Possible Protection by Notoginsenoside R1 against Glutamate Neurotoxicity Mediated by N-methyl-D-aspartate Receptors Composed of an NR1/NR2B Subunit Assembly
Possible Protection by Notoginsenoside R1 against Glutamate Neurotoxicity Mediated by N-methyl-D-aspartate Receptors Composed of an NR1/NR2B Subunit Assembly
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DOI：
10.1002/jnr.22021
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发表时间：
2009-07-01
影响因子：
4.2
通讯作者：
Yoneda, Yukio
中科院分区：
文献类型：
--
作者：
Gu, Bin;Nakamichi, Noritaka;Yoneda, Yukio
三七皂苷R1（NTR 1）是三七中的主要活性成分，三七是一种在亚洲广泛使用多年的草药。本研究的目的是探讨NTR 1对谷氨酸（Glu）神经毒性的药理学特性沿着可能的作用机制。我们发现，NTR 1显着保护神经元的细胞活力的损失所造成的短暂暴露于10 μ M的谷氨酸1小时，在浓度为0.1至10 μ M的剂量依赖性的方式，而不影响单独的生存能力。NTR 1可显著抑制Glu诱导的PI染色阳性细胞数的增加、细胞内游离Ca ~（2+）的增加、细胞内活性氧的过度产生以及线粒体膜电位的去极化，并阻断Bcl-2的下降和Bax的表达水平的升高。我们进一步评估了NTR 1保护神经元免受Glu毒性的靶位点，通过使用人胚肾293细胞中N-甲基-D-天冬氨酸（NMDA）受体亚基的获得性表达策略。我们发现，10 μ M NTR 1保护NR 1/NR 2B亚基表达细胞免于100 μ M NMDA引起的细胞死亡，但不保护NR 1/NR 2A亚基表达细胞。这些结果表明，NTR 1可能优先保护神经元免受由脑中NR 1/NR 2B亚基组装体组成的NMDA受体介导的Glu兴奋毒性。(C)2009威利-利斯公司
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 mu M Glu for 1 hr in a dose-dependent manner at concentrations from 0.1 to 10 mu M, without affecting the viability alone. NTR1 significantly inhibited the increased number of cells positive to propidium iodide (PI) staining, increase of intracellular free Ca2+ 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 mu M NTR1 protected NR1/NR2B subunit expressing cells from cell death by 100 mu M 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. (C) 2009 Wiley-Liss, Inc.