Anti-inflammatory effect of kamebakaurin in in vivo animal models.
We have identified kamebakaurin as an inhibitor of NF-KB and elucidated its molecular mechanism as a specific inhibitor in the DNA-binding activity of the p50 subunit of NF-KB. Here, we describe its anti-inflammatory activity in in vitro and in vivo models. Kamebakaurin dose-dependently inhibited not only the expression of inflammatory NF-KB target genes such as iNOS,COX-2, and TNF-x, but also the production of PGE2 and TNF-a in LPS-stimulated RAW264.7 cells. Moreover, in an air pouch model of inflammation, it suppressed the recruitment of neutrophils,production of TNF-a as well as PGE2 in the pouch exudates induced by carrageenan. In addition, kamebakaurin dose-dependently suppressed the inflammation in an adjuvant arthritis model. Oral administration of 20 mg/kg kamebakaurin resulted in the 75% decrease of paw volume. Taken together, kamebakaurin, a specific inhibitor of DNA-binding activity of the p50 subunit, is a valuable candidate for the intervention in NF-KB-dependent pathological conditions such as inflammation.
Lee
Jeong-Hyung
JH
Anticancer Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon 305-600, Korea.
Choi
Jin Kyu
JK
Noh
Min Soo
MS
Hwang
Bang Yeon
BY
Hong
Young Soo
YS
Lee
June Joon
JJ
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001170:Arthritis, Infectious / Q000139:chemically induced / Q000517:prevention & control; D015153:Blotting, Western; D002351:Carrageenan; D004195:Disease Models, Animal; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D037602:Isodon; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D010936:Plant Extracts; C047382:kamebakaurin; D002351:Carrageenan