Esculin alleviates LPS-induced acute lung injury via inhibiting neutrophil recruitment and migration

doi:10.1016/j.intimp.2023.110177

科研成果详情

题名	Esculin alleviates LPS-induced acute lung injury via inhibiting neutrophil recruitment and migration
作者	Ni, Jiangwei 1; Li, Ge2; Dai, Ningfeng 3; Quan, Zijiao 4; Tong, Haibin 4; Liu, Yu1
发表日期	2023-06
发表期刊	International immunopharmacology 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Acute lung injury Esculin Integrin Neutrophil
其他关键词	LEUKOCYTE RECRUITMENT ; EFALIZUMAB
摘要	Acute lung injury (ALI) poses a serious threat to human health globally, particularly with the Coronavirus 2019 (COVID-19) pandemic. Excessive recruitment and infiltration of neutrophils is the major etiopathogenesis of ALI. Esculin, also known as 6,7-dihydroxycoumarin, is a remarkable compound derived from traditional Chinese medicine Cortex fraxini. Accumulated evidence indicates that esculin has potent anti-inflammatory effects, but its pharmaceutical effect against ALI and potential mechanisms are still unclear., This study evaluated the protective effect of esculin against ALI by histopathological observation and biochemical analysis of lung tissues and bronchoalveolar lavage fluid (BALF) in lipopolysaccharide (LPS)-challenged ALI mice in vivo. The effects of esculin on N-formyl-met-leu-phe (fMLP)-induced neutrophil migration and chemotaxis were quantitatively assessed using a Transwell assay and an automated cell imaging system equipped with a Zigmond chamber, respectively. The drug affinity responsive target stability (DARTS) assay, in vitro protein binding assay and molecular docking were performed to identify the potential therapeutic target of esculin and the potential binding sites and pattern., {AbstractText=Esculin significantly attenuated LPS-induced lung pathological injury, reduced the levels of pro-inflammatory cytokines in both BALF and lung, and suppressed the activation of NF-κB signaling. Esculin also significantly reduced the number of total cells and neutrophils as well as myeloperoxidase (MPO) activity in the BALF. Esculin impaired neutrophil migration and chemotaxis as evidenced by the reduced migration distance and velocity. Furthermore, esculin remarkably inhibited Vav1 phosphorylation, suppressed Rac1 activation and the PAK1/LIMK1/cofilin signaling axis. Mechanistically, esculin could interact with β2 integrin and then diminish its ligand affinity with intercellular adhesion molecule-1 (ICAM-1).}, {AbstractText=Esculin inhibits β2 integrin-dependent neutrophil migration and chemotaxis, blocks the cytoskeletal remodeling process required for neutrophil recruitment, thereby contributing to its protective effect against ALI. This study demonstrates the new therapeutic potential of esculin as a novel lead compound
资助项目	National Natural Science Foundation of China[81872952];Natural Science Foundation of Zhejiang Province[LY21H160059];
出版者	ELSEVIER
ISSN	1567-5769
EISSN	1878-1705
卷号	119
DOI	10.1016/j.intimp.2023.110177
页数	10
WOS类目	Immunology ; Pharmacology & Pharmacy
WOS研究方向	Immunology ; Pharmacology & Pharmacy
WOS记录号	WOS:000982978700001
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2023-04
URL	查看原文
PubMed ID	37068336
SCOPUSEID	2-s2.0-85153492974
通讯作者地址	[Tong, Haibin]Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection,College of Life and Environmental Science,Wenzhou University,Wenzhou,325000,China
Scopus学科分类	Immunology and Allergy;Immunology;Pharmacology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/175120
专题	附属第一医院其他_附属第三医院（瑞安市人民医院）其他_附属苍南医院（苍南县人民医院）
通讯作者	Tong, Haibin
作者单位	1.Department of Thoracic Surgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 2.Department of Thoracic Surgery,The Third Affiliated Hospital of Wenzhou Medical University,Wenzhou,325200,China; 3.Department of Thoracic Surgery,The Affiliated Cangnan Hospital of Wenzhou Medical University,Wenzhou,325800,China; 4.Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection,College of Life and Environmental Science,Wenzhou University,Wenzhou,325000,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Ni, Jiangwei,Li, Ge,Dai, Ningfeng,et al. Esculin alleviates LPS-induced acute lung injury via inhibiting neutrophil recruitment and migration[J]. International immunopharmacology,2023,119.
APA	Ni, Jiangwei, Li, Ge, Dai, Ningfeng, Quan, Zijiao, Tong, Haibin, & Liu, Yu. (2023). Esculin alleviates LPS-induced acute lung injury via inhibiting neutrophil recruitment and migration. International immunopharmacology, 119.
MLA	Ni, Jiangwei,et al."Esculin alleviates LPS-induced acute lung injury via inhibiting neutrophil recruitment and migration".International immunopharmacology 119(2023).