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Possible protection by notoginsenoside R1 against glutamate neurotoxicity mediated by N-methyl-D-aspartate receptors composed of an NR1/NR2B subunit assembly.
J Neurosci Res. 2009 Jul; 87(9):2145-56.JN

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.

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Authors+Show Affiliations

Gu B
Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kanazawa, Japan.
Nakamichi N
No affiliation info available
Zhang WS
No affiliation info available
Nakamura Y
No affiliation info available
Kambe Y
No affiliation info available
Fukumori R
No affiliation info available
Takuma K
No affiliation info available
Yamada K
No affiliation info available
Takarada T
No affiliation info available
Taniura H
No affiliation info available
Yoneda Y
No affiliation info available

MeSH

AnimalsApoptosis Regulatory ProteinsCalcium SignalingCell LineCell SurvivalCerebral CortexDose-Response Relationship, DrugExcitatory Amino Acid AgonistsGinsenosidesGlutamic AcidHumansIndicators and ReagentsMembrane Potential, MitochondrialMiceNeuronsNeuroprotective AgentsNeurotoxinsOxidative StressPropidiumRatsReceptors, N-Methyl-D-Aspartate

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19224577

Citation

Gu, Bin, et al. "Possible Protection By Notoginsenoside R1 Against Glutamate Neurotoxicity Mediated By N-methyl-D-aspartate Receptors Composed of an NR1/NR2B Subunit Assembly." Journal of Neuroscience Research, vol. 87, no. 9, 2009, pp. 2145-56.
Gu B, Nakamichi N, Zhang WS, et al. Possible protection by notoginsenoside R1 against glutamate neurotoxicity mediated by N-methyl-D-aspartate receptors composed of an NR1/NR2B subunit assembly. J Neurosci Res. 2009;87(9):2145-56.
Gu, B., Nakamichi, N., Zhang, W. S., Nakamura, Y., Kambe, Y., Fukumori, R., Takuma, K., Yamada, K., Takarada, T., Taniura, H., & Yoneda, Y. (2009). Possible protection by notoginsenoside R1 against glutamate neurotoxicity mediated by N-methyl-D-aspartate receptors composed of an NR1/NR2B subunit assembly. Journal of Neuroscience Research, 87(9), 2145-56. https://doi.org/10.1002/jnr.22021
Gu B, et al. Possible Protection By Notoginsenoside R1 Against Glutamate Neurotoxicity Mediated By N-methyl-D-aspartate Receptors Composed of an NR1/NR2B Subunit Assembly. J Neurosci Res. 2009;87(9):2145-56. PubMed PMID: 19224577.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Possible protection by notoginsenoside R1 against glutamate neurotoxicity mediated by N-methyl-D-aspartate receptors composed of an NR1/NR2B subunit assembly. AU - Gu,Bin, AU - Nakamichi,Noritaka, AU - Zhang,Wen-Sheng, AU - Nakamura,Yukary, AU - Kambe,Yuki, AU - Fukumori,Ryo, AU - Takuma,Kazuhiro, AU - Yamada,Kiyofumi, AU - Takarada,Takeshi, AU - Taniura,Hideo, AU - Yoneda,Yukio, PY - 2009/2/19/entrez PY - 2009/2/19/pubmed PY - 2009/8/15/medline SP - 2145 EP - 56 JF - Journal of neuroscience research JO - J Neurosci Res VL - 87 IS - 9 N2 - 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. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/19224577/Possible_protection_by_notoginsenoside_R1_against_glutamate_neurotoxicity_mediated_by_N_methyl_D_aspartate_receptors_composed_of_an_NR1/NR2B_subunit_assembly_ L2 - https://doi.org/10.1002/jnr.22021 DB - PRIME DP - Unbound Medicine ER -