Tetrahydroxystilbene glucoside protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity

Eur J Pharmacol. 2011 Jun 25;660(2-3):283-90. doi: 10.1016/j.ejphar.2011.03.046. Epub 2011 Apr 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / toxicity*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Survival / drug effects
  • Cytoprotection / drug effects*
  • Gene Expression Regulation / drug effects
  • Glucosides / pharmacology*
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Neuroblastoma / pathology*
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Stilbenes / pharmacology*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Glucosides
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Stilbenes
  • bcl-2-Associated X Protein
  • 2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside
  • Caspase 3
  • 1-Methyl-4-phenylpyridinium