The effects of isoimperatorin isolated from Angelicae dahuricae on cyclooxygenase-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells.
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.
Moon
Tae Chul
TC
Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, AB T6G 252, Canada.
Jin
Meihua
M
Son
Jong Keun
JK
Chang
Hyeun Wook
HW
D029969:Angelica / Q000737:chemistry*; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000201:enzymology*; D000440:Butanols; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D011564:Furocoumarins / Q000302:isolation & purification / Q000494:pharmacology*; D006596:Hexosaminidases / Q000378:metabolism; D017997:Leukotriene C4 / Q000096:biosynthesis / Q000235:genetics; D016859:Lipoxygenase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D015230:Prostaglandin D2 / Q000096:biosynthesis / Q000235:genetics; D012997:Solvents; D013778:Tetrazolium Salts; D013844:Thiazoles
D000440:Butanols; D052246:Cyclooxygenase 2 Inhibitors; D011564:Furocoumarins; D016859:Lipoxygenase Inhibitors; D010936:Plant Extracts; D012997:Solvents; D013778:Tetrazolium Salts; D013844:Thiazoles; C055542:isoimperatorin; D017997:Leukotriene C4; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; D006596:Hexosaminidases; C022616:thiazolyl blue; D015230:Prostaglandin D2