Possible protection by notoginsenoside R1 against glutamate neurotoxicity mediated by N‐methyl‐D‐aspartate receptors composed of an NR1/NR2B subunit assembly

Abstract

Notoginsenoside R1 (NTR1) is the main active ingredient in Panax notoginseng, a herbal medicine widely used in Asia for years. The purpose of this study was to investigate pharmacological properties of NTR1 on neurotoxicity of glutamate (Glu) in primary cultured mouse cortical neurons along with its possible mechanism of action. We found that NTR1 significantly protected neurons from the loss of cellular viability caused by brief exposure to 10 microM Glu for 1 hr in a dose-dependent manner at concentrations from 0.1 to 10 microM, without affecting the viability alone. NTR1 significantly inhibited the increased number of cells positive to propidium iodide (PI) staining, increase of intracellular free Ca(2+) ions, overproduction of intracellular reactive oxygen species, and depolarization of mitochondrial membrane potential in cultured neurons exposed to Glu, in addition to blocking decreased Bcl-2 and increased Bax expression levels. We further evaluated the target site at which NTR1 protects neurons from Glu toxicity by using the acquired expression strategy of N-methyl-D-aspartate (NMDA) receptor subunits in human embryonic kidney 293 cells. We found that 10 microM NTR1 protected NR1/NR2B subunit expressing cells from cell death by 100 microM NMDA, but not cells expressing NR1/NR2A subunits, when determined by PI staining. These results suggest that NTR1 may preferentially protect neurons from Glu excitotoxicity mediated by NMDA receptor composed of an NR1/NR2B subunit assembly in the brain.

The effects of notoginsenoside R1 on the intestinal absorption of geniposide by the everted rat gut sac model

“…1). It has exhibited various health promotion activities, including being neuroprotective (Gu et al, 2009), hepatic protective (Chen et al, 2008), cardiovascular protective (Zhang et al, 1994), and exhibiting immune stimulation effects.…”

Notoginsenoside R1 increases neuronal excitability and ameliorates synaptic and memory dysfunction following amyloid elevation

“…NTR1 is specifically distributed in Panax notoginseng, unlike other ginsenosides such as ginsenoside R1, Rg1, R3, etc., which are distributed in both Panax notoginseng and Panax ginseng . NTR1 has the same chemical structure as ginsenosides such as Rg1, Rb1, Rg2, and Rg3, a common four-ring hydrophobic steroid-like structure attached with sugar moieties22. Recent studies have shown that ginsenosides have multifaceted neuroprotective effects in AD and related models both in vitro and in vivo .…”

Neuroprotective Effects of Hydroxysafflor Yellow A Against Excitotoxic Neuronal Death Partially Through Down-Regulation of NR2B-Containing NMDA Receptors

“…levels, and caspase activation [41,42]. Moreover, the expression ratio between the anti-apoptotic Bcl-2 and the pro-apoptotic Bax proteins is shown to be at least partly responsible for excitotoxic apoptotic cell death mediated by NMDAR in neurons [29,43,44]. In this study, the level of Bcl-2 protein was significantly decreased while Bax was significantly increased in the cortical neurons by NMDA stimuli.…”