Maackiain protects against sepsis via activating AMPK/Nrf2/HO-1 pathway
Maackiain protects against sepsis via activating AMPK/Nrf2/HO-1 pathway
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Maackiain通过激活AMPK/Nrf 2/HO-1通路抗脓毒症
DOI：
10.1016/j.intimp.2022.108710
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发表时间：
2022-04-08
影响因子：
5.6
通讯作者：
Luo, Jingjing
中科院分区：
文献类型：
--
作者：
Bai, Xiaoxue;Zhu, Yingjie;Luo, Jingjing
脓毒症是一种由感染引发的异常免疫反应引起的危及生命的疾病，导致宿主组织和器官损伤。尽管在医疗干预方面取得了进展，感染性休克的死亡率仍然很高。最近的研究强调了氧化应激在脓毒症发生发展中的作用，为预防脓毒症相关器官损伤提供了潜在的治疗靶点。在这项研究中，我们证明了Maackiain，一种从苦参中分离出来的天然化合物，在盲肠结扎和穿孔(CLP)诱导的小鼠败血症模型中发挥了保护作用。Maackiain治疗减少了脓毒症小鼠的器官损伤，并减轻了全身炎症和氧化应激。Maackiain还降低了脂多糖(LPS)刺激的RAW264.7巨噬细胞中炎性细胞因子和活性氧(ROS)的水平。我们进一步证明Maackiain通过AMPK依赖的方式启动RAW264.7细胞核因子红系相关因子2(NRF2)/血红素氧合酶-1(HO-1)通路的激活。此外，抑制AMPK/Nrf2轴可阻断Maackiain的抗炎和抗氧化作用。综上所述，我们的研究表明，Maackiain治疗通过激活AMPK/Nrf2/HO-1通路来抑制炎症反应和氧化应激，从而对脓毒症起到保护作用，为脓毒症的预防提供了另一种选择。
Sepsis is a life-threatening medical condition caused by infection-triggered aberrant immune responses, leading to host tissue and organ injury. Despite advances in medical interventions, the mortality rate for septic shock remains high. Recent studies highlight the role of oxidative stress in the occurrence and development of sepsis, providing a potential therapeutic target for preventing sepsis-associated organ injury. In this study, we showed that Maackiain, a natural compound isolated from Sophora flavescens, exerted a protective role in a cecal ligation and puncture (CLP)-induced murine model of sepsis. Maackiain treatment reduced organ injury, and mitigated systematic inflammation and oxidative stress in septic mice. Maackiain also reduced the levels of inflammatory cytokines and reactive oxygen species (ROS) in RAW264.7 macrophage cells stimulated with lipopolysaccharide (LPS). We further demonstrated that Maackiain initiated activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in RAW264.7 cells in an AMP-activated protein kinase (AMPK)dependent way. Moreover, inhibition of AMPK/Nrf2 axis abrogated the anti-inflammatory and anti-oxidant effects of Maackiain both in vitro and in vivo. Collectively, our study indicates that Maackiain treatment inhibits inflammatory response and oxidative stress via activation of AMPK/Nrf2/HO-1 pathway, thus exerting a protective effect against sepsis, providing an alternative option for sepsis prevention.