Inhibition by Magnolol of Formylmethionyl-leucyl-phenyl alanine-induced Respiratory Burst in Rat Neutrophils

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Abstract
The influence of the plant product magnolol on neutrophil superoxide anion (O2-.) generation has been investigated in the rat. Intraperitoneal injection of magnolol (30mgkg-1) significantly inhibited the formyl-methionyl-leucyl-phenylalanine (fMLP)-induced respiratory burst in rat whole blood ex-vivo. Magnolol also inhibited the O2-. generation with an IC50 (concentration resulting in 50% inhibition) of 15.4 ± 1.6 μM and O2 consumption in rat neutrophils in-vitro. Magnolol weakly inhibited the O2-. generation in the xanthine-xanthine oxidase system, decreased cellular cyclic AMP level and had no effect on cyclic GMP levels. It weakly inhibited neutrophil cytosolic protein kinase C activity but did not alter porcine heart protein kinase A activity. Magnolol attenuated fMLP-induced protein tyrosine phosphorylation with an IC50 of 24.0 ± 1.9 μM and the phosphorylation of mitogen-activated protein kinase p42/44 with an IC50 of 28.5 ± 4.5 μM. However, magnolol alone activated neutrophil phospholipase D activity as determined by the formation of phosphatidic acid and phosphatidylethanol in the presence of ethanol. In the presence of NADPH, the arachidonate-activated NADPH oxidase activity in a cell-free system was weakly suppressed by magnolol. These results suggest that the inhibition of respiratory burst in fMLP-activated neutrophils by magnolol is probably attributable mainly to the attenuation of protein tyrosine phosphorylation and p42/44 mitogen-activated protein kinase activation, and partly to the suppression of protein kinase C and NADPH oxidase activities.