title: Structure-activity relationship of schisandrins in enhancing liver mitochondrial glutathione status in CCl4-poisoned mice.
abstract: OBJECTIVE
  To explore whether the methylenedioxy group and cyclooctadiene ring of the dibenzocyclooctadiene skeleton of schisandrins (Sch) play a role in the liver mitochondrial glutathione status enhancing activity.
  
  
  METHODS
  The effects of three dibenzocyclooctadiene derivatives, Sch A, Sch B, Sch C, and a synthetic intermediate of Sch C, (dimethyl biphenyl dicarboxylate, DBD) on carbon tetrachloride (CCl4)-hepatotoxicity and liver mitochondrial glutathione status were examined in mice.
  
  
  RESULTS
  Pretreating mice with intragastric Sch B, Sch C, or DBD 1.mmol.kg-1.d-1 for 3 d protected against CCl4-hepatotoxicity. The hepatoprotection afforded by Sch B or Sch C pretreatment was associated with increases in liver mitochondrial reduced glutathione (mtGSH) level and glutathione reductase (mtGRD) activity, an indication of enhanced mitochondrial glutathione status. In contrast, the hepatoprotective action of DBD was not accompanied by any detectable changes in mtGSH level and mtGRD activity.
  
  
  CONCLUSIONS
  Both the methylenedioxy group and the cyclooctadiene ring of the dibenzocyclooctadiene molecule are important structural determinants in the enhancement of liver mitochondrial glutathione status.
authors.affiliation: Department of Biochemistry, Hong Kong University of Science & Technology, Clear Water Bay, China.
authors.forename: S P
authors.initials: SP
authors.lastname: Ip
authors.forename: C T
authors.initials: CT
authors.lastname: Che
authors.forename: K M
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism*; D034242:Cyclooctanes; D004149:Dioxoles / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism*; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008930:Mitochondria, Liver / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D034242:Cyclooctanes; D004149:Dioxoles; D004365:Drugs, Chinese Herbal; D017705:Lignans; D011083:Polycyclic Compounds; C015499:schizandrin B; C041398:7,7'-dimethoxy-(4,4'-bi-1,3-benzodioxole)-5,5'-dicarboxylic acid dimethyl ester; C031409:schizandrin C; D005980:Glutathione Reductase; C011105:schizandrin; D005978:Glutathione