title: 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 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.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyongsan, Japan.
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Son
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Ju
authors.forename: Chang Xiu
authors.initials: CX
authors.lastname: Lin
authors.forename: Tae Chul
authors.initials: TC
authors.lastname: Moon
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.forename: Jong Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Hyeun Wook
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000818:Animals; D019661:Apiaceae; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000201:enzymology; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D018517:Plant Roots; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; D010936:Plant Extracts; C014451:deoxypodophyllotoxin; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D011034:Podophyllotoxin