The effects of isoimperatorin isolated from Angelicae dahuricae on cyclooxygenase-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells

Arch Pharm Res. 2008 Feb;31(2):210-5. doi: 10.1007/s12272-001-1143-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angelica / chemistry*
  • Animals
  • Arachidonate 5-Lipoxygenase / metabolism
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / enzymology*
  • Butanols
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / isolation & purification
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Electrophoresis, Polyacrylamide Gel
  • Furocoumarins / isolation & purification
  • Furocoumarins / pharmacology*
  • Hexosaminidases / metabolism
  • Leukotriene C4 / biosynthesis
  • Leukotriene C4 / genetics
  • Lipoxygenase Inhibitors / isolation & purification
  • Lipoxygenase Inhibitors / pharmacology*
  • Male
  • Mast Cells / drug effects
  • Mast Cells / enzymology*
  • Mice
  • Mice, Inbred BALB C
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Plant Roots / chemistry
  • Prostaglandin D2 / biosynthesis
  • Prostaglandin D2 / genetics
  • Solvents
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Butanols
  • Cyclooxygenase 2 Inhibitors
  • Furocoumarins
  • Lipoxygenase Inhibitors
  • Plant Extracts
  • Solvents
  • Tetrazolium Salts
  • Thiazoles
  • isoimperatorin
  • Leukotriene C4
  • Arachidonate 5-Lipoxygenase
  • Cyclooxygenase 2
  • Hexosaminidases
  • thiazolyl blue
  • Prostaglandin D2