Effects of Ginkgetin from Ginkgo biloba Leaves on cyclooxygenases and in vivo skin inflammation

• Published in: Planta medica Vol. 68; no. 4; p. 316
• Main Authors: Kwak, Wie-Jong, Han, Chang Kyun, Son, Kun Ho, Chang, Hyeun Wook, Kang, Sam Sik, Park, Byoung Kyu, Kim, Hyun Pyo
• Format: Journal Article
• Language: English
• Published: Germany 01.04.2002
• Subjects: Animals; Biflavonoids; Blotting, Western; Cell Line; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone - antagonists & inhibitors; Dose-Response Relationship, Drug; Flavonoids - chemistry; Flavonoids - pharmacology; Ginkgo biloba; Indomethacin - pharmacology; Inflammation - chemically induced; Inflammation - prevention & control; Isoenzymes - drug effects; Isoenzymes - metabolism; Macrophages - drug effects; Male; Membrane Proteins; Mice; Mice, Inbred ICR; Monocytes - drug effects; Nitrobenzenes - pharmacology; Phospholipases - metabolism; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Leaves - chemistry; Prostaglandin-Endoperoxide Synthases - drug effects; Prostaglandin-Endoperoxide Synthases - metabolism; Skin - drug effects; Skin - pathology; Sulfonamides - pharmacology
• ISSN: 0032-0943
• DOI: 10.1055/s-2002-26742

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.