Protective effects of standardized Thuja orientalis leaves against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells

• Published in: Toxicology in vitro Vol. 24; no. 3; pp. 759 - 765
• Main Authors: Ju, Mi Sun, Lee, Pyeongjae, Kim, Hyo Geun, Lee, Ki Yong, Hur, Jinyoung, Cho, Seung-Hun, Sung, Sang Hyun, Oh, Myung Sook
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2010
• Subjects: 6-Hydroxydopamine; Antiapoptotic; Antioxidant; Antioxidants - pharmacology; Apoptosis - drug effects; Benzothiazoles - metabolism; Biphenyl Compounds - metabolism; Caspase 3 - metabolism; Cell Line, Tumor; Cell Nucleus - drug effects; Cell Nucleus - ultrastructure; Cell Survival - drug effects; Enzyme Activation - drug effects; Extracellular Signal-Regulated MAP Kinases - metabolism; Free Radical Scavengers - pharmacology; Humans; Membrane Potentials - drug effects; Mitochondrial Membranes - drug effects; Neuroprotective; Neurotoxicity Syndromes - prevention & control; Nitric Oxide - metabolism; Oxidopamine - antagonists & inhibitors; Oxidopamine - toxicity; Phosphorylation; Picrates - metabolism; Plant Extracts - pharmacology; Plant Leaves - chemistry; Reactive Oxygen Species - metabolism; Sulfonic Acids - metabolism; Sympatholytics - antagonists & inhibitors; Sympatholytics - toxicity; Thuja - chemistry; Thuja orientalis; Neuroprotective; Thuja orientalis; Antiapoptotic; Antioxidant; 6-Hydroxydopamine
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2009.12.026

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.