Pinusolide Isolated from Biota orientalis Inhibits 5-Lipoxygenase Dependent Leukotriene C-4 Generation by Blocking c-Jun N-Terminal Kinase Pathway in Mast Cells

Abstract

Pinusolide, an herbal medicine isolated from Biota orientalis L. (B. orientalis), inhibited 5-lipoxygenase (5-LO)-dependent leukotriene C-4 (LTC4) generation in immunoglobulin E (IgE)/Ag-induced bone marrow-derived mast cells (BMMCs) in a concentration-dependent manner. To clarify the action mechanism of pinusolide on the inhibition of LTC4 generation, we examined the effect of pinusolide on phosphorylation of cytosolic phospholipase A(2) (cPLA(2)), as well as translocation phospho-cPLA(2) and 5-LO to nucleus. Inhibition of LTC4 generation by pinusolide was accompanied by a decrease in cPLA(2) phosphorylation which occurred via a decrease in intracellular Ca2+ influx and blocking the c-Jun N-terminal kinase (JNK) pathways. However, pinusolide had no effect on extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinas phosphorylation. Taken together, the present results suggest that potent inhibition of 5-LO dependent LTC4 generation by pinusolide requires both suppression of calcium influx and JNK phosphorylation.