Schisandrin B-Induced Glutathione Antioxidant Response and Cardioprotection Are Mediated by Reactive Oxidant Species Production in Rat Hearts
Schisandrin B-Induced Glutathione Antioxidant Response and Cardioprotection Are Mediated by Reactive Oxidant Species Production in Rat Hearts
复制标题
DOI：
10.1248/bpb.33.825
复制
发表时间：
2010-05-01
影响因子：
2
通讯作者：
Ko, Kam Ming
中科院分区：
文献类型：
--
作者：
Chen, Na;Ko, Kam Ming
为研究五味子乙素（Schisandrin B，Sch B）经细胞色素P-450（CYP）催化代谢产生的活性氧化物（ROS）参与触发谷胱甘肽抗氧化反应的情况，在大鼠心脏微粒体中检测了Sch B诱导的还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）依赖性和CYP催化的反应以及相关的ROS产生。还研究了Sch B类似物用于比较。以大鼠心脏微粒体为底物，发现五味子乙素（Sch B）和五味子甲素（SchC），而不是五味子甲素（SchA）和二苯基二甲酸二甲酯（SchC合成的中间体），可作为CYP催化的NADPH氧化反应的共底物，并伴随产生ROS。Sch B或Sch C刺激CYP催化的NADPH氧化反应和/或ROS产生与增加线粒体还原型谷胱甘肽水平和保护大鼠心脏缺血/再灌注（I/R）损伤有关。通过N-乙酰半胱氨酸或α-生育酚预处理产生的抑制作用进一步证实了ROS参与Sch B诱导的心脏保护。综上所述，这些结果表明，Sch B诱导的谷胱甘肽抗氧化反应和心脏保护作用可能是由CYP催化反应产生的ROS介导的。
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.