title: Saucerneol F, a new lignan, inhibits iNOS expression via MAPKs, NF-κB and AP-1 inactivation in LPS-induced RAW264.7 cells.
abstract: Saucerneol F (SF), a new tetrahydrofuran-type sesquilignan isolated from Saururus chinensis, dose-dependently inhibited nitric oxide (NO) production, with concomitant reduction of inducible nitric oxide synthase (iNOS) protein and mRNA expression in lipopolysaccharide (LPS)-stimulated murine macrophage RAW264.7 cells. To elucidate the molecular mechanism underlying the inhibition of iNOS expression by SF, we assessed the effects of SF on nuclear factor-κB (NF-κB) DNA-binding activity, NF-κB-dependent reporter gene activity, inhibitory factor-κB (IκB) phosphorylation and degradation, and p65 nuclear translocation. Treatment with SF decreased the luciferase activities of NF-κB reporter promoters in a dose-dependent manner and translocation of NF-κB p65. In addition, pretreatment of SF reduced LPS-stimulated activation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, and c-Jun NH(2)-terminal kinase (JNK). Furthermore, SF attenuated the luciferase activities of AP-1 reporter promoters and the DNA-binding capacity of AP-1. Taken together, the present results indicate that SF attenuates NO production and iNOS expression by blocking LPS-induced activation of NF-κB, MAPKs, and AP-1, suggesting that SF is potentially applicable as an anti-inflammatory drug.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Seok-Jong
authors.initials: SJ
authors.lastname: Suh
authors.forename: Choong-Hwan
authors.initials: CH
authors.lastname: Kwak
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Kwon
authors.forename: Chang-Seob
authors.initials: CS
authors.lastname: Seo
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Ye
authors.initials: Y
authors.lastname: Jin
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.forename: Seung-Lark
authors.initials: SL
authors.lastname: Hwang
authors.forename: Okyun
authors.initials: O
authors.lastname: Kwon
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
authors.forename: Young-Guk
authors.initials: YG
authors.lastname: Park
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Park
authors.forename: Jong-Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Hyeun Wook
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D051550:I-kappa B Kinase / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D008070:Lipopolysaccharides; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D032134:Saururaceae; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D017705:Lignans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C572382:saucerneol F; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051550:I-kappa B Kinase; D020928:Mitogen-Activated Protein Kinases