No abstract

Schisandrin B (Sch B) ( Fig. 1) is the most abundant active dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis (FS), a traditional Chinese herb commonly used as astringent and clinically used for the treatment of viral and chemical hepatitis.1) Previous studies in our laboratory have demonstrated the ability of Sch B to protect against myocardial ischemia/reperfusion (I/R) injury.2) The cardioprotection afforded by Sch B pretreatment was associated with enhancement in tissue glutathione antioxidant status, particularly in the mitochondrion.2-4) Recent studies also showed that Sch B protected against myocardial I/R injury partly by inducing heat shock protein (Hsp) 25 and Hsp 70 expression in rats. 5) In regard to the action on mitochondria, Sch B treatment was found to decrease the sensitivity of myocardial mitochondria to Ca 2ϩ -induced permeability transition, particularly under I/R condition. 6) However, the biochemical mechanism(s) underlying the Sch B-induced glutathione antioxidant and/or heat shock responses in the myocardium remains unclear. In this connection, it has been suggested that reactive oxidant species (ROS) generated from cytochrome P-450 (CYP)-catalyzed reaction with Sch B may trigger the glutathione antioxidant and heat shock responses in mouse livers. 7,8) CYP are a superfamily of hemoproteins that catalyze the oxidative metabolism of many endogenous (endobiotic) and xenobiotic compounds including Sch B.9) To explore the role of CYP in Sch B-induced glutathione antioxidant response in the myocardium, we first examined CYP-catalyzed reaction with Sch B and associated ROS production in rat heart microsomes. Sch B analogs [schisandrin A (Sch A), schisandrin C (Sch C), and dimethyl diphenyl bicarboxylate (DDB)] (see also Fig. 1), which were found to produce differential cardioprotective effects, 10) were also studied for comparison. The in vitro studies were then paralleled by in vivo investigations on Sch B or its analogs-induced changes in myocardial mitochondrial reduced glutathione (GSH) and susceptibility to I/R injury in rats. To confirm the determinant role of ROS arising from Sch B metabolism in cardioprotection, we also examined the effect of antioxidant pretreatment on the cardioprotective action of Sch B in rats. MATERIALS AND METHODS Chemicals

No abstract

No abstract