A role for the carbohydrate portion of ginsenoside Rg3 in Na+ channel inhibition.
We showed recently that ginsenosides inhibit the activity of various types of ion channel. Here we have investigated the role of the carbohydrate component of ginsenoside Rg3 in the inhibition of Na+ channels. The channels were expressed in Xenopus oocytes by injecting cRNAs encoding rat brain Nav1.2 alpha and beta1 subunits, and analyzed by the two-electrode voltage clamp technique. Treatment with Rg3 reversibly inhibited the inward Na+ peak current (INa) with an IC50 of 32.2 +/- 4.5 microM, and the inhibition was voltage-dependent. To examine the role of the sugar moiety, we prepared a straight chain form of the second glucose and a conjugate of this glucose with 3-(4-hydroxyphenyl) propionic acid hydrazide (HPPH). Neither derivative inhibited INa. Treatment with the carbohydrate portion of ginsenoside Rg3, sophorose [beta-D-glucopyranosyl (1-->2)- beta-glucopyranoside], or the aglycone (protopanaxadiol), on their own or in combination had no effect on INa. These observations indicate that the carbohydrate portion of ginsenoside Rg3 plays an important role in its effect on the Na+ channel.
Kim
Jong-Hoon
JH
Research Laboratory for the Study of Ginseng Signal Transduction, Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea.
Hong
Yoon-Hee
YH
Lee
Jun-Ho
JH
Kim
Dong-Hyun
DH
Nam
Ghilsoo
G
Jeong
Sang Min
SM
Lee
Byung-Hwan
BH
Lee
Sang-Mok
SM
Nah
Seung-Yeol
SY
D000818:Animals; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology*; D005936:Glucans / Q000494:pharmacology; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D012502:Sapogenins / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000494:pharmacology; D014981:Xenopus
D036145:Ginsenosides; D005936:Glucans; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D012502:Sapogenins; C568253:Scn2A protein, rat; D015222:Sodium Channels; D014315:Triterpenes; C097367:ginsenoside Rg3; C062916:protopanaxadiol; C003328:sophorose