Pinusolide Isolated from Biota orientalis Inhibits 5-Lipoxygenase Dependent Leukotriene C₄ 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 C₄ (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 A₂ (cPLA₂), as well as translocation phospho-cPLA₂ and 5-LO to nucleus. Inhibition of LTC₄ generation by pinusolide was accompanied by a decrease in cPLA₂ 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.