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 (O2-*) generation has been investigated in the rat. Intraperitoneal injection of magnolol (30mg kg(-1)) significantly inhibited the formylmethionyl-leucyl-phenylalanine (fMLP)-induced respiratory burst in rat whole blood ex-vivo. Magnolol also inhibited the 02-* generation with an IC50 (concentration resulting in 50% inhibition) of 15.4+/-1.6 microM 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 microM and the phosphorylation of mitogen-activated protein kinase p42/44 with an IC50 of 28.5+/-4.5 microM. However, magnolol alone activated neutrophil phospholipase D activity as determined by the formation of phosphatidic acid and phosphatidyl-ethanol 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.
Wang
J P
JP
Department of Medical Research, Taichung Veterans General Hospital, China Medical College, Taiwan, Republic of China.
Hsu
M F
MF
Raung
S L
SL
Chang
L C
LC
Tsao
L T
LT
Lin
P L
PL
Chen
C C
CC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004347:Drug Interactions; D017705:Lignans; D008163:Luminescent Measurements; D008934:Mitogens / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D017705:Lignans; D008934:Mitogens; C005498:magnolol; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000242:Cyclic AMP; D014969:Xanthine Oxidase; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010739:Phospholipase D; D006152:Cyclic GMP; D010100:Oxygen