Schisandrin B-Induced Glutathione Antioxidant Response and Cardioprotection Are Mediated by Reactive Oxidant Species Production in Rat Hearts

• Published in: Biological & Pharmaceutical Bulletin Vol. 33; no. 5; pp. 825 - 829
• Main Authors: Chen, Na, Ko, Ming
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 2010; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Acetylcysteine; alpha-Tocopherol; Animals; Antioxidants - metabolism; Cardiovascular Agents - pharmacology; Cyclooctanes - pharmacology; cytochrome P-450; Cytochrome P-450 Enzyme System; Drugs, Chinese Herbal - pharmacology; Female; glutathione; Glutathione - metabolism; Lignans - pharmacology; Microsomes; Mitochondria - metabolism; mitochondrion; Myocardial Ischemia - prevention & control; myocardial ischemia reperfusion injury; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; NADP; Oxidation-Reduction; Phytotherapy; Polycyclic Compounds - pharmacology; Rats; Rats, Sprague-Dawley; reactive oxidant species; Reactive Oxygen Species - metabolism; Schisandra - chemistry; schisandrin B
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.33.825

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 Binduced 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 α-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.