Effects of Protopanaxatriol-Ginsenoside Metabolites on Rat N -Methyl- D -Aspartic Acid Receptor-Mediated Ion Currents

• Published in: The Korean journal of physiology & pharmacology 2012, 16(2), , pp.113-118
• Main Authors: Shin, Tae-Joon, Hwang, Sung-Hee, Choi, Sun-Hye, Lee, Byung-Hwan, Kang, Jiyeon, Kim, Hyeon-Joong, Zukin, R. Suzanne, Rhim, Hyewhon, Nah, Seung-Yeol
• Format: Article
• Language: English
• Subjects: Original; 약리학
• ISSN: 1226-4512; 2093-3827
• DOI: 10.4196/kjpp.2012.16.2.113

Ginsenosides are low molecular weight glycosides found in ginseng that exhibit neuroprotective effects through inhibition of N -methyl- D -aspartic acid (NMDA) receptor channel activity. Ginsenosides, like other natural compounds, are metabolized by gastric juices and intestinal microorganisms to produce ginsenoside metabolites. However, little is known about how ginsenoside metabolites regulate NMDA receptor channel activity. In the present study, we investigated the effects of ginsenoside metabolites, such as compound K (CK), protopanaxadiol (PPD), and protopanaxatriol (PPT), on oocytes that heterologously express the rat NMDA receptor. NMDA receptor-mediated ion current ( I NMDA ) was measured using the 2-electrode voltage clamp technique. In oocytes injected with cRNAs encoding NMDA receptor subunits, PPT, but not CK or PPD, reversibly inhibited I NMDA in a concentration-dependent manner. The IC 50 for PPT on I NMDA was 48.1±4.6 µM, was non-competitive with NMDA, and was independent of the membrane holding potential. These results demonstrate the possibility that PPT interacts with the NMDA receptor, although not at the NMDA binding site, and that the inhibitory effects of PPT on I NMDA could be related to ginseng-mediated neuroprotection.