Ginsenosides inhibit NMDA receptor-mediated epileptic discharges in cultured hippocampal neurons.
Epilepsy or the occurrence of spontaneous recurrent epileptiform discharges (SREDs, seizures) is one of the most common neurological disorders. Shift in the balance of brain between excitatory and inhibitory functions due to different types of structural or functional alterations may cause epileptiform discharges. N-Methyl-D-aspartate (NMDA) receptor dysfunctions have been implicated in modulating seizure activities. Seizures and epilepsy are clearly dependent on elevated intracellular calcium concentration ([Ca2+]i) by NMDA receptor activation and can be prevented by NMDA antagonists. This perturbed [Ca2+]i levels is forerunner of neuronal death. However, therapeutic tools of elevated [Ca2+]i level during status epilepticus (SE) and SREDs have not been discovered yet. Our previous study showed fast inhibition of ginseng total saponins and ginsenoside Rg3 on NMDA receptor-mediated [Ca2+]i in cultured hippocampal neurons. We, therefore, examined the direct modulation of ginseng on hippocampal neuronal culture model of epilepsy using fura-2-based digital Ca2+ imaging and neuronal viability assays. We found that ginseng total saponins and ginsenoside Rg3 inhibited Mg2+ free-induced increase of [Ca2+]i and spontaneous [Ca2+]i oscillations in cultured rat hippocampal neurons. These results suggest that ginseng may play a neuroprotective role in perturbed homeostasis of [Ca2+]i and neuronal cell death via the inhibition of NMDA receptor-induced SE or SREDs.
Kim
Sunoh
S
Biomedical Research Center, Korea Institute of Science and Technology, Seoul 136-791, Korea.
Rhim
Hyewhon
H
D000818:Animals; D002478:Cells, Cultured; D004827:Epilepsy / Q000503:physiopathology; D036145:Ginsenosides / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology
D036145:Ginsenosides; D016194:Receptors, N-Methyl-D-Aspartate