Fisetin alleviates sepsis-induced multiple organ dysfunction in mice via inhibiting p38 MAPK/MK2 signaling  

作　　者：Hai-feng Zhang Hai-bo Zhang Xue-ping Wu Ya-ling Guo Wei-dong Cheng Feng Qian 

机构地区：[1]Department of Nephrology,First Affiliated Hospital of Bengbu Medical College,Anhui Province Key Laboratory of Translational Cancer Research,Bengbu Medical College,Bengbu 233004,China [2]Engineering Research Center of Cell&Therapeutic Antibody,Ministry of Education,School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240,China [3]Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy,Cancer Institute,Xuzhou Medical University,Xuzhou 221004,China

出　　处：《Acta Pharmacologica Sinica》2020年第10期1348-1356,共9页中国药理学报（英文版）

基　　金：supported by the Natural Science Research Project of Education Office of Anhui Province(KJ2019A0300);The National Key Clinical Specialty Construction Project of Pulmonary Critical Care Medicine(2012-649);The Key Research and Development Program of Anhui Province(1804h08020287);National Natural Science Foundation of China(81673791,81973329,81773741,and 81573438).

摘　　要：Sepsis-induced multiple organ dysfunction and inflammatory response are life-threatening symptoms without effective treatment.Fisetin,a dietary flavonoid extracted from berries and family Fabaceae,has displayed neuroprotective and anti-oxidant activities.In this study we investigated whether fisetin exerted a protective effect against sepsis-induced multiple organ dysfunction in mouse cecum ligation and puncture(CLP)model.The mice were injected with fisetin(10 mg/kg,ip)0.5 h prior to CLP,and sacrificed 18 h after CLP.We found that fisetin administration significantly alleviated CLP-induced lung,liver and kidney injury,as well as the expression levels of interleukin(IL)-6,tumor necrosis factor(TNF)-αand IL-1βin bronchoalveolar lavage fluid(BALF).In lipopolysaccharide(LPS)-treated mouse bone marrow-derived macrophages(BMDMs),application of fisetin(3–10μM)dose-dependently inhibited the expression levels of IL-6,TNF-α,IL-1β,and inducible nitric oxide synthase(iNOS).Furthermore,fisetin dose-dependently inhibited the phosphorylation of p38 MAPK,MK2,and transforming growth factor-β-activated kinase(TAK)1 via attenuating the interaction between TAK1 and TAK-binding proteins(TAB)1.These results demonstrate that fisetin is a promising agent for protecting against sepsis-induced inflammatory response and organ injury via inhibiting macrophage activation.

关 键 词：FISETIN sepsis multiple organ dysfunction inflammation mouse cecum ligation and puncture(CLP)model macrophages 

分 类 号：R285.5[医药卫生—中药学]