Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 323, Issue 2, Pages 416-424Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2004.08.106
Keywords
ginseng; ginsenoside Rg(3); neurotoxicity; NMDA; MTT assay; glycine; intracellular Ca2+; fura-2/AM; hippocampal neurons
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We previously reported that ginseng, a well-known herbal medicine, inhibited NMDA receptors in cultured hippocampal neurons. Here, we further examined the detailed mechanism of ginseng-mediated inhibition using its main active ingredient, ginsenoside Rg(3). Co-application of ginsenoside Rg(3) with increasing concentrations of NMDA did not change the EC50 of NMDA to the receptor, suggesting that ginsenoside Rg(3) inhibits NMDA receptors without competing with the NMDA-binding site. Ginsenoside Rg(3)-mediated inhibition also occurred in a distinctive manner from the well-characterized NMDA receptor open channel blocker, MK-801. However, ginsenoside Rg(3) produced its effect in a glycine concentration-dependent manner and shifted the glycine concentration-response curve to the right without changing the maximal response, suggesting the role of ginsenoside Rg(3) as a competitive NMDA receptor antagonist. We also demonstrated that ginsenoside Rg(3) significantly protected neurons against NMDA insults. Therefore, these results suggest that ginsenoside Rg(3) protects NMDA-induced neuronal death via a competitive interaction with the glycine-binding site of NMDA receptors in cultured hippocampal neurons. (C) 2004 Elsevier Inc. All rights reserved.
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