Methylenedioxy group as determinant of schisandrin in enhancing hepatic mitochondrial glutathione in carbon tetrachloride-intoxicated mice.
As a preliminary approach to exploring whether the methylenedioxy group of the dibenzocyclooctadiene skeleton of schisandrins plays an important role in hepatic mitochondrial-reduced glutathione (GSH) stimulatory activity, we examined the effects of three schisandrins, namely schisandrin A (Sch A), schisandrin B (Sch B), and schisandrin C (Sch C), on carbon tetrachloride (CCl4) hepatotoxicity and hepatic mitochondrial GSH status in mice. Pretreating mice with Sch A at a daily oral dose of 1 mmol/kg for 3 days did not protect against CCl4 hepatotoxicity, whereas pretreatment with Sch B or Sch C at the same dosage regimen produced almost complete protection. The hepatoprotection afforded by Sch B or Sch C pretreatment was associated with significant increases in the hepatic mitochondrial GSH level and glutathione reductase (EC 1.6.4.2) activity. Our results indicate that the methylenedioxy group of the dibenzocyclooctadiene skeleton of schisandrin is an important structural determinant in the stimulation of hepatic mitochondrial GSH, particularly under conditions of CCl4 intoxication.
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Department of Biochemistry, The Hong Kong University of Science & Technology, Clear Water Bay.
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D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000517:prevention & control*; D034242:Cyclooctanes; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage; D005260:Female; D005978:Glutathione / Q000378:metabolism; D017705:Lignans; D051379:Mice; D008807:Mice, Inbred BALB C; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D011083:Polycyclic Compounds / Q000008:administration & dosage* / Q000737:chemistry; D013329:Structure-Activity Relationship
D034242:Cyclooctanes; D004365:Drugs, Chinese Herbal; D017705:Lignans; D011083:Polycyclic Compounds; C015499:schizandrin B; C034734:schizandrin A; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase; D005978:Glutathione