title: Maslinic acid promotes synaptogenesis and axon growth via Akt/GSK-3β activation in cerebral ischemia model.
abstract: Maslinic acid, a natural pentacyclic triterpene from Olea europaea plants, possesses neuroprotective effects both in vivo and in vitro. However, the mechanism of its action is not well understood. In this study, we investigated the potential effects of maslinic acid on synaptogenesis and axonal regeneration, as well as the possible signal pathway involved in a cerebral ischemia mouse model. Adult male C57BL/6J mice were subjected to 1h of cerebral ischemia by middle cerebral artery occlusion (MCAO). Maslinic acid (0.1, 1 and 10mg/kg) was administered intragastrically 24h after MCAO once daily for 7 consecutive days. Axonal loss and synaptophysin expression in the ischemic boundary area was evaluated by histological assay. The Akt/GSK-3β signal pathway was determined by western blot analysis. Two Akt inhibitors, LY294002 and MK2206, were used to verify the involvement of Akt/GSK-3β pathway in maslinic acid-mediated neuroprotection. Maslinic acid significantly prevented axonal damage, promoted axonal regeneration and increased synaptophysin expression 7 days after ischemia. In addition, maslinic acid treatment was shown to enhance Akt activity and promote GSK-3β phorsphorylation in stoke mice. The increased neurite outgrowth and synaptophysin expression by maslinic acid treatment was blocked by the Akt inhibitors both in vivo and in vitro.. These findings suggested that maslinic acid promotes synaptogenesis and axonal regeneration by regulating Akt/GSK-3β signaling pathway, which may, in turn, provide neuroprotection.
authors.affiliation: Institute of Translational Medicine, Nanchang University, 1299 Xuefu Avenue, Nanchang 330001, PR China.
authors.forename: Yisong
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Physiology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Menghao
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada R3E0J9.
authors.forename: Teng
authors.initials: T
authors.lastname: Guan
authors.affiliation: Department of Physiology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Physiology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Liangxun
authors.initials: L
authors.lastname: Cao
authors.affiliation: Institute of Translational Medicine, Nanchang University, 1299 Xuefu Avenue, Nanchang 330001, PR China.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Han
authors.affiliation: Department of Physiology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Physiology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Xuzhen
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Physiology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: phy.lym@gmail.com.
authors.forename: Yunman
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center for Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, PR China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Sun
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D009828:Oleanolic Acid / Q000031:analogs & derivatives
chemical_list: D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D018696:Neuroprotective Agents; D051057:Proto-Oncogene Proteins c-akt; D016708:Synaptophysin; D014315:Triterpenes; C569015:Syp protein, mouse; C412811:maslinic acid; D009828:Oleanolic Acid; C000605506:GSK3B protein, human; C000605507:Gsk3b protein, mouse
keywords: Akt; Axon; Cerebral ischemia; GSK-3β; Maslinic acid; synaptophysin