Artemisolide from Artemisia asiatica: nuclear factor-kappaB (NF-kappaB) inhibitor suppressing prostaglandin E2 and nitric oxide production in macrophages.
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.
Reddy
Alavala Matta
AM
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, Korea.
Lee
Jun-Young
JY
Seo
Jee Hee
JH
Kim
Byung Hak
BH
Chung
Eun Yong
EY
Ryu
Shi Yong
SY
Kim
Young Sup
YS
Lee
Chong-Kil
CK
Min
Kyung Rak
KR
Kim
Youngsoo
Y
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*
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