Luteolin-7-O-glucoside suppresses leukotriene C 4 production and degranulation by inhibiting the phosphorylation of mitogen activated protein kinases and phospholipase Cγ1 in activated mouse bone marrow-derived mast cells

Abstract

In this study, luteolin-7-O-glucoside (L7G), an herbal medicine isolated from Ailanthus altissima, inhibited 5-lipoxygenase (5-LOX)-dependent leukotriene C 4 (LTC 4) production in bone marrow-derived mast cells (BMMCs) in a concentration-dependent manner with an IC 50 of 3.0 μM. To determine the action mechanism of L7G, we performed immunoblotting for cytosolic phospholipase A 2 (cPLA 2) and mitogen-activated protein kinases (MAPKs) following c-kit ligand (KL)-induced activation of BMMCs with or without L7G. Inhibition of LTC 4 production by L7G was accompanied by a decrease in cPLA 2 phosphorylation, which occurred via the extracellular signal-regulated protein kinase-1/2 (ERK1/2) and p38 and c-Jun N-terminal kinase (JNK) pathways. In addition, L7G also attenuated mast cell degranulation in a dose-dependent manner (IC 50, 22.8 μM) through inhibition of phospholipase Cγ1 (PLCγ1) phosphorylation. Our results suggest that the anti-asthmatic activity of L7G may be mediated in part via the inhibition of LTC 4 generation and mast cell degranulation. © 2011 Pharmaceutical Society of Japan.