Inhibition by magnolol of formylmethionyl-leucyl-phenyl alanine-induced respiratory burst in rat neutrophils

The influence of the plant product magnolol on neutrophil superoxide anion (O-2(-.)) generation has been investigated in the rat. Intraperitoneal injection of magnolol (30 mg kg(-1)) significantly inhibite d the formyl-methionyl-leucyl-phenylalanine (fMLP)-induced respiratory burs t in rat whole blood exvivo. Magnolol also inhibited the O-2(-.) generation with an IC50 (concentration resulting in 50% inhibition) of 15.4+/-1.6 mu M and O-2 consumption in rat neutrophils in-vitro. Magnolol weakly inhibite d the O-2(-.) generation in the xanthine-xanthine oxidase system, decreased cellular cyclic AMP level and had no effect on cyclic GMP levels. It weakl y inhibited neutrophil cytosolic protein kinase C activity but did not alte r porcine heart protein kinase A activity. Magnolol attenuated fMLP-induced protein tyrosine phosphorylation with an IC50 of 24.0+/-1.9 mu M and the p hosphorylation of mitogen-activated protein kinase p42/44 with an IC50 of 2 8.5+/-4.5 mu M. However, magnolol alone activated neutrophil phospholipase D activity as determined by the formation of phosphatidic acid and phosphat idylethanol in the presence of ethanol. In the presence of NADPH, the arach idonate-activated NADPH oxidase activity in a cell-free system was weakly s uppressed by magnolol. These results suggest that the inhibition of respiratory burst in fMLP-acti vated neutrophils by magnolol is probably attributable mainly to the attenu ation of protein tyrosine phosphorylation and p42/44 mitogen-activated prot ein kinase activation, and partly to the suppression of protein kinase C an d NADPH oxidase activities.