He Guodong, Zhang Xu, Chen Yanhua, Chen Jing, Li Li, Xie Yubo
Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Biomed Pharmacother. 2017 Jun;90:598-607. doi: 10.1016/j.biopha.2017.03.095. Epub 2017 Apr 11.
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, PEG and cytokines (IL-6, TNF-α) 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-κB pathway in peritoneal macrophages. In vivo, IAL reduced the secretion of IL-6 and TNF-α in serum, and increased the survival rate of mice with LPS-induced sepsis. In addition, IAL attenuated the activation of NF-κB pathway in liver. Taken together, our data suggest that IAL may represent a potentially new drug candidate for the treatment of sepsis.
脓毒症是感染或受伤患者中出现的一种临床综合征，是全球范围内主要的死亡原因。它涉及不受控制的炎症反应，导致多器官功能衰竭甚至死亡。异去甲二氢愈创木内酯（IAL）是一种倍半萜内酯，以其抗癌作用而闻名。然而，关于IAL的抗炎作用知之甚少，IAL在脓毒症中的作用尚不清楚。在本研究中，我们证明IAL可降低脂多糖（LPS）介导的腹膜巨噬细胞和RAW 264.7巨噬细胞中一氧化氮、PEG和细胞因子（IL-6、TNF-α）的产生。此外，分子机制研究表明，IAL通过抑制LPS诱导的腹膜巨噬细胞中NF-κB通路的激活发挥抗炎作用。在体内，IAL降低了血清中IL-6和TNF-α的分泌，并提高了LPS诱导的脓毒症小鼠的存活率。此外，IAL减弱了肝脏中NF-κB通路的激活。综上所述，我们的数据表明IAL可能是一种治疗脓毒症的潜在新药候选物。
