Structural determinants of schisandrin B which enhance mitochondrial functional ability and glutathione status as well as heat shock protein expression in rat hearts and H9c2 cells.
Using an ex vivo model of isolated-perfused rat hearts and cultured H9c2 cells, the structure-activity relationships of schisandrin B (Sch B), and analogs lacking either the methylendioxy group or cyclooctadiene ring, schisandrin A (Sch A) and dimethyl diphenyl bicarboxylate (DDB), respectively, were investigated. Pretreatment with Sch B, but not with Sch A or DDB, protected against myocardial ischemia-reperfusion (I-R) injury in rats. Although Sch B pretreatment largely prevented H9c2 cells from menadione-induced cytotoxicity, Sch A pretreatment produced only a marginal protection. However, DDB pretreatment did not cause any detectable effect. The myocardial and cellular protection afforded by Sch B pretreatment correlated with increases in mitochondrial ATP generation capacity and/or reduced glutathione level as well as heat shock protein (Hsp)25/70 expression, under both control and oxidative stress conditions. The results indicate that the methylenedioxy group and the cyclooctadiene ring are important structural determinants of Sch B in enhancing mitochondrial functional ability and glutathione status, as well as tissue Hsp 25/70 expression, thereby protecting the myocardium against I-R injury.
Ko
Kam Ming
KM
Department of Biochemistry, The Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China. bcrko@ust.hk
Chiu
Po Yee
PY
D000818:Animals; D002460:Cell Line; D034242:Cyclooctanes / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005978:Glutathione / Q000032:analysis / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D066298:In Vitro Techniques; D017705:Lignans / Q000737:chemistry* / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology*; D015394:Molecular Structure; D015428:Myocardial Reperfusion Injury / Q000473:pathology; D009206:Myocardium / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D034242:Cyclooctanes; D006360:Heat-Shock Proteins; D017705:Lignans; D011083:Polycyclic Compounds; C015499:schizandrin B; D005978:Glutathione