20(S)-ginsenoside Rh2, a newly identified active ingredient of ginseng, inhibits NMDA receptors in cultured rat hippocampal neurons

Eunyoung Lee, Sunoh Kim, Kwang Chul Chung, Min Kyung Choo, Dong Hyun Kim, Ghilsoo Nam, Hyewhon Rhim

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48 Citations (Scopus)


Most herbal medicines that are orally administrated have been known to be metabolized before they are absorbed from the gastrointestinal tract. We, therefore, examined the effects of 20(S)-ginsenosides Rb1, Rg1 and Rg3, the three most commonly studied ginsenosides in the central nervous system, and their main metabolites on NMDA receptors using fura-2-based digital imaging and perforated whole-cell patch-clamp techniques. Among the nine ginsenosides tested, 20(S)-ginsenoside Rh2 (20(S)-Rh2) along with 20(S)-ginsenoside Rg3 (20(S)-Rg3) produced the highest inhibitory effect in cultured hippocampal neurons. Although 20(S)-Rg3 and 20(S)-Rh2 selectively targeted NMDA receptors with similar potency, they produced additive effects and seemed to modulate different NMDA receptor regulatory sites. As a competitive antagonist, 20(S)-Rh2 seems to inhibit the receptor via its interaction with polyamine-binding sites, and 20(S)-Rg3 does so using glycine-binding sites. Therefore, these results suggest that the treatment of 20(S)-Rh2, a newly identified active ingredient of ginseng, might be a novel preventive candidate in treating neurodegenerative disorders.

Original languageEnglish
Pages (from-to)69-77
Number of pages9
JournalEuropean Journal of Pharmacology
Issue number1-2
Publication statusPublished - 2006 Apr 24

Bibliographical note

Funding Information:
This work was supported by KIST Core-Competence Program to H.R. and Brain Research Center of the 21st Century Frontier Research Program (M103KV010004-04K2201-00420) from MOST, the Republic of Korea.

All Science Journal Classification (ASJC) codes

  • Pharmacology


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