title: 4'-O-β-D-Glucosyl-5-O-Methylvisamminol, A Natural Histone H3 Phosphorylation Epigenetic Suppressor, Exerts a Neuroprotective Effect Through PI3K/Akt Signaling Pathway on Focal Cerebral Ischemia in Rats.
abstract: BACKGROUND
  A bursting inflammation has been observed that compromises neurologic function in patients who experience stroke. We sought to examine the neuroprotective efficacy of 4'-O-β-D-glucosyl-5-O-methylvisamminol (OGOMV), a novel histone H3 phosphorylation epigenetic suppressor) in a transient middle cerebral artery occlusion (tMCAO).
  
  
  METHODS
  A rodent tMCAO model was used. Administration with 400 μg/kg/day OGOMV was initiated 12 hours before (prevention) and 1 hour after animals were subjected to tMCAO (reversal). The cerebral cortex was harvested to examine protein kinase B (PI3D/Akt), 5-bromo-2'-deoxyuridine (Western blot), and caspases (reverse-transcription polymerase chain reaction). In addition, cerebrospinal fluid samples were collected to examine interleukin 1-β, interleukin-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α (reverse-transcription polymerase chain reaction).
  
  
  RESULTS
  Cortical 5-bromo-2'-deoxyuridine and phospho-PI3D/Akt were reduced in tMCAO animals, compared with the healthy controls but increased in the OGOMV treatment and prevention groups. Activated cortical caspase-3,-6, and -9a as well as increased IL-1β and TNF-α levels were observed in the tMCAO animals (P < 0.05). Both prevention and treatment with OGOMV significantly reduced cleaved caspase-3 and -9a groups, but no significant change in caspase-6 was noted. Perifosine, an Akt inhibitor, was added to reduce the bioexpression of phospho-P13D/Akt, and Bcl-2 level and increased cleaved caspase-9a level in both OGOMV prevention and treatment tMCAO groups (P > 0.05).
  
  
  CONCLUSIONS
  Our study suggests that OGOMV could exert a neuroprotective effect by inhibiting the P13D/Akt protein, attenuating inflammation, and cleaved caspase-3- and -9a-related apoptosis. This study also lends credence to support the notion that the prevention of OGOMV could attenuate proinflammatory cytokine mRNA and late-onset caspases in tMCAO and merits further study.
authors: Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Surgery, Kaohsiung Municipal Ta Tung Hospital, Kaohsiung, Taiwan. Electronic address: changchihzen2002@yahoo.com.tw.
authors: Chih-Zen
authors: CZ
authors: Chang
authors: Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors: Shu-Chuan
authors: SC
authors: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C000596311:4'-O-glucosyl-5-O-methylvisamminol; D002867:Chromones; D005960:Glucosides; D006657:Histones; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9
keywords: 4′-O-β-D-glucosyl-5-O-methylvisamminol; Phosphatidylinositol-3-kinase; Protein kinase B; Transient middle cerebral artery occlusion; Tumor necrotic factor-α