title: Neuroprotection by Paeoniflorin in the MPTP mouse model of Parkinson's disease.
abstract: Paeoniflorin (PF) is a major bioactive ingredient in Radix Paeonia alba roots that has low toxicity and has been shown to have neuroprotective effects. Our in vitro experiments suggested that PF affords a significant neuroprotective effect against MPP+-induced damage and apoptosis in PC12 cells through Bcl-2/Bax/caspase-3 pathway. The objectives of the present study were to explore the potential neuroprotective effect of PF in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease (PD). Our results demonstrated that PF treatment ameliorated the behavioral deficits of "in spontaneous motor activity and latency to fall of the rotarod test", and reduced dopaminergic cell loss that were induced by MPTP in a dose-dependent manner in an in vivo model of PD. In addition, we found that treatment of PF protected dopaminergic neurons by preventing MPTP-induced decreases in striatal and substantia nigra dopaminergic transporter (DAT) and tyrosine hydroxylase (TH) protein levels, and by changing dopamine catabolism and inhibiting dopamine turnover. Furthermore, it was also associated with up-regulation of the Bcl-2/BAD ratio, and inhibition of the activation of caspase-9 and caspase-3. These results showed that PF promoted dopamine neuron survival in vivo due to the MAO-B inhibition, and the PI3K/Akt signaling pathway may have mediated the protection of PF against MPTP, suggesting that PF treatment might represent a neuroprotective treatment for PD.
authors.affiliation: The Central Laboratory, Changchun Normal University, Changchun, Jilin, PR China.
authors.forename: Meizhu
authors.initials: M
authors.lastname: Zheng
authors.affiliation: The Central Laboratory, Changchun Normal University, Changchun, Jilin, PR China. Electronic address: zhengmz605@mail.cncnc.edu.cn.
authors.forename: Chunming
authors.initials: C
authors.lastname: Liu
authors.affiliation: College of Life Science, Changchun Normal University, Changchun, Jilin, PR China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Higher Education Research Institute, Changchun Normal University, Changchun, Jilin, PR China.
authors.forename: Pan
authors.initials: P
authors.lastname: Yan
authors.affiliation: The Central Laboratory, Changchun Normal University, Changchun, Jilin, PR China.
authors.forename: Dongfang
authors.initials: D
authors.lastname: Shi
authors.affiliation: The Central Laboratory, Changchun Normal University, Changchun, Jilin, PR China.
authors.forename: Yuchi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005960:Glucosides / Q000494:pharmacology*; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D039821:Monoterpenes / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism; D006027:Glycosides
chemical_list: D053148:Caspase 3; D053453:Caspase 9; D004298:Dopamine; D050483:Dopamine Plasma Membrane Transport Proteins; D005960:Glucosides; D008995:Monoamine Oxidase; D008996:Monoamine Oxidase Inhibitors; D039821:Monoterpenes; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D014446:Tyrosine 3-Monooxygenase; D051025:bcl-Associated Death Protein; C494820:Bad protein, mouse; C052617:Bcl2 protein, mouse; C015423:peoniflorin; D006027:Glycosides; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse
keywords: Neuroprotective effect; Paeoniflorin; Parkinson's disease; Phosphatidylinositol 3-kinase (PI3K)/Akt