title: Promoting neurogenesis via Wnt/β-catenin signaling pathway accounts for the neurorestorative effects of morroniside against cerebral ischemia injury.
abstract: Ischemic stroke is a leading cause of mortality and permanent disability in adults worldwide. Neurogenesis triggered by ischemia in the adult mammalian brain may provide insights into stroke treatment. Morroniside is an active component of sarcocarp of C. officinalis that have shown neuroprotective effects. The aim of the present study is to test whether morroniside promotes neurogenesis via Wnt/β-catenin signaling pathway for brain recovery in a rat model of focal cerebral ischemia. Morroniside was administered intragastrically once daily at the concentrations of 30, 90 and 270 mg/kg for 7 days post-ischemia. Neurological functions were detected by Ludmila Belayev score tests. Endogenous neural stem cells responses were investigated with immunofluorescence staining of Ki-67 and Nestin to identify the neurogenesis in the subventricular zone (SVZ). The expression of proteins involved in and related to Wnt/β-catenin signaling pathway was detected by western blotting analysis. Morroniside significantly promoted neurogenesis for brain recovery 7 days post-ischemia. Increased expression of Wnt 3a, β-catenin and T-cell transcription factor-4 (Tcf-4), along with activation of downstream transcription factors Pax6 and neurogenin2 (Ngn2), indicated that the neurorestorative effects of morroniside may be associated with Wnt/β-catenin signaling pathway. These data provide support for understanding the mechanisms of morroniside in neurorestorative effects and suggest a potential new strategy for ischemic stroke treatment.
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, 45 Chang-chun Street, Beijing 100053, China.
authors.forename: Fang-Ling
authors.initials: FL
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, 45 Chang-chun Street, Beijing 100053, China. Electronic address: lzwwang@163.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, 45 Chang-chun Street, Beijing 100053, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zuo
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, 45 Chang-chun Street, Beijing 100053, China.
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Xue
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Jing-dong
authors.initials: JD
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, 45 Chang-chun Street, Beijing 100053, China.
authors.forename: Hou-Xi
authors.initials: HX
authors.lastname: Ai
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, 45 Chang-chun Street, Beijing 100053, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men Beijing 100069, China. Electronic address: xmwang@ccmu.edu.cn.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Xuanwu Hospital of Capital Medical University, 45 Chang-chun Street, Beijing 100053, China. Electronic address: robertjixm@hotmail.com.
authors.forename: Xun-Ming
authors.initials: XM
authors.lastname: Ji
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D006027:Glycosides / Q000494:pharmacology* / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D006027:Glycosides; D018696:Neuroprotective Agents; D014157:Transcription Factors; C488401:morroniside
keywords: Ischemic stroke; Morroniside; Neurogenesis; Wnt/β-catenin signaling