Wogonin inhibits inducible prostaglandin E(2) production in macrophages.
Effects of 5,7-dihydroxy-8-methoxyflavone (wogonin) on cyclooxygenase-2 (COX-2)-mediated prostaglandin E(2) production in macrophages were investigated. Stimulation with lipopolysaccharide (LPS; 1 microg/ml) greatly increased prostaglandin E(2) production in RAW 264.7 murine macrophages. The stimulated prostaglandin E(2) production was abolished in the presence of indomethacin (1 microM) or cycloheximide (2 microM), suggesting that the increased production of prostaglandin E(2) by LPS reflects the inducible synthesis of prostaglandin E(2) by COX-2. Wogonin (0.1-50 microM) concentration-dependently inhibited inducible prostaglandin E(2) production. Wogonin at concentrations as low as 0.5 microM directly attenuated enzymatic activity of COX-2. The protein expression of COX-2 was depressed by wogonin at concentrations of 10 microM and more. These results suggest that wogonin decreases inducible prostaglandin E(2) production in macrophages by inhibiting both COX-2 activity and COX-2 expression. The former action requires much lower doses of wogonin. These wogonin actions may explain, in part, its anti-inflammatory action.
Wakabayashi
I
I
Department of Hygiene and Preventive Medicine, School of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585, Yamagata, Japan. wakabaya@med.id.yamagata-u.ac.jp
Yasui
K
K
D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D005419:Flavonoids; D007527:Isoenzymes; D008070:Lipopolysaccharides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C085514:wogonin