title: Neuroprotective effects of oxysophocarpine on neonatal rat primary cultured hippocampal neurons injured by oxygen-glucose deprivation and reperfusion.
abstract: BACKGROUND
  Oxysophocarpine (OSC), a quinolizidine alkaloid extracted from leguminous plants of the genus Robinia, is traditionally used for various diseases including neuronal disorders.
  
  
  OBJECTIVE
  This study investigated the protective effects of OSC on neonatal rat primary-cultured hippocampal neurons were injured by oxygen-glucose deprivation and reperfusion (OGD/RP).
  
  
  METHODS
  Cultured hippocampal neurons were exposed to OGD for 2 h followed by a 24 h RP. OSC (1, 2, and 5 μmol/L) and nimodipine (Nim) (12 μmol/L) were added to the culture after OGD but before RP. The cultures of the control group were not exposed to OGD/RP. MTT and LDH assay were used to evaluate the protective effects of OSC. The concentration of intracellular-free calcium [Ca(2+)]i and mitochondrial membrane potential (MMP) were determined to evaluate the degree of neuronal damage. Morphologic changes of neurons following OGD/RP were observed with a microscope. The expression of caspase-3 and caspase-12 mRNA was examined by real-time quantitative PCR.
  
  
  RESULTS
  The IC50 of OSC was found to be 100 μmol/L. Treatment with OSC (1, 2, and 5 μmol/L) attenuated neuronal damage (p < 0.001), with evidence of increased cell viability (p < 0.001) and decreased cell morphologic impairment. Furthermore, OSC increased MMP (p < 0.001), but it inhibited [Ca(2+)]i (p < 0.001) elevation in a dose-dependent manner at OGD/RP. OSC (5 μmol/L) also decreased the expression of caspase-3 (p < 0.05) and caspase-12 (p < 0.05).
  
  
  CONCLUSIONS
  The results suggested that OSC has significant neuroprotective effects that can be attributed to inhibiting endoplasmic reticulum (ER) stress-induced apoptosis.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Ningxia Medical University , Yinchuan , China .
authors.forename: Qing-Luan
authors.initials: QL
authors.lastname: Zhu
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Li
authors.forename: Ru
authors.initials: R
authors.lastname: Zhou
authors.forename: Ning-Tian
authors.initials: NT
authors.lastname: Ma
authors.forename: Ren-Yuan
authors.initials: RY
authors.lastname: Chang
authors.forename: Teng-Fei
authors.initials: TF
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: Yin-Ju
authors.initials: YJ
authors.lastname: Hao
authors.forename: Shao-Ju
authors.initials: SJ
authors.lastname: Jin
authors.forename: Lin
authors.initials: L
authors.lastname: Ma
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Jian-Qiang
authors.initials: JQ
authors.lastname: Yu
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D016896:Treatment Outcome; D000093842:Matrines
chemical_list: D000470:Alkaloids; D005947:Glucose; D018696:Neuroprotective Agents; D010100:Oxygen; C046246:oxysophocarpine; D000093842:Matrines
keywords: Apoptosis; endoplasmic reticulum; ischemic injury; neuron