Evidence that a Novel Chalcone Derivative, Compound 27, Acts on the Epithelium Via the PI3K/AKT/Nrf2-Keap1 Signaling Pathway, to Mitigate LPS-Induced Acute Lung Injury in Mice

doi:10.1007/s10753-024-02051-0

科研成果详情

题名	Evidence that a Novel Chalcone Derivative, Compound 27, Acts on the Epithelium Via the PI3K/AKT/Nrf2-Keap1 Signaling Pathway, to Mitigate LPS-Induced Acute Lung Injury in Mice
作者	Zhou, Liqin 1; Lin, Yuting 1; Zhou, Tengfei 3; Xue, Yincong1; Bellusci, Saverio 5; Shen, Mengya4; Chen, Chengshui1,2; Chen, Chaolei1
发表日期	2024
发表期刊	Inflammation; 影响因子和分区
语种	英语
原始文献类型	Article
关键词	acute lung injury apoptosis chalcone derivatives mitochondrial dysfunction oxidative stress
其他关键词	RESPIRATORY-DISTRESS-SYNDROME ; PATHOGENESIS ; INFLAMMATION ; ACTIVATION ; MECHANISMS ; CLEARANCE ; PNEUMONIA ; PROTEINS ; PROTECTS ; FEATURES
摘要	Acute lung injury (ALI) is a highly heterogeneous clinical syndrome and an important cause of mortality in critically ill patients, with limited treatment options currently available. Chalcone, an essential secondary metabolite found in edible or medicinal plants, exhibits good antioxidant activity and simple structure for easy synthesis. In our study, we synthesized a novel chalcone derivative, compound 27 (C27). We hypothesized that C27 could be a potential treatment for acute respiratory distress syndrome (ARDS). Therefore, the protective effects of C27 on lung epithelial cells during ALI and the underlying molecular mechanisms were investigated. In vivo, Intratracheal instillation of LPS (10 mg/kg) was used to induce acute lung injury in mice. In vitro, the bronchial epithelial cell line (Beas-2b) was treated with 30 μM tert-butyl hydroperoxide (t-BHP) to simulate oxidative stress. Our findings demonstrate that pretreatment with C27 reduces LPS-induced oxidative destruction and cellular apoptosis in lung tissues of mice. Furthermore, it significantly attenuates t-BHP-induced cellular reactive oxygen species (ROS) generation, mitochondrial damage, and apoptosis in vitro. Mechanistically, the signaling pathway involving Nrf2-Keap1 and the downstream antioxidative proteins were activated by C27 in vivo. Additionally, PI3K inhibitor LY294002 and Nrf2 inhibitor ML385 abolished the effect of C27 in vitro, indicating that the protective effect of C27 is mediated via the PI3K/AKT/Nrf2-Keap1 pathway. Our study provides evidence that C27 protects against LPS-induced ALI by mitigating oxidative stress via activation of the PI3K/AKT/Nrf2-Keap1 signaling pathway. Therefore, we hypothesize that C27 represents a viable alternative for ALI therapy.
资助项目	Key Laboratory of Interventional Pulmonology of Zhejiang Province[2019E10014];National Nature Science Foundation of China[82170017];National Key Research and Development Program of China[2016YFC1304000];
出版者	SPRINGER/PLENUM PUBLISHERS
ISSN	0360-3997
EISSN	1573-2576
DOI	10.1007/s10753-024-02051-0
页数	19
WOS类目	Cell Biology ; Immunology
WOS研究方向	Cell Biology ; Immunology
WOS记录号	WOS:001234041300001
收录类别	SCOPUS ; SCIE ; PUBMED
URL	查看原文
PubMed ID	38789816
SCOPUSEID	2-s2.0-85194281588
通讯作者地址	[Chen, Chaolei]Zhejiang Provincial Key Laboratory of Interventional Pulmonology,Department of Pulmonary and Critical Care Medicine,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China
Scopus学科分类	Immunology and Allergy;Immunology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/213469
专题	附属第一医院药学院（分析测试中心）其他_温州医科大学附属衢州医院
通讯作者	Chen, Chaolei
作者单位	1.Zhejiang Provincial Key Laboratory of Interventional Pulmonology,Department of Pulmonary and Critical Care Medicine,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 2.Department of Pulmonary and Critical Care Medicine,The Quzhou Affiliated Hospital of Wenzhou Medical University,Quzhou People’s Hospital,Quzhou,324000,China; 3.Department of Physiology,Zhejiang University School of Medicine,Zhejiang,Hangzhou,310058,China; 4.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China; 5.Department of Internal Medicine,German Center for Lung Research (DZL),Universities of Giessen and Marburg Lung Center (UGMLC),Cardio-Pulmonary Institute (CPI),Member of the,Justus-Liebig University Giessen,Giessen,35392,Germany
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
通讯作者单位	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	Zhou, Liqin,Lin, Yuting,Zhou, Tengfei,et al. Evidence that a Novel Chalcone Derivative, Compound 27, Acts on the Epithelium Via the PI3K/AKT/Nrf2-Keap1 Signaling Pathway, to Mitigate LPS-Induced Acute Lung Injury in Mice[J]. Inflammation;,2024.
APA	Zhou, Liqin., Lin, Yuting., Zhou, Tengfei., Xue, Yincong., Bellusci, Saverio., ... & Chen, Chaolei. (2024). Evidence that a Novel Chalcone Derivative, Compound 27, Acts on the Epithelium Via the PI3K/AKT/Nrf2-Keap1 Signaling Pathway, to Mitigate LPS-Induced Acute Lung Injury in Mice. Inflammation;.
MLA	Zhou, Liqin,et al."Evidence that a Novel Chalcone Derivative, Compound 27, Acts on the Epithelium Via the PI3K/AKT/Nrf2-Keap1 Signaling Pathway, to Mitigate LPS-Induced Acute Lung Injury in Mice".Inflammation; (2024).