Schisandrin B-induced glutathione antioxidant response and cardioprotection are mediated by reactive oxidant species production in rat hearts.
To investigate the involvement of reactive oxidant species (ROS), presumably arising from cytochrome P-450 (CYP)-catalyzed metabolism of schisandrin B (Sch B), in triggering glutathione antioxidant response, Sch B induced reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent and CYP-catalyzed reaction and associated ROS production were examined in rat heart microsomes. Sch B analogs were also studied for comparison. Using rat heart microsomes as a source of CYP, Sch B and schisandrin C (Sch C), but not schisandrin A and dimethyl diphenyl bicarboxylate (an intermediate compound derived from the synthesis of Sch C), were found to serve as co-substrate for the CYP-catalyzed NADPH oxidation reaction, with concomitant production of ROS. The stimulation of CYP-catalyzed NADPH oxidation reaction and/or ROS production by Sch B or Sch C correlated with the increase in mitochondrial reduced glutathione level and protection against ischemia/reperfusion (I/R) injury in rat hearts. The involvement of ROS in Sch B-induced cardioprotection was further confirmed by the suppressive effect produced by N-acetylcysteine or alpha-tocopherol pretreatment. Taken together, these results suggest that Sch B-induced glutathione antioxidant response and cardioprotection may be mediated by ROS arising from CYP-catalyzed reaction.
Chen
Na
N
Department of Biochemistry, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong SAR, China.
Ko
Ming
M
D000111:Acetylcysteine; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D034242:Cyclooctanes / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D017705:Lignans / Q000494:pharmacology*; D008861:Microsomes; D008928:Mitochondria / Q000378:metabolism; D017202:Myocardial Ischemia / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism*; D009249:NADP; D010084:Oxidation-Reduction; D008517:Phytotherapy; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D032141:Schisandra / Q000737:chemistry; D024502:alpha-Tocopherol
D000975:Antioxidants; D002317:Cardiovascular Agents; D034242:Cyclooctanes; D004365:Drugs, Chinese Herbal; D017705:Lignans; D011083:Polycyclic Compounds; D017382:Reactive Oxygen Species; C015499:schizandrin B; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; C031409:schizandrin C; D005978:Glutathione; D024502:alpha-Tocopherol; D000111:Acetylcysteine