Time-Series-Dependent Global Data Filtering Strategy for Mining and Profiling of Xenobiotic Metabolites in a Dynamic Complex Matrix: Application to Biotransformation of Flavonoids in the Extract of Ginkgo biloba by Gut Microbiota.

Efficient characterization of xenobiotic metabolites and their dynamics in a changing complex matrix remains difficult. Herein, we proposed a time-series-dependent global data filtering strategy for the rapid and comprehensive characterization of xenobiotic metabolites and their dynamic variation based on metabolome data. A set of data preprocessing methods was used to screen potential xenobiotic metabolites, considering the differences between the treated and control groups and the fluctuations over time. To further identify metabolites of the target, an in-house accurate mass database was constructed by potential metabolic pathways and applied. Taking the extract of Ginkgo biloba (EGB) co-incubated with gut microbiota as an example, 107 compounds were identified as flavonoid-derived metabolites (including 67 original from EGB and 40 new) from 7468 ions. Their temporal metabolic profiles and regularities were also investigated. This study provided a systematic and feasible method to elucidate and profile xenobiotic metabolism.

Ginkgo Biloba Leaf Extract Improves an Innate Immune Response of Peripheral Blood Leukocytes of Alzheimer's Disease Patients.

BACKGROUND: One of the main features of Alzheimer's disease (AD) pathology is failure in innate immune response and chronic inflammation. Lack of effective AD treatment means that more attention is paid to alternative therapy and drugs of natural origin, such as extract of Ginkgo biloba (EGb). The purpose of this study was to investigate the effect of EGb on the mechanisms of innate immune response of peripheral blood leukocytes (PBLs) in AD patients. METHODS: In AD patients and healthy-age matched controls, the effect of EGb on two of innate immune reactions, i.e., PBLs resistance to viral infection ex vivo and production of cytokines, namely TNF-α, IFN-γ, IL-1ß, IL-10, IL-15, and IFN-α, were investigated. The influence of EGb on inflammatory-associated genes expression that regulate innate immune response to viral infection and cytokine production, namely IRF-3, IRF-7, tetherin, SOCS1, SOCS3, NFKB1, p65, and MxA was also examined. RESULTS: A beneficial effect of EGb especially in AD women was observed. EGb decreased production of TNF-α, IFN-γ, and IL-10 and increased IL-15 and IL-1ß. The effect was more pronouncement in AD group. EGb also downregulated expression of investigated genes. CONCLUSIONS: EGb may have an advantageous properties for health management in elderly and AD sufferers but especially in women with AD. Improving peripheral innate immune cells' activity by adding EGb as accompanying treatment in AD may be, in the long term, a good course to modify the disease progression.

Clinical and economic analysis of Gastrodin injection for dizziness or vertigo: a retrospective cohort study based on electronic health records in China.

BACKGROUND: Dizziness and vertigo are common clinical symptoms. Gastrodin injection has shown clinical effects on dizziness or vertigo. However, little is known about the effectiveness and costs of combining Gastrodin injection with conventional treatment on dizziness or vertigo in daily practice. This study aimed to analyze the clinical and economic effects of Gastrodin injection for patients with dizziness or vertigo in comparison to Extract of Ginkgo Biloba Leaves injection in real-world practice. METHODS: Data was collected from the Hospital Information System of 131 hospitals across China from January to December 2018. Patients whose primary discharge diagnosis was dizziness or vertigo according to ICD-10 diagnostic coding were included and divided into two samples: sample of dizziness or vertigo; sample of dizziness or vertigo, with the complication of cerebral infarction. Comparative analysis of the medical cost per hospitalization, hospitalization duration, effective rates, and cure rates between the group of Gastrodin injection and the group of Extract of Ginkgo Biloba Leaves injection was conducted. Propensity Score Matching was used to control potential confounding factors. RESULTS: In the sample of dizziness or vertigo, although there was no significant differences on hospitalization duration (P = 0.080), the group of Gastrodin injection was significantly better than the group of Extract of Ginkgo Biloba Leaves injection (P < 0.001) in terms of treatment effect and the per capita hospitalization cost. In the sample of dizziness or vertigo, with the complication of cerebral infarction, there was no significant difference (P = 0.371) in terms of hospitalization duration, but the group of Gastrodin injection was significantly better than the group of Extract of Ginkgo Biloba Leaves injection (P = 0.009) in terms of treatment effect, and significant difference regarding the per capita hospitalization cost (P < 0.001). CONCLUSIONS: Gastrodin injection showed advantages for inpatients with dizziness or vertigo compared with Extract of Ginkgo Biloba Leaves injection. Future studies using prospective pragmatic controlled trials can test and explore more about the effects of Gastrodin injections on dizziness or vertigo.

Pharmacokinetic herb-disease-drug interactions: Effect of ginkgo biloba extract on the pharmacokinetics of pitavastatin, a substrate of Oatp1b2, in rats with non-alcoholic fatty liver disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. is a traditional Chinese medicine for hyper lipaemia. Ginkgo flavonols and terpene lactones are responsible for the lipid-lowering effect in non-alcoholic fatty liver disease (NAFLD). However, the pharmacokinetics of ginkgo flavonols and terpene lactones in NAFLD was not clarified. AIM OF THE STUDY: To investigate the effects of Ginkgo biloba L. leaves extracts (EGB) and NAFLD on hepatocyte organic anion transporting polypeptide (Oatp)1b2, and to assess the pharmacokinetics of EGB active ingredients in NAFLD rats. MATERIALS AND METHODS: Male rats were fed with a high-fat diet to induce NAFLD models. The pharmacokinetic characteristics of EGB active ingredients were studied in NAFLD rats after two or four weeks of treatment with 3.6, 10.8, and 32.4 mg/kg EGB. The effects of NAFLD and EGB were investigated on the systemic exposure of pitavastatin, a probe substrate of Oatp1b2. The inhibitory effects of ginkgo flavonols and terpene lactones on OATP1B1-mediated uptake of 3H-ES were tested in hOATP1B1-HEK293 cells. RESULTS: The plasma exposure of ginkgolides and flavonols in NAFLD rats increased in a dose-dependent manner following oral administration of EGB at 3.6-32.4 mg/kg. The half-lives of ginkgolides A, B, C, and bilobalide (2-3 h) were shorter than quercetin, kaempferol, and isorhamnetin (approximately 20 h). NAFLD reduced the plasma pitavastatin exposure by about 50 % due to the increased Oatp1b2 expression in rat liver. Increased EGB (from 3.6 to 32.4 mg/kg) substantially increased the Cmax and AUC0-t of pitavastatin by 1.8-3.2 and 1.3-3.0 folds, respectively. In hOATP1B1-HEK293 cells, kaempferol and isorhamnetin contributed to the inhibition of OATP1B1-mediated uptake of 3H-ES with IC50 values of 3.28 ± 1.08 µM and 46.12 ± 5.25 µM, respectively. CONCLUSIONS: NAFLD and EGB can alter the activity of hepatic uptake transporter Oatp1b2 individually or in combination. The pharmacokinetic herb-disease-drug interaction found in this research will help inform the clinical administration of EGB or Oatp1b2 substrates.

Hampering Herpesviruses HHV-1 and HHV-2 Infection by Extract of Ginkgo biloba (EGb) and Its Phytochemical Constituents.

Despite the availability of several anti-herpesviral agents, it should be emphasized that the need for new inhibitors is highly encouraged due to the increasing resistant viral strains as well as complications linked with periods of recurring viral replication and reactivation of latent herpes infection. Extract of Ginkgo biloba (EGb) is a common phytotherapeutics around the world with health benefits. Limited studies, however, have addressed the potential antiviral activities of EGb, including herpesviruses such as Human alphaherpesvirus 1 (HHV-1) and Human alphaherpesvirus 2 (HHV-2). We evaluated the antiviral activity of EGb and its phytochemical constituents: flavonoids and terpenes against HHV-1 and HHV-2. Pretreatment of the herpesviruses with EGb prior to infection of cells produced a remarkable anti-HHV-1 and anti-HHV-2 activity. The extract affected the viruses before adsorption to cell surface at non-cytotoxic concentrations. In this work, through a comprehensive anti-HHV-1 and anti-HHV-2 activity study, it was revealed that flavonoids, especially isorhamnetin, are responsible for the antiviral activity of EGb. Such activity was absent in quercetin and kaempferol. However, EGb showed the most potent antiviral potency compared to isorhamnetin. EGb could augment current therapies for herpes labialis and genital herpes. Moreover, the potential use of EGb in multidrug therapy with synthetic anti-herpes compounds might be considered.

[Effects of extract of Ginkgo biloba on magnetic resonance imaging and electroencephalography in patients with delayed encephalopathy after acute carbon monoxide poisoning].

Objective: To observe the effects of extract of Ginkgo biloba (Ginaton) on magnetic resonance imaging (MRI) and electroencephalography (EEG) in patients with delayed encephalopathy after acute carbon monoxide poisoning. Methods: The 84 patients with delayed encephalopathy after acute carbon monoxide poisoning treated in our hospital from Jan. 2011 to Apr. 2016 were randomly divied into therapy group and observation group. The therapy group received routine treatments of hyperbaric oxygen, cure cerebral edema and promote brain cell metabolism, and observation group was given intravenous injection (intravenous drip) Ginaton 70 mg (adding 0.9% sodium chloride injection 250 ml) , once a day, 2 weeks for one therapeutic course. The changes of MRI and EEG before and after treatment between therapy group and observation group were observed. Results: In the observation group, the white matter and globus pallidus lesions of 14 d after treatment were smaller than those in the treatment group, and the abnormal signal intensity was decreased. At 14 days after treatment the improvement of EEG in observation group were better than therapy group (P<0.05) . Conclusion: Early treatment of extract of Ginkgo biloba (Ginaton) in delayed encephalopathy after acute carbon monoxide poisoning can effectively improve lesion and signal on MRI and abnormal rate on EEG. It has a certain therapeutic effect in clinical.

[Clinical treatment effect of glucocorticoids and extract of ginkgo biloba on post-viral olfactory dysfunction].

Objective:To observe the effect of ginkgo biloba extraction combined with glucocorticoids on postviral olfactory dysfunction.Method:Forty-two patients were diagnosed as postviral olfactory dysfunction. All patients underwent olfactory test, including T&T test and Sniffin Sticks test before and after treatment. The treatment lasted up to 3 months based on effectiveness. The results of olfactory test were recorded every month.Result:Twenty patients received the treatment with prednisone acetate. T&T test showed that the effective and improvement rate of the treatment with prednisone acetate were 25.00%(5/20) and 45.00%(9/20),respectively; Sniffin Sticks test showed that the effective and improvement rate of the treatment were 20.00%(4/20)and 50.00%(10/20),respectively. Twenty-two patients received the treatment combined with extract of ginkgo biloba. T&T test showed that the effective and improvement rate of the treatment with prednisone acetate were 31.82%(7/22)and 50.00%(11/22),respectively; through Sniffin Sticks test showed that the effective and improvement rate of the treatment were 27.27%(6/22)and 54.55%(12/22),respectively.Conclusion:Olfactory function in patients with postviral olfactory dysfunction was improved with two therapy. There was no significant difference on effect between the two therapeutic groups, but the effect of combination of extract of ginkgo biloba was better than the effect of prednisone acetate. Prolong duration of treatment is help for the recovery of the olfaction.

Effects of extract of Ginkgo biloba on magnetic resonance imaging and electroencephalography in patients with delayed encephalopathy after acute carbon monoxide poisoning / 中华劳动卫生职业病杂志

Objective@#To observe the effects of extract of Ginkgo biloba (Ginaton) on magnetic resonance imaging (MRI) and electroencephalography (EEG) in patients with delayed encephalopathy after acute carbon monoxide poisoning.@*Methods@#The 84 patients with delayed encephalopathy after acute carbon monoxide poisoning treated in our hospital from Jan. 2011 to Apr. 2016 were randomly divied into therapy group and observation group. The therapy group received routine treatments of hyperbaric oxygen, cure cerebral edema and promote brain cell metabolism, and observation group was given intravenous injection (intravenous drip) Ginaton 70 mg (adding 0.9% sodium chloride injection 250 ml) , once a day, 2 weeks for one therapeutic course. The changes of MRI and EEG before and after treatment between therapy group and observation group were observed.@*Results@#In the observation group, the white matter and globus pallidus lesions of 14 d after treatment were smaller than those in the treatment group, and the abnormal signal intensity was decreased. At 14 days after treatment the improvement of EEG in observation group were better than therapy group (P<0.05) .@*Conclusion@#Early treatment of extract of Ginkgo biloba (Ginaton) in delayed encephalopathy after acute carbon monoxide poisoning can effectively improve lesion and signal on MRI and abnormal rate on EEG. It has a certain therapeutic effect in clinical.

Changes of nerve function in patients with delayed encephalopathy after acute carbon monoxide poisoning following treatment with ginkgo biloba extract / 实用医学杂志

Objective To observe the impact of ginkgo biloba extract(Ginaton) on nerve functioninpa-tients withdelayed encephalopathy after acute carbon monoxide poisoning(DEACMP). Methods 96 patients with DEACMP treated in our hospital from April 2011 to February 2017 were randomly divided into a control group and a study group. The control group received hyperbaric oxygen ,control of intracranial pressure ,and improvement of brain cell metabolism;while the study group receivedintravenous injection of Ginaton 70 mg(adding into 250 mL of 0.9% sodium chloride) once daily fora 2-week therapeutic course. MRIand EEGwere used forexamination in DEACMP patients within 24 h after onset and 14 days after treatment. Changes in MRI and EEG examination , clinical symptoms ,mini-mental state examination (MMSE) score ,Barthel index (BI),and Montreal cognitive assessment(MoCA)were assessed before and after treatment between the two groups. Results The therapy wasef-fective in 39 patients in the study group,with a total effectiveness rate of 81.25%;and in 29 patients in the control group,with a total effectiveness rate of 60.42%. There was significant difference between the two groups (χ2 =5.042,P = 0.025). Inadmission,there were no differences between the two groups in the abnormal signals of MRI,abnormal rate of EEG,and the scores on MMSE,BI,andMoCA(P>0.05). After a 14-day treatment,the abnormal signals of MRI,abnormal rate of EEG,andthe scores on MMSE,BI,and MoCA score were improved better in the study than in the control group(P < 0.05). The MMSE score was negatively correlated with disease severity in DEACMP patients(r=-0.832,P=0.000). Conclusions Early treatment with Ginaton can effectively improvethe cerebral lesions on MR,the abnormal rate of EEG,andthe scores on MMSE,BI,and MoCA. It has certain clinical efficacy.

Ginkgo biloba and vitamin E ameliorate haloperidol-induced vacuous chewingmovement and brain-derived neurotrophic factor expression in a rat tardive dyskinesia model.

Neurodegeneration may be involved in the development of tardive dyskinesia (TD), and low levels of brain-derived neurotrophic factor (BDNF) may play a role. Ginkgo biloba (EGb761), a potent antioxidant, may have neuroprotective effects. We hypothesized that there would be decreased BDNF expression in TD, but that treatment with EGb761 would increase BDNF expression and reduce TD manifestations in a rat model. Forty rats were treated with haloperidol (2mg/kg/day via intraperitoneal injections) for 5weeks. EGb761 (50mg/kg/day) and vitamin E (20mg/kg/day) were then administered by oral gavage for another 5weeks, and we compared the effects of treatment with EGb761 or vitamin E on haloperidol-induced vacuous chewing movements (VCMs) and BDNF expression in four brain regions: prefrontal cortex (PFC), striatum (ST), substantia nigra (SNR), and globus pallidus (GP). Our results showed that haloperidol administration led to a progressive increase in VCMs, but both EGb761 and vitamin E significantly decreased VCMs. Haloperidol also decreased BDNF expression in all four brain regions, but both EGb761 and vitamin E administration significantly increased BDNF expression. Our results showed that both EGb761 and VE treatments exerted similar positive effects in a rat model of TD and increased BDNF expression levels in the four tested brain regions, suggesting that both EGb761 and vitamin E improve TD symptoms, possibly by enhancing BDNF in the brain and/or via their free radical-scavenging actions.

Oleic acid derivative of polyethylenimine-functionalized proliposomes for enhancing oral bioavailability of extract of Ginkgo biloba.

The present systematic study focused to investigate the oleic acid derivative of branched polyethylenimine (bPEI-OA)-functionalized proliposomes for improving the oral delivery of extract of Ginkgo biloba (GbE). The GbE proliposomes were prepared by a spray drying method at varying ratios of egg yolk phosphatidylcholine and cholesterol, and the optimized formulation was tailored with bPEI-OA to obtain bPEI-OA-functionalized proliposomes. The formulations were characterized for particle size, zeta potential, and entrapment efficiency. The release of GbE from proliposomes exhibited a sustained release. And the release rate was regulated by changing the amount of bPEI-OA on the proliposomes. The physical state characterization studies showed some interactions between GbE and other materials, such as hydrogen bonds and van der Waals forces during the process of preparation of proliposomes. The in situ single-pass perfusion and oral bioavailability studies were performed in rats. The significant increase in absorption constant (Ka) and apparent permeability coefficient (Papp) from bPEI-OA-functionalized proliposomes indicated the importance of positive charge for effective uptake across the gastrointestinal tract. The oral bioavailability of bPEI-OA-functionalized proliposomes was remarkable enhanced in comparison with control and conventional proliposomes. The bPEI-OA-functionalized proliposomes showed great potential of improving oral absorption of GbE as a suitable carrier.

Effects of Extract of Ginkgo biloba Leaves EGb761 on MPP+-induced Injury in SH-SY5Y Cells / 中国中医药信息杂志

Objective To investigate the effects of extract of Ginkgo biloba leaves EGb761 on 1-methy-l 4-phenylpyridium (MPP+)-induced injury in human neuroblastoma SH-SY5Y cells; To discuss its mechanism of action.Methods Cell culture method was used and SH-SY5Y cell damage model was induced with different concentrations of MPP+ to build Parkinson’s disease model in vitro. The experiment was divided into control group, MPP+ model group, low-, medium-, and high-dose EGb761 groups. The survival rate was determined by MTT assay, and the apoptotic rate was detected by flow cytometry according to AnnexinV apoptosis detection kit. The cell morphology was observed by inverted microscope. NO content in SH-SY5Y cells was detected by Nitric acid reduction method.Results Compared with the control group, the survival rate of SH-SY5Y cells decreased and the apoptotic rate and NO content increased in the model group (P<0.05); Compared with the model group, the survival rate of SH-SY5Y cells increased and the apoptotic rate and NO content decreased in the low-, medium- and high-dose EGb761 groups (P<0.05).Conclusion EGb761 can protect MPP+-induced SH-SY5Y cell from damage by the inhibition of the content of NO free radical.

Effects of Ginkgo biloba extract on the apoptosis of oxygen and glucose-deprived SH-SY5Y cells and its mechanism.

OBJECTIVE: The aim was to observe the effects of the extract of Ginkgo biloba (EGb761) on the apoptosis of oxygen and glucose-deprived (OGD) human neuroblastoma cells (SH-SY5Y) cells and explore its mechanism. MATERIALS AND METHODS: SH-SY5Y cells were divided into normal control group, OGD group, OGD for 4 h and EGb761-pretreated groups including very low-concentration (20 µg/ml), low-concentration group (25 µg/ml), moderate-concentration group (50 µg/ml) and high-concentration group (100 µg/ml). Twenty four hours after reoxygenation, cell viability was determined with 3-[4, 5-dimehyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide assay, apoptosis rate was detected with annexin V-fluorescein isothiocyanate/propidium iodide double staining flow cytometry and the protein level of apoptosis-inducing factor (AIF) was observed with immunofluorescence technique in each group. RESULTS: Cell viability was significantly lower in OGD group than in EGb761-pretreated groups, especially in moderate-concentration group (50 µg/ml) (P < 0.005). Apoptosis rate was significantly lower in EGb761-pretreated groups than in OGD group (P < 0.001). Immunofluorescent staining showed that there was AIF nuclear translocation in both EGb761-pretreated groups and OGD group, but AIF nuclear translocation was less in EGb761-pretreated groups than in OGD group. CONCLUSION: EGb761 can reduce the apoptosis of OGD SH-SY5Y cells probably through inhibiting AIF nuclear translocation. This study provides a theoretical basis for the application of EGb761 in clinical practice.

Bacteriostatic effect of extract of Ginkgo Ailoba leaves on Porphyromonas gingivalisinvitro / 吉林大学学报(医学版)

Objective To explore the antibacterial activity of extract of Ginkgo biloba leaves on Porphyromonas gingivalis in vitro ,and to provid pharmacological reference for developing a new type of antibacterial drugs in the treatment of periodontal disease.Methods This experiment was divided into negative control group,imipenem control group and different concentrations and forms of extract of Ginkgo biloba leaves groups.Solvent extraction method was used to extract the extract of Ginkgo biloba leaves, punching method and test tube method were performed to detect the antibacterial activity of extract of Ginkgo biloba leaves in anaerobic environment invitro and compared with Staphylococcusaureus and E.coli.By observing the antibacterial ring diameter and determination of the minimum bacteriostasis concentration (MIC),the antibacterial activities of extract of Ginkgo biloba leaves in vitro were measured.Results In the experiment of bacteriostatic ring,Porphyromonas gingivalis was treated with extract of Ginkgo biloba leaves,Ginkgo biloba leaf tablet and Ginkgo biloba soft capsule concentrate and 1∶4 diluent,the bacteriostatic ring diameters were decreased with the decreasing of the concentration.The maximum bacteriostatic diameter of Ginkgo biloba extract was 1 6.5 mm,and the maximum bacteriostasis diameters of Ginkgo biloba leaf tablet and soft capsule were 15.3 and 14.5 mm,respectively;the bacteriostatic diameter of the exact of Ginkgo biloba leaves was bigger than those of Ginkgo biloba leaf tablet and Ginkgo biloba soft capsule (P 0.05);E.coli and Staphylococcusaureus groups get the same results.When the concentration of extract of Ginkgo biloba leaves was more than 1.95 mg·L-1 ,there was no growth of Porphyromonas gingivalis but E. coli and Staphylococcus aureusa still grew;only the concentrations of exact of Girkgo biloba leaves were more than 6.25 and 12.5 mg· L-1 ,E. coli and Staphylococcus aureus didn’t grow;the bacteriostatic effect of extract of Ginkgo biloba on Porphromonas gingivalis was better than E.coli and Staphylococcus aureus . Conclusion Extract of Ginkgo biloba leaves has antibacterial effect on Porphyromonas gingivalis.

Effect of EGB on SOD, MDA of ventilator-induced lung injury in rats / 实用医学杂志

Objective To investigate the effect of EGB on SOD, MDA of ventilator-induced lung injury in rats and its possible mechanisms. Methods Thirty male SD rats were randomly divided into 3 groups: control group (C group), high tidal ventilation group (H group) and EGB group (E group). The setting mechanical ventilation was VT=30 mL/kg, RR=40/min, I/E=1/3, PEEP=0 cmH2 O and FiO2=21%. The broncho-alveolar lavage fluid (BLAF) and serum were obtained for determination of the levels of SOD and MDA at the end of 4 h mechanical ventilation. The Lungs were removed, and the wet-to-dry weight ratio (W/D) and pulmonary pathologic changes were measured. Results As compared with C group, W/D and the levels of MDA were significantly increased in H group, but the levels of SOD were reduced in H group. As compared with H group, W/D and the levels of MDA were significantly decreased in E group, but the levels of SOD were increased in E group. Pulmonary pathologic changes were alleviated in E group comparing with H group. Conclusion EGB injection may have a protective role against hyperoxia and induced pulmonary damage in rats.

Effects ofEGbon expression of CREBandpCREBd in cortex of aging rats / 中华行为医学与脑科学杂志

Objective To investigate effects of Ginkgo biloba extract(EGb) on expression of CREB and pCREB in cortex of aging rats.Methods Male Wistar rats were divided into three groups:young control group,old control group and EGb group.Rats in EGb group were treated with intragastric administration of EGb,while rats in the other two groups were treated with distilled water.The spatial learning and memory were evaluated by Morris water maze,and the expression of CREB,pCREB were detected by western blot.Results( 1 ) Compared with young control group (9.6 ± 2.88,41.55 ± 6.30),the swimming time and times through platform in the target quardrant of rats in old control group(6.8 ± 2.49,34.92 ± 4.56) were reduced (P ＜ 0.05 ).The times passing through the platform and the time exploring the target quadrant were more and longer in EGb group(9.4 ± 2.63,41.0 ± 6.68 ) than those in old control group(P ＜ 0.05 ).(2)Compared with rats in young control group( 1.07 ±0.33,0.26 ± 0.04),relative contents of CREB and p-CREB proteins in cortex (0.70 ± 0.21,0.13 ± 0.05 ) weredecreased in old control group(P＜0.05 ).CREB and p-CREB Levels were higher in EGb group ( 1.02 ±0.18,0.18 ±0.02)than those in old control group(P ＜ 0.05 ).Conclusion EGb can ameliorate spatial learning and memory of rats by increasing the expression of CREB and p-CREB in cortex.

Effects of extract of Ginkgo biloba on cognitive function and apoptosis of hippocampus neuronal cells in type 1 diabetic rats / 中国病理生理杂志

AIM: To investigate the protective mechanism of extract of Ginkgo biloba (EGB) on apoptosis of hippocampus neuronal cells in type 1 diabetic encephalopathic rats. METHODS: Thirty-six male Sprague-Dauley rats were divided into 3 groups: control group, diabetic group and EGB-treated group. Streptozotocin was injected intraperitoneally to the animals in later two groups to induce diabetes. The rats in EGB-treated group were injected intraperitoneally with EGB, and the same volume of normal saline was injected to the rats in other groups. At the end of the 12th week, the spatial learning and memory abilities of rats in each group were examined by Morris water maze test. Blood glucose and serum insulin concentration were measured. The neuron densities in hippocampus were measured by Image-Pro Plus 6.0 software. The expressions of Bax, Bcl-2, caspase-3 were assayed by Western blotting and immunohistochemistry. RESULTS: Compared to control group, the level of blood glucose (P<0.01), the protein expression of Bax (P<0.01) and caspase-3 (P<0.01) in hippocampus neuronal cells, and the ratio of Bax/Bcl-2 (P<0.01) and the escape latency (P<0.01) in diabetic group, were significantly increased, while the serum insulin concentration (P<0.01), the neuronal density (P<0.05) in CA1,CA2 hippocampal regions and the platform searching score (P<0.01) were significantly deceased. After treated with EGB, the serum insulin concentration (P<0.05), the neuronal density (P<0.05) in CA1,CA2 hippocampal regions and the platform searching score (P<0.01) were significantly increased, while the level of blood glucose (P<0.01), the protein expression of Bax (P<0.05), caspase-3 (P<0.05) in hippocampus neuronal cells, the ratio of Bax/Bcl-2 (P<0.01) and the escape latency (P<0.05) were significantly deceased than those in diabetic group. The protein expression of Bcl-2 in hippocampus neuronal cells did not alter in any experimental rats. CONCLUSION: EGB improves the spatial learning and memory capacity in diabetic rats by decreasing the expression of Bax, Bax/Bcl-2 ratio and down-regulating caspase-3 to reduce neurocyte apoptosis and increase the neuron density in CA1, CA2 hippocampal regions, suggesting that effective regulation of neuron apoptosis associated genes may be one of the mechanisms for EGB to treat diabetic encephalopathy.

An Experimental Study on the Protective Effects of Ginkgo Biloba Extract on the Spiral Ganglion Neuron of the Rat Cochlea / 听力学及言语疾病杂志

Objective To investigate the protective effects of the extract of ginkgo biloba(EGb)on the spiralganglion neuron(SGNs)in cochlea tissues on the hearing loss induced by noise in rats.Methods Thirty-six healthy animals were randomly divided into three groups:the normal control group(n=12).the noise exposured group(n =12)and the EGb treamment group(n=12).The control group received no noise and no medications.The other two groups were exposed to the noise of 110 dB SPL for consecutively 10 days,6 hours per day.The treatment group rats were injected with 10 ml/d EGb while the other two groups with 0.9%saline of the same amount.The experiment lasted for ten days.The rats were measured by auditory brainsterm response(ABR)before and after niose exposure.The ultrastructural changes of SGNs were detected by tranismision electron microscpoe(TEM) and the contents of malondiadehyde(MDA) and activities of superoxide dismutase(SOD)were also measured.Results Hearing were signifcantlly decreased in the experimental group.Nevertheless,EGb relatively reduced the contents of MDA while increased the activities of SOD.Conclusion EGb seems to be able to moderately pretect SGNs and to play a preventive and remedial role in noise-induced hearing loss.

Dual antioxidant activities of Gingko biloba extract: induction of antioxidant enzymes and direct reaction with reactive oxygen species / 中成药

AIM:Antioxidants act mainly through two routes:induction of antioxidant enzymes(enzymatic)or direct reaction with reactive oxygen species(ROS)(non-enzymatic),but the one taken by the extract of Ginkgo biloba(EGb)remains to be investigated.In present study,EGb was tested for both of the antioxidant routes in vitro.METHODS:The induction of EGb on two antioxidant enzymes,glutamate cysteine ligase catalytic subunit (GCLC)and glutathione-S-transferage subunit-P1(GST-P1),in cell lines wag detected by Western-blot.The effects of EGb on superoxide anion radical(O2·-),hydroxyl radical(OH·),rat erythrocyte hemolysis and lipid peroxidation of rat liver homogenate were determined by activity methods respectively.RESULTS:EGb was dem onstrated significantly to induce the two antioxidant enzymes(GCLC and GST-P1),directly scavenge superoxide anion radical(O2·-),hydroxyl radical(OH·)and inhibit rat erythroeyte hemolysis and lipid peroxidation of rat liver homogenate.CONCLUSION:The results strongly support the notion that EGb plays dual antioxidant roles: induction of antioxidant enzymes and direct reaction with ROS.

Protective Effect of the Extract of Ginkgo biloba on the Kidney in Diabetic Rats / 中国药房

OBJECTIVE:To investigate the effect of extract of Ginkgo biloba(EGb) on levels of Endothelin-1(ET-1) and transforming growth factor ?1(TGF-?1) in renal tissue of diabetic rats.METHODS:Twenty-four male Sprague-Dawley rats were randomly divided into three groups:normal control group,diabetic model group and EGb-treated group.The levels of blood glucose,insulin,total cholesterol(TC),total triglycerides(TG),creatinine clearance(Ccr),urinary albumin excretion(UAE),and urinary ?2-MG were measured after 8-week corresponding treatment.Expression of SET-1,UET-1,and RET-1 was examined by radioimmunoassay technique.Expression of STGF-?1 and UTGF-?1 in serum and urine was examined by enzyme linked immunosorbent assay(ELISA).RESULTS:The concentrations of blood glucose,blood insulin,TC and TG increased significantly in diabetic group,which were down-regulated by EGb.Levels of ET-1 and TGF-?1.in both blood and urine and the ET-1 level in renal tissues were significantly higher in diabetic model group than in normal control group(P