Electrophysiological effects of ginseng and ginsenoside Re in guinea pig ventricular myocytes

https://doi.org/10.1016/S0014-2999(03)02174-5Get rights and content

Abstract

Panax ginseng is a folk medicine with various cardiovascular actions; however, its underlying mechanisms of action are not well known. In the present study, we examined the effects of ginseng and its main component, ginsenoside Re, on action potentials and membrane currents recorded from isolated guinea pig ventricular myocytes with the whole-cell patch clamp technique. Ginseng (1 mg/ml) shortened the action potential duration in a rate-dependent manner. Ginseng depressed the L-type Ca2+ current (ICa-L) in a mode of both tonic block and use-dependent block, and enhanced the slowly activating component of the delayed rectifier K+ current (IKs). Ginsenoside Re 3 μM exhibited similar electrophysiological effects to those of 1 mg/ml ginseng, but of slightly smaller magnitude. Inhibition of ICa,L and enhancement of IKs by ginsenoside Re appear to be one of the main electrophysiological actions of ginseng in the heart, although contributions from other ingredients should be considered.

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)

  • Y. Jiang et al.

    Calcium channel blockade and anti-free-radical actions of panaxatriol saponins in cultured myocardiocytes

    Zhongguo Yaoli Xuebao

    (1996)
  • Z.Q. Jin

    The action of ginsenoside Re on inotropy and chronotropy of isolated atria prepared from guinea pigs

    Planta Med.

    (1996)
  • Z.Q. Jin et al.

    Effects of ginsenoside Re on the electrophysiological activity of the heart

    Planta Med.

    (1994)
  • N.K. Jurkiewicz et al.

    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.

    (1993)
  • R.S. Kass et al.

    Channel structure and drug-induced cardiac arrhythmias

    Proc. Natl. Acad. Sci. U. S. A.

    (2000)
  • M.T. Keating

    The long QT syndrome. A review of recent molecular genetic and physiologic discoveries

    Medicine (Baltimore)

    (1996)
  • Cited by (57)

    • Chemical constituents of Panax ginseng and Panax notoginseng explain why they differ in therapeutic efficacy

      2020, Pharmacological Research
      Citation Excerpt :

      Furthermore, researchers have suggested that administration of ginsenoside Rd can reduce hypertensive remodeling by reversing the increase in store-operated or receptor-operated Ca2+ channels [43]. Subsequently, ginseng and ginsenoside Re have been reported to delay K+ currents in ventricular myocytes of guinea pig [40]. Another study showed that ginsenoside Re protects the heart against ischemia-reperfusion (IR) injury and induces cardiac K+ channel activation through nitric oxide modulation [44].

    View all citing articles on Scopus
    1

    Present address: Faculty of Human Life Science, Jissen Women's University, 4-1-1 Oosakaue, Hino-shi, Tokyo 191-8510, Japan.

    View full text