title: Protective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1, 4-diol on ischemic and hypoxic neuronal injury.
abstract: BACKGROUND
  Stroke is one of the leading causes of neuronal death. Sesamin is known for neuroprotection by its antioxidant and anti-inflammatory properties but it lacks blood-brain barrier (BBB) activity. A panel of sesamin derivatives was screened and 3-bis (3-methoxybenzyl) butane-1,4-diol (BBD) was selected for high BBB activity and tested for its neuroprotective effect.
  
  
  METHODS
  The focal cerebral ischemia of Sprague-Dawley rats and hypoxia models of murine BV-2 microglia or PC12 cells under oxygen/glucose deprivation were used for in vivo and in vitro test, respectively. Lipid peroxidation and superoxide dismutase (SOD) activity from the ischemic brain were tested and reactive oxygen species (ROS), cytokine production, prostaglandin (PGE2) and related signaling pathways from hypoxic cells were examined by ELISA or Western blot assay, respectively.
  
  
  RESULTS
  BBD showed a protective effect when given 90 min after the focal cerebral ischemia. It also reduced lipid peroxidation and preserved SOD activity from the ischemic brain. The mechanism of BBD was further confirmed by attenuating ROS, cytokine production, and PGE2 release from hypoxic BV-2 or PC12 cells. BBD significantly reduced hypoxia-induced c-Jun N-terminal kinases (JNK) and modulated AKT-1 and caspase-3 (survival and apoptotic pathways) in BV-2 cells, and inhibited hypoxia-induced JNK and cyclooxygenase-2 activation in PC12 cells.
  
  
  CONCLUSIONS
  The neuroprotective effect of BBD on ischemia/hypoxia models was involved with antioxidant and anti-inflammatory effects. The result would help the development of new CNS drug for protection of ischemia/hypoxia injury.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Hou
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Chen
authors.forename: Shih-Hsien
authors.initials: SH
authors.lastname: Chuang
authors.forename: Jen-Shu
authors.initials: JS
authors.lastname: Wang
authors.affiliation: Department of Medical Research, Tungs' Taichung MetroHarbor Hospital, 699 Taiwan Boulevard, Sec,8, Taichung 43503, Taiwan. kcjeng@gmail.com.
authors.forename: Kee-Ching
authors.initials: KC
authors.lastname: Jeng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002072:Butylene Glycols / Q000008:administration & dosage*; D015687:Cell Hypoxia / Q000187:drug effects; D004149:Dioxoles / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D017705:Lignans / Q000008:administration & dosage* / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000096:biosynthesis
chemical_list: C000591381:3-bis(3-methoxybenzyl)butane-1,4-diol; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002072:Butylene Glycols; D004149:Dioxoles; D017705:Lignans; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; C054125:sesamin