Magnolol reduces myocardial ischemia/reperfusion injury via neutrophil inhibition in rats

The accumulation of oxygen-free radicals and activation of neutrophils are strongly implicated as important pathophysiological mechanisms mediating my ocardial ischemia/reperfusion injury. It has been proven that various antio xidants have cardioprotective effects. Magnolol, an active component extrac ted from the Chinese medicinal herb Magnolia officinalis, possesses potent antioxidant and free radical scavenging activities. In this study, the card ioprotective activity of magnolol was evaluated in an open-chest anesthetiz ed rat model of myocardial ischemia/reperfusion injury. The results demonst rated that pretreatment with magnolol (0.2 and 0.5 mug/kg, i.v. bolus) at 1 0 min before 45 min of left coronary artery occlusion, significantly suppre ssed the incidence of ventricular fibrillation and mortality when compared with the control group. Magnolol (0.2 and 0.5 mug/kg) also significantly re duced the total duration of ventricular tachycardia and ventricular fibrill ation. After 1 h of reperfusion, pretreatment with magnolol (0.2 and 0.5 mu g/kg) caused a significant reduction in infarct size. In addition, magnolol (0.2 mug/kg) significantly reduced superoxide anion production and myelope roxidase activity, an index of neutrophil infiltration in the ischemic myoc ardium. In addition, pretreatment with magnolol (0.3 and 0.5 mug/kg) suppre ssed ventricular arrhythmias elicited by reperfusion following 5 min of isc hemia. In vitro studies of magnolol (5, 20 and 50 muM) significantly suppre ssed N-formylmethionyl-leucyl-phenylalanine (fMLP; 25 nM)-activated human n eutrophil migration in a concentration-dependent manner, It is concluded th at magnolol suppresses ischemia- and reperfusion-induced ventricular arrhyt hmias and reduces the size of the infarct resulting from ischemia/reperfusi on injury. This pronounced cardioprotective activity of magnolol may be med iated by its antioxidant activity and by its capacity for neutrophil inhibi tion in myocardial ischemia/reperfusion. (C) 2001 Published by Elsevier Sci ence B.V.