Inhibition of lipopolysaccharide-induced inflammatory responses by piperine
Inhibition of lipopolysaccharide-induced inflammatory responses by piperine
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DOI：
10.1016/j.ejphar.2010.05.026
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发表时间：
2010-09-10
影响因子：
5
通讯作者：
Park, Sung-Joo
中科院分区：
文献类型：
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作者：
Bae, Gi-Sang;Kim, Min-Sun;Park, Sung-Joo
Piperine，Piper Landum Linn的主要组成部分。 Piper nigrum Linn。是一种植物生物碱，具有悠久的医疗用途史。胡椒碱具有抗炎活性；但是，基本机制仍然未知。我们检查了哌啉对脂多糖（LPS）诱导的炎症反应的影响。侵蚀蛋白的给药抑制了LPS诱导的内毒素休克，白细胞积累和肿瘤坏死因子-Alpha（TNF-Alpha）的产生，但不是白介素（IL）-1β和IL-6。在腹膜巨噬细胞中，胡椒碱抑制LPS/Poly（I：C）/CpG-ODN诱导的TNF-Alpha产生。胡椒碱还抑制了LPS诱导的TNF-Alpha敲除（KO）小鼠中的内毒素休克。为了阐明LPS诱导的内毒素休克的抑制作用机制，确定了1型干扰素（IFN）mRNA表达。哌啶抑制LPS诱导的1型IFN mRNA的表达。胡须素抑制干扰素调节因子（IRF）-1和IRF-7 mRNA的水平，以及IRF-3的磷酸化和核易位。哌啶还降低了信号传感器和转录激活因子的激活（STAT）-1。另外，尖锐的IFN-α/β处理细胞抑制了STAT-1的激活。这些结果表明，哌啶通过抑制1型IFN产生而抑制LPS诱导的内毒素冲击。 （c）2010 Elsevier B.V.保留所有权利。
Piperine, a main component of Piper longum Linn. and Piper nigrum Linn., is a plant alkaloid with a long history of medical use. Piperine exhibits anti-inflammatory activity; however, the underlying mechanism remains unknown. We examined the effects of piperine on lipopolysaccharide (LPS)-induced inflammatory responses. Administration of piperine inhibited LPS-induced endotoxin shock, leukocyte accumulation and the production of tumor necrosis factor-alpha (TNF-alpha), but not of interleukin (IL)-1 beta and IL-6. In peritoneal macrophages, piperine inhibited LPS/poly (I:C)/CpG-ODN-induced TNF-alpha production. Piperine also inhibited LPS-induced endotoxin shock in TNF-alpha knockout (KO) mice. To clarify the inhibitory mechanism of LPS-induced endotoxin shock, type 1 interferon (IFN) mRNA expression was determined. Piperine inhibited LPS-induced expression of type 1 IFN mRNA. Piperine inhibited the levels of interferon regulatory factor (IRF)-1 and IRF-7 mRNA, and the phosphorylation and nuclear translocation of IRF-3. Piperine also reduced activation of signal transducer and activator of transcription (STAT)-1. In addition, activation of STAT-1 was inhibited in IFN-alpha/beta-treated cells by piperine. These results suggest that piperine inhibits LPS-induced endotoxin shock through inhibition of type 1 IFN production. (C) 2010 Elsevier B.V. All rights reserved.