Antiinflammatory effects of genipin, an active principle of gardenia.
Genipin, the aglycone of geniposide, is metabolically produced from the geniposide in body tissues. The purpose of this study is to clarify some pharmacological actions of genipin. Genipin showed concentration-dependent inhibition on lipid peroxidation induced by Fe++/ascorbate in rat brain homogenate. Genipin exhibited significant topical antiinflammatory effect shown as an inhibition of croton oil-induced ear edema in mice. Nitric oxide (NO) synthesis by inducible nitric oxide synthase (iNOS) is increased in inflammatory diseases and leads to cellular injury. Genipin concentration-dependently (50-300 microM) inhibited NO production and iNOS expression upon stimulation by lipopolysaccharide/interferon-gamma (IFN-gamma) in RAW 264.7, a murine macrophage cell line. Genipin markedly blocked lipopolysaccharide-evoked degradation of inhibitor-kappaB-beta (IkappaB-beta), indicating that it exhibits inhibitory effect on NO production through the inhibition of nuclear factor-kappaB (NF-kappaB) activation. It was also shown to contain potent antiangiogenic activity in a dose-dependent manner, which was detected by chick embryo chorioallantoic membrane assay. In summary, we demonstrate that genipin possesses antiinflammatory and is a specific hydroxyl radical scavenger. Its antiangiogenic and NO production-inhibitory properties are also presented.
Koo
Hye-Jin
HJ
College of Pharmacy, Sookmyung Women's University, Cheongpa-dong, Yongsan, Seoul 140-742, Republic of Korea.
Song
Yun Seon
YS
Kim
Hee-Jeong
HJ
Lee
Yong-Ha
YH
Hong
Sung-Min
SM
Kim
Su-Jung
SJ
Kim
Byung-Chul
BC
Jin
Changbae
C
Lim
Chang-Jin
CJ
Park
Eun-Hee
EH
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004423:Ear / Q000473:pathology; D004487:Edema / Q000517:prevention & control; D005260:Female; D032062:Gardenia / Q000737:chemistry*; D015151:Immunoblotting; D007371:Interferon-gamma / Q000494:pharmacology; D057889:Iridoid Glycosides; D039823:Iridoids; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D057889:Iridoid Glycosides; D039823:Iridoids; D008070:Lipopolysaccharides; D011714:Pyrans; D009569:Nitric Oxide; D007371:Interferon-gamma; C007834:genipin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat