• DOI:10.1038/sj.bjp.0705231
• Corpus ID: 85162534

Inhibition of lipopolysaccharide‐inducible nitric oxide synthase, TNF‐α and COX‐2 expression by sauchinone effects on I‐κBα phosphorylation, C/EBP and AP‐1 activation

@article{Lee2003InhibitionOL,
  title={Inhibition of lipopolysaccharide‐inducible nitric oxide synthase, TNF‐$\alpha$ and COX‐2 expression by sauchinone effects on I‐$\kappa$B$\alpha$ phosphorylation, C/EBP and AP‐1 activation},
  author={Ae-Kyung Lee and Sang Hyun Sung and Young Choong Kim and Sang -Geon Kim},
  journal={British Journal of Pharmacology},
  year={2003},
  volume={139}
}

• Ae-Kyung Lee, S. Sung, +1 author Sang -Geon Kim
• Published 1 May 2003
• Biology, Chemistry
• British Journal of Pharmacology

Sauchinone, a lignan isolated from Saururus chinensis (Saururaceae), is a diastereomeric lignan with cytoprotective and antioxidant activities in cultured hepatocytes. The effects of sauchinone on the inducible nitric oxide synthase (iNOS), tumor necrosis factor‐α (TNF‐α) and cyclooxygenase 2 (COX‐2) gene expression and on the activation of transcription factors, nuclear factor‐κB (NF‐κB), CCAAT/enhancer‐binding protein (C/EBP), activator protein‐1 (AP‐1) and cAMP‐response element‐binding protein (CREB) were determined in Raw264.7 cells as part of the studies on its anti‐inflammatory effects. Expression of the iNOS, TNF‐α and COX‐2 genes was assessed by Northern and Western blot analyses. NO production was monitored by chemiluminescence detection using a NO analyzer. To identify the transcriptional factors affected by sauchinone, the extents of NF‐κB, C/EBP, AP‐1 and CREB activation were measured. Activation of the transcription factors was monitored by gel mobility shift assay, whereas p65 and I‐κBα were analyzed by immunocytochemical and immunoblot analyses. Sauchinone inhibited the induction of iNOS, TNF‐α and COX‐2 by lipopolysaccharide (LPS) (IC5010 μM) with suppression of the mRNAs. Sauchinone (1–30 μM) inhibited LPS‐inducible nuclear NF‐κB activation and nuclear translocation of p65, which was accompanied by inhibition of I‐κBα phosphorylation. LPS‐inducible increase in the intensity of C/EBP binding to its consensus sequence was also inhibited by sauchinone. The AP‐1, but not CREB, DNA binding activity was weakly inhibited by sauchinone. These results demonstrate that sauchinone inhibits LPS‐inducible iNOS, TNF‐α and COX‐2 expression in macrophages through suppression of I‐κBα phosphorylation and p65 nuclear translocation and of C/EBP and/or AP‐1 activation, which may constitute anti‐inflammatory effects of the lignan.