脂多糖
化学
一氧化氮
肿瘤坏死因子α
炎症
MAPK/ERK通路
p38丝裂原活化蛋白激酶
促炎细胞因子
激酶
信号转导
蛋白激酶B
蛋白激酶A
NF-κB
细胞生物学
药理学
伊诺斯
下调和上调
作者
Ae Kyung Lee,Sang Hyun Sung,Young Choong Kim,Sang Geon Kim
标识
DOI:10.1038/sj.bjp.0705231
摘要
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-alpha (TNF-alpha) and cyclooxygenase 2 (COX-2) gene expression and on the activation of transcription factors, nuclear factor-kappaB (NF-kappaB), 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-alpha 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-kappaB, 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-kappaBalpha were analyzed by immunocytochemical and immunoblot analyses. 3. Sauchinone inhibited the induction of iNOS, TNF-alpha and COX-2 by lipopolysaccharide (LPS) (IC50=10 micro M) with suppression of the mRNAs. 4. Sauchinone (1-30 micro M) inhibited LPS-inducible nuclear NF-kappaB activation and nuclear translocation of p65, which was accompanied by inhibition of I-kappaBalpha 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-alpha and COX-2 expression in macrophages through suppression of I-kappaBalpha 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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