Allergic diseases, such as
asthma and
allergic rhinitis, are common. Therefore, the discovery of therapeutic drugs for these conditions is essential.
Methyleugenol (ME) is a natural compound with
antiallergic, antianaphylactic, antinociceptive, and anti-inflammatory effects. This study examined the
antiallergic effect of ME on
IgE-mediated inflammatory responses and its antiallergy mechanism in the mast cell line, RBL-2H3. We found that ME significantly inhibited the release of β-
hexosaminidase,
tumor necrosis factor- (TNF-) α, and
interleukin- (IL-) 4, and was not cytotoxic at the tested concentrations (0-100 μM). Additionally, ME markedly reduced the production of the proinflammatory
lipid mediators
prostaglandin E2 (
PGE2),
prostaglandin D2 (
PGD2),
leukotriene B4 (
LTB4), and
leukotriene C4 (
LTC4). We further evaluated the effect of ME on the early stages of the FcεRI cascade. ME significantly inhibited Syk phosphorylation and expression but had no effect on Lyn. Furthermore, it suppressed ERK1/2, p38, and JNK phosphorylation, which is implicated in proinflammatory
cytokine expression. ME also decreased cytosolic
phospholipase A2 (cPLA2) and
5-lipoxygenase (5-LO) phosphorylation and
cyclooxygenase-2 (COX-2) expression. These results suggest that ME inhibits allergic response by suppressing the activation of Syk, ERK1/2, p38, JNK, cPLA2, and 5-LO. Furthermore, the strong inhibition of COX-2 expression may also contribute to the
antiallergic action of ME. Our study provides further information about the
biological functions of ME.