Changes of [3H]MK-801, [3H]muscimol and [3H]flunitrazepam Binding in Rat Brain by the Prolonged Ventricular Infusion of Transformed Ginsenosides

Abstract

Ameliorating effects of ginseng were observed on neuronal cell death associated with ischemia or glutamate toxicity. Ginseng saponins are transformed by intestinal microflora and the transformants would be absorbed from intestine. In the present study, we have investigated the effects of transformed ginsenoside Rg3, Rh2 and compound K on the modulation of NMDA receptor and GABAA receptor binding in rat brain. The NMDA receptor binding was analyzed by quantitative autoradiography using [3H]MK-801 binding, and GABAA receptor bindings were analyzed by using [3H]muscimol and [3H]flunitrazepam binding in rat brain slices. Ginsenoside Rg3, Rh2 and compound K were infused (10 microg/10 microl/h) into rat brain lateral ventricle for 7 days, through pre-implanted cannula by osmotic minipumps (Alzet, model 2ML). The levels of [3H]MK-801 binding were highly decreased in almost all regions of frontal cortex and hippocampus by ginsenoside Rh2 and compound K. The levels of [3H]muscimol binding were elevated in part of frontal cortex and granule layer of cerebellum by the treatment of ginsenoside Rh2 and compound K. However, the [3H]flunitrazepam binding was not modulated by any tested ginsenosides. Ginsenoside Rh2 and compound K induced the downregulation of the [3H]MK-801 binding as well as upregulation of the and [3H]muscimol binding in a region-specific manner after prolonged infusion into lateral ventricle. However, ginsenoside Rg3 did not show the significant changes of ligand bindings. In addition, ginsenoside Rh2 decreased the expression of nNOS in the hippocampus although Rg3 decreased the expression in the cortex. These results suggest that biotransformed ginsenoside Rh2 and compound K could play an important role in the biological activities in the central nervous systems and neurodegenerative disease.

Protective effects of ginseng on neurological disorders

“…As with iNOS, neuronal nitric oxide synthase (nNOS) is inhibited by ginseng. Ginseng saponins are transformed by intestinal microflora, and a product Rh2 decreased the expression of nNOS in the hippocampus, while another product Rg3 decreased its expression in the neocortex (Jang et al, 2004 ). Ginsenoside Rg1 has neuroprotective effects on ischemia-reperfusion injury in cultured hippocampal cells by blocking calcium influx into neuronal cells and decreasing nNOS activity (He et al, 2014 ).…”

A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system

“…Although part of the reason that much of the pharmacological intervention study against neurological diseases using ginseng and/or ginsenosides are focused on cerebral ischemia are related to the ginseng’s potent anti-inflammatory and anti-oxidative activity in microglia and astrocytes as well as in insulted brain [30,80,101,112], many other studies suggest that other mechanisms are also involved in the potent neuroprotective or neurorestorative actions such as regulation of channel proteins including TRM, ASIC and NMDA receptors [91], Potassium channel [113], Na channel [114], inhibition of mitochondrial permeability transition pores [86], regulation of anti-apoptotic proteins [87], changes in receptor binding activity including NMDA and GABA receptors [115], defense against excessive endoplasmic reticulum stress [116], regulation of angiogenesis and the expression of vascular endothelial growth factor [99,117,118], cerebral vasorelaxation possibly via NO pathway [119], and induction of hypoxia inducible factor-1α [120], which may affects cell survival, angiogenesis, and neurogenesis after ischemic injury.…”

Yin and Yang of ginseng pharmacology: ginsenosides vs gintonin

“…Gintonin evokes cell proliferation and migration and morphological changes in human umbilical vein endothelial cells and PC12 neuronal cells 4,5,41,45 . These effects of gintonin are consistent with those caused by LPAs via GPCRs and diverse G proteins, such as Gα i/o , Gα 12/13 , and Gα q/11 1 .…”

“…For example, ginsenoside Rg 3 inhibits not only voltage-gated Ca 2+ and Na + channels but also ligand-gated ion channels such as 5-HT 3 receptors 2,3,4 . Furthermore, ginsenosides stimulate anion-gated GABA A and glycine receptors 5,6 . Therefore, ginsenosides decrease the excitability of excitable cells by inhibition of cation influx and stimulation of anion influx across the plasma membrane.…”