Cynandione A attenuates lipopolysaccharide-induced production of inflammatory mediators via MAPK inhibition and NF-κB inactivation in RAW264.7 macrophages and protects mice against endotoxin shock
Cynandione A attenuates lipopolysaccharide-induced production of inflammatory mediators via MAPK inhibition and NF-κB inactivation in RAW264.7 macrophages and protects mice against endotoxin shock
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DOI：
10.1177/1535370214558022
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发表时间：
2015-07-01
影响因子：
3.2
通讯作者：
Kim, Jiyoung
中科院分区：
文献类型：
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作者：
Kim, Sung Hwan;Lee, Tae Hoon;Kim, Jiyoung
在东亚地区，传统上使用虎尾草治疗胃肠道疾病和动脉硬化等各种疾病。青醌A （Cynandione A， CA）是一种苯乙酮类化合物，是紫藤根的主要成分之一。本研究对脂多糖（LPS）处理的RAW264.7巨噬细胞和LPS给药的C57BL/6N小鼠进行了CA的抗炎活性研究。CA以剂量依赖的方式显著降低lps诱导的一氧化氮和前列腺素E2的产生，而CA高达200 μ M时不表现出细胞毒性活性。我们的数据还显示，CA显著降低lps刺激的巨噬细胞中iNOS和COX-2的表达。CA抑制I κ b - α和MAP激酶如ERK和p38的磷酸化。此外，我们证明了CA抑制NF-kappa B向细胞核的易位，NF-kappa B最小启动子的转录和NF-kappa B DNA结合活性。CA可显著降低lps注射小鼠血浆中促炎细胞因子如tnf - α、IL-6和IL-1 β的水平，提高致死性内毒素血症脓毒症小鼠的存活率。这些结果表明，CA通过抑制NF-kappa B和MAPK信号通路的激活，对炎症介质的产生有有效的抑制作用，提示CA可能作为一种潜在的抗炎剂用于预防和治疗炎症性疾病。
Cynanchum wilfordii has been traditionally used in eastern Asia for the treatment of various diseases such as gastrointestinal diseases and arteriosclerosis. Cynandione A (CA), an acetophenone, is one of major constituents from roots of C. wilfordii. In the present study, the anti-inflammatory activities of CA were investigated in lipopolysaccharide (LPS)-treated RAW264.7 macrophages and LPS-administered C57BL/6N mice. CA significantly decreased LPS-induced production of nitric oxide and prostaglandin E2 in a dose-dependent manner, while CA up to 200 mu M did not exhibit cytotoxic activity. Our data also showed that CA significantly attenuated expression of iNOS and COX-2 in LPS-stimulated macrophages. CA inhibited phosphorylation of I kappa B-alpha and MAP kinases such as ERK and p38. Furthermore, we demonstrated that CA inhibited translocation of NF-kappa B to the nucleus, transcription of the NF-kappa B minimal promoter and NF-kappa B DNA binding activity. Administration of CA significantly decreased the plasma levels of pro-inflammatory cytokines such as TNF-alpha, IL-6, and IL-1 beta in LPS-injected mice and improved survival of septic mice with lethal endotoxemia. These results demonstrate that CA has effective inhibitory effects on production of inflammatory mediators via suppressing activation of NF-kappa B and MAPK signaling pathways, suggesting that CA may be used as a potential anti-inflammatory agent for the prevention and treatment of inflammatory diseases.