Papyriflavonol A from Broussonetia papyrifera Inhibits the Passive Cutaneous Anaphylaxis Reaction and Has a Secretory Phospholipase A₂-Inhibitory Activity

Abstract

Papyriflavonol A, a new prenylated flavonol isolated from Broussonetia papyrifera, selectively inhibits recombinant human secretory phospholipase A₂s (sPLA₂s). Papyriflavonol A was found to inhibit human group IIA and V sPLA₂s potently and irreversibly in a dose-dependent manner, with respective IC₅₀ values of 3.9 and 4.5 μM. The inhibitory effects of papyriflavonol A against bovine group IB (IC₅₀ of 76.9 μM) and the human group X (IC₅₀ of 225 μM) sPLA₂s were weaker than those against human group IIA and V sPLA₂s, and human group IIF sPLA₂ was not inhibited. In addition, papyriflavonol A potently inhibited the stimulus-induced production of leukotriene C₄ with an IC₅₀ value of approximately 0.64 μM in mouse bone marrow-derived mast cells. In addition, papyriflavonol A significantly reduced IgE-dependent passive cutaneous anaphylaxis in rats. These results indicate that papyriflavonol A provides a basis for novel types of antiinflammatory drugs.