Role of glycine receptors and glycine release for the neuroprotective activity of bilobalide

Kiewert, Cornelia; Kumar, Vikas; Hildmann, Oksana; Hartmann, J.; Hillert, Markus; Klein, Jochen

doi:10.1016/j.brainres.2008.01.052

Cited by 27 publications

(18 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Bilobalide was also identified as active ingredient by other groups (Chandradsekaran et al, 2001; reviewed by DeFeudis, 2002). In subsequent work, we further characterized bilobalide's effects in hippocampal slices (Kiewert et al, 2008), and in a preliminary study in vivo , we found that bilobalide strongly reduced brain edema in mice subjected to middle cerebral artery occlusion (Mdzinarishvili et al, 2007). Here, we report dose- and time-dependency of drug action and demonstrate functional improvements of the treated animals.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective effects of bilobalide are accompanied by a reduction of ischemia-induced glutamate release in vivo

et al. 2011

Self Cite

View full text Add to dashboard Cite

Neuroprotective properties of bilobalide, a specific constituent of Ginkgo extracts, were tested in a mouse model of stroke. After 24 hours of middle cerebral artery occlusion (MCAO), bilobalide reduced infarct areas in the core region (striatum) by 40-50% when given at 10 mg/kg one hour 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.

show abstract

Section: Introductionmentioning

confidence: 99%

Neuroprotective effects of bilobalide are accompanied by a reduction of ischemia-induced glutamate release in vivo

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…Bilobalide has been found to improve mitochondrial activity and to preserve ATP levels during ischemia [3,13]. We have investigated interactions of bilobalide with amino acid neurotransmitters such as GABA, glycine, and glutamate [14,15]. Very recently, several constituents of EGb761 were implied in the induction of heme oxygenase-1 in ischemic neurons [16].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

Self Cite

View full text Add to dashboard Cite

-Purpose -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. Methods -We have used oxygenglucose 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. Results -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. Conclusions -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.

show abstract

“…[73] Ginkgolides act as a very effective anti-platelet-activating factor (PAF) antagonist to treat cardiovascular diseases. [71,72] Furthermore, bilobalide is known for its neuroprotective effects [74] and negative allosteric modulator of some GABA receptors. [75] Two total syntheses of bilobalide adopting entirely different strategies to create the contiguous quaternary centers have been reported.…”

Section: Bilobalidementioning

confidence: 99%

Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms

et al. 2016

View full text Add to dashboard Cite

Strategies for the total synthesis of complex natural products that contain two or more contiguous stereogenic quarternary carbon atoms in their intricate structures are reviewed with twelve representative examples. Emphasis has been put on the methods to create quarternary carbon stereocenters, including syntheses of the same natural product from different groups, thereby showcasing diversity of thought and individual creativity. A compendium of selected natural products containing two or more contiguous stereogenic quarternary carbon atoms and key reactions in their total or partial syntheses is provided in the Supporting Information section.

show abstract

Role of glycine receptors and glycine release for the neuroprotective activity of bilobalide

Cited by 27 publications

References 31 publications

Neuroprotective effects of bilobalide are accompanied by a reduction of ischemia-induced glutamate release in vivo

Neuroprotective effects of bilobalide are accompanied by a reduction of ischemia-induced glutamate release in vivo

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

Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms

Contact Info

Product

Resources

About