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 Rg 2 has been shown to block the nicotinic acetylcholine receptors in bovine chromaffin cells. We have studied the effect of Rg 2 on different types of human neuronal nicotinic acetylcholine receptors (nAChRs), both homomeric and heteromeric, expressed in Xenopus oocytes. Rg 2 did not affect the acetylcholine (ACh)-induced currents in ␣ 7 human receptors, however Rg 2 affected the peak currents, and mainly the desensitization of heteromeric receptors ␣ 3 ␤ 4 , ␣ 3 ␤ 2 , ␣ 4 ␤ 4 , and ␣ 4 ␤ 2 . 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 ␣ 3 ␤ 4 and ␣ 4 ␤ 2 receptors where we found a negligible shift in the ACh dose-response curves and a persistence of the Rg 2 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 Rg 2 does not act as an open channel blocker of human nAChR. The results indicate that Rg 2 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.

Use of Ginseng in Medicine With Emphasis on Neurodegenerative Disorders

“…Additionally, it has been shown that ginseng total saponins can modulate dopaminergic activity at both pre-synaptic and post-synaptic receptors (58); and they can block behavioral sensitization induced by psychostimulants such as morphine (59), cocaine (58), methamphetamines (60), and nicotine (61 -63). Furthermore, it was found that ginseng increased serotonin in the cortex (64), ginseng saponins raised the levels of biogenic amines in normal rat brain (65), ginsenoside Rg2 directly interacted with nicotinic receptor subtypes (66), and ginseng administration lead to regulation of GABAergic transmission in animals (67,68).…”

Effects of Ginsenoside Rg₃ on α9α10 Nicotinic Acetylcholine Receptor-Mediated Ion Currents

“…23,24) However, ginsenosides Rg 3 had no effects on homomeric α7 nicotinic acetylcholine receptor. 21) Instead, Rg 3 inhibited mutant homomeric α7 nicotinic acetylcholine receptor, which was mutated at channel pore regions.…”

“…In previous studies, we have demonstrated that ginsenosides regulates subsets of nicotinic acetylcholine receptor channel activity such as α3β4 and other heteromeric nicotinic acetylcholine receptors. 23,24) Interestingly, Rg 3 had no effects on homomeric α7 nicotinic acetylcholine receptor. Although expression of the α9α10 nicotinic acetylcholine receptor is limited in several tissues, [9][10][11][12][13][14] little is known about the effects of Rg 3 on the α9α10 nicotinic acetylcholine receptor.…”

Perspectives for Ginsenosides in Models of Parkinson's Disease

“…Additionally, it has been shown that ginseng total saponins modulates dopaminergic activity at both presynaptic and postsynaptic receptors 75) , and blocks behavioral sensitization induced by psychostimulants such as morphine 76) , cocaine 77) , methamphetamines 78) and nicotine 79) . Ginseng increased serotonin in the cortex 80) , ginseng saponins raised the levels of biogenic amines in normal rat brain 81) , ginsenoside Rg 2 directly interacted with nicotinic receptor subtypes 82) and ginseng administration led to regulation of GABAergic transmission in animals 83,84) .…”