Effects of methyl gallate on arachidonic acid metabolizing enzymes: Cyclooxygenase-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells.
Methyl gallate (MG) is a medicinal herbal product that is isolated from Paeonia lactiflora that inhibits cyclooxygenase-2 (COX-2) dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with an IC50 values of 17.0 microM. This compound also found inhibited the COX-2-dependent conversion of the exogenous arachidonic acid to PGD2 in a dose-dependent manner with an IC50 values of 19.0 microM, using a COX enzyme assay kit. However, at concentrations up to 80 microM, MG did not inhibit COX-2 protein expression in BMMC, indicating that MG inhibits COX-2 activity directly. Furthermore, MG consistently inhibited the production of leukotriene C4 (LTC4) in a dose dependent manner, with an IC50 value of 5.3 microM. These results demonstrate that MG has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity, which might provide the basis for novel anti-inflammatory drugs.
Kim
Se Jong
SJ
Research Institute of Natural Product Kyongbuk Provincial A T A, Uisung 769-803, Korea.
Jin
Meihua
M
Lee
Eunkyung
E
Moon
Tae Chul
TC
Quan
Zhejiu
Z
Yang
Ju Hye
JH
Son
Kun Ho
KH
Kim
Kil-Ung
KU
Son
Jong Kun
JK
Chang
Hyeun Wook
HW
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000201:enzymology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D029596:Paeonia / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D015230:Prostaglandin D2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019089:Stem Cell Factor / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D010936:Plant Extracts; D019089:Stem Cell Factor; D016753:Interleukin-10; D016718:Arachidonic Acid; D017997:Leukotriene C4; C052082:methyl gallate; D005707:Gallic Acid; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; D015230:Prostaglandin D2