Anti-inflammatory effects of (Z)-ligustilide through suppression of mitogen-activated protein kinases and nuclear factor-κB activation pathways

Anti-inflammatory effects of (Z)-ligustilide through suppression of mitogen-activated protein kinases and nuclear factor-κB activation pathways
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DOI:
10.1007/s12272-012-0417-z
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发表时间:
2012-03-01
影响因子:
6.7
通讯作者:
Kim, Yeong Shik
Kim, Yeong Shik
中科院分区:
医学2区
文献类型:
--
作者:
Chung, Ji Won;Choi, Ran Joo;Kim, Yeong Shik

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在中国和韩国等亚洲国家,细当归的根通常用于治疗心血管疾病和月经不适。主要挥发性风味成分是精油成分、苯酞内酯。在这项研究中,测试了 (Z)-藁本内酯在脂多糖 (LPS) 刺激的 RAW264.7 巨噬细胞中的抗炎活性。我们发现 (Z)-藁本内酯在 mRNA 和蛋白质水平上以剂量依赖性方式强烈抑制 LPS 诱导的诱导型一氧化氮合酶 (iNOS) 和环氧合酶-2 (COX-2) 的诱导。核因子κB (NF-B) 的转录活性也以浓度依赖性方式下调。进一步研究表明,(Z)-藁本内酯可抑制 NF-B 抑制剂蛋白 IB α 的磷酸化和随后的降解。此外,(Z)-藁本内酯以剂量依赖性方式抑制 p38 丝裂原激活蛋白激酶 (p38 MAPK)、细胞外信号调节激酶 (ERK) 和 c-Jun NH2 末端激酶 (JNK) 的磷酸化。综上所述,这些数据表明 (Z)-藁本内酯可以通过调节 NF-B 和 MAPK 信号通路发挥其抗炎作用。
The roots of Angelica tenuissima have been commonly used for the treatment of cardiovascular diseases and menstrual discomfort in Asian countries, such as China and Korea. The primary volatile flavor components are essential oil ingredients, phthalide lactones. In this study, (Z)-ligustilide was tested for its anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We found that (Z)-ligustilide strongly inhibitis the induction of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at both the mRNA and protein levels in a dose-dependent manner. The transcriptional activity of nuclear factor kappa B (NF-B) was also down-regulated in a concentration-dependent manner. Further study revealed that (Z)-ligustilide inhibited the phosphorylation and subsequent degradation of IB alpha, an inhibitor protein of NF-B. In addition, (Z)-ligustilide inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) in a dose-dependent manner. Taken together, these data suggest that (Z)-ligustilide can exert its antiinflammatory effects by regulating the NF-B and MAPK signal pathways.