title: 4'-O-β-D-glucosyl-5-O-methylvisamminol, an active ingredient of Saposhnikovia divaricata, attenuates high-mobility group box 1 and subarachnoid hemorrhage-induced vasospasm in a rat model.
abstract: BACKGROUND
  High-mobility group box 1 (HMGB1) was observed to be an important extracellular mediator involved in vascular inflammation associated with subarachnoid hemorrhage (SAH). This study is of interest to examine the efficacy of 4'-O-β-D-glucosyl-5-O-methylvisamminol (4OGOMV), C22H28O10, on the alternation of cytokines and HMGB1 in an animal model.
  
  
  METHODS
  A rodent double hemorrhage SAH model was employed. Administration with 4OGOMV was initiated 1 h after animals were subjected to SAH. Basilar arteries (BAs) were harvested and cortexes examined for HMGB1 mRNA, protein expression (Western blot) and monocyte chemoattractant protein-1 (MCP-1) immunostaining. Cerebrospinal fluid samples were collected to examine IL-1β, IL-6, IL-8 and MCP-1 (rt-PCR).
  
  
  RESULTS
  Morphological findings revealed endothelial cell deformity, intravascular elastic lamina torture, and smooth muscle necrosis in the vessels of SAH groups. Correspondently, IL-1β, IL-6 and MCP-1 in the SAH-only and SAH-plus vehicle groups was also elevated. 4OGOMV dose-dependently reduced HMGB1 protein expression when compared with the SAH groups.(p < 0.01) Likewise, 400 μg/kg 4OGOMV reduced IL-1β, MCP-1 and HMGB1 mRNA levels as well as MCP-1(+) monocytes when compared with the SAH groups..
  
  
  CONCLUSIONS
  4OGOMV exerts its neuro-protective effect partly through the dual effect of inhibiting IL-6 and MCP-1 activation and also reduced HMGB1 protein, mRNA and MCP-1(+) leukocytes translocation. This study lends credence to validating 4OGOMV as able to attenuate pro-inflammatory cytokine mRNA, late-onset inflammasome, and cellular basis in SAH-induced vasospasm.
authors.affiliation: Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. changchihzen2002@yahoo.com.tw.|Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung, Taiwan, ROC. changchihzen2002@yahoo.com.tw.|Department of Surgery, Kaohsiung Municipal Ta Tung Hospital, Kaohsiung, Taiwan. changchihzen2002@yahoo.com.tw.
authors.forename: Chih-Zen
authors.initials: CZ
authors.lastname: Chang
authors.affiliation: Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung, Taiwan, ROC. shuchuan@kmu.edu.tw.
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Wu
authors.affiliation: Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. A_LKWAN@yahoo.com.|Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung, Taiwan, ROC. A_LKWAN@yahoo.com.
authors.forename: Aij-Lie
authors.initials: AL
authors.lastname: Kwan
authors.affiliation: Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. chihlung1@yahoo.com.|Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung, Taiwan, ROC. chihlung1@yahoo.com.
authors.forename: Chih-Lung
authors.initials: CL
authors.lastname: Lin
mesh_terms: D000818:Animals; D019661:Apiaceae / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000134:cerebrospinal fluid; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000096:biosynthesis*; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020301:Vasospasm, Intracranial / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C000596311:4'-O-glucosyl-5-O-methylvisamminol; D002867:Chromones; D016207:Cytokines; D005960:Glucosides; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D018696:Neuroprotective Agents; D053148:Caspase 3; D053453:Caspase 9