Fimasartan, anti-hypertension drug, suppressed inducible nitric oxide synthase expressions via nuclear factor-kappa B and activator protein-1 inactivation.
Fimasartan, anti-hypertension drug, suppressed inducible nitric oxide synthase expressions via nuclear factor-kappa B and activator protein-1 inactivation.
复制标题
DOI：
10.1248/bpb.b12-00859
复制
发表时间：
2013-03
影响因子：
2
通讯作者：
S. Ryu;Ji-Sun Shin;Young-Wuk Cho;H. Kim;S. Paik;J. Lee;Y. Chi;Ji Han Kim;Je Hak Kim;Kyung-Tae Lee
中科院分区：
文献类型：
--
作者：
S. Ryu;Ji-Sun Shin;Young-Wuk Cho;H. Kim;S. Paik;J. Lee;Y. Chi;Ji Han Kim;Je Hak Kim;Kyung-Tae Lee
由于抑制血管紧张素 II 1 型 (AT1) 受体可减少与高血压相关的慢性炎症，因此我们评估了韩国食品和药物管理局批准的抗高血压药物非马沙坦在脂多糖 (LPS) 刺激的 RAW264.7 巨噬细胞中的抗炎潜力和潜在机制。非马沙坦通过下调诱导型一氧化氮合酶 (iNOS) 的转录来抑制其表达，从而抑制一氧化氮 (NO) 的产生。此外，非马沙坦还可减弱 LPS 诱导的核因子 kappa B (NF-κB) 和激活蛋白 1 (AP-1) 的转录和 DNA 结合活性。这些减少伴随着 NF-κB 和 AP-1 核转位的平行减少。综上所述，我们的数据表明非马沙坦通过 NF-κB 和 AP-1 失活下调巨噬细胞中 iNOS 的表达。
Since inhibition of angiotensin II type 1 (AT1) receptor reduces chronic inflammation associated with hypertension, we evaluated the anti-inflammatory potential and the underlying mechanism of fimasartan, a Korean Food and Drug Administration approved anti-hypertension drug, in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Fimasartan suppressed the expressions of inducible nitric oxide synthase (iNOS) by down-regulating its transcription, and subsequently inhibited the productions of nitric oxide (NO). In addition, fimasartan attenuated LPS-induced transcriptional and DNA-binding activities of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). These reductions were accompanied by parallel reductions in the nuclear translocation of NF-κB and AP-1. Taken together, our data suggest that fimasartan down-regulates the expression of the iNOS in macrophages via NF-κB and AP-1 inactivation.