Ginseng ginsenoside pharmacology in the nervous system: involvement in the regulation of ion channels and receptors

Abstract

Ginseng, the root of Panax ginseng C.A. Meyer, is one of the oldest traditional medicines and is thought to be a tonic. It has been claimed that ginseng may improve vitality and health. Recent studies have advanced ginseng pharmacology and shown that ginseng has various pharmacological effects in the nervous system. Ginsenosides, steroid glycosides extracted from ginseng, were one of the first class of biologically active plant glycosides identified. The diverse pharmacological effects of ginsenosides have been investigated through the regulation of various types of ion channels and receptors in neuronal cells and heterologous expression systems. Ginsenoside Rg3 regulates voltage-gated ion channels such as Ca2+, K+, and Na+ channels, and ligand-gated ion channels such as GABAA, 5-HT3, nicotinic acetylcholine, and N-methyl-D-aspartate (NMDA) receptors through interactions with various sites including channel blocker binding sites, toxin-binding sites, channel gating regions, and allosteric channel regulator binding sites when the respective ion channels or receptors are stimulated with depolarization or ligand treatment. Treatment with ginsenoside Rg3 has been found to stabilize excitable cells by blocking influxes of cations such as Ca2+ and Na+, or by enhancing Cl− influx. The aim of this review is to present recent findings on the pharmacological functions of the ginsenosides through the interactions with ion channels and receptors. This review will detail the pharmacological applications of ginsenosides as neuroprotective drugs that target ion channels and ligand-gated ion channels.

Gintonin Attenuates D-Galactose-Induced Hippocampal Senescence by Improving Long-Term Hippocampal Potentiation, Neurogenesis, and Cognitive Functions

“…5a). Moreover, there was no difference in the discrimination ratio (F [3,34] = 0.775, p = 0.516; Fig. 5b).…”

“…The ginseng extract contains several bioactive ingredients, such as acidic polysaccharides, which are known to stimulate the immune system; ginsenoside, one of the saponins produced by this plant, exhibits diverse but nonspecific biological effects [3]. However, these ginseng ingredients do not fully account for the molecular mechanism(s) responsible for the ginseng extract-mediated beneficial effects on brain functions and anti-brain aging because they do not target a specific membrane protein [3]. Moreover, recent studies have demonstrated that ginseng extract includes a novel component called gintonin, which is a non-acidic polysaccharide and a non-saponin.…”

“…Ginseng is extracted with water and/or alcohol to obtain the water-soluble and/or water-insoluble components respectively [2]. The ginseng extract contains several bioactive ingredients, such as acidic polysaccharides, which are known to stimulate the immune system; ginsenoside, one of the saponins produced by this plant, exhibits diverse but nonspecific biological effects [3]. However, these ginseng ingredients do not fully account for the molecular mechanism(s) responsible for the ginseng extract-mediated beneficial effects on brain functions and anti-brain aging because they do not target a specific membrane protein [3].…”

Involvement of N-Methyl-D-Aspartic Acid Receptor and DL-α-Amino-3-Hydroxy-5- Methyl-4-Isoxazole Propionic Acid Receptor in Ginsenosides Rb1 and Rb3 against Oxygen-Glucose Deprivation-Induced Injury in Hippocampal Slices from Rat

“…In previous studies, the effects of ginsenosides on glutamatergic transmission have been found, which could regulate presynaptic neurotransmitter release and postsynaptic receptor activity [9]. Duan and Nicholson [10] reported that ginsenoside Rh2 inhibited Na + channel-dependent amino acid neurotransmitter release from presynaptic nerve terminals.…”

“…Ginsenosides, the major active components from stems and leaves of Panax ginseng, have been reported to show various protective effects on ischemic brain injury [3-5]. To search for the neuroprotective agents, we had compared the neuroprotective effects of 9 individual ginsenosides (Rb1, Rb3, Rd, Re, Rg1, Rg2, Rh1, Rh2, and F11) in hippocampal slices, and found that Rb1, Rb3, Rg1, Rh2, and F11 could protect neurons among them [6].…”