The anti-inflammatory effect of honokiol on neutrophils: mechanisms in the inhibition of reactive oxygen species production.
Reactive oxygen species produced by neutrophils contribute to the pathogenesis of focal cerebral ischemia/reperfusion injury and signal the inflammatory response. We have previously shown that honokiol, an active principle extracted from Magnolia officinalis, has a protective effect against focal cerebral ischemia/reperfusion injury in rats that paralleled a reduction in reactive oxygen species production by neutrophils. To elucidate the underlying mechanism(s) of the antioxidative effect of honokiol, peripheral neutrophils isolated from rats were activated with phorbol-12-myristate-13-acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP) in the presence or absence of honokiol. In this study, we found that honokiol inhibited PMA- or fMLP-induced reactive oxygen species production by neutrophils by three distinct mechanisms: (1) honokiol diminished the activity of assembled-NADPH oxidase, a major reactive oxygen species producing enzyme in neutrophils by 40% without interfering with its protein kinase C (PKC)-dependent assembly; (2) two other important enzymes for reactive oxygen species generation in neutrophils, i.e., myeloperoxidase and cyclooxygenase, were also inhibited by honokiol by 20% and 70%, respectively; and (3) honokiol enhanced glutathione (GSH) peroxidase activity by 30%, an enzyme that triggers the metabolism of hydrogen peroxide (H2O2). These data suggested that honokiol, acting as a potent reactive oxygen species inhibitor/scavenger, could achieve its focal cerebral ischemia/reperfusion injury protective effect by modulating enzyme systems related to reactive oxygen species production or metabolism, including NADPH oxidase, myeloperoxidase, cyclooxygenase, and GSH peroxidase in neutrophils.
Liou
Kuo-Tong
KT
Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Shen
Yuh-Chiang
YC
Chen
Chieh-Fu
CF
Tsao
Cheng-Ming
CM
Tsai
Shen-Kou
SK
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D017705:Lignans; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000498:Allyl Compounds; D010636:Phenols
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D017705:Lignans; D017382:Reactive Oxygen Species; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols