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  • Title: Saucerneol F, a new lignan, inhibits iNOS expression via MAPKs, NF-κB and AP-1 inactivation in LPS-induced RAW264.7 cells.
    Author: Lu Y, Suh SJ, Kwak CH, Kwon KM, Seo CS, Li Y, Jin Y, Li X, Hwang SL, Kwon O, Chang YC, Park YG, Park SS, Son JK, Kim CH, Chang HW.
    Journal: Int Immunopharmacol; 2012 Jan; 12(1):175-81. PubMed ID: 22155103.
    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.
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