Dual Inhibition of Cyclooxygenases-2 and 5-Lipoxygenase by Deoxypodophyllotoxin in Mouse Bone Marrow-Derived Mast Cells

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 D₂ (PGD₂) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC₅₀ values of 1.89 μM and 65.3 μM, respectively. This study also found that this compound inhibited COX-1 and 2-dependent conversion of the exogenous arachidonic acid to PGD₂ in a dose-dependent manner with an IC₅₀ values of 0.01 μM and 12.1 μM, respectively using a COX enzyme assay kit. However, this compound did not inhibit COX-2 protein expression up to a concentration of 30 μM in the BMMC, indicating that deoxypodophyllotoxin directly inhibits COX-2 activity. Furthermore, this compound consistently inhibited the production of leukotriene C₄ (LTC₄) in a dose dependent manner, with an IC₅₀ value of 0.37 μM. 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.