Isoalantolactone inhibits LPS-induced inflammation via NF-κB inactivation in peritoneal macrophages and improves survival in sepsis
Isoalantolactone inhibits LPS-induced inflammation via NF-κB inactivation in peritoneal macrophages and improves survival in sepsis
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DOI：
10.1016/j.biopha.2017.03.095
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发表时间：
2017-06-01
影响因子：
7.5
通讯作者：
Xie, Yubo
中科院分区：
文献类型：
--
作者：
He, Guodong;Zhang, Xu;Xie, Yubo
脓毒症是一种发生于患者感染或损伤后的临床综合征，是世界范围内死亡的主要原因。它涉及不受控制的炎症反应，导致多器官衰竭，甚至死亡。异土木香内酯（IAL）是一种倍半萜内酯，因其抗癌作用而闻名。然而，关于IAL的抗炎作用知之甚少，IAL在脓毒症中的作用也不清楚。在这项研究中，我们证明了IAL减少了腹腔巨噬细胞和RAW 264.7巨噬细胞中脂多糖（LPS）介导的一氧化氮、PEG 2和细胞因子（IL-6、TNF-α）的产生。分子机制研究表明，IAL可能通过抑制LPS诱导的腹腔巨噬细胞NF-κ B通路的活化而发挥抗炎作用。在体内，IAL减少血清中IL-6和TNF-α的分泌，并增加LPS诱导的脓毒症小鼠的存活率。此外，IAL还能抑制肝脏NF-κ B B通路的激活。综上所述，我们的数据表明，IAL可能代表一种潜在的治疗脓毒症的新候选药物。(C)2017年Elsevier Masson SAS。All rights reserved.
Sepsis, a clinical syndrome occurring in patients following infection or injury, is a leading cause of mortality worldwide. It involves uncontrolled inflammatory response resulting in multi-organ failure and even death. Isoalantolactone ( IAL), a sesquiterpene lactone, is known for its anti-cancer effects. Nevertheless, little is known about the anti-inflammatory effects of IAL, and the role of IAL in sepsis is unclear. In this study, we demonstrated that IAL decreased lipopolysaccharide ( LPS)-mediated production of nitric oxide, PEG2 and cytokines ( IL-6, TNF-alpha) in peritoneal macrophages and RAW 264.7 macrophages. Moreover, molecular mechanism studies indicated that IAL plays an anti-inflammatory role by inhibiting LPS-induced activation of NF-kappa B pathway in peritoneal macrophages. In vivo, IAL reduced the secretion of IL-6 and TNF-alpha in serum, and increased the survival rate of mice with LPS- induced sepsis. In addition, IAL attenuated the activation of NF-kappa B pathway in liver. Taken together, our data suggest that IAL may represent a potentially new drug candidate for the treatment of sepsis. (C) 2017 Elsevier Masson SAS. All rights reserved.