Respiratory burst mediates crucial bactericidal mechanism in neutrophils. However, undesirable respiratory burst leads to pathological inflammation and tissue damage. This study investigates the effect and the underlying mechanism of 2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol (honokiol), a lignan extracted from the stem bark of Magnolia officinalis Rehd. et Wils (Magnoliaceae), on N-formyl-Lmethionyl-L-leucyl-L-phenylalanine (fMLP)-induced human neutrophils activation. Signaling pathways regulated by honokiol to oppose fMLP-induced respiratory burst were evaluated by Lyn kinase (a member of Src kinase family) activity in an in vitro kinase assay and by immunoblotting analysis of downstream phosphorylation targets of Lyn. Briefly, honokiol specific inhibited fMLP-induced superoxide anion production and cathespin G release in a concentration-dependent manner (IC 50 = 9.80 AE 0.21; 14.23 AE 1.43 lM respectively). Further, honokiol specific suppressed fMLP-induced Lyn phosphorylation and Lyn kinase activity. Moreover, honokiol attenuated the signaling followed by Lyn kinase, such as Tec translocation from the cytosol to the inner leaflet of the plasma membrane, phosphorylation of AKT, P38, PLCc2, protein kinase C and membrane localization of p47 phox , however, honokiol did not affect fMLP-induced Hck phosphorylation, Fgr kinase activity, and the signaling followed by Hck/Fgr kinases, such as Vav1 and extracellular signal-regulated kinase phosphorylation. Moreover, honokiol, like PP2, attenuated intracellular calcium concentration. However, honokiol neither inhibited NADPH oxidase activity nor increased cyclicAMP levels. Honokiol is not a competitive or allosteric antagonist of fMLP. Additionally, in an in vivo study, honokiol prevents fMLP-induced neutrophil infiltration in mice. Conclusion: honokiol opposes fMLP-mediated neutrophil activation by inhibiting Lyn activation and subsequent interfered with the activation of PLCc2, AKT, p38, protein kinase C, and p47 phox .
4-HYDROXYBENZALDEHYDE ISOLATED FROM GASTRODIA ELATA, ENHANCED SLEEPING BEHAVIORS THROUGH GABAA-ERGIC SYSTEMSChoi J., Han J., Oh E., Hong J., Yun Y., Yoo H., Oh K.Gastrodia elata (GE), one of famous oriental herb medicine, has been used for the treatment of headache, blood pressure and convulsion. Recent studies have been suggested it has sedative and inhibitory effects of platelet aggregation. 4-Hydroxybenzaldehyde (4-HD) is one of the major compounds of GE, which is well known as an inhibitor of GABA-transaminase. This research was investigated to know whether 4-HD enhanced sleeping behaviors through GABA A ergic systems in mice. 4-HD (50, 100, and 200 mg/kg, p.o.) inhibited locomotor activity in mice. 4-HD not only increased total sleep time, but also decreased sleep latency in pentobarbital induced sleeping mice. 4-HD showed synergistic effects with muscimol, suggesting interactions with GABA A ergic drugs. 4-HD increased intracellular chloride in primary cultured hypothalamic granular cells at the dose-dependent manner. The GABA A re...