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

Lee E, Kim S, Chul Chung K, Choo MK, Kim DH, Nam G, Rhim H

Biomedical Research Center, Korea Institute of Science and Technology (KIST), 39-1 Hawholgok-dong Sungbuk-gu, Seoul 136-791, Republic of Korea.

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.

Published 17 April 2006 in Eur J Pharmacol, 536(1): 69-77.
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