title: Artemisolide from Artemisia asiatica: nuclear factor-kappaB (NF-kappaB) inhibitor suppressing prostaglandin E2 and nitric oxide production in macrophages.
abstract: Aerial parts of Artemisia asiatica (Compositae) have been traditionally used as an oriental medicine for the treatment of inflammatory and ulcerogenic diseases. In the present study, artemisolide was isolated as a nuclear factor (NF)-kappaB inhibitor from A. asiatica by activity-guided fractionation. Artemisolide inhibited NF-kappaB transcriptional activity in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 with an IC50 value of 5.8 microM. The compound was also effective in blocking NF-kappaB transcriptional activities elicited by the expression vector encoding the NF-kappaB p65 or p50 subunits bypassing the inhibitory kB degradation signaling NF-kappaB activation. The macrophages markedly increased their PGE2 and NO production upon exposure to LPS alone. Artemisolide inhibited LPS-induced PGE2 and NO production with IC50 values of 8.7 microM and 6.4 microM, respectively, but also suppressed LPS-induced synthesis of cyclooxygenase (COX)-2 or inducible NO synthase (iNOS). Taken together, artemisolide is a NF-kappaB inhibitor that attenuates LPS-induced production of PGE2 or NO via down-regulation of COX-2 or iNOS expression in macrophages RAW 264.7. Therefore, artemisolide could represent and provide the anti-inflammatory principle associated with the traditional medicine, A. asiatica.
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, Korea.
authors.forename: Alavala Matta
authors.initials: AM
authors.lastname: Reddy
authors.forename: Jun-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jee Hee
authors.initials: JH
authors.lastname: Seo
authors.forename: Byung Hak
authors.initials: BH
authors.lastname: Kim
authors.forename: Eun Yong
authors.initials: EY
authors.lastname: Chung
authors.forename: Shi Yong
authors.initials: SY
authors.lastname: Ryu
authors.forename: Young Sup
authors.initials: YS
authors.lastname: Kim
authors.forename: Chong-Kil
authors.initials: CK
authors.lastname: Lee
authors.forename: Kyung Rak
authors.initials: KR
authors.lastname: Min
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D019306:Artemisia / Q000737:chemistry*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D035261:Plant Components, Aerial; D012717:Sesquiterpenes / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D052002:NF-kappa B p50 Subunit; D012717:Sesquiterpenes; D051996:Transcription Factor RelA; D014315:Triterpenes; C513233:artemisolide; C482199:lipopolysaccharide, E coli O55-B5; C002669:parthenolide; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone