Inhibitory effects of biseokeaniamide A against lipopolysaccharide-induced signal transduction
Inhibitory effects of biseokeaniamide A against lipopolysaccharide-induced signal transduction
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DOI：
10.1016/j.bmcl.2020.127069
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发表时间：
2020-06-01
影响因子：
2.7
通讯作者：
Matsuno, Kenji
中科院分区：
文献类型：
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作者：
Ohno, Osamu;Terasaki, Takuro;Matsuno, Kenji
内毒素与多种炎症性疾病密切相关，因此抑制内毒素诱导的一氧化氮(NO)的产生可能具有广泛的治疗应用。我们从海洋生物的甲醇提取物中寻找在脂多糖刺激的小鼠巨噬细胞样细胞系RAW264.7中产生NO的抑制剂。采自日本冲绳的海洋蓝藻Okeania sp.的甲醇提取物具有抑制活性。采用层析分离的方法，从甲醇提取物中分离得到双取代芳香胺A。双乙烯酰胺A可抑制NO的产生，且无细胞毒性。降低脂多糖刺激的RAW264.7细胞诱导型一氧化氮合酶水平，抑制IL-1β的表达。双环芳酰胺A不能抑制I kappa BA的降解，但能抑制I kappa BA的表达。因此，双乙酰胺A是一种自然产生的脂肽，被认为是一种选择性的内毒素信号转导抑制剂。
Lipopolysaccharides (LPS) are associated with various inflammatory diseases; therefore, the inhibition of LPS-induced nitric oxide (NO) production may have extensive therapeutic applications. We searched for inhibitors of NO production in the LPS-stimulated murine macrophage-like cell line RAW264.7 from MeOH extracts of marine organisms. The MeOH extract of the marine cyanobacterium Okeania sp., collected in Okinawa, Japan, showed inhibitory activity. Biseokeaniamide A was isolated from the MeOH extract by chromatographic separation. Biseokeaniamide A inhibited NO production without cytotoxicity. It reduced inducible nitric oxide synthase levels and suppressed the expression of IL-1 beta in LPS-stimulated RAW264.7 cells. Biseokeaniamide A did not inhibit I kappa Ba degradation but inhibited I kappa Ba expression. Thus, biseokeaniamide A, a naturally occurring lipopeptide, was identified as a selective inhibitor of LPS signal transduction.