Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
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Arthritis, Infectious / chemically induced
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Arthritis, Infectious / prevention & control
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Blotting, Western
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Carrageenan
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Disease Models, Animal
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Diterpenes / administration & dosage
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Diterpenes / pharmacology*
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Diterpenes / therapeutic use
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Dose-Response Relationship, Drug
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Drugs, Chinese Herbal / administration & dosage
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Drugs, Chinese Herbal / pharmacology*
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Drugs, Chinese Herbal / therapeutic use
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Edema / chemically induced
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Edema / prevention & control
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Female
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Isodon*
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Macrophages / drug effects
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Macrophages / metabolism
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Mice
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NF-kappa B / genetics
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Phytotherapy*
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Plant Extracts / administration & dosage
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Plant Extracts / pharmacology
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Plant Extracts / therapeutic use
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Rats
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Rats, Sprague-Dawley
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Diterpenes
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Drugs, Chinese Herbal
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NF-kappa B
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Plant Extracts
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kamebakaurin
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Carrageenan