Inhibitors of the LPS-induced NF-kappaB activation from Artemisia sylvatica.
Three guaianolide sesquiterpene lactones, 3alpha,4alpha-epoxyrupicolins C-E, together with six known sesquiterpenes, artemisolide, 3-methoxytanapartholide, deacetyllaurenobiolide, moxartenolide as well as arteminolides B and D were isolated by bioassay-guided fractionation from the methanol extract of the aerial parts of Artemisia sylvatica using the NF-kappaB mediated reporter gene assay. All isolated compounds displayed inhibitory activity on the LPS-induced NF-kappaB activation, NO production, and TNF-alpha production with IC50 values of 0.49-7.17, 1.46-6.16, and 3.19-27.76 microM, respectively, in RAW264.7 cells. It was also established that arteminolide B suppressed the expression of NF-kappaB target genes such as iNOS and COX-2. This is the first report of NF-kappaB inhibitory activities of these compounds and supports the pharmacological use of Artemisia sylvatica, which has been employed as an herbal medicine for the treatment of inflammation.
Jin
Hui Zi
HZ
Anticancer Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon 305-600, Korea.
Lee
Jeong Hyung
JH
Lee
Dongho
D
Hong
Young Soo
YS
Kim
Young Ho
YH
Lee
Jung Joon
JJ
D000818:Animals; D019306:Artemisia / Q000737:chemistry*; D015153:Blotting, Western; D002460:Cell Line; D051546:Cyclooxygenase 2; D007527:Isoenzymes / Q000096:biosynthesis; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007527:Isoenzymes; D007783:Lactones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases