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Jochen Klein - One of the best experts on this subject based on the ideXlab platform.
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Neurodegeneration after transient brain ischemia in aged mice: beneficial effects of Bilobalide.
Brain research, 2013Co-Authors: Tina M. Schwarzkopf, Konrad Koch, Jochen KleinAbstract:Abstract Bilobalide, an active constituent of Ginkgo biloba , has neuroprotective properties in experimental stroke models, but nearly all published studies were carried out in young animals. As ischemic strokes in humans are much more frequent in old age, we investigated Bilobalide's effects in aged mice (age 18–22 month) using a model of transient ischemia induced by occlusion of the middle cerebral artery (MCAO) for 60 min. When Bilobalide was administered locally into the striatum via microdialysis, a significant reduction of infarct size by almost 70% was observed. Concomitantly, the extensive, twelve-fold increase of extracellular glutamate which was observed in untreated animals was strongly reduced during the infusion of Bilobalide. Glucose levels, in contrast, were not affected by Bilobalide. In further experiments, Bilobalide was given as an intraperitoneal injection (10/mg/kg) 1 h before MCAO onset. ATP levels (measured in brain homogenates) were significantly reduced by transient MCAO but pretreatment with Bilobalide prevented this loss. In ex vivo experiments with isolated mitochondria from aged mice, we found that the activity of the mitochondrial respiratory chain was only slightly impaired after 60 min of ischemia, and Bilobalide showed no benefit in this experiment. However, aged mitochondria proved to be very sensitive to calcium-induced swelling which was significantly increased after ischemia. In this assay, pretreatment with Bilobalide lowered the extent of swelling nearly to control levels. In behavioural tests, pretreatment of aged mice with Bilobalide significantly improved the outcome in the Rotarod and the Corner test. In conclusion, aged mice show some differences in their response to transient ischemia when compared with young mice. Bilobalide has prominent neuroprotective properties in mice of all ages.
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Neuroprotective effects of Bilobalide are accompanied by a reduction of ischemia-induced glutamate release in vivo.
Brain research, 2011Co-Authors: Dorothee Lang, Tina M. Schwarzkopf, Alexander Mdzinarishvili, Cornelia Kiewert, Joachim Hartmann, Rachita K. Sumbria, Jochen KleinAbstract:Abstract Neuroprotective properties of Bilobalide, a specific constituent of Ginkgo extracts, were tested in a mouse model of stroke. After 24 h of middle cerebral artery occlusion (MCAO), Bilobalide reduced infarct areas in the core region (striatum) by 40–50% when given at 10 mg/kg 1 h prior to MCAO. Neuroprotection was also observed at lower doses, or when the drug was given 1 h past stroke induction. Sensorimotor function in mice was improved by Bilobalide as shown by corner and chimney tests. When brain metabolism in situ was monitored by microdialysis, MCAO caused a rapid disappearance of extracellular glucose in the striatum which returned to baseline levels after reperfusion. Extracellular levels of glutamate were increased by more than ten-fold in striatal tissue, and by four- to fivefold in hippocampal tissue (penumbra). Bilobalide did not affect glucose levels but strongly attenuated glutamate release in both core and penumbra regions. Bilobalide was equally active when given locally via the microdialysis probe and also reduced ischemia-induced glutamate release in vitro in brain slices. We conclude that Bilobalide is a strong neuroprotectant in vivo at doses that can be used therapeutically in humans. The mechanism of action evidently involves reduction of glutamate release, thereby reducing excitotoxicity.
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Brain permeability of Bilobalide as probed by microdialysis before and after middle cerebral artery occlusion in mice.
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences Societe canadienne des sciences phar, 2010Co-Authors: Dorothee Lang, Christian Ude, Mario Wurglics, Manfred Schubert-zsilavecz, Jochen KleinAbstract:ABSTRACT. Purpose. Bilobalide is an active constituent of Ginkgo biloba and has shown neuroprotective effects in mice with cerebral ischemia. In the present study, we investigated brain permeability of Bilobalide (i) in healthy mice and (ii) in mice before or after stroke. Methods. We have used in vivo microdialysis and LC-MS to estimate extracellular levels of Bilobalide. 10 mg/kg of Bilobalide was given by i.p. injection to control mice, and 60 minutes before and after middle cerebral artery occlusion (MCAO). Results. Bilobalide was already detectable in brain striatal microdialysates 10 min after i.p. administration and reached maximum levels (19 ng/mL, corresponding to 0.92 µM) after 40 min. Maximum plasma Bilobalide levels were 5.9 µM. After an ischemic insult, the drug could be dialysed with similar efficiency as in control mice indicating slow elimination from the ischemic brain. When the drug was given after MCAO, availability in the brain was low, but measurable, at approx. 10% of control values. Conclusions. Our data demonstrate that Bilobalide easily crosses the blood brain barrier and reaches extracellular concentrations in the brain that allow efficient interaction with target molecules such as neurotransmitter receptors. Availability of the drug in ischemic tissue is high when given before ischemia, but severely limited after MCAO.
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Role of glycine receptors and glycine release for the neuroprotective activity of Bilobalide.
Brain Research, 2008Co-Authors: Cornelia Kiewert, Vikas Kumar, Markus Hillert, Oksana Hildmann, Joachim Hartmann, Jochen KleinAbstract:Abstract Bilobalide, a constituent of Ginkgo biloba , has neuroprotective properties. Its mechanism of action is unknown but it was recently found to interact with neuronal transmission mediated by glutamate, γ-aminobutyric acid (GABA) and glycine. The goal of this study was to test the interaction of Bilobalide with glycine in assays of neuroprotection. In rat hippocampal slices exposed to N -methyl- d -aspartate (NMDA), release of choline indicates breakdown of membrane phospholipids. NMDA-induced choline release was almost completely blocked in the presence of Bilobalide (10 µM). Glycine (10–100 µM) antagonized the inhibitory action of Bilobalide in this assay. In a second assay of excitotoxicity, we measured tissue water content as an indicator of cytotoxic edema formation in hippocampal slices which were exposed to NMDA. In this assay, edema formation was suppressed by Bilobalide but Bilobalide's action was attenuated in the presence of glycine and of d -serine (100 µM each). To investigate Bilobalide's interaction with glycine receptors directly, we determined 36 chloride flux in rat cortico-hippocampal synaptoneurosomes. Glycine (100 µM) was inactive in this assay indicating an absence of functional glycine-A receptors in this preparation. [ 3 H]Glycine was used to assess binding at the glycine binding site of the NMDA receptor but Bilobalide was found to be inactive in this assay. Finally, [ 3 H]glycine release was monitored in hippocampal slices exposed to oxygen-glucose deprivation. In this model, glycine release was induced by ischemia, an effect that was strongly reduced by Bilobalide. We conclude that Bilobalide does not interact with glycine receptors in neurochemical assays but it significantly reduces the release of glycine under ischemic conditions. This effect likely contributes to Bilobalide's neuroprotective effects in assays of excitotoxicity and ischemia.
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Role of GABAergic antagonism in the neuroprotective effects of Bilobalide.
Brain research, 2006Co-Authors: Cornelia Kiewert, Vikas Kumar, Oksana Hildmann, Joachim Hartmann, Misty Rueda, Runa S. Naik, Jochen KleinAbstract:Abstract Bilobalide, a constituent of Ginkgo biloba , has neuroprotective properties. Its mechanism of action is unknown but it was recently found to block GABA A receptors. The goal of this study was to test the potential role of a GABAergic mechanism for the neuroprotective activity of Bilobalide. In rat hippocampal slices exposed to NMDA, release of choline indicates breakdown of membrane phospholipids. NMDA-induced choline release was almost completely blocked in the presence of Bilobalide (10 μM) and under low-chloride conditions. Bicuculline (100 μM), a competitive antagonist at GABA A receptors, reduced NMDA-induced choline release to a small extent (− 23%). GABA (100 μM) partially antagonized the inhibitory action of Bilobalide. Exposure of hippocampal slices to NMDA also caused edema formation as measured by increases of tissue water content. NMDA-induced edema formation was suppressed by Bilobalide and by low-chloride conditions. Bicuculline exerted partial protection (by 30%) while GABA reduced Bilobalide's effect by about one third. To investigate Bilobalide's interaction with GABA A receptors directly, we measured binding of [ 35 S]-TBPS to rat cortical membranes. TBPS binding was competitively inhibited by Bilobalide in the low micromolar range (IC 50 = 3.7 μM). As a functional test, we determined 36 chloride flux in rat corticohippocampal synaptoneurosomes. GABA (100 μM) significantly increased 36 chloride flux (+ 65%), and this increase was blocked by Bilobalide, but with low potency (IC 50 : 39 μM). We conclude that, while antagonism of GABA A receptors may contribute to Bilobalide's neuroprotective effects, additional mechanisms must be postulated to fully explain Bilobalide's actions.
Chun Shi - One of the best experts on this subject based on the ideXlab platform.
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Bilobalide prevents apoptosis through activation of the PI3K/Akt pathway in SH-SY5Y cells
Apoptosis : an international journal on programmed cell death, 2010Co-Authors: Chun Shi, David T. Yew, Yonghong ZhuAbstract:Bilobalide, a sesquiterpene trilactone constituent of Ginkgo biloba leaf extracts, has been proposed to exert protective and trophic effects on neurons. However, mechanisms underlying the protective effects of Bilobalide remain unclear. Using human SH-SY5Y neuroblastoma cells and primary hippocampal neurons, this study investigated the neuroprotective effects of Bilobalide. We mimicked aging-associated neuronal impairments by applying external factors (beta amyloid protein (Abeta) 1-42, H(2)O(2) and serum deprivation) consequently inducing cell apoptosis. As markers for apoptosis, cell viability, DNA fragmentation, mitochondrial membrane potential and levels of cleaved caspase 3 were measured. We found that, Bilobalide prevented Abeta 1-42-, H(2)O(2)- and serum deprivation-induced apoptosis. To better understand the neuroprotective effects of Bilobalide, we also tested the ability of Bilobalide to modulate pro-survival signaling pathways such as protein kinase C (PKC), extracellular-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways. It was found that, Bilobalide dose-dependently increased PI3K activity and levels of phosphorylated Akt (p-Akt Ser473 and Thr308), which could be maintained up to at least 2 h after Bilobalide withdrawal in cells treated with or without Abeta 1-42, H(2)O(2) or serum-free medium. In addition, application of PI3K/Akt inhibitor LY294002 could abrogate both the protective effects of Bilobalide against Abeta 1-42-, H(2)O(2)- and serum deprivation-induced apoptotic cell damage and Bilobalide-induced increase in PI3K activity and levels of p-Akt (Ser473 and Thr308). In contrast, application of PKC inhibitor staurosporine (STS) did not affect the protective effects of Bilobalide. Moreover, no change in levels of phosphorylated ERK1/2 (p-ERK1/2) was observed in Bilobalide-treated cells. These results further suggested that the PI3K/Akt pathway might be involved in the protective effects of Bilobalide. Since modern technology allows production of purified Bilobalide with high bioavailability, Bilobalide may be useful in developing therapy for diseases involving age-associated neurodegeneration.
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Bilobalide prevents apoptosis through activation of the pi3k akt pathway in sh sy5y cells
Apoptosis, 2010Co-Authors: Chun Shi, David T. Yew, Yonghong ZhuAbstract:Bilobalide, a sesquiterpene trilactone constituent of Ginkgo biloba leaf extracts, has been proposed to exert protective and trophic effects on neurons. However, mechanisms underlying the protective effects of Bilobalide remain unclear. Using human SH-SY5Y neuroblastoma cells and primary hippocampal neurons, this study investigated the neuroprotective effects of Bilobalide. We mimicked aging-associated neuronal impairments by applying external factors (beta amyloid protein (Abeta) 1-42, H(2)O(2) and serum deprivation) consequently inducing cell apoptosis. As markers for apoptosis, cell viability, DNA fragmentation, mitochondrial membrane potential and levels of cleaved caspase 3 were measured. We found that, Bilobalide prevented Abeta 1-42-, H(2)O(2)- and serum deprivation-induced apoptosis. To better understand the neuroprotective effects of Bilobalide, we also tested the ability of Bilobalide to modulate pro-survival signaling pathways such as protein kinase C (PKC), extracellular-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways. It was found that, Bilobalide dose-dependently increased PI3K activity and levels of phosphorylated Akt (p-Akt Ser473 and Thr308), which could be maintained up to at least 2 h after Bilobalide withdrawal in cells treated with or without Abeta 1-42, H(2)O(2) or serum-free medium. In addition, application of PI3K/Akt inhibitor LY294002 could abrogate both the protective effects of Bilobalide against Abeta 1-42-, H(2)O(2)- and serum deprivation-induced apoptotic cell damage and Bilobalide-induced increase in PI3K activity and levels of p-Akt (Ser473 and Thr308). In contrast, application of PKC inhibitor staurosporine (STS) did not affect the protective effects of Bilobalide. Moreover, no change in levels of phosphorylated ERK1/2 (p-ERK1/2) was observed in Bilobalide-treated cells. These results further suggested that the PI3K/Akt pathway might be involved in the protective effects of Bilobalide. Since modern technology allows production of purified Bilobalide with high bioavailability, Bilobalide may be useful in developing therapy for diseases involving age-associated neurodegeneration.
Yonghong Zhu - One of the best experts on this subject based on the ideXlab platform.
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Bilobalide prevents apoptosis through activation of the PI3K/Akt pathway in SH-SY5Y cells
Apoptosis : an international journal on programmed cell death, 2010Co-Authors: Chun Shi, David T. Yew, Yonghong ZhuAbstract:Bilobalide, a sesquiterpene trilactone constituent of Ginkgo biloba leaf extracts, has been proposed to exert protective and trophic effects on neurons. However, mechanisms underlying the protective effects of Bilobalide remain unclear. Using human SH-SY5Y neuroblastoma cells and primary hippocampal neurons, this study investigated the neuroprotective effects of Bilobalide. We mimicked aging-associated neuronal impairments by applying external factors (beta amyloid protein (Abeta) 1-42, H(2)O(2) and serum deprivation) consequently inducing cell apoptosis. As markers for apoptosis, cell viability, DNA fragmentation, mitochondrial membrane potential and levels of cleaved caspase 3 were measured. We found that, Bilobalide prevented Abeta 1-42-, H(2)O(2)- and serum deprivation-induced apoptosis. To better understand the neuroprotective effects of Bilobalide, we also tested the ability of Bilobalide to modulate pro-survival signaling pathways such as protein kinase C (PKC), extracellular-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways. It was found that, Bilobalide dose-dependently increased PI3K activity and levels of phosphorylated Akt (p-Akt Ser473 and Thr308), which could be maintained up to at least 2 h after Bilobalide withdrawal in cells treated with or without Abeta 1-42, H(2)O(2) or serum-free medium. In addition, application of PI3K/Akt inhibitor LY294002 could abrogate both the protective effects of Bilobalide against Abeta 1-42-, H(2)O(2)- and serum deprivation-induced apoptotic cell damage and Bilobalide-induced increase in PI3K activity and levels of p-Akt (Ser473 and Thr308). In contrast, application of PKC inhibitor staurosporine (STS) did not affect the protective effects of Bilobalide. Moreover, no change in levels of phosphorylated ERK1/2 (p-ERK1/2) was observed in Bilobalide-treated cells. These results further suggested that the PI3K/Akt pathway might be involved in the protective effects of Bilobalide. Since modern technology allows production of purified Bilobalide with high bioavailability, Bilobalide may be useful in developing therapy for diseases involving age-associated neurodegeneration.
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Bilobalide prevents apoptosis through activation of the pi3k akt pathway in sh sy5y cells
Apoptosis, 2010Co-Authors: Chun Shi, David T. Yew, Yonghong ZhuAbstract:Bilobalide, a sesquiterpene trilactone constituent of Ginkgo biloba leaf extracts, has been proposed to exert protective and trophic effects on neurons. However, mechanisms underlying the protective effects of Bilobalide remain unclear. Using human SH-SY5Y neuroblastoma cells and primary hippocampal neurons, this study investigated the neuroprotective effects of Bilobalide. We mimicked aging-associated neuronal impairments by applying external factors (beta amyloid protein (Abeta) 1-42, H(2)O(2) and serum deprivation) consequently inducing cell apoptosis. As markers for apoptosis, cell viability, DNA fragmentation, mitochondrial membrane potential and levels of cleaved caspase 3 were measured. We found that, Bilobalide prevented Abeta 1-42-, H(2)O(2)- and serum deprivation-induced apoptosis. To better understand the neuroprotective effects of Bilobalide, we also tested the ability of Bilobalide to modulate pro-survival signaling pathways such as protein kinase C (PKC), extracellular-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways. It was found that, Bilobalide dose-dependently increased PI3K activity and levels of phosphorylated Akt (p-Akt Ser473 and Thr308), which could be maintained up to at least 2 h after Bilobalide withdrawal in cells treated with or without Abeta 1-42, H(2)O(2) or serum-free medium. In addition, application of PI3K/Akt inhibitor LY294002 could abrogate both the protective effects of Bilobalide against Abeta 1-42-, H(2)O(2)- and serum deprivation-induced apoptotic cell damage and Bilobalide-induced increase in PI3K activity and levels of p-Akt (Ser473 and Thr308). In contrast, application of PKC inhibitor staurosporine (STS) did not affect the protective effects of Bilobalide. Moreover, no change in levels of phosphorylated ERK1/2 (p-ERK1/2) was observed in Bilobalide-treated cells. These results further suggested that the PI3K/Akt pathway might be involved in the protective effects of Bilobalide. Since modern technology allows production of purified Bilobalide with high bioavailability, Bilobalide may be useful in developing therapy for diseases involving age-associated neurodegeneration.
Keiko Sasaki - One of the best experts on this subject based on the ideXlab platform.
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Mixed antagonistic effects of Bilobalide at ρ1 GABAC receptor
Neuroscience, 2005Co-Authors: Shelley H. Huang, Rujee K. Duke, Keiko Sasaki, Keiji Wada, Mary Chebib, Graham A.r. JohnstonAbstract:Bilobalide was found to be a moderately potent antagonist with a weak use-dependent effect at recombinant human rho(1) GABA(C) receptors expressed in Xenopus oocytes using two-electrode voltage clamp methodology. Antagonism of Bilobalide at homomeric rho(1) GABA(C) receptors appeared to be mixed. At low concentration, Bilobalide (3 microM) caused a parallel right shift and surmountable GABA maximal response of the GABA dose-response curve characteristic of a competitive antagonist. At high concentrations, Bilobalide (10-100 microM) caused nonparallel right shifts and reduced maximal GABA responses of GABA dose-response curves characteristic of a noncompetitive antagonist. The potency of Bilobalide appears to be dependent on the concentrations of GABA and was more potent at lower GABA concentrations. The mechanism of action of Bilobalide at rho(1) GABA(C) receptors appears to be similar to that of the chloride channel blocker picrotoxinin.
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Preventive effects of extract of leaves of ginkgo (Ginkgo biloba) and its component Bilobalide on azoxymethane-induced colonic aberrant crypt foci in rats.
Cancer letters, 2004Co-Authors: Rikako Suzuki, Keiko Sasaki, Keiji Wada, Hiroyuki Kohno, Shigeyuki Sugie, Teruki Yoshimura, Takuji TanakaAbstract:The modifying effects of dietary feeding of extract of leaves of ginkgo (Ginkgo biloba) (EGb) and Bilobalide isolated from EGb on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. We also assessed the effects of EGb and Bilobalide on proliferating cell nuclear antigen (PCNA) index in 'normal-appearing' crypts and activities of detoxifying enzymes of cytochrome P450 (CYP), glutathione S-transferase (GST) and quinine reductase (QR) activity in the liver. To induce ACF, rats were given two weekly subcutaneous injections of AOM (20 mg/kg body wt). They also received the experimental diets containing EGb (50 or 500 ppm) and Bilobalide (15 or 150 ppm) for 4 weeks, starting 1 week before the first dosing of AOM. AOM exposure produced a substantial number of ACF (106 +/- 10) at the end of the study (week 4). Dietary administration of EGb and Bilobalide caused significant reduction in the frequency of ACF: 50 ppm EGb, 73 +/- 17 (31% reduction, P < 0.001); 500 ppm EGb, 56 +/- 13 (47% reduction, P < 0.001); 15 ppm Bilobalide, 79 +/- 17 (25% reduction, P < 0.001); and 150 ppm Bilobalide, 71 +/- 30 (33% reduction, P < 0.01). Immunohistochemically, EGb or Bilobalide administration significantly lowered PCNA index in normal-appearing crypts. Feeding with EGb or Bilobalide increased activities of CYP as well as GST and QR in the liver. These findings might suggest possible chemopreventive ability of EGb or Bilobalide, through alterations in cryptal cell proliferation activity and drug metabolizing enzymes' activities, in colon tumorigenesis.
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Bilobalide, a sesquiterpene trilactone from Ginkgo biloba, is an antagonist at recombinant α1β2γ2L GABAA receptors
European journal of pharmacology, 2003Co-Authors: Shelley H. Huang, Rujee K. Duke, Keiko Sasaki, Keiji Wada, Mary Chebib, Graham A.r. JohnstonAbstract:Abstract The sesquiterpene trilactone Bilobalide is one of the active constituents of the 50:1 Ginkgo biloba leaf extract widely used to enhance memory and learning. Bilobalide was found to antagonise the direct action of γ-aminobutyric acid (GABA) on recombinant α1β2γ2L GABAA receptors. The effect of Bilobalide on the direct action of GABA at α1β2γ2L GABAA receptors expressed in Xenopus laevis oocytes using two-electrode voltage-clamp method was evaluated and compared with the effects of the classical GABAA receptor competitive antagonist bicuculline and noncompetitive antagonist picrotoxinin. Bilobalide (IC50=4.6±0.5 μM) was almost as potent as bicuculline and pictrotoxinin (IC50=2.0±0.1 and 2.4±0.5 μM, respectively) at α1β2γ2L GABAA receptors against 40 μM GABA (GABA EC50). While Bilobalide and picrotoxinin were clearly noncompetitive antagonists, the potency of Bilobalide decreased at high GABA concentrations suggesting a component of competitive antagonism.
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Effects of chronic administration of Bilobalide on amino acid levels in mouse brain.
Cellular and molecular biology (Noisy-le-Grand France), 2002Co-Authors: Keiko Sasaki, Shinichi Hatta, Keiji Wada, Teruki Yoshimura, Masahiro Itoh, Masanobu HagaAbstract:Abstract We have previously demonstrated that 4-day-treatment of mice with Bilobalide, a sesquiterpene of Ginkgo biloba L., increases GABA levels in mouse brain, but, effects of chronic treatment with it are not clear. To study effects of chronic treatment of mice with Bilobalide on amino acid levels in the brain, we determined the levels of aspartate, glutamate, serine, glutamine, glycine, taurine and GABA in the hippocampus, striatum and cortex. Bilobalide (3 mg/kg/day) was administered orally to 4-week-old mice for 40 days. Bilobalide treatment resulted in a significant increase in the levels of glutamate, aspartate, gamma-aminobutyric acid (GABA), and glycine in the hippocampus of mice compared with the control. An increased level of glycine after Bilobalide treatment was also detected in the striatum. In the cortex, Bilobalide increased the GABA level, whereas it decreased the level of aspartate. These changes in the levels of various amino acids may be involved in the broad spectrum of pharmacological activities of the extract of Ginkgo biloba on the central nervous system.
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Bilobalide prevents reduction of γ-aminobutyric acid levels and glutamic acid decarboxylase activity induced by 4-O-methylpyridoxine in mouse hippocampus
Life sciences, 2000Co-Authors: Keiko Sasaki, Shinichi Hatta, Keiji Wada, Hideyo Ohshika, Masanobu HagaAbstract:Abstract We previously reported that Bilobalide, a constituent of Ginkgo biloba L. leaves, protected mice against convulsions induced by 4-O-methylpyridoxine (MPN). To elucidate the mechanism of the anticonvulsant activity of Bilobalide, this study examined the effect of Bilobalide on MPN-induced changes in the levels of γ -aminobutyric acid (GABA) and glutamate, and in the activity of glutamic acid decarboxylase (GAD) in the hippocampus, cerebral cortex and striatum of the mouse. GABA levels and GAD activity in the hippocampus and cerebral cortex were significantly enhanced by Bilobalide treatment (30 mg/kg, p.o., for 4 days) alone. MPN significantly decreased GABA levels and GAD activity in the three brain regions tested compared with those in the control. Pretreatment with Bilobalide effectively suppressed the MPN-induced reduction in GABA levels and GAD activity in the hippocampus and cerebral cortex. On the other hand, there were no significant differences in the glutamate levels in the three regions despite various treatments. These results suggested that Bilobalide prevents MPN-induced reduction in GABA levels through potentiation by Bilobalide of GAD activity, and this effect of Bilobalide contributes to its anticonvulsant effect against MPN-induced convulsions.
Pierluigi Mauri - One of the best experts on this subject based on the ideXlab platform.
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liquid chromatography atmospheric pressure chemical ionization ion trap mass spectrometry of Bilobalide in plasma and brain of rats after oral administration of its phospholipidic complex
Journal of Pharmaceutical and Biomedical Analysis, 2009Co-Authors: Rossana Rossi, Fabrizio Basilico, Giuseppe Rossoni, Antonella Riva, Paolo Morazzoni, Pierluigi MauriAbstract:Abstract Standardized extracts of Ginkgo biloba L. leaves are widely used in clinical practice for the symptomatic treatment of mild to moderate dementia syndromes, cerebral insufficiency and for the enhancement of cognitive function. The main active components present in G. biloba extracts are flavonol-glycosides and terpene-lactones. In recent investigations, the sesquiterpene trilactone Bilobalide has been described to exert an interesting neuroprotective effect when administered systemically to experimental animals. Oral administration of terpene-lactones either as standardized extracts or purified products is characterized by a low bioavailability. While preparing phospholipidic complex of G. biloba extracts or Bilobalide, plasma levels of terpenes and sesquiterpene increase. In the present study, phospholipidic complex of Bilobalide (IDN 5604) has been administered orally to rats and Bilobalide levels have been determined in plasma and brain by means of a validated method based on liquid chromatography coupled to atmospheric pressure chemical ionization ion trap mass spectrometry (LC/APCI-ITMS). Due to its sensitivity (about 3 pmol/ml) and specificity, LC/APCI-ITMS method proved to be a very powerful tool for pharmacokinetic studies of Ginkgo terpene-lactones. The results of the present study clearly confirm the improvement of oral bioavailability of Bilobalide administered as phospholipidic complex and, for the first time, demonstrate the detection of significative amounts of Bilobalide in brain. This last finding agrees with the neuroprotective activity observed for Bilobalide.
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Liquid chromatography/atmospheric pressure chemical ionization ion trap mass spectrometry of Bilobalide in plasma and brain of rats after oral administration of its phospholipidic complex.
Journal of pharmaceutical and biomedical analysis, 2009Co-Authors: Rossana Rossi, Fabrizio Basilico, Giuseppe Rossoni, Antonella Riva, Paolo Morazzoni, Pierluigi MauriAbstract:Abstract Standardized extracts of Ginkgo biloba L. leaves are widely used in clinical practice for the symptomatic treatment of mild to moderate dementia syndromes, cerebral insufficiency and for the enhancement of cognitive function. The main active components present in G. biloba extracts are flavonol-glycosides and terpene-lactones. In recent investigations, the sesquiterpene trilactone Bilobalide has been described to exert an interesting neuroprotective effect when administered systemically to experimental animals. Oral administration of terpene-lactones either as standardized extracts or purified products is characterized by a low bioavailability. While preparing phospholipidic complex of G. biloba extracts or Bilobalide, plasma levels of terpenes and sesquiterpene increase. In the present study, phospholipidic complex of Bilobalide (IDN 5604) has been administered orally to rats and Bilobalide levels have been determined in plasma and brain by means of a validated method based on liquid chromatography coupled to atmospheric pressure chemical ionization ion trap mass spectrometry (LC/APCI-ITMS). Due to its sensitivity (about 3 pmol/ml) and specificity, LC/APCI-ITMS method proved to be a very powerful tool for pharmacokinetic studies of Ginkgo terpene-lactones. The results of the present study clearly confirm the improvement of oral bioavailability of Bilobalide administered as phospholipidic complex and, for the first time, demonstrate the detection of significative amounts of Bilobalide in brain. This last finding agrees with the neuroprotective activity observed for Bilobalide.