Effects of bilobalide on amino acid release and electrophysiology of cortical slices

Abstract

This study investigated the effects of bilobalide, a constituent of Ginkgo biloba, on potassium and veratridine-induced release of glutamate and aspartate from mouse cortical slices. We also studied its effects on spontaneous and N-methyl-D-aspartate (NMDA)-induced depolarizations elicited in magnesium-free artificial cerebrospinal fluid (aCSF) as well as its effect on NO-711 (a gamma-aminobutyric acid (GABA) uptake inhibitor)-induced depolarizations. Bilobalide, 100 microM significantly reduced both glutamate and aspartate release elicited by potassium or veratridine. Bilobalide (5-100 microM) also significantly reduced the frequency of NO-711 induced depolarizations, however, it had no effect on spontaneous or on NMDA-induced depolarizations at 5-200 microM. These results suggest that the neuroactive properties of bilobalide may be mediated by a reduction in excitatory amino acid neurotransmitter release.

Terpene Trilactones from Ginkgo biloba Are Antagonists of Cortical Glycine and GABAA Receptors

“…BB is structurally related to ginkgolides and shares several functional groups, in particular three lactone groups and a tert-butyl group, and has been postulated to have anxiolytic properties and possibly to be useful as a neuroprotective agent (27). Recent studies indicated that BB might modulate GABAergic neurotransmission, as BB has been reported to elevate the GABA levels, probably by enhancing glutamic acid decarboxylase activity (14,15), reduce muscimol responses (16), and decrease the frequency of GABA uptake inhibitor-induced depolarizations (28). BB has also been reported to antagonize recombinant ␣ 1 ␤ 2 ␥ 2L GABA A R (23).…”

Chemistry and Biology of Terpene Trilactones fromGinkgo Biloba

“…[211] It was also shown that BB (6) could reduce potassium-and veratridine-induced release of excitatory amino acids such as glutamate and aspartate, and block the effect of a GABA uptake inhibitor, NO-711. [212] Weichel et al found that BB (6) inhibited N-methyl-d-aspartate (NMDA)induced phospholipid breakdown in rat hippocampus and suggested an effect downstream of the NMDA receptor. [213] However, it was recently found that BB (6) does not affect NMDA-induced depolarizations, strongly suggesting that it had no effect on the NMDA receptor.…”

“…[213] However, it was recently found that BB (6) does not affect NMDA-induced depolarizations, strongly suggesting that it had no effect on the NMDA receptor. [212] Potential medicinal applications of BB (6) have been described in patents, including the use of BB (6) for the protection of neurons from ischemia, [214] as an anticonvulsant, [215] and for the treatment of tension and anxiety. [216] Two other targets were also described for BB (6): phospholipase A 2 (PLA 2 ) and mitochondrial respiration.…”

Chemie und Biologie von Terpentrilactonen ausGinkgo biloba

“…In cortikalen Hirnschnitten der Ratte unter Hypoxie/Hypoglykämie‐Bedingungen reduzierte Bilobalid signifikant die Freisetzung von Glutamat, was darauf schließen lässt, dass die neuronalen Schutzwirkungen von BB ( 6 ) durch einen verringerten Glutamat‐Ausstrom und eine dementsprechend verringerte Excitotoxizität vermittelt sein könnten 211. Es zeigte sich auch, dass BB ( 6 ) die Kalium‐ und Veratridin‐induzierte Freisetzung von stimulierenden Aminosäuren wie Glutaminsäure und Asparaginsäure reduzieren und die Wirkung des GABA‐Aufnahme‐Inhibitors NO‐711 blockieren könnte 212. Weichel et al fanden heraus, dass BB ( 6 ) den N ‐Methyl‐ D ‐aspartat(NMDA)‐induzierten Phospholipid‐Breakdown im Rattenhippocampus inhibiert und schlugen einen dem NMDA‐Rezeptor nachgeschalteten Effekt vor 213.…”

“…Weichel et al fanden heraus, dass BB ( 6 ) den N ‐Methyl‐ D ‐aspartat(NMDA)‐induzierten Phospholipid‐Breakdown im Rattenhippocampus inhibiert und schlugen einen dem NMDA‐Rezeptor nachgeschalteten Effekt vor 213. Kürzlich wurde aber erkannt, dass BB ( 6 ) NMDA‐induzierte Depolarisationen nicht beeinflusst, was stark darauf hinweist, dass es keine Wirkung auf den NMDA‐Rezeptor ausübt 212. Potenzielle medizinische Anwendungen von BB ( 6 ) sind in Patenten niedergelegt.…”