title: Phosphatidylinositol 3 kinase/protein kinase B is responsible for the protection of paeoniflorin upon H₂O₂-induced neural progenitor cell injury.
abstract: Promoting neural stem/progenitor cell (NSC/NPC) survival in the pro-apoptotic environment is critical to stem cell replacement for neurodegenerative disease therapy. Paeoniflorin (PF), one of the principal bioactive components in Paeoniae Radix, has been used widely in central nervous system (CNS) diseases treatment and serves as an antioxidant to protect neurons against oxidative stress. The present study investigated the protective effects of PF on NPC injury induced by hydrogen peroxide (H₂O₂). After challenge with 200 μM H₂O₂ for 2h, loss of cell viability and excessive apoptotic cell death were observed in cultured NPC, PF treatment conferred protective effects against the loss of cellular viability in a concentration-dependent manner. PF pretreatment also inhibited NPC apoptosis induced by H₂O₂ by reversing the decreased level of Procaspase-3 and balancing Bcl-2 and Bax expression. Furthermore, PF-mediated NPC protection was associated with an increase in phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt-1) phosphorylation in a time- and concentration-dependent manner. Selective inhibition of PI3K using LY294002 abolished PF-mediated phosphorylation of Akt-1 and NPC protection upon oxidative stress. These data suggest that PF-mediated NPC protection on H₂O₂ injury is reliant on the activation of the PI3K/Akt-1 pathway, giving insight to an essential role of PF in NPC protection.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China.
authors.forename: Y-M
authors.initials: YM
authors.lastname: Wu
authors.forename: R
authors.initials: R
authors.lastname: Jin
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Guo
authors.forename: X-B
authors.initials: XB
authors.lastname: Li
authors.forename: S-B
authors.initials: SB
authors.lastname: Liu
authors.forename: X-X
authors.initials: XX
authors.lastname: Luo
authors.forename: M-G
authors.initials: MG
authors.lastname: Zhao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D001921:Brain / Q000166:cytology; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D039821:Monoterpenes; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D058953:Neural Stem Cells / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D006027:Glycosides
chemical_list: D001565:Benzoates; D001952:Bridged-Ring Compounds; D004791:Enzyme Inhibitors; D005960:Glucosides; D006861:Hydrogen Peroxide; D007381:Intermediate Filament Proteins; D039821:Monoterpenes; D009419:Nerve Tissue Proteins; D064231:Nestin; D018696:Neuroprotective Agents; D016877:Oxidants; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C577485:Nes protein, mouse; C015423:peoniflorin; D006027:Glycosides