers’ distress evaluation revealed similar baseline pattern and improvements.Conclusion:Treatment with EGb 761®, at a once-daily dose of 240 mg, was safe, effectively alleviated behavioral and neuropsychiatric symptoms in patients with mild to moderate dementia, and improved the wellbeing of their caregivers.

Efficacy and safety of a once‐daily formulation of Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: a randomized controlled trial

To test the efficacy and safety of a once-daily formulation of EGb 761 in the treatment of patients with dementia with neuropsychiatric features. Multi-centre trial of 410 outpatients with mild to moderate dementia (Alzheimer's disease, vascular dementia or mixed form) scoring between 9 and 23 on the SKT cognitive test battery, at least five on the Neuropsychiatric Inventory (NPI) and three or higher in at least one item of the NPI. Patients were randomly allocated to double-blind treatment with 240 mg of EGb 761 or placebo once daily for 24 weeks. Primary outcomes were the changes from baseline in the SKT total score and the NPI total score. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC), Activities of Daily Living International Scale (ADL-IS), NPI distress score, DEMQOL-Proxy quality-of-life scale and Verbal Fluency Test were secondary outcomes. At endpoint, patients treated with EGb 761 (n = 202) improved by -1.4 (95% confidence interval -1.8; -1.0) points on the SKT and by -3.2 (-4.0; -2.3) on the NPI total score, whereas those receiving placebo (n = 202) deteriorated by +0.3 (-0.1; 0.7) on the SKT and did not change on the NPI total score (-0.9; 0.9). Both drug-placebo comparisons were significant at p < 0.001. EGb 761 was significantly superior to placebo with respect to all secondary outcome measures. Adverse event rates were similar for both treatment groups. EGb 761, 240 mg once-daily, was found significantly superior to placebo in the treatment of patients with dementia with neuropsychiatric symptoms.

Cardiac Oxidative Stress and Inflammation are Similar in SAMP8 and SAMR1 Mice and Unaltered by Curcumin and Ginkgo biloba Extract Intake

Chronic inflammation and oxidative stress increase with advancing age and appear to be involved in the pathogenesis of coronary heart disease, the leading cause of death worldwide. There is a need for animal models that reflect the increases in pro-inflammatory cytokines and oxidative damage observed during aging in humans. We therefore aimed to investigate the suitability of the fast-aging senescence-accelerated mouse-prone 8 (SAMP8) strain and its normally aging control senescence-accelerated mouse-resistant 1 (SAMR1) to study the age-dependent changes in cytokines, oxidative damage and antioxidants in the heart. To this end, 2-months-old male SAMR1 and SAMP8 mice were fed a Western type diet (control groups) for 5 months. Two groups of SAMP8 mice were simultaneously fed identical diets fortified with 0.5 g curcumin or 1.0 g Ginkgo biloba extract EGb 761(®) per kg diet. Heart tissue homogenates were analysed for protein carbonyls, glutathione, glutathione disulfide, methionine, cysteine and uric acid as well as the cytokines tumor-necrosis factor-α, interleukin-1β, interleukin-6, and monocyte chemoattractant protein 1. Neither the strain (SAMR1 or SAMP8) nor antioxidant intake (curcumin or EGb 761(®)) affected the concentrations of the measured parameters. In conclusion, our data do not support the suitability of the SAMP8 and SAMR1 strains as a model to study age-related changes in pro-inflammatory cytokines and oxidative stress parameters in the heart.

Effect of Ginkgo biloba extract on protein expression in light-damaged retinal pigment epithelial cells

Objective To investigate the effect and mechanism of Ginkgo biloba extract EGb761 on protein expression in light-damaged retinal pigment epithelial (RPE) cells. Methods The human RPE cells (ARPE-19) were divided into normal control group, light damage group and EGb761 treatment group;the cells of latter 2 groups were exposed to the cold white light [(2200±300)1x] to induce light damage responses. The light-damaged RPE cells were treated with or without EGb761 (100 g/ml). The soluble protein of those cells were extracted and separated by two-dimension electrophoresis and stained by silverstaining. Different proteins in the gel were analyzed by ImageMaster and identified by MALDI-TOF-MS, and were further analyzed by mass spectrometry and bioinformatics. Results ImageMaster and MALDITOF-MS identified 25, 33 and 11 different proteins between light damage group and EGb761 treatment group, between normal control and light damage group, between normal control and EGb761 treatment group of RPE cells respectively. Mass spectrometry and bioinformatics analysis successfully identified 16 proteins, including metabolic enzymes, cytoskeleton proteins, anti-oxidation protein and other types of proteins expressed differentially. Conclusion Protein expression profiles are different between normal control group, light damage group and Ginkgo biloba extract treatment group of RPE cells. The mechanism of protective effect of EGb761 may involve cathepsin B, heat shock protein, cytochrome C reductase, and other proteins. Key words: Ginkgo biloba/drug effects; Pigment epithelium of eye/cytology; Proteome/physiology; Mass spectrometry

Effects of Ginkgo biloba extract on levels of MMP-2 and MMP-9 in canine lung tissues during cardiopulmonary bypass

Objective To investigate the effects of Ginkgo biloba extract (Egb) on the levels of matrix metalloproteinase2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in canine lung tissues during cardiopulmonary bypass (CPB) .Methods Fourteen health canines weighing 14-20 kg were randomly divided into 2 groups (n = 7 each): control group and Egb group. EGb 8 mg/kg in 100 ml normal saline was infused via central vein before opening the thoracic cavity in Egb group, while equal volume of normal saline was used instead of Egb in control group. Blood samples were taken from internal jugular vein at 120 min after aortic unclamping,broncho-alveolar larage fluid was collected and lung permeability index was calculated. Then the animals were killed and the lungs removed for determination of W/D lung weight ratio and contents of MMP-2 and MMP-9.Results Egb significantly decreased lung permeability index, W/D lung weight ratio and contents of MMP-2 and MMP-9 (P ＜ 0.05 or 0.01). Conclusion Egb can attenuate CPB-induced lung injury though decreasing the activities of MMP-2 and MMP-9 in canine lung tissues. Key words: Ginkgo biloba; Plant extracts; Matrix mmetalloproteinase 2; Matrix metalloproteinase 9; Lung; Cardiopulmonary bypass

Ginkgo biloba extract EGb761 protects against aging-associated mitochondrial dysfunction in platelets and hippocampi of SAMP8 mice

Standardized Ginkgo biloba extract, EGb761, has been shown to possess polyvalent properties, such as anti-oxidation, anti-apoptosis and anti-inflammation. Recently, it has also been proposed to have direct protective effects on mitochondria. The effects of EGb761 make it a potential anti-aging drug. Despite that, the ‘anti-aging’ effect of EGb761, particularly its effect on the central nervous system, is still inconclusive. Using two age groups (3-week-old and 40-week-old) of SAMP8 mice (a senescence-accelerated strain of mice), the effects of EGb761 on mitochondrial function in platelets and hippocampi were investigated in this study. It was found that mitochondrial functions, evaluated as cytochrome c oxidase (COX) activity, mitochondrial ATP (adenosine-5′-triphosphate) content and mitochondrial glutathione (GSH) content, decreased with age. EGb761 protected against mitochondrial dysfunction in platelets of young and old mice, suggesting a peripheral effect of this herb in the prevention and treatment of age-associated degeneration. In contrast, in hippocampi, protective effects of EGb761 were observed only in the old mice, probably due to an age-associated increase in the permeability of the blood brain barrier (BBB). Therefore, while EGb761 has a potential anti-aging effect, its central effect can be affected by in vivo factors such as the BBB permeability. A better understanding of the in vivo pharmacological actions of EGb761 may contribute to a better understanding of the effectiveness and complexity of this drug.

H2O2 and PAF mediate Aβ1-42-induced Ca2+ dyshomeostasis that is blocked by EGb761

Calcium (Ca2+) dyshomeostasis may be of pivotal importance in mediating the neurotoxic action of amyloid β peptide (Aβ), but the mechanism whereby Aβ disrupts Ca2+ homeostasis remains unclear. Using hippocampal neuronal cultures, the present study investigated possible mechanisms underlying Ca2+ dyshomeostasis induced by the oligomeric form of Aβ1-42 and two possible mediators of its toxicity, hydrogen peroxide (H2O2) and platelet-activating factor (PAF). It was found that, both H2O2 and PAF were able to reproduce each of the events induced by oligomeric Aβ1-42, including (a) Ca2+ influx via N-methyl-d-aspartic acid (NMDA) receptors, (b) enhancement of Ca2+ response to NMDA via activation of protein kinase C (PKC), (c) the increase of extracellular concentrations of glutamate and (d) the increase in cytosolic free Ca2+ ([Ca2+]i). Moreover, each of these events could be blocked by Ginkgo biloba extract EGb761, a free radical scavenger with PAF antagonism, and by quercetin, a constituent with well-established free radical scavenging property. In contrast, ginkgolide B, another constituent of EGb761 with well-established PAF-antagonizing activity protected the neurons against Ca2+ dyshomeostasis induced by Aβ1-42 and PAF, but not by H2O2. These results suggested the possibility that Aβ1-42-induced Ca2+ dyshomeostasis might be mediated by formation of toxic mediators such as H2O2 and PAF. Therefore, increased production of toxic mediators such as H2O2 and PAF in the brain may be critical in the pathological mechanism of neurodegenerative diseases, particularly Alzheimer's disease (AD), and may serve as major therapeutic targets for these diseases.