Neuroprotective effects of Ginkgo biloba constituents

Krieglstein, Josef; Ausmeier, Franz; El‐Abhar, Hanan S.; Lippert, Klaus; Welsch, M.; Rupalla, Katrin; Henrich‐Noack, Petra

doi:10.1016/0928-0987(94)00073-9

Cited by 98 publications

(63 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Experimental work during the last ten years has shown that Ginkgo extracts and their constituents, such as ginkgolides and bilobalide, also exert beneficial effects in animal models of acute neurodegeneration, e.g. in cerebral hypoxia and ischemia (Krieglstein et al, 1995;Chandrasekaran et al, 2001). In an experimental model of hypoxia-induced phospholipid breakdown, we found that bilobalide, a sesquiterpene lactone which constitutes ca.…”

Section: Introductionmentioning

confidence: 88%

Role of GABAergic antagonism in the neuroprotective effects of bilobalide

et al. 2007

View full text Add to dashboard Cite

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 (100μM) 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.

show abstract

Section: Introductionmentioning

confidence: 88%

Role of GABAergic antagonism in the neuroprotective effects of bilobalide

et al. 2007

View full text Add to dashboard Cite

show abstract

“…EGb761 promotes flow of cerebral blood (Krieglstein et al, 1995), which is associated with improvements in cognitive function in brain damaged subjects (Defeudis, 1991). EGb761 also enhances cognitive function in aged people suffering from insufficient cerebral blood flow (Krieglstein et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…In clinical trials, improvement in cognitive function is demonstrated in older people with dementia or ageassociated memory impairment (Curtis-Prior et al, 1999; Le Bars et al, 2000). It is also applied to treatment of cerebral vascular disorders (Krieglstein et al, 1995;Le Bars et al, 1997;Diamond et al, 2000). Even though the EGb761 is widely used in prescription drugs, the efficacy of EGb761 as a nootropic agent is somewhat controversial.…”

Section: Introductionmentioning

confidence: 99%

Extract of Ginkgo biloba EGb761 Facilitates Extinction of Conditioned Fear Measured by Fear-Potentiated Startle

Yang

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

A standard extract of Ginkgo biloba (EGb761) has been used in the treatment of various common geriatric complaints including vertigo, short-term memory loss, hearing loss, lack of attention, or vigilance. We demonstrated that acute systemic administration of EGb761 facilitated the acquisition of conditioned fear. Many studies suggest the neural mechanism underlies extinction is similar to the acquisition. This raises a possibility that EGb761 may modulate and accelerate the fear extinction process. We tested this possibility by using fearpotentiated startle (FPS) on laboratory rats. Acute systemic injection of EGb761 (10, 20, or 50 mg/kg) 30 min before extinction training facilitated extinction in a dose-dependent manner. Intra-amygdaloid infusion of EGb761 (28 ng/side, bilaterally) 10 min before extinction training also facilitated extinction. Control experiments showed that facilitation effect of EGb761 was not the result of impaired expression of conditioned fear or accelerated forgetting. Rats previously injected with EGb761 showed significant FPS after retraining. Extinction of conditioned fear appeared to result from acute drug effects rather than from toxic action. Systemic administration of EGb761 immediately after extinction training did not facilitate extinction, suggested the EGb761 facilitation effect is contributed to the acquisition phase of extinction learning. Western blot results showed that extinction induced amygdaloid extracellular signal-regulated kinase (ERK1/2) phosphorylation was significantly elevated by EGb761 treatment. Intra-amygdala injection of ERK1/2 inhibitor PD98059 completely blocked the EGb761 effect. Therefore, acute EGb761 administration modulated extinction of conditioned fear by activating ERK1/2.

show abstract

“…The EGb 761 is neuroprotective in various in vitro and in vivo models [16]. In an in vitro study EGb 761 protected the neurons against the hypoxia induced cell death [17] glutamate toxicity [18]. EGb 761 attenuated the verapamil induced neurodegeneration [19].…”

Section: Introductionmentioning

confidence: 99%