title: Paeoniflorin Attenuates Cerebral Ischemia-Induced Injury by Regulating Ca2+/CaMKII/CREB Signaling Pathway.
abstract: Paeoniflorin (PF) is an active ingredient of Paeoniae Radix which possesses the neuroprotective effect. However, so far, the neuroprotective mechanism of PF has still not been fully uncovered. The Ca2+/Ca2+/calmodulin-dependent protein kinase II (CaMKII)/cAMP response element-binding (CREB) signaling pathway plays an important role in the intracellular signal transduction pathway involved in cell proliferation, cell survival, inflammation and metabolism. Herein, the neuroprotective roles of PF in the models of middle cerebral artery occlusion (MCAO) followed by reperfusion in rats andN-methyl-d-aspartic acid (NMDA)-induced excitotoxicity in primary hippocampal neurons were investigated. Moreover, we attempted to confirm the hypothesis that its protection effect is via the modulation of the Ca2+/CaMKI)/CREB signaling pathway. In this study, PF not only significantly decreased neurological deficit scores and infarct volume in vivo, but also improved neurons' cell viability, and inhibited neurons' apoptosis and intracellular Ca2+concentration in vitro. Furthermore, PF significantly up-regulated p-CREB and p-CaMKII, and down-regulated calmodulin (CaM) in vivo and in vitro. The results indicate that the protective effect of PF on cerebral ischemia reperfusion injury is possible through regulating the Ca2+/CaMKII/CREB signaling pathway.
authors.affiliation: College of Pharmacy of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. zyqfj@hotmail.com.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Pharmacy of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. qlffjtcm@sina.com.
authors.forename: Lifei
authors.initials: L
authors.lastname: Qiao
authors.affiliation: College of Pharmacy of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. xwfjtcm@126.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.affiliation: College of Pharmacy of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. wxyfjtcm@sina.com.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Pharmacy of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. lihuang3413@gmail.com.
authors.forename: Huang
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Pharmacy of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. xwfjlab@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: College of Pharmacy of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. chukedan@gmail.com.
authors.forename: Kedan
authors.initials: K
authors.lastname: Chu
authors.affiliation: College of Pharmacy of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. lyfjlab@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lin
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005960:Glucosides / Q000008:administration & dosage* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D039821:Monoterpenes / Q000008:administration & dosage* / Q000494:pharmacology; D016202:N-Methylaspartate / Q000009:adverse effects; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D006027:Glycosides
chemical_list: D002118:Calcium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017362:Cyclic AMP Response Element-Binding Protein; D005960:Glucosides; D039821:Monoterpenes; D016202:N-Methylaspartate; D018696:Neuroprotective Agents; C015423:peoniflorin; D006027:Glycosides
keywords: CREB; CaMKII; ischemic stroke; middle cerebral artery occlusion; paeoniflorin