Esculetin protects against early sepsis via attenuating inflammation by inhibiting NF-κB and STAT1/STAT3 signaling

被引:21
作者
Cheng Yao-Jun [1 ,2 ]
Tian Xin-Lei [2 ]
Zeng Ya-Zhi [1 ]
Lan Nan [2 ]
Guo Ling-Feng [2 ]
Liu Ke-Feng [1 ]
Fang Hui-Long [1 ]
Fan Hong-Ye [2 ]
Peng Zhong-Lu [1 ]
机构
[1] Xiangnan Univ, Key Lab Univ Hunan Prov Cardiovasc & Cerebrovasc, Chenzhou 423000, Peoples R China
[2] China Pharmaceut Univ, Sch Life Sci & Technol, State Key Lab Nat Med, Nanjing 210009, Peoples R China
关键词
Esculetin; NF-kappa B; STAT1; STAT3; Early sepsis; ENDOTOXIC-SHOCK; CECAL LIGATION; CYTOKINE STORM; SEPTIC SHOCK; MICE; STAT3; MACROPHAGES; ACTIVATION; PATHWAY; DISEASE;
D O I
10.1016/S1875-5364(21)60042-0
中图分类号
R [医药、卫生];
学科分类号
10 ;
摘要
Esculetin, a natural derivative from the traditional and widely-used Chinese medicinal herb Cortex Fraxini, has a variety of pharmacological effects, especially in anti-inflammation. However, it is not clear whether esculetin has a therapeutic effect on sepsis. This study aimed to investigate the anti-inflammatory and protective effects of esculetin on early sepsis. The results showed that the lung injury was significantly relieved with the treatment of esculetin, accompanied with the restrained production of inflammatory factors including IL-1 beta, IL-6, TNF-alpha, CCL2 and iNOS during the early phase of E.coli-induced sepsis. Of note, activation of NF-kappa B and STAT1/STAT3 signals, the main upstream signals of many inflammatory factors, were attenuated by esculetin in both lung tissues from septic mice and LPS-stimulated macrophage. These findings suggested that the protection of esculetin against early sepsis should be related to its anti-inflammatory effect, which was at least partly due to its inhibition on NF-kappa B and STAT1/STAT3 signaling pathway in macrophage. Thus, esculetin could serve as a potential therapeutic agent by rebalancing innate immune response in macrophage for the treatment of early sepsis.
引用
收藏
页码:432 / 441
页数:10
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