prostaglandin-d2 and isoimperatorin

Isoimperatorin (4-[(3-Methyl-2-butenyl)oxy]-7H-furo[3,2-g][1]benzopyran-7-one) is a medicinal herbal product that is isolated from the dried roots of Angelicae dahuricae. Isoimperatorin inhibits the cyclooxygenase-2 (COX-2) and COX-1-dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner, with IC50 values of 10.7 microM and 24 microM, respectively. However, this compound was not able to inhibit COX-1 and 2 protein expression in BMMC that were treated with concentrations of up to 50 microM, which indicates that isoimperatorin directly inhibits COX-2 activity. Furthermore, this compound consistently inhibited the production of leukotriene C4 (LTC4), as well as the degranulation reaction in BMMC, with an IC50 value of 5.7 microM and 9 microM, respectively, and these effects occurred in a dose dependent fashion. These results demonstrate that isoimperatorin has a dual cyclooxygenase-2 selective/5-lipoxygenase inhibitory activity, and therefore may provide the basis for novel anti-inflammatory drugs.

Topics: Angelica; Animals; Arachidonate 5-Lipoxygenase; Bone Marrow Cells; Butanols; Cell Survival; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Electrophoresis, Polyacrylamide Gel; Furocoumarins; Hexosaminidases; Leukotriene C4; Lipoxygenase Inhibitors; Male; Mast Cells; Mice; Mice, Inbred BALB C; Plant Extracts; Plant Roots; Prostaglandin D2; Solvents; Tetrazolium Salts; Thiazoles