title: Effects of Ginkgetin from Ginkgo biloba Leaves on cyclooxygenases and in vivo skin inflammation.
abstract: Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a phospholipase A2 inhibitor and this compound showed the potent antiarthritic activity in rat adjuvant-induced arthritis as well as analgesic activity. This investigation was carried out to find effects on cyclooxygenase (COX)-1 and -2 including an in vivo effect. Ginkgetin (1 - 10 microM) and the biflavonoid mixture (10 - 50 microg/ml), mainly a 1 : 1 mixture of ginkgetin and isoginkgetin, from G. biloba leaves, inhibited production of prostaglandin E2 from lipopolysaccharide-induced RAW 264.7 cells. This inhibition was mediated, at least in part, by down-regulation of COX-2 expression, but not by direct inhibition of COX-1 or COX-2 activity. Down-regulation of COX-2 by ginkgetin was also proved in the dorsal skin of ICR mouse treated by 12-O-tetradecanoylphorbol 13-acetate (TPA). At total doses of 1,000 microg/site on the dorsal skin (15 mm x 15 mm), ginkgetin inhibited prostaglandin E2 production by 65.6 % along with a marked suppression of COX-2 induction. In addition, ginkgetin and the biflavonoid mixture (100 - 1,000 microg/ear) dose-dependently inhibited skin inflammation of croton oil induced ear edema in mice by topical application. The present study suggests that ginkgetin from G. biloba leaves down-regulates COX-2 induction in vivo and this down-regulating potential is associated with an anti-inflammatory activity against skin inflammatory responses.
authors: SK Chemicals Ltd., Suwon, Korea.
authors: Wie-Jong
authors: WJ
authors: Kwak
authors: Chang Kyun
authors: CK
authors: Han
authors: Kun Ho
authors: KH
authors: Son
authors: Hyeun Wook
authors: HW
authors: Chang
authors: Sam Sik
authors: SS
authors: Kang
authors: Byoung Kyu
authors: BK
authors: Park
authors: Hyun Pyo
authors: HP
authors: Kim
mesh_terms: D000818:Animals; D044946:Biflavonoids; D015153:Blotting, Western; D002460:Cell Line; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D020441:Ginkgo biloba; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D009000:Monocytes / Q000187:drug effects; D009578:Nitrobenzenes / Q000494:pharmacology; D010740:Phospholipases / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D044946:Biflavonoids; D005419:Flavonoids; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D010936:Plant Extracts; D013449:Sulfonamides; C452984:isoginkgetin; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C077458:ginkgetin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D010740:Phospholipases; D015232:Dinoprostone; D007213:Indomethacin