title: Tetrahydroxystilbene glucoside protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity.
abstract: 1-methyl-4-phenylpyridinium (MPP+), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin for inducing a cell model of Parkinson's disease. This study aimed to evaluate the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component extracted from Polygonum multiflorum, on MPP+-induced cytotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells. The results from the MTT and lactate dehydrogenase (LDH) assays showed that incubating cells with 500 μM MPP+ for 24 h decreased cell viability and increased LDH leakage, whereas preincubating cells with 3.125 to 50 μM TSG for 24 h protected the cells against MPP+-induced cell damage. Using 2',7'-dichlorofluorescin diacetate (DCFH-DA) and rhodamine 123, respectively, we found that TSG inhibited both the elevation of intracellular reactive oxygen species and the disruption of mitochondrial membrane potential induced by MPP+. In addition, TSG suppressed both the upregulation of the ratio of Bax to Bcl-2 and the activation of caspase-3 induced by MPP+, and TSG inhibited apoptosis as detected by flow cytometric analysis using Annexin-V and propidium (PI) label. These results suggest that TSG may protect neurons against MPP+-induced cell death through improving mitochondrial function, decreasing oxidative stress and inhibiting apoptosis, and this may provide a potentially new strategy for preventing and treating neurodegenerative disorders such as Parkinson's disease.
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
authors.forename: Fang-ling
authors.initials: FL
authors.lastname: Sun
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.forename: Ru-yi
authors.initials: RY
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Li
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D005960:Glucosides; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013267:Stilbenes; D051028:bcl-2-Associated X Protein; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside; D053148:Caspase 3; D015655:1-Methyl-4-phenylpyridinium