title: Fulgidic Acid Isolated from the Rhizomes of Cyperus rotundus Suppresses LPS-Induced iNOS, COX-2, TNF-α, and IL-6 Expression by AP-1 Inactivation in RAW264.7 Macrophages.
abstract: To identify bioactive natural products possessing anti-inflammatory activity, the potential of fulgidic acid from the rhizomes of Cyperus rotundus and the underlying mechanisms involved in its anti-inflammatory activity were evaluated in this study. Fulgidic acid reduced the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Consistent with these findings, fulgidic acid suppressed the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein level, as well as iNOS, COX-2, TNF-α, and IL-6 at mRNA levels. Fulgidic acid suppressed the LPS-induced transcriptional activity of activator protein-1 (AP-1) as well as the phosphorylation of c-Fos and c-Jun. On the other hand, fulgidic acid did not show any effect on LPS-induced nuclear factor κB (NF-κB) activity. Taken together, these results suggest that the anti-inflammatory effect of fulgidic acid is associated with the suppression of iNOS, COX-2, TNF-α, and IL-6 expression through down-regulating AP-1 activation in LPS-induced RAW264.7 macrophages.
authors.affiliation: Department of Pharmaceutical Biochemistry, Kyung Hee University.
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Shin
authors.forename: Yujin
authors.initials: Y
authors.lastname: Hong
authors.forename: Hwi-Ho
authors.initials: HH
authors.lastname: Lee
authors.forename: Byeol
authors.initials: B
authors.lastname: Ryu
authors.forename: Young-Wuk
authors.initials: YW
authors.lastname: Cho
authors.forename: Nam-Jung
authors.initials: NJ
authors.lastname: Kim
authors.forename: Dae Sik
authors.initials: DS
authors.lastname: Jang
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D029786:Cyperus; D015232:Dinoprostone / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008041:Linoleic Acids / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D027343:Rhizome; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C000606310:9,12,13-trihydroxy-10,15-octadecadienoic acid; D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008041:Linoleic Acids; D008070:Lipopolysaccharides; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone