Ginsenosides: are any of them candidates for drugs acting on the central nervous system?

Abstract

The last two decades have shown a marked expansion in the number of publications regarding the effects of Panax ginseng. Ginsenosides, which are unique saponins isolated from Panax ginseng, are the pharmacologically active ingredients in ginseng, responsible for its effects on the central nervous system (CNS) and the peripheral nervous system. Recent studies have shown that ginsenosides regulate various types of ion channels, such as voltage-dependent and ligand-gated ion channels, in neuronal and heterologously expressed cells. Ginsenosides inhibit voltage-dependent Ca(2+), K(+), and Na(+) channel activities in a stereospecific manner. Ginsenosides also inhibit ligand-gated ion channels such as N-methyl-d-aspartate, some subtypes of nicotinic acetylcholine, and 5-hydroxytryptamine type 3 receptors. Competition and site-directed mutagenesis experiments revealed that ginsenosides interact with ligand-binding sites or channel pore sites and inhibit open states of ion channels. This review will introduce recent findings and advances on ginsenoside-induced regulation of ion channel activities in the CNS, and will further expand the possibilities that ginsenosides may be useful and potentially therapeutic choices in the treatment of neurodegenerative disorders.

Figure 1

The root of Panax ginseng C.A. Meyer (Araliaceae).

Figure 2

Chemical structures of the major types of ginsenosides. Numbers indicate the carbon in the glucose ring that links the two carbohydrates. Abbreviations for carbohydrates are as follows: Glc = glucopyranoside; Ara(fur) = arabinofuranose; Ara(pyr) = arabinopyranoside; and Rha = rhamnopyranoside. PD and PT stand for protopanaxadiol and protopanaxatriol ginsenosides, respectively.

Figure 3

Structures and metabolic pathways of ginsenoside Rb₁, Re, Rg₁, and Rg₃ by human intestinal microflora (→, main pathway by intestinal microflora; , minor pathway by intestinal microflora; ⇒, chemical transformation by steaming). Adapted from Lee et al. (2006a).

Figure 4

Identification of active components responsible for ginseng‐mediated inhibition on hippocampal NMDA receptors and the additive effect of 20(S)‐Rg₃ and 20(S)‐Rh₂ when used at submaximal concentration. In A, black dot (•) represents acute application of 100 μM NMDA in cultured rat hippocampal cells. ***P < 0.001 versus 20(S)‐Rg₁ in B and indicated controls in D. **P < 0.01 versus 20(S)‐Rh₂ in C. In A‐C, each ginsenoside was used at 10‐μM concentration. In D, a submaximal concentration (3 μM) was used for the additive effect. Adapted from Lee et al. (2006a).

Figure 5

Neuroprotective effect of ginseng total saponins (GTS) against 3‐NP in Cresyl Violet (CV), GFAP, and NADPH‐diaphorase staining in coronal rat brain sections at the level of the striatum and anterior commissure from saline (Con), 3‐NP‐treated, or GTS + 3‐NP animals. Adapted from Kim et al. (2005).