Neougonin A Inhibits Lipopolysaccharide-Induced Inflammatory Responses via Downregulation of the NF-kB Signaling Pathway in RAW 264.7 Macrophages

Neougonin A Inhibits Lipopolysaccharide-Induced Inflammatory Responses via Downregulation of the NF-kB Signaling Pathway in RAW 264.7 Macrophages
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Neougonin A 通过下调 RAW 264.7 巨噬细胞中 NF-kB 信号通路抑制脂多糖诱导的炎症反应

DOI:
10.1007/s10753-016-0429-9
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发表时间:
2016-12-01
期刊:
影响因子:
5.1
通讯作者:
Liu, Dan
Liu, Dan
中科院分区:
医学2区
文献类型:
--
作者:
Cao, Lang;Li, Rongtao;Liu, Dan

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Neougonin A是从麦冬属(Ophioglossaceae)线虫属(Helminthostachys Zeylanica)植物中分离得到的一种异戊烯基黄酮类化合物,常用作治疗发热和炎症的中草药。本研究探讨了新牛膝素A对内毒素(LPS)诱导的炎症反应的药理作用及其分子机制。我们观察到新月桂素A能减少脂多糖诱导的小鼠巨噬细胞RAW 264.7细胞产生炎症介质(肿瘤坏死因子α、前列腺素E_2、NO、IL-1β和IL-6;P< 0.001)和炎症相关蛋白(iNOS和COX-2)。此外,免疫印迹和免疫荧光分析表明,即使在1.25α时,新胡萝卜素A也能抑制IkB/p65的磷酸化,阻止核转录因子-kB/p65的转位(P<μ),但对 、ERK1/2和p38MAPK的磷酸化没有影响。提示新月桂素A的抗炎作用可能是通过抑制核因子-kB信号转导通路,下调肿瘤坏死因子α、IL-1β、IL-6、NO和PGE_2的表达。
Neougonin A is a prenylated flavonoid isolated from the whole plants ofHelminthostachys zeylanica(Ophioglossaceae), which was usually used as traditional Chinese herbal medicine for the treatment of fever and inflammation. In this study, the pharmacological effects and underlying molecular mechanisms of neougonin A on lipopolysaccharide (LPS)-induced inflammatory responses were investigated. We observed that neougonin A reduced the production of inflammatory mediators (TNFα, PGE2, NO, IL-1β, and IL-6;P< 0.001) and inflammation-related proteins (iNOS and COX-2) induced by LPS in murine macrophage RAW 264.7 cells. Furthermore, Western blot and immunofluorescence analysis indicated that neougonin A could inhibit the phosphorylation of IkBα and block the translocation of NF-kB/p65 into the nucleus even at 1.25 μM (P< 0.05), but have no effect on JNK, ERK1/2, and p38MAPK phosphorylation. It was suggested that the anti-inflammatory actions of neougonin A might be due to the downregulation of TNFα, IL-1β, IL-6, NO, and PGE2via the suppression of NF-kB signal transduction pathway.