kamebakaurin and Disease-Models--Animal

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.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Infectious; Blotting, Western; Carrageenan; Disease Models, Animal; Diterpenes; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Edema; Female; Isodon; Macrophages; Mice; NF-kappa B; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction