title: Effects of protopanaxatriol-ginsenoside metabolites on rat N-methyl-d-aspartic Acid receptor-mediated ion currents.
abstract: 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.
authors.affiliation: Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Shin
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Hwang
authors.forename: Sun-Hye
authors.initials: SH
authors.lastname: Choi
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Kang
authors.forename: Hyeon-Joong
authors.initials: HJ
authors.lastname: Kim
authors.forename: R Suzanne
authors.initials: RS
authors.lastname: Zukin
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah