Saucerneol F, a new lignan, inhibits iNOS expression via MAPKs, NF-kappa B and AP-1 inactivation in LPS-induced RAW264.7 cells

Title
Saucerneol F, a new lignan, inhibits iNOS expression via MAPKs, NF-kappa B and AP-1 inactivation in LPS-induced RAW264.7 cells
Author(s)
장현욱유예[유예]서석종곽충환[곽충환]서창섭[서창섭]이응[이응]김엽[김엽]이선[이선]황승락권오균[권오균]장영채[장영채]박영국[박영국]박성수[박성수]손종근김철호[김철호]
Keywords
NITRIC-OXIDE SYNTHASE; ACTIVATED PROTEIN-KINASE; NECROSIS-FACTOR-ALPHA; SAURURUS-CHINENSIS; GENE-EXPRESSION; DOWN-REGULATION; MANASSANTIN-A; IFN-GAMMA; MACROPHAGES; MATRIX-METALLOPROTEINASE-9
Issue Date
201201
Publisher
ELSEVIER SCIENCE BV
Citation
INTERNATIONAL IMMUNOPHARMACOLOGY, v.12, no.1, pp.175 - 181
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-kappa B (NF-kappa B) DNA-binding activity, NF-kappa B-dependent reporter gene activity, inhibitory factor-kappa B (I kappa B) phosphorylation and degradation, and p65 nuclear translocation. Treatment with SF decreased the luciferase activities of NF-kappa B reporter promoters in a dose-dependent manner and translocation of NF-kappa B 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 NH2-terminal kinase (INK). 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-kappa B, MAPKs, and AP-1, suggesting that SF is potentially applicable as an anti-inflammatory drug. (C) 2011 Elsevier B.V. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/30081http://dx.doi.org/10.1016/j.intimp.2011.11.008
ISSN
1567-5769
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약학대학 > 약학부 > Articles
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