Protective effects of standardized Thuja orientalis leaves against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells
Protective effects of standardized Thuja orientalis leaves against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells
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DOI：
10.1016/j.tiv.2009.12.026
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发表时间：
2010-04-01
影响因子：
3.2
通讯作者：
Oh, Myung Sook
中科院分区：
文献类型：
--
作者：
Ju, Mi Sun;Lee, Pyeongjae;Oh, Myung Sook
尽管帕金森病（PD）的病因尚不清楚，但最近的研究表明，线粒体缺陷导致的氧化应激（OS）和细胞凋亡可能在其发病机制中发挥重要作用。 6-羟基多巴胺 (6-OHDA) 是一种常用于 PD 模型的神经毒素，可诱导活性氧 (ROS) 和线粒体缺陷介导的选择性儿茶酚胺能细胞死亡。本研究探讨了著名东方传统药物侧柏叶 (TOFE) 对 6-OHDA 诱导的 SH-SY5Y 细胞神经毒性的保护作用。 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物测定和Hoechst染色表明TOFE减轻了6-OHDA应激引起的细胞损伤。 TOFE 在 2,2-二苯基-2-三硝苯肼和 2,2-偶氮双-(3-乙基-苯并噻唑啉-6-磺酸) 测定中表现出强大的自由基清除作用，并减少 6-OHDA 诱导的细胞内 ROS 和细胞外一氧化氮的产生。此外，TOFE 还可阻断线粒体膜电位的降低、细胞色素 c 的释放以及 caspase-3 的激活。此外，TOFE 降低了具有促凋亡功能的细胞外信号调节激酶 (pERK) 的磷酸化。总而言之，TOFE 可能通过下调 OS 和线粒体介导的细胞凋亡以及调节 pERK 来保护 SH-SY5Y 细胞免受 6-OHDA 的影响。 (C) 2009 Elsevier Ltd. 保留所有权利。
Although the etiology of Parkinson's disease (PD) remains unknown, recent studies have suggested that oxidative stress (OS) and apoptosis, as a result of mitochondrial defects, may play important roles in its pathogenesis. 6-Hydroxydopamine (6-OHDA), a neurotoxin commonly used in models of PD, induces selective catecholaminergic cell death, mediated by reactive oxygen species (ROS) and mitochondrial defects. This study investigated the protective effect of Thuja orientalis leaves (TOFE), a well-known oriental traditional medicine, on 6-OHDA-induced neurotoxicity in SH-SY5Y cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Hoechst staining showed that TOFE attenuated the cell damage caused by 6-OHDA stress. TOFE showed strong radical scavenging effects in 2,2-diphenyl-2-picrylhydrazyl and 2,2-azinobis-(3-ethyl-benzthiazoline-6-sulphonic acid) assays, and it reduced the intracellular ROS and extracellular nitric oxide production induced by 6-OHDA. Additionally, TOFE blocked the reduction in the mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase-3. Moreover, TOFE decreased the phosphorylation of extracellular signal-regulated kinase (pERK), which has pro-apoptotic functions. Taken together, TOFE might protect SH-SY5Y cells from 6-OHDA through the downregulation of OS and mitochondrial-mediated apoptosis, and regulation of pERK. (C) 2009 Elsevier Ltd. All rights reserved.