Electrophysiological effects of ginseng and ginsenoside Re in guinea pig ventricular myocytes
Introduction
Panax ginseng and its main active component, ginsenosides, exhibit a variety of cardiovascular actions Chen, 1996, Zhang et al., 1999, including an antihypertensive effect (Sohn et al., 1980), protection against ischemia/reperfusion injury (Zhan et al., 1994), a negative chronotropic effect (Wu and Chen, 1988), a negative inotropic effect (Wu and Chen, 1988), a vasorelaxing effect Chen et al., 1984, Lee et al., 1981, and an antiarrhythmic effect Zhang et al., 1990, Li and Zhang, 1988. Folk medicines are frequently used empirically without fully understanding the mechanisms of their actions. The mechanisms underlying the cardiovascular effects of ginseng are also unclear. Electrophysiologically, ginseng inhibits L-type Ca2+ channels in rat-cultured cardiomyocytes (Jiang et al., 1996), but its effects on other classes of ion currents are not known. Thus, one of the aims of the present study is to investigate the effects of ginseng on the membrane potential and various ion currents of guinea pig ventricular myocytes.
Currently, at least 30 different ginsenosides have been identified. They have a common structure with a four-ring, steroid-like frame with sugar moieties (Fig. 1) (Shibata et al., 1985). Among 30 different ginsenosides, ginsenoside Re is one of the ingredients with the highest content (0.15%) in ginseng (Gillis, 1997). Cardiovascular effects of ginsenoside Re are similar to those of ginseng, including protection against ischemia/reperfusion injury Liu et al., 2002, Scott et al., 2001, a negative chronotropic effect (Jin, 1996), a negative inotropic effect (Jin, 1996), and an antiarrhythmic effect (Jin and Liu, 1994). In the present study, therefore, we examined and compared the effects of ginsenoside Re to those of ginseng, to test whether ginsenoside Re is the main active component of ginseng regarding its cardiovascular effects.
Section snippets
Materials and methods
The investigation was conducted in accordance with the rules and regulations of the Institutional Animal Care and Use Committee of Tokyo Medical and Dental University.
Effects of ginseng and ginsenoside Re on action potentials
Fig. 2A and B shows representative examples of action potentials recorded at a rate of 1 Hz (panel A) or 4 Hz (panel B) in the control state (○), in the presence of drug (1 mg/ml ginseng [●] or 3 μM ginsenoside Re [■]), and after wash-out of the drug (△). Ginseng (1 mg/ml) significantly shortened both APD20 and APD90 (P<0.05), an effect that was partially reversed upon drug wash-out: the percent shortening in APD20 and APD90 was 25.4±3.6% and 18.1±2.9%, respectively, at 1 Hz, and 35.7±4.3% and
Shortening of APD by ginseng and ginsenoside Re
Ginseng (1 mg/ml) and ginsenoside Re (3 μM) shortened both APD20 and APD90, which may be a reflection of their effects on ICa,L and IKs. The shortening of APD20 and APD90 induced by ginseng and ginsenoside Re was dependent on the stimulation frequency: it was greater at a rate of 4 Hz than at 1 Hz. At a high stimulation rate, IKs progressively accumulates in the open state and contributes significantly to the APD shortening (Jurkiewicz and Sanguinetti, 1993). ICa,L was inhibited in the mode of
Acknowledgments
We thank Miss K. Totsuka for secretarial services and Mrs. K. Yamamoto for technical assistant.
References (32)
Panax ginseng pharmacology: a nitric oxide link
Biochem. Pharmacol.
(1997)- et al.
Ginseng and ginsenoside Rg3, a newly identified active ingredient of ginseng modulate Ca2+ channel currents in rat sensory neurons
Eur. J. Pharmacol.
(2002) - et al.
Protective effects of pretreatment with ginsenosides on cardiac and coronary vascular function after hypothermic rat heart preservation
Hiroshima J. Med. Sci.
(1999) A study of the effect of the rate of stimulation on the transient outward current in sheep cardiac Purkinje fibers
J. Physiol.
(1981)Cardiovascular protection by ginsenosides and their nitric oxide releasing action
Clin. Exp. Pharmacol. Physiol.
(1996)- et al.
Vascular effects of ginsenosides in vitro
Br. J. Pharmacol.
(1984) - et al.
A novel activation of Ca2+ -activated Cl− channel in Xenopus oocytes by Ginseng saponins: evidence for the involvement of phospholipase C and intracellular Ca2+ mobilization
Br. J. Pharmacol.
(2001) - et al.
Potassium rectifier currents differ in myocytes of endocardial and epicardial origin
Circ. Res.
(1992) - et al.
Modulation of guinea-pig cardiac L-type calcium current by nitric oxide synthase inhibitors
J. Physiol.
(1998) - et al.
Barium-induced automatic activity in isolated ventricular myocytes from guinea-pig hearts
J. Physiol.
(1988)
Calcium channel blockade and anti-free-radical actions of panaxatriol saponins in cultured myocardiocytes
Zhongguo Yaoli Xuebao
The action of ginsenoside Re on inotropy and chronotropy of isolated atria prepared from guinea pigs
Planta Med.
Effects of ginsenoside Re on the electrophysiological activity of the heart
Planta Med.
Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agents. Specific block of rapidly activating delayed rectifier K+ current by dofetilide
Circ. Res.
Channel structure and drug-induced cardiac arrhythmias
Proc. Natl. Acad. Sci. U. S. A.
The long QT syndrome. A review of recent molecular genetic and physiologic discoveries
Medicine (Baltimore)
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Present address: Faculty of Human Life Science, Jissen Women's University, 4-1-1 Oosakaue, Hino-shi, Tokyo 191-8510, Japan.