title: Neuroprotection by Kukoamine A against oxidative stress may involve N-methyl-D-aspartate receptors.
abstract: BACKGROUND
  Accumulative evidences have indicated that oxidative-stress and over-activation of N-methyl-d-aspartate receptors (NMDARs) are important mechanisms of brain injury. This study investigated the neuroprotection of Kukoamine A (KuA) and its potential mechanisms.
  
  
  METHODS
  Molecular docking was used to discover KuA that might have the ability of blocking NMDARs. Furthermore, the MTT assay, the measurement of LDH, SOD and MDA, the flow cytometry for ROS, MMP and Annexin V-PI double staining, the laser confocal microscopy for intracellular Ca2+ and western-blot analysis were employed to evaluate the neuroprotection of KuA.
  
  
  RESULTS
  KuA attenuated H2O2-induced cell apoptosis, LDH release, ROS production, MDA level, MMP loss, and intracellular Ca2+ overload (both induced by H2O2 and NMDA), as well as increased the SOD activity. In addition, it could modulate the apoptosis-related proteins (Bax, Bcl-2, p53, procaspase-3 and procaspase-9), the SAPKs (ERK, p38), AKT, CREB, NR2A and NR2B expression.
  
  
  CONCLUSIONS
  All the results indicated that KuA has the ability of anti-oxidative stress and this effect may partly via blocking NMDARs in SH-SY5Y cells.
  
  
  CONCLUSIONS
  KuA might have the potential therapeutic interventions for brain injury.
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, China; Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Hu
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Ling-Yue
authors.initials: LY
authors.lastname: Gao
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Yi-Xuan
authors.initials: YX
authors.lastname: Niu
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Meng
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Can
authors.initials: C
authors.lastname: Cui
authors.affiliation: Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, China. Electronic address: zhaoqingchun1967@163.com.
authors.forename: Qing-Chun
authors.initials: QC
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D018696:Neuroprotective Agents; D016877:Oxidants; D016194:Receptors, N-Methyl-D-Aspartate; C096274:kukoamine A; D013096:Spermine; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D002118:Calcium
keywords: Hydrogen peroxide; Kukoamine A; Molecular docking; NMDA; Neuroprotection; SH-SY5Y