Ginseng and ginsenoside Rg3, a newly identified active ingredient of ginseng, modulate Ca2+ channel currents in rat sensory neurons.
There is increasing evidence that ginseng influences pain modulation. In spite of extensive behavior studies, the detailed mechanism of ginseng actions at the cellular level and the identity of the active substance have not been elucidated yet. Whole-cell patch-clamp recordings were used to examine the modulation of high-voltage-activated Ca2+ channel currents by ginseng total saponins and its various individual ginsenosides in rat dorsal root ganglion neurons. Application of ginseng total saponins suppressed Ca2+ channel currents in a dose-dependent manner. Occlusion experiments using selective blockers revealed that ginseng total saponins could modulate L-, N-, and P-type currents. The co-application of ginseng total saponins and the gamma-opioid receptor agonist, D-Ala(2), N-MePhe(4), Gly(5)-ol-enkephalin (DAMGO), produced non-additive effects in most cells tested and each effect was significantly relieved by a depolarizing prepulse. Overnight treatment of cells with pertussis toxin profoundly reduced the inhibition. Furthermore, we now report that ginsenoside Rg3, among the major fractions of ginseng saponins, is a newly identified active component for the inhibition. These results suggest that the modulation of Ca2+ channels by ginseng total saponins, in particular by ginsenoside Rg3, could be part of the pharmacological basis of ginseng-mediated antinociception.
Rhim
Hyewhon
H
Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawholgok-dong Sungbuk-gu, Seoul 136-791, South Korea. hrkim@kist.re.kr
Kim
Hyeno
H
Lee
Dong Yoon
DY
Oh
Tae Hwan
TH
Nah
Seung Yeol
SY
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D036145:Ginsenosides; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D005894:Panax / Q000737:chemistry*; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000701:Analgesics, Opioid; D000972:Antineoplastic Agents, Phytogenic; D015220:Calcium Channels; D036145:Ginsenosides; D012503:Saponins; D010566:Virulence Factors, Bordetella; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C097367:ginsenoside Rg3; D037342:Pertussis Toxin