1 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-a (TNF-a) and cyclooxygenase 2 (COX-2) gene expression and on the activation of transcription factors, nuclear factor-kB (NF-kB), 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. 2 Expression of the iNOS, TNF-a 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-kB, 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-kBa were analyzed by immunocytochemical and immunoblot analyses. 3 Sauchinone inhibited the induction of iNOS, TNF-a and COX-2 by lipopolysaccharide (LPS) (IC50p10 mM) with suppression of the mRNAs. 4 Sauchinone (1 -30 mM) inhibited LPS-inducible nuclear NF-kB activation and nuclear translocation of p65, which was accompanied by inhibition of I-kBa phosphorylation. 5 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. 6 These results demonstrate that sauchinone inhibits LPS-inducible iNOS, TNF-a and COX-2 expression in macrophages through suppression of I-kBa phosphorylation and p65 nuclear translocation and of C/EBP and/or AP-1 activation, which may constitute anti-inflammatory effects of the lignan.

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