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香芹酚通过调节 ERK1/2 通路保护 LPS 诱导脓毒症的小鼠并减轻巨噬细胞的炎症反应。

Carvacrol protects mice against LPS-induced sepsis and attenuates inflammatory response in macrophages by modulating the ERK1/2 pathway.

机构信息

College of Traditional Chinese Medicine/College of Life Sciences, Jiangxi University of Chinese Medicine, Nanchang, 330004, China.

Institute of Microbiology, Jiangxi Academy of Sciences, Nanchang, 330029, China.

出版信息

Sci Rep. 2023 Aug 7;13(1):12809. doi: 10.1038/s41598-023-39665-7.

Abstract

Macrophages play an important role in the development of life-threatening sepsis, which is characterized by multiorgan dysfunction, through their ability to produce inflammatory cytokines. Carvacrol is a phenolic compound that has been confirmed to possess strong anti‑inflammatory activity. In this study, we mainly investigated the effect of carvacrol on lipopolysaccharide (LPS)-induced macrophage proinflammatory responses and endotoxic shock. The results showed that carvacrol significantly reduced mouse body weight loss and ameliorated pathological damage to the liver, lung, and heart under LPS-induced sepsis. Carvacrol attenuated inflammatory responses by inhibiting the LPS-induced production of inflammatory cytokine interleukin-6 (IL-6) in vivo and in vitro. Mechanistically, carvacrol inhibited IL-6 production mainly through the ERK1/2 signalling pathway in macrophages. Furthermore, carvacrol improved the survival of septic mice. This study sheds light on the role of carvacrol in the pathogenesis of LPS-induced sepsis, and thus, its potential in treating sepsis patients may be considered.

摘要

巨噬细胞通过产生炎症细胞因子在危及生命的脓毒症的发展中发挥重要作用,脓毒症的特征是多器官功能障碍。香芹酚是一种酚类化合物,已被证实具有很强的抗炎活性。在这项研究中,我们主要研究了香芹酚对脂多糖(LPS)诱导的巨噬细胞促炎反应和内毒素休克的影响。结果表明,香芹酚可显著减轻 LPS 诱导的脓毒症小鼠体重减轻,并改善肝脏、肺和心脏的病理损伤。香芹酚通过抑制 LPS 诱导的体内和体外炎症细胞因子白细胞介素-6(IL-6)的产生来减轻炎症反应。在机制上,香芹酚主要通过 ERK1/2 信号通路抑制巨噬细胞中 IL-6 的产生。此外,香芹酚还提高了脓毒症小鼠的存活率。这项研究揭示了香芹酚在 LPS 诱导的脓毒症发病机制中的作用,因此可以考虑将其用于治疗脓毒症患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f6d/10406886/62452d3bc5a5/41598_2023_39665_Fig1_HTML.jpg

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