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Published on: January 4, 2015
Tetrahydroxystilbene glucoside protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity
Fang-ling Sun1, Lan Zhang, Ru-yi Zhang
1Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
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.
Insights
2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) protects human neuroblastoma cells from Parkinson
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- 1-methyl-4-phenylpyridinium (MPP+) is a neurotoxin used to model Parkinson's disease.
- Parkinson's disease is characterized by dopaminergic neurodegeneration.
- Polygonum multiflorum contains compounds with potential therapeutic properties.
Purpose of the Study:
- To evaluate the neuroprotective effects of 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) against MPP+-induced cytotoxicity.
- To investigate the mechanisms underlying TSG's protective effects in human dopaminergic neuroblastoma SH-SY5Y cells.
Main Methods:
- Cell viability assays (MTT, LDH leakage).
- Measurement of intracellular reactive oxygen species (ROS) and mitochondrial membrane potential.
- Analysis of apoptosis-related proteins (Bax, Bcl-2, caspase-3) and flow cytometry (Annexin-V/PI staining).
Main Results:
- TSG (3.125–50 μM) significantly protected SH-SY5Y cells from MPP+-induced damage.
- TSG inhibited MPP+-induced ROS elevation and mitochondrial dysfunction.
- TSG suppressed apoptosis by downregulating Bax/Bcl-2 ratio and inhibiting caspase-3 activation.
Conclusions:
- TSG exhibits neuroprotective effects against MPP+-induced neurotoxicity in SH-SY5Y cells.
- TSG's mechanism involves improving mitochondrial function, reducing oxidative stress, and inhibiting apoptosis.
- TSG represents a potential therapeutic strategy for neurodegenerative disorders like Parkinson's disease.
