title: Effect of wogonin, a plant flavone from Scutellaria radix, on the suppression of cyclooxygenase-2 and the induction of inducible nitric oxide synthase in lipopolysaccharide-treated RAW 264.7 cells.
abstract: Plant flavonoids show anti-inflammatory activity both in vitro and in vivo. Some flavonoids, such as flavone derivatives, have been reported previously to inhibit nitric oxide (NO) production by suppressing inducible nitric oxide synthase (iNOS) expression. In this investigation, the effects of wogonin, a potent inhibitor of NO production among the flavonoids tested, on cyclooxygenase-2 (COX-2) induction and activity were elucidated further in connection with iNOS, using a mouse macrophage cell line, RAW 264.7. Wogonin inhibited NO and prostaglandin E(2) (PGE(2)) production from lipopolysaccharide-induced RAW cells with IC(50) values of 31 and 0.3 microM, respectively. When added after the induction of iNOS and COX-2, wogonin inhibited the formation of PGE(2) (IC(50) = 0.8 microM), but not the production of NO. Wogonin inhibited COX-2 activity directly (IC(50) = 46 microM) from the homogenate of aspirin-pretreated RAW cells, as determined by measuring [(14)C]PGE(2) formation from [(14)C]arachidonic acid. However, it did not inhibit iNOS or phospholipase A(2) activity. Western blotting showed that wogonin suppressed the induction of both iNOS and COX-2. Prednisolone also suppressed the induction of iNOS and COX-2. Whereas RU-486 (a steroid receptor antagonist) reversed the suppressive activity of prednisolone, it did not affect the suppressive activity of wogonin, suggesting that the suppressive activity of wogonin is not mediated by binding to a steroid receptor. Results from the present study demonstrated that wogonin is a direct COX-2 inhibitor, as well as an inhibitor of iNOS and COX-2 induction. Wogonin may be a potential agent for use in the treatment of inflammatory diseases.
authors.affiliation: College of Pharmacy, Kangwon National University, 200-701, Chunchon, South Korea.
authors.forename: Y S
authors.initials: YS
authors.lastname: Chi
authors.forename: B S
authors.initials: BS
authors.lastname: Cheon
authors.forename: H P
authors.initials: HP
authors.lastname: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D020868:Gene Silencing / Q000187:drug effects*; D007527:Isoenzymes / Q000096:biosynthesis* / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II; D010741:Phospholipases A / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000187:drug effects
chemical_list: D000975:Antioxidants; D044950:Flavanones; D005419:Flavonoids; D007527:Isoenzymes; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D015232:Dinoprostone; C085514:wogonin