title: 4'-bromo-5,6,7-trimethoxyflavone represses lipopolysaccharide-induced iNOS and COX-2 expressions by suppressing the NF-κB signaling pathway in RAW 264.7 macrophages.
abstract: The regulations of the NO and PGE(2) productions are research topics of interest in the field of anti-inflammatory drug development. In the present study, 5,6,7-trimethoxy- and 5,6,7-trihydroxyflavones 3a-3g were synthesized from cinnamic acid derivatives. In particular, 4'-bromo-5,6,7-trimethoxyflavone (3b) most potently inhibited the productions of NO and PGE(2) in LPS-treated RAW 264.7 cells (IC(50)=14.22 ± 1.25 and 10.98 ± 6.25 μM, respectively), and these inhibitory effects were more potent than those of oroxylin A or baicalein. Consistent with these findings, 3b concentration-dependently reduced the LPS-induced expressions of iNOS and COX-2 at the protein and mRNA levels. In addition, the release of TNF-α, IL-6, and IL-1β and the mRNA expressions of these cytokines were reduced by 3b in a concentration-dependent manner. Furthermore, 3b attenuated the LPS-induced transcriptional activities of NF-κB and this was accompanied by parallel reductions in the degradation and phosphorylation of IκB-α, and consequently by a decrease in the nuclear translocation of the p65 subunit of NF-κB. Taken together, these results suggest that suppressions of the expressions of iNOS, COX-2, TNF-α, IL-6, and IL-1β via NF-κB inactivation are responsible for the anti-inflammatory effects of 3b.
authors.affiliation: Department of Life and Nanopharmaceutical Science & Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130 701, Republic of Korea.
authors.forename: Dong Han
authors.initials: DH
authors.lastname: Kim
authors.forename: Chang Hyeon
authors.initials: CH
authors.lastname: Yun
authors.forename: Min Hwan
authors.initials: MH
authors.lastname: Kim
authors.forename: Ch
authors.initials: Ch
authors.lastname: Naveen Kumar
authors.forename: Bo Hee
authors.initials: BH
authors.lastname: Yun
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Shin
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: An
authors.forename: Young Hun
authors.initials: YH
authors.lastname: Lee
authors.forename: Yong Don
authors.initials: YD
authors.lastname: Yun
authors.forename: Hong-Kun
authors.initials: HK
authors.lastname: Rim
authors.forename: Min-Sang
authors.initials: MS
authors.lastname: Yoo
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002470:Cell Survival; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D047309:Flavones / Q000138:chemical synthesis* / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D007249:Inflammation; D020128:Inhibitory Concentration 50; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D008956:Models, Chemical; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C573894:4'-bromo-5,6,7-trimethoxyflavone; C107364:5,6,7-trimethoxyflavone; D000893:Anti-Inflammatory Agents; D047309:Flavones; D005419:Flavonoids; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2