TY - JOUR
T1 - Effects of protopanaxatriol-ginsenoside metabolites on rat N-methyl-D-aspartic acid receptor-mediated ion currents
AU - Shin, Tae Joon
AU - Hwang, Sung Hee
AU - Choi, Sun Hye
AU - Lee, Byung Hwan
AU - Kang, Jiyeon
AU - Kim, Hyeon Joong
AU - Zukin, R. Suzanne
AU - Rhim, Hyewhon
AU - Nah, Seung Yeol
PY - 2012/4
Y1 - 2012/4
N2 - 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 INMDA 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.
AB - 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 INMDA 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.
KW - Ginseng
KW - Ginsenoside metabolites
KW - N-methyl-D-aspartic acid receptor
UR - http://www.scopus.com/inward/record.url?scp=84861050601&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861050601&partnerID=8YFLogxK
U2 - 10.4196/kjpp.2012.16.2.113
DO - 10.4196/kjpp.2012.16.2.113
M3 - Article
C2 - 22563256
AN - SCOPUS:84861050601
SN - 1226-4512
VL - 16
SP - 113
EP - 118
JO - Korean Journal of Physiology and Pharmacology
JF - Korean Journal of Physiology and Pharmacology
IS - 2
ER -