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


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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    • "Earlier studies have demonstrated that ginsenosides, the main components of ginseng, act on either glutamate or GABAA receptors in Xenopus oocytes and hippocampus neurons [24-26]. Further, our recent study in substantia gelatinosa neurons of the trigeminal subnucleus caudalis demonstrated that KRGE acts on non NMDA glutamate and GABA receptors [27]. "
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    ABSTRACT: Korean red ginseng (KRG) has been used worldwide as a traditional medicine for the treatment of various reproductive diseases. Gonadotropin releasing hormone (GnRH) neurons are the fundamental regulators of pulsatile release of gonadotropin required for fertility. In this study, an extract of KRG (KRGE) was applied to GnRH neurons to identify the receptors activated by KRGE. The brain slice patch clamp technique in whole cell and perforated patch was used to clarify the effect of KRGE on the membrane currents and membrane potentials of GnRH neurons. Application of KRGE (3 μg/μL) under whole cell patch induced remarkable inward currents (56.17±7.45 pA, n=25) and depolarization (12.91±3.80 mV, n=4) in GnRH neurons under high Cl(-) pipette solution condition. These inward currents were not only reproducible, but also concentration dependent. In addition, inward currents and depolarization induced by KRGE persisted in the presence of the voltage gated Na(+) channel blocker tetrodotoxin (TTX), suggesting that the responses by KRGE were postsynaptic events. Application of KRGE under the gramicidin perforated patch induced depolarization in the presence of TTX suggesting its physiological significance on GnRH response. Further, the KRGE-induced inward currents were partially blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; non-NMDA glutamate receptor antagonist, 10 μM) or picrotoxin (PIC; GABAA receptor antagonist, 50 μM), and almost blocked by PIC and CNQX mixture. Taken together, these results suggest that KRGE contains ingredients with possible GABA and non-NMDA glutamate receptor mimetic activity, and may play an important role in the endocrine function of reproductive physiology, via activation of GABAA and non-NMDA glutamate receptors in GnRH neurons.
    Journal of ginseng research 01/2012; 36(1):47-54. DOI:10.5142/jgr.2012.36.1.47 · 2.82 Impact Factor
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