Biomol Ther.  2015 Sep;23(5):421-427. 10.4062/biomolther.2015.023.

Imperatorin Suppresses Degranulation and Eicosanoid Generation in Activated Bone Marrow-Derived Mast Cells

• Jeong KT
• Lee E
• Park NY
• Kim SG
• Park HH
• Lee J
• Lee YJ
• Lee E

• KMID: 2380290
• DOI: http://doi.org/10.4062/biomolther.2015.023

Abstract

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent LTC4 and cyclooxygenase-2-dependent PGD2 through the inhibition of intracellular calcium influx/phospholipase Cgamma1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-kappaB pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.

Keyword

Leukotriene C4; Prostaglandin D2; Cytosolic phospholipase A2; Mitogen-activated protein kinases; Phospholipase Cgamma1

MeSH Terms

Animals
Calcium
Cytosol
Eicosanoids
Inflammation
Leukotriene C4
Mast Cells*
Mice
Mitogen-Activated Protein Kinases
Phospholipases
Prostaglandin D2
Protein Kinases
Calcium
Eicosanoids
Leukotriene C4
Mitogen-Activated Protein Kinases
Phospholipases
Prostaglandin D2
Protein Kinases