Inhibition of fMLP‐stimulated respiratory burst in human neutrophils by 5‐hydroxy‐2‐(4‐hydroxy‐3‐methoxyphenyl)‐3,7‐dimethoxy‐4H‐chromen‐4‐one (MSF‐2), a natural lignan extract from Melicope Semecarpifolia: specific inhibition of phosphatidylinositol 3‐kinase activity

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We examined the underlying inhibitory mechanisms of a lignan, MSF‐2, extracted from the fruit of Melicope. Semecarpifolia in human neutrophils.To clarify the effect of MSF‐2 on fMLP‐induced neutrophil activation, intracellular signals induced by fMLP were evaluated. MSF‐2 inhibited the fMLP‐induced superoxide anion production and cathepsin G release in a concentration‐dependent manner with respective IC50 values of 22.8±4.8 and 14.2±1.7 μM. MSF‐2 was found to suppress fMLP‐induced phosphorylation of on Akt and intracellular calcium mobilization, however, it was not observed to inhibit the phosphorylation of ERK and p38 induced by fMLP. Moreover, MSF‐2 inhibited the PDK1, which subsequently phosphorylated on Akt. This could be its underlying inhibitory mechanism of phosphorylation because. In addition, MSF‐2 demonstrated inhibitory effects on PI3K activity and it was found to inhibit phosphorylation of PLCγ2 which was activated by PI3K. MSF‐2 inhibited fMLP‐induced superoxide anion production by inhibiting fMLP‐induced Akt activation.