[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.

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.

[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.

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 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.