Dual inhibition of cyclooxygenases-2 and 5-lipoxygenase by deoxypodophyllotoxin in mouse bone marrow-derived mast cells.
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.
Lee
Seung Ho
SH
College of Pharmacy, Yeungnam University, Gyongsan, Japan.
Son
Min Jung
MJ
Ju
Hye Kyung
HK
Lin
Chang Xiu
CX
Moon
Tae Chul
TC
Choi
Han-Gon
HG
Son
Jong Keun
JK
Chang
Hyeun Wook
HW
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
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