• Proceedings of the Ginseng society Conference
• /
• 2005.11a
• /
• pp.32-40
• /
• 2005

The last two decades have shown a marked expansion in publications of diverse effects of Panax ginseng. Ginsenosides, as active ingredients of Panax ginseng, are saponins found in only ginseng. Recently, a line of evidences shows that ginsenosides regulate various types of ion channel activity such as Ca$^{2+}$, K$^+$, Na$^+$, Cl$^-$, or ligand gated ion channels (i.e. 5-HT$_3$, nicotinic acetylcholine, or NMDA receptor) in neuronal, non-neuronal cells, and heterologously expressed cells. Ginsenosides inhibit voltage-dependent Ca$^{2+}$, K$^+$, and Na$^+$ channels, whereas ginsenosides activate Ca$^{2+}$-activated Cl$^-$ and Ca$^{2+}$-activated K$^+$ channels. Ginsenosides also inhibit excitatory ligand-gated ion channels such as 5-HT$_3$. nicotinic acetylcholine, and NMDA receptors. This presentation will introduce recent findings on the ginsenoside-induced differential regulations of ion channel activities as a ligand as other drugs do.

• Bulletin of Food Technology
• /
• v.18 no.2
• /
• pp.52-58
• /
• 2005

최근 20여년 동안 Panax ginseng의 다양한 효과가 연구 되어져 왔다. Panax ginseng의 주요 활성 성분인 ginsenosides는 오직 인삼에서만 발견되어지는 saponin이다. 최근 들어 신경, 非신경 또는 복합적으로 분포된 세포에서 ginsenoside가 $Ca^2+$, $K^+$,$Na^+$,$Cl^-$ channel이나 ligand gated ionchannel (5-HT3, nicotinic acetylcholine, NMDA receptor)과 같은 다양한 ion channel을 조절하는증거들이 발표되고 있다. Ginsenoside는 voltage-dependent $Ca^2+$, $K^+$,$Na^+$ channel의 활성을 억제하는 반면 $Ca^2+$-activated $Cl^-$ channel이나 $Ca^2+$-activated $K^+$ channel의 활성은 증가 시키는 것으로 나타났다. 또한 흥분성 ligand-gated ion channel인 $5-HT_3$, nicotinic acetylcholine, NMDA receptor의 활성은 억제한다. 본 총설에서는 현재까지 알려진 ion channel 활성에 대한 ginsenoside의 조절작용과 이것으로 인해 어떻게 생물학적 효능과 연결이 되어있는지에 대하여 이야기하고자 한다.

• Journal of Ginseng Research
• /
• v.29 no.1
• /
• pp.19-26
• /
• 2005

The last two decades have shown a marked expansion in publications of diverse effects of Panax ginseng. Ginsenosides, as active ingredients of Panax ginseng, are saponins found in only ginseng. Recently, a line of evidences shows that ginsenosides regulate various types of ion channel activity such as $Ca^{2+},\;K^+,\;Na^+,\;Cl^-$, or ligand gated ion channels (i.e. $5-HT_3$, nicotinic acetylcholine, or NMDA receptor) in neuronal, non-neuronal cells, and heterologously expressed cells. Ginsenosides inhibit voltage-dependent $Ca^{2+},\;K^+,\;and\;Na^+$ channels, whereas ginsenosides activate $Ca^{2+}-activated\;Cl^-\;and\;Ca^{2+}-activated\;K^+$ channels. Ginsenosides also inhibit excitatory ligand-gated ion channels such as $5-HT_3$, nicotinic acetylcholine, and NMDA receptors. This review will introduce recent findings on the ginsenoside-induced differential regulations of ion channel activities and will further expand the possibilities how these ginsenoside-induced ion channel regulations are coupled to biological effects of Panax ginseng.

• Journal of Ginseng Research
• /
• v.32 no.2
• /
• pp.99-106
• /
• 2008

A ligand - whether an endogenous hormone, neurotransmitter, exogenous toxin or synthetic drug - binds to plasma membrane proteins (e.g., ion channels, receptors or other functional proteins) to exert its physiological or pharmacological effects. Ligands can also have functional groups, showing stereospecificity for interaction sites on their counterpart plasma membrane proteins. Previous reports have shown that the ginsenoside Rg$_3$, a bioactive ginsenoside, meets these criteria in that: 1) an aliphatic side chain of $Rg_3$ plays a role as a functional group, 2) Rg$_3$ regulates voltage- and ligand-gated ion channels in a stereospecific manner with respect to carbon-20, and 3) $Rg_3$ regulates subsets of ligand-gated and voltage-gated ion channels through specific interactions with identified amino acid residues inside the channel pore, in the outer pore entryway, or in toxin binding sites. Rg$_3$, therefore, could be a candidate for a novel ginseng-derived glycosidic ligand regulating ion channels and receptors. This review will examine how Rg$_3$ regulates voltage-gated and ligand-gated ion channels through interactions with its target proteins in the plasma membrane. Hopefully, this review will advance understanding of ginseng pharmacology at the cellular and molecular levels.

• Archives of Pharmacal Research
• /
• v.26 no.1
• /
• pp.28-33
• /
• 2003

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 (${\alpha}_1{\beta}_1{\gamma}_{2s}$) channel activity expressed in Xenopus oocytes using a two-electrode voltage-clamp technique. Among the eight individual ginsenosides examined, namely, $Rb_1$, $Rb_2$, Rc, Rd, Re, Rf, $Rg_1$ and $Rg_2$, 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 ($EC_{50}$) of ginsenoside Rc was 53.2$\pm$12.3 $\mu$M. 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 $CI^{-1}$ channel blockers, attenuated the effect of ginsenoside Rc on I$I_{GABA}$. 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.

• Journal of Ginseng Research
• /
• v.31 no.2
• /
• pp.69-73
• /
• 2007

Since chemical structures of ginsenoside as active ingredient of Panax ginseng are known, accumulating evidence have shown that ginsenoside is one of bio-active ligands through the diverse physiological and pharmacological evaluations. Chemical structures of ginsenoside could be divided into three parts depending on diol or triol ginsenoside: Steroid- or cholesterol-like backbone structure, carbohydrate portions, which are attached at the carbon-3, -6 or -20, and aliphatic side chain coupled to the backbone structure at the carbon-20. Ginsenosides also exist as stereoisomer at the carbon-20. Bioactive ligands usually exhibit the their structure-function relationships. In ginsenosides, there is little known about the relationship of chemical structure and biological activity. Recent reports have shown that ginsenoside $Rg_3$, one of active ginsenosides, exhibits its differential physiological or pharmacological actions depending on its chemical structure. This review will show how ginsenoside $Rg_3$, as a model compound, is functionally coupled to voltage-gated ion channel or ligand-gated ion channel regulations in related with its chemical structure.

• The Korean Journal of Physiology and Pharmacology
• /
• v.17 no.2
• /
• pp.175-180
• /
• 2013

Resveratrol is a phytoalexin found in grapes, red wine, and berries. Resveratrol has been known to have many beneficial health effects, such as anti-cancer, neuroprotective, anti-inflammatory, and life-prolonging effects. However, relatively little is known about the effects of resveratrol on the regulation of ligand-gated ion channels. We have previously reported that resveratrol regulates subsets of homomeric ligand-gated ion channels such as those of 5-$HT_{3A}$ receptors. The ${\gamma}$-aminobutyric $acid_C$($GABA_C$) receptor is mainly expressed in retinal bipolar cells and plays an important role in visual processing. In the present study, we examined the effects of resveratrol on the channel activity of homomeric $GABA_C$ receptor expressed in Xenopus oocytes injected with cRNA encoding human $GABA_C$ ${\rho}$ subunits. Our data show that the application of GABA elicits an inward peak current ($I_{GABA}$) in oocytes that express the $GABA_C$ receptor. Resveratrol treatment had no effect on oocytes injected with $H_2O$ or with $GABA_C$ receptor cRNA. Co-treatment with resveratrol and GABA inhibited $I_{GABA}$ in oocytes with $GABA_C$ receptors. The inhibition of $I_{GABA}$ by resveratrol was in a reversible and concentration-dependent manner. The $IC_{50}$ of resveratrol was $28.9{\pm}2.8{\mu}M$ in oocytes expressing $GABA_C$ receptor. The inhibition of $I_{GABA}$ by resveratrol was in voltage-independent and non-competitive manner. These results indicate that resveratrol might regulate $GABA_C$ receptor expression and that this regulation might be one of the pharmacological actions of resveratrol on the nervous system.

• Proceedings of the Ginseng society Conference
• /
• 2004.12a
• /
• pp.57-57
• /
• 2004

• Development and Reproduction
• /
• v.24 no.4
• /
• pp.297-306
• /
• 2020

Repetitive changes in the intracellular calcium concentration ([Ca²⁺]i) triggers egg activation, including cortical granule exocytosis, resumption of second meiosis, block to polyspermy, and initiating embryonic development. [Ca²⁺]i oscillations that continue for several hours, are required for the early events of egg activation and possibly connected to further development to the blastocyst stage. The sources of Ca²⁺ ion elevation during [Ca²⁺]i oscillations are Ca²⁺ release from endoplasmic reticulum through inositol 1,4,5 tri-phosphate receptor and Ca²⁺ ion influx through Ca²⁺ channel on the plasma membrane. Ca²⁺ channels have been characterized into voltage-dependent Ca²⁺ channels (VDCCs), ligand-gated Ca²⁺ channel, and leak-channel. VDCCs expressed on muscle cell or neuron is specified into L, T, N, P, Q, and R type VDCs by their activation threshold or their sensitivity to peptide toxins isolated from cone snails and spiders. The present study was aimed to investigate the localization pattern of N and P/Q type voltage-dependent calcium channels in mouse eggs and the role in fertilization. [Ca²⁺]i oscillation was observed in a Ca²⁺ contained medium with sperm factor or adenophostin A injection but disappeared in Ca²⁺ free medium. Ca²⁺ influx was decreased by Lat A. N-VDCC specific inhibitor, ω-Conotoxin CVIIA induced abnormal [Ca²⁺]i oscillation profiles in SrCl₂ treatment. N or P/Q type VDC were distributed on the plasma membrane in cortical cluster form, not in the cytoplasm. Ca²⁺ influx is essential for [Ca²⁺]i oscillation during mammalian fertilization. This Ca²⁺ influx might be controlled through the N or P/Q type VDCCs. Abnormal VDCCs expression of eggs could be tested in fertilization failure or low fertilization eggs in subfertility women.

• The Korean Journal of Physiology and Pharmacology
• /
• v.15 no.1
• /
• pp.17-22
• /
• 2011

Quercetin mainly exists in the skin of colored fruits and vegetables as one of flavonoids. Recent studies show that quercetin, like other flavonoids, has diverse pharmacological actions. However, relatively little is known about quercetin effects in the regulations of ligand-gated ion channels. In the previous reports, we have shown that quercetin regulates subsets of homomeric ligand-gated ion channels such as glycine, 5-$HT_{3A}$ and ${\alpha}7$ nicotinic acetylcholine receptors. In the present study, we examined quercetin effects on heteromeric neuronal ${\alpha}3{\beta}4$ nicotinic acetylcholine receptor channel activity expressed in Xenopus oocytes after injection of cRNA encoding bovine neuronal ${\alpha}3$ and ${\beta}4$ subunits. Treatment with acetylcholine elicited an inward peak current ($I_{ACh}$) in oocytes expressing ${\alpha}3{\beta}4$ nicotinic acetylcholine receptor. Co-treatment with quercetin and acetylcholine inhibited $I_{ACh}$ in oocytes expressing ${\alpha}3{\beta}4$ nicotinic acetylcholine receptors. The inhibition of $I_{ACh}$ by quercetin was reversible and concentration-dependent. The half-inhibitory concentration ($IC_{50}$) of quercetin was $14.9{\pm}0.8\;{\mu}M$ in oocytes expressing ${\alpha}3{\beta}4$ nicotinic acetylcholine receptor. The inhibition of $I_{ACh}$ by quercetin was voltage-independent and non-competitive. These results indicate that quercetin might regulate ${\alpha}3{\beta}4$ nicotinic acetylcholine receptor and this regulation might be one of the pharmacological actions of quercetin in nervous systems.