title: Suppression of iNOS and COX-2 expression by flavokawain A via blockade of NF-κB and AP-1 activation in RAW 264.7 macrophages.
abstract: Flavokawain A, a major constituent of chalcones derived from kava extracts, exerts various biological activities such as anti-tumor activities. In this study, we examined the suppressive effect of flavokawain A on LPS-induced expression of pro-inflammatory mediators and the molecular mechanisms responsible for these activities in the murine macrophages. Flavokawain A significantly suppressed expression of iNOS and COX-2, as well as the subsequent production of NO and PGE2 in the LPS-stimulated RAW 264.7 cells. Flavokawain A significantly inhibited LPS-induced activation of NF-κB and AP-1 signaling pathways. In addition, flavokawain A inhibited activation of JNK and p38 MAPK which was responsible for expression of iNOS and COX-2 in the LPS-stimulated RAW 264.7 cells. Furthermore, flavokawain A suppressed LPS-induced expression of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6. These results suggest that flavokawain A may exert anti-inflammatory responses by suppressing LPS-induced expression of pro-inflammatory mediators via blockage of NF-κB-AP-1-JNK/p38 MAPK signaling pathways in the murine macrophages.
authors.affiliation: Department of Biomedical Science, Hallym University, Chunchon, Republic of Korea.
authors.forename: Dong-Joo
authors.initials: DJ
authors.lastname: Kwon
authors.forename: Sung Mi
authors.initials: SM
authors.lastname: Ju
authors.forename: Gi Soo
authors.initials: GS
authors.lastname: Youn
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017931:DNA Primers; D016328:NF-kappa B; D018808:Transcription Factor AP-1; C500809:flavokawain A; D002599:Chalcone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D011494:Protein Kinases
keywords: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; AP-1; COX-2; DMEM; Dulbecco’s modified eagle medium; ELISA; FBS; Flavokawain A; HRP; Inflammation; IκBα; LPS; MTT; Macrophages; NF-κB; NO; PCR; PGE(2); SDS; TLR4; activator protein-1; cyclooxygenase; enzyme linked immune sorbent assay; fetal bovine serum; horseradish peroxidase; iNOS; inducible NO synthase; inhibitor of kappa B alpha; lipopolysaccharides; nitric oxide; nuclear factor-κB; polymerase chain reaction; prostaglandin E(2); sodium dodecyl sulphate; toll-like receptor 4