Effects of Ginsenoside Rg₂ on Human Neuronal Nicotinic Acetylcholine Receptors

Abstract

Ginseng saponins, major active components of ginseng root used by folk medicine in the treatment of various diseases, produce multiple pharmacological responses having many effects on the central and peripheral nervous system. Specifically, ginsenoside Rg₂has been shown to block the nicotinic acetylcholine receptors in bovine chromaffin cells. We have studied the effect of Rg₂ on different types of human neuronal nicotinic acetylcholine receptors (nAChRs), both homomeric and heteromeric, expressed inXenopus oocytes. Rg₂ did not affect the acetylcholine (ACh)-induced currents in α₇ human receptors, however Rg₂ affected the peak currents, and mainly the desensitization of heteromeric receptors α₃β₄, α₃β₂, α₄β₄, and α₄β₂. Both effects, a diminution of peak current and an increase of desensitization, are dose-dependent and are very similar for all the receptors. The mechanism of action has been studied in more detail in α₃β₄ and α₄β₂receptors where we found a negligible shift in the ACh dose-response curves and a persistence of the Rg₂ effects at high ACh concentrations, indicative of a noncompetitive antagonism. A lack of voltage dependence on the reduction of the peak currents induced by ACh also suggests that Rg₂ does not act as an open channel blocker of human nAChR. The results indicate that Rg₂ acts specifically on heteromeric human nAChRs modulating their desensitization and suggest a possible mechanism by which this saponin contributes to the multiple therapeutic effects of ginseng.