title: Dihydromyricetin protects neurons in an MPTP-induced model of Parkinson's disease by suppressing glycogen synthase kinase-3 beta activity.
abstract: OBJECTIVE
  It is general believed that mitochondrial dysfunction and oxidative stress play critical roles in the pathology of Parkinson's disease (PD). Dihydromyricetin (DHM), a natural flavonoid extracted from Ampelopsis grossedentata, has recently been found to elicit potent anti-oxidative effects. In the present study, we explored the role of DHM in protecting dopaminergic neurons.
  
  
  METHODS
  Male C57BL/6 mice were intraperitoneally injected with 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 d to induce PD. Additionally, mice were treated with either 5 or 10 mg/kg DHM for a total of 13 d (3 d before the start of MPTP, during MPTP administration (7 d) and 3 d after the end of MPTP). For the saline or DHM alone treatment groups, mice were injected with saline or DHM for 13 d. On d 14, behavioral tests (locomotor activity, the rotarod test and the pole test) were administered. After the behavioral tests, the mice were sacrificed, and brain tissue was collected for immunofluorescence staining and Western blotting. In addition, MES23.5 cells were treated with MPP+and DHM, and evaluated using cell viability assays, reactive oxygen species (ROS) measurements, apoptosis analysis and Western blotting.
  
  
  RESULTS
  DHM significantly attenuated MPTP-induced mouse behavioral impairments and dopaminergic neuron loss. In the MES23.5 cells, DHM attenuated MPP+-induced cell injury and ROS production in a dose-dependent manner. In addition, DHM increased glycogen synthase kinase-3 beta phosphorylation in a dose- and time-dependent manner, which may be associated with DHM-induced dopaminergic neuronal protection.
  
  
  CONCLUSIONS
  The present study demonstrated that DHM is a potent neuroprotective agent for DA neurons by modulating the Akt/GSK-3β pathway, which suggests that DHM may be a promising therapeutic candidate for PD.
authors.affiliation: Jiangsu Key Laboratory for Translational Research and Therapy for Neuropsychiatric Disorders & the Collaborative Innovation Center for Brain Science, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Zhao-Xiang
authors.initials: ZX
authors.lastname: Ren
authors.affiliation: Jiangsu Key Laboratory for Translational Research and Therapy for Neuropsychiatric Disorders & the Collaborative Innovation Center for Brain Science, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Ya-Fei
authors.initials: YF
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory for Translational Research and Therapy for Neuropsychiatric Disorders & the Collaborative Innovation Center for Brain Science, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Cao
authors.affiliation: Jiangsu Key Laboratory for Translational Research and Therapy for Neuropsychiatric Disorders & the Collaborative Innovation Center for Brain Science, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Xue-Chu
authors.initials: XC
authors.lastname: Zhen
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002460:Cell Line; D044948:Flavonols / Q000627:therapeutic use*; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors*; D008297:Male; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051381:Rats
chemical_list: D044948:Flavonols; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000071679:Glycogen Synthase Kinase 3 beta; C472036:dihydromyricetin