Protective effects of standardized Thuja orientalis leaves against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells.
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.
Ju
Mi Sun
MS
Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Lee
Pyeongjae
P
Kim
Hyo Geun
HG
Lee
Ki Yong
KY
Hur
Jinyoung
J
Cho
Seung-Hun
SH
Sung
Sang Hyun
SH
Oh
Myung Sook
MS
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D052160:Benzothiazoles / Q000378:metabolism; D001713:Biphenyl Compounds / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism; D016627:Oxidopamine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010766:Phosphorylation; D010851:Picrates / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D013451:Sulfonic Acids / Q000378:metabolism; D013565:Sympatholytics / Q000037:antagonists & inhibitors* / Q000633:toxicity; D029783:Thuja / Q000737:chemistry*
D000975:Antioxidants; D052160:Benzothiazoles; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D010851:Picrates; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D013451:Sulfonic Acids; D013565:Sympatholytics; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D009569:Nitric Oxide; D016627:Oxidopamine; C004931:1,1-diphenyl-2-picrylhydrazyl; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3