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 ginsenosideinduced 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.

Effect of sugar positions in ginsenosides and their inhibitory potency on Na+/K+-ATPase activity

“…Cumulated research outcomes have indicated that identical and variable ginsenosides in these 2 herbs are possibly responsible for the comparable and distinct therapeutic effects between ginseng and sanqi [7] . Ginsenosides are triterpene saponins that have a common 4 ring hydrophobic steroid-like structure with sugar moieties attached mostly at the C-3, C-6, or C-20 position [8] . So far, more than 80 ginsenosides have been isolated from over 10 Panax taxa, and most of these are derived from 4 types of aglycones: protopanaxadiol, protopanaxatriol, oleanolic acid, and ocotillol [9] .…”

Anti-fatigue Effects of 20(<i>S</i>)-Protopanaxadiol and 20(<i>S</i>)-Protopanaxatriol in Mice

“…7) Of constituents, ginsenosides have been reported to show biological activities, including anti-inflammatory, anti-fatigue, anti-stress, and anti-tumor activities. [8][9][10][11][12] The ginsenosides are classified as protopanaxadiols or protopanaxatriols. Orally administered protopanaxadiol-type and protopanaxatriol-type ginsenosides are metabolized to 20(S)-protopanaxadiol (PPD) via compound K and 20(S)-protopanaxatriol (PPT) via ginsenoside Rh1, respectively, by gut microbiota.…”

Ginsenoside Rb1 selectively inhibits the activity of L-type voltage-gated calcium channels in cultured rat hippocampal neurons

“…Its perturbed neuronal Ca 2+ homeostasis is implicated in aging and age-related cognitive impairments [12] . Chen also showed that it could decrease the Aβ-induced elevation of intracellular calcium and stabilize microtubule integrity [18] .…”

“…Nifedipine is an L-type Ca 2+ channel inhibitor, ω-conotoxin GVIA is an N-type Ca 2+ channel inhibitor, and ω-agatoxin IVA is a P/Q-type Ca 2+ channel inhibitor [4][5][6][7][8][9] . Because the elevation of intracellular Ca 2+ levels ([Ca 2+ ] i ) caused by the excessive stimulation of Ca 2+ channels plays a key role in the excitotoxic damage of neurons, agents blocking the elevation of [Ca 2+ ] i by regulating Ca 2+ channels might have neuroprotective effects [10][11][12] .…”