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

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概要

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• 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.

• 公益社団法人　日本薬学会の論文

著者

• Ko Kam

  Department Of Biochemistry The Hong Kong University Of Science And Technology

• Chen Na

  Department Of Biochemistry The Hong Kong University Of Science And Technology

• Ko Ming

  Department of Biochemistry, Hong Kong University of Science & Technology

• Ko Ming

  Department of Biochemistry, Hong Kong University of Science & Technology

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

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