Effects of ginsenosides on GABA(A) receptor channels expressed in Xenopus oocytes

Department of Physiology, College of Veterinary Medicine Konkuk University, Seoul 143-701, Korea.
Archives of Pharmacal Research (Impact Factor: 2.05). 02/2003; 26(1):28-33. DOI: 10.1007/BF03179927
Source: PubMed

ABSTRACT Ginsenosides, major active ingredients of Panax ginseng, are known to regulate excitatory ligand-gated ion channel activity such as nicotinic acetylcholine and NMDA receptor channel activity. However, it is not known whether ginsenosides affect inhibitory ligand-gated ion channel activity. We investigated the effect of ginsenosides on human recombinant GABA(A) receptor (alpha1beta1gamma2S) channel activity expressed in Xenopus oocytes using a two-electrode voltage-clamp technique. Among the eight individual ginsenosides examined, namely, Rb1, Rb2, Rc, Rd, Re, Rf, Rg1 and Rg2, we found that Rc most potently enhanced the GABA-induced inward peak current (I(GABA)). Ginsenoside Rc alone induced an inward membrane current in certain batches of oocytes expressing the GABA(A) receptor. The effect of ginsenoside Rc on I(GABA) was both dose-dependent and reversible. The half-stimulatory concentration (EC50) of ginsenoside Rc was 53.2 +/- 12.3 microM. Both bicuculline, a GABA(A) receptor antagonist, and picrotoxin, a GABA(A) channel blocker, blocked the stimulatory effect of ginsenoside Rc on I(GABA). Niflumic acid (NFA) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), both Cl- channel blockers, attenuated the effect of ginsenoside Rc on I(GABA). This study suggests that ginsenosides regulated GABA(A) receptor expressed in Xenopus oocytes and implies that this regulation might be one of the pharmacological actions of Panax ginseng.

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Available from: Paul Whiting, Jun 05, 2015
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    • "In a GABAA receptor channel activity study, ginsenosides were also shown to regulate GABAA receptor channel activity by enhancing GABA-mediated channel activity (Choi et al., 2003a). Thus, in studies using Xenopus oocytes expressing human recombinant GABAA receptor, ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, and Rg2 affected GABAA receptor channel activity, and ginsenoside Rc most potently enhanced the GABA-induced inward peak current (IGABA). "
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    ABSTRACT: Ginseng, the root of Panax ginseng C.A. Meyer, is one of the oldest traditional medicines and is thought to be a tonic. It has been claimed that ginseng may improve vitality and health. Recent studies have advanced ginseng pharmacology and shown that ginseng has various pharmacological effects in the nervous system. Ginsenosides, steroid glycosides extracted from ginseng, were one of the first class of biologically active plant glycosides identified. The diverse pharmacological effects of ginsenosides have been investigated through the regulation of various types of ion channels and receptors in neuronal cells and heterologous expression systems. Ginsenoside Rg3 regulates voltage-gated ion channels such as Ca(2+), K(+), and Na(+) channels, and ligand-gated ion channels such as GABAA, 5-HT3, nicotinic acetylcholine, and N-methyl-D-aspartate (NMDA) receptors through interactions with various sites including channel blocker binding sites, toxin-binding sites, channel gating regions, and allosteric channel regulator binding sites when the respective ion channels or receptors are stimulated with depolarization or ligand treatment. Treatment with ginsenoside Rg3 has been found to stabilize excitable cells by blocking influxes of cations such as Ca(2+) and Na(+), or by enhancing Cl(-) influx. The aim of this review is to present recent findings on the pharmacological functions of the ginsenosides through the interactions with ion channels and receptors. This review will detail the pharmacological applications of ginsenosides as neuroprotective drugs that target ion channels and ligand-gated ion channels.
    Frontiers in Physiology 03/2014; 5:98. DOI:10.3389/fphys.2014.00098 · 3.53 Impact Factor
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    • "The ginsenoside Rg3 not only inhibits voltage-gated Ca2+, K+, and Na+ channels, ligand-gated 5-HT3, α7 nicotinic acetylcholine, and NMDA receptors but also activates K+ channels such as KCNQ K+, BKCa, and hERG K+4,14,15,16,17,18,19,20,21. Other ginsenosides enhance the activation of anion GABAA and glycine receptors22,23 (Table 1). Therefore, ginsenosides decrease the cellular excitability of excitable cells by inhibiting cation influx and by stimulating anion influx across plasma membranes. "
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    ABSTRACT: Ginseng, the root of Panax ginseng, has been used in traditional Chinese medicine as a tonic herb that provides many beneficial effects. Pharmacologic studies in the last decades have shown that ginsenosides (ginseng saponins) are primarily responsible for the actions of ginseng. However, the effects of ginseng are not fully explained by ginsenosides. Recently, another class of active ingredients called gintonin was identified. Gintonin is a complex of glycosylated ginseng proteins containing lysophosphatidic acids (LPAs) that are the intracellular lipid mitogenic media¬tor. Gintonin specifically and potently activates the G protein-coupled receptors (GPCRs) for LPA. Thus, the actions of ginseng are now also linked to LPA and its GPCRs. This linkage opens new dimensions for ginseng pharmacology and LPA therapeutics. In the present review, we evaluate the pharmacology of ginseng with the traditional viewpoint of Yin and Yang components. Furthermore, we will compare ginsenoside and gintonin based on the modern view of molecular pharmacology in terms of ion channels and GPCRs.
    Acta Pharmacologica Sinica 10/2013; 34(11). DOI:10.1038/aps.2013.100 · 2.91 Impact Factor
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    • "A custom-made Plexiglas net chamber was used for two-electrode voltage-clamp recordings as previously reported [8]. The oocytes were impaled with two microelectrodes filled with 3M KCl (0.2-0.7 MΩ), and electrophysiological experiments were carried out at room temperature using an Oocyte Clamp (OC-725C; Warner Instruments, Hamsden, CT, USA). "
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    ABSTRACT: In a previous report, we demonstrated that ginsenoside Rc, one of major ginsenosides from Panax ginseng, enhances γ-aminobutyric acid (GABA) receptorA (GABAA)-mediated ion channel currents. However, little is known about the effects of ginsenoside metabolites on GABAA receptor channel activity. The present study investigated the effects of ginsenoside metabolites on human recombinant GABAA receptor (α1β1γ2s) channel activity expressed in Xenopus oocytes using a two-electrode voltage clamp technique. M4, a metabolite of protopanaxatriol ginsenosides, more potently inhibited the GABA-induced inward peak current (IGABA ) than protopanaxadiol (PPD), a metabolite of PPD ginsenosides. The effect of M4 and PPD on IGABA was both concentration-dependent and reversible. The half-inhibitory concentration (IC50) values of M4 and PPD were 17.1±2.2 and 23.1±8.6 μM, respectively. The inhibition of IGABA by M4 and PPD was voltage-independent and non-competitive. This study implies that the regulation of GABAA receptor channel activity by ginsenoside metabolites differs from that of ginsenosides.
    Journal of ginseng research 01/2012; 36(1):55-60. DOI:10.5142/jgr.2012.36.1.55 · 2.82 Impact Factor
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