Effects of Ginkgetin from Ginkgo biloba Leaves on cyclooxygenases and in vivo skin inflammation.
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.
Kwak
Wie-Jong
WJ
SK Chemicals Ltd., Suwon, Korea.
Han
Chang Kyun
CK
Son
Kun Ho
KH
Chang
Hyeun Wook
HW
Kang
Sam Sik
SS
Park
Byoung Kyu
BK
Kim
Hyun Pyo
HP
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
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