title: Neuroprotection by tetrahydroxystilbene glucoside in the MPTP mouse model of Parkinson's disease.
abstract: Our in vitro experiments suggested that tetrahydroxystilbene glucoside (TSG) affords a significant neuroprotective effect against MPP⁺-induced damage and apoptosis in PC12 cells though activation of the PI3K/Akt pathway. This study was aimed to investigate the potential neuroprotective effect of TSG in 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP)-treated mouse model of Parkinson's disease (PD). We found that treatment of TSG protected dopaminergic neurons by preventing MPTP-induced decreases in substantia nigra tyrosine hydroxylase (TH)-positive cells and striatal dopaminergic transporter (DAT) protein levels. Furthermore, it was also associated with increasing striatal Akt and GSK3β phosphorylation, up-regulation of the Bcl-2/BAD ratio, and inhibition of the activation of caspase-9 and caspase-3. These results showed that TSG promoted dopamine neuron survival in vivo, the PI3K/Akt signaling pathway may have mediated the protection of TSG against MPTP, suggesting that TSG treatment might represent a neuroprotective treatment for PD.
authors.affiliation: Department of Scientific Research, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710054, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.forename: LinHong
authors.initials: L
authors.lastname: Huang
authors.forename: Liangwei
authors.initials: L
authors.lastname: Chen
authors.forename: Dingjun
authors.initials: D
authors.lastname: Hao
authors.forename: Jianzong
authors.initials: J
authors.lastname: Chen
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001259:Ataxia / Q000209:etiology / Q000517:prevention & control; D001522:Behavior, Animal / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005960:Glucosides / Q000627:therapeutic use*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000627:therapeutic use*; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D005960:Glucosides; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C493215:Slc6a3 protein, mouse; D013267:Stilbenes; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; C514862:Akt1 protein, mouse; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: Neuroprotection; Parkinson's disease; Phosphatidylinositol 3-kinase (PI3K)/Akt; Tetrahydroxystilbene glucoside; Tyrosine hydroxylase