Dual inhibition of cyclooxygenases-2 and 5-lipoxygenase by deoxypodophyllotoxin in mouse bone marrow-derived mast cells

Biol Pharm Bull. 2004 Jun;27(6):786-8. doi: 10.1248/bpb.27.786.

Abstract

Deoxypodophyllotoxin (Anthricin) is a medicinal herbal product isolated from Anthriscus sylvestris HOFFM. that inhibits cyclooxygenase-2 (COX-2) and COX-1-dependent phases of prostaglandin D(2) (PGD(2)) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC(50) values of 1.89 microM and 65.3 microM, respectively. This study also found that this compound inhibited COX-1 and 2-dependent conversion of the exogenous arachidonic acid to PGD(2) in a dose-dependent manner with an IC(50) values of 0.01 microM and 12.1 microM, respectively using a COX enzyme assay kit. However, this compound did not inhibit COX-2 protein expression up to a concentration of 30 microM in the BMMC, indicating that deoxypodophyllotoxin directly inhibits COX-2 activity. Furthermore, this compound consistently inhibited the production of leukotriene C(4) (LTC(4)) in a dose dependent manner, with an IC(50) value of 0.37 microM. These results demonstrate that deoxypodophyllotoxin has a dual cyclooxygenase-2 selective/5-lipoxygenase inhibitory activity, and therefore this compound might provide a basis for novel anti-inflammatory drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apiaceae
  • Arachidonate 5-Lipoxygenase / metabolism
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / enzymology
  • Cyclooxygenase 2
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / metabolism
  • Lipoxygenase Inhibitors*
  • Male
  • Mast Cells / drug effects*
  • Mast Cells / enzymology
  • Mice
  • Mice, Inbred BALB C
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Plant Roots
  • Podophyllotoxin / analogs & derivatives*
  • Podophyllotoxin / isolation & purification
  • Podophyllotoxin / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / metabolism

Substances

  • Drugs, Chinese Herbal
  • Enzyme Inhibitors
  • Isoenzymes
  • Lipoxygenase Inhibitors
  • Plant Extracts
  • deoxypodophyllotoxin
  • Arachidonate 5-Lipoxygenase
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Podophyllotoxin