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Costunolide attenuates LPS-induced inflammation and lung injury through inhibiting IKK/NF-κB signaling
Naunyn-Schmiedeberg's Archives of Pharmacology ( IF 3.1 ) Pub Date : 2023-09-09 , DOI: 10.1007/s00210-023-02705-0
Xiaona Zhu 1 , Bin Bai 2 , Xiangting Ge 3 , Bin Zheng 2 , Zhongxiang Xiao 1 , Yue Tang 2 , Letong Fang 2 , Yelin Tang 2 , Yuanrong Dai 3 , Bing Zhang 1 , Yali Zhang 1, 2
Affiliation  

Inflammation is an important pathological process of many acute and chronic diseases, such as sepsis, arthritis, and cancer. Many factors can lead to an inflammatory state of the body, among which bacterial infection plays an important role. Bacterial infection often leads to sepsis, acute lung injury (ALI), or its more serious form of acute respiratory distress syndrome, which are the main fatal diseases in intensive care units. Costunolide has been reported to possess excellent anti-inflammatory activity; however, whether it can affect inflammation induced by gram-negative bacterial is still unclear. Lipopolysaccharide (LPS) stimulated mouse peritoneal macrophages (MPMs) to release proinflammatory cytokines was used as the cell model. The mouse model of sepsis and ALI was built through injecting intravenously and intratracheally of LPS. In the present study, costunolide inhibited LPS-induced inflammatory response through IKK/NF-κB signaling pathway in macrophages. In vivo, costunolide attenuated LPS-induced septic death in mice. Meanwhile, costunolide treatment alleviated LPS-induced lung injury and inflammation via inhibiting the infiltration of inflammatory cells and the expression of inflammatory cytokines. Taken together, these results demonstrated that costunolide could attenuate gram-negative bacterial induced inflammation and diseases and might be a potential candidate for the treatment of inflammatory diseases.



中文翻译:


木香内酯通过抑制 IKK/NF-κB 信号传导减轻 LPS 诱导的炎症和肺损伤



炎症是许多急慢性疾病的重要病理过程,如败血症、关节炎、癌症等。许多因素可导致机体出现炎症状态,其中细菌感染起着重要作用。细菌感染常常导致败血症、急性肺损伤(ALI)或更严重的急性呼吸窘迫综合征,这些都是重症监护病房的主要致命疾病。据报道,木香内酯具有优异的抗炎活性;但是否能影响革兰氏阴性菌引起的炎症尚不清楚。脂多糖(LPS)刺激小鼠腹腔巨噬细胞(MPM)释放促炎细胞因子被用作细胞模型。通过静脉和气管内注射LPS建立脓毒症和ALI小鼠模型。在本研究中,木香烯内酯通过 IKK/NF-κB 信号通路抑制巨噬细胞中 LPS 诱导的炎症反应。在体内,木香烯内酯可减轻 LPS 诱导的小鼠脓毒症死亡。同时,木香内酯治疗通过抑制炎症细胞的浸润和炎症细胞因子的表达来减轻LPS引起的肺损伤和炎症。总而言之,这些结果表明木香内酯可以减轻革兰氏阴性细菌引起的炎症和疾病,并且可能是治疗炎症性疾病的潜在候选者。

更新日期:2023-09-09
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