Emodin attenuates cardiomyocyte pyroptosis in doxorubicin-induced cardiotoxicity by directly binding to GSDMD

doi:10.1016/j.phymed.2023.155105

科研成果详情

题名	Emodin attenuates cardiomyocyte pyroptosis in doxorubicin-induced cardiotoxicity by directly binding to GSDMD
作者	Dai, Shanshan 2; Chen, Yunxuan1; Fan, Xiaoxi 1; Han, Jibo 3; Zhong, Lingfeng1; Zhang, Yucong1; Liu, Qingran 4; Lin, Jiahui4; Huang, Weijian1; Su, Lan1; Huang, Zhouqing1; Ye, Bozhi1
发表日期	2023-12
发表期刊	Phytomedicine : international journal of phytotherapy and phytopharmacology 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Doxorubicin-induced cardiotoxicity Emodin Gasdermin D Pyroptosis
其他关键词	GASDERMIN D ; CELL-DEATH ; MECHANISMS ; CASPASE-11
摘要	Doxorubicin (Dox), which is an anticancer drug, has significant cardiac toxicity and side effects. Pyroptosis occurs during Dox-induced cardiotoxicity (DIC), and drug inhibition of this process is one therapeutic approach for treating DIC. Previous studies have indicated that emodin can reduce pyroptosis. However, the role of emodin in DIC and its molecular targets remain unknown., We aimed to clarify the protective role of emodin in mitigating DIC, as well as the mechanisms underlying this effect., {AbstractText=The model of DIC was established via the intraperitoneal administration of Dox at a dosage of 5 mg/kg per week for a span of 4 weeks. Emodin at two different doses (10 and 20 mg/kg) or a vehicle was intragastrically administered to the mice once per day throughout the Dox treatment period. Cardiac function, myocardial injury markers, pathological morphology of the heart, level of pyroptosis and mitochondrial function were assessed. Protein microarray, biolayer interferometry and pull-down assays were used to confirm the target of emodin. Moreover, GSDMD-overexpressing plasmids were transfected into GSDMD-/- mice and HL-1 cells to further verify whether emodin suppressed GSDMD activation.}, {AbstractText=Emodin therapy markedly enhanced cardiac function and reduced cardiomyocyte pyroptosis in mice induced by Dox. Mechanistically, emodin binds to GSDMD and inhibits the activation of GSDMD by targeting the Trp415 and Leu290 residues. Moreover, emodin was able to mitigate Dox-induced cardiac dysfunction and myocardial injury in GSDMD-/- mice overexpressing GSDMD, as shown by increased EF and FS, decreased serum levels of CK-MB, LDH and IL-1β and mitigated cell death and cell morphological disorder. Additionally, emodin treatment significantly reduced GSDMD-N expression and plasma membrane disruption in HL-1 cells overexpressing GSDMD induced by Dox. In addition, emodin reduced mitochondrial damage by alleviating Dox-induced GSDMD perforation in the mitochondrial membrane.}, Emodin has the potential to attenuate DIC by directly binding to GSDMD to inhibit pyroptosis. Emodin may become a promising drug for prevention and treatment of DIC.
资助项目	National Natural Science Founda- tion of China [82003750, 82202380]; Nat- ural Science Foundation of Zhejiang Province [LQ23H310005, LY22H020004]; Medical and Health Science and Technology Project of Zhejiang Province [2022RC046]; Traditional Chinese Medicine Administration of Zhejiang Province [2022ZA096]; Science and Technology Project of Wenzhou [20220082]; University -Industry Collaborative Education Program of Ministry of Education [22097154062650]
出版者	ELSEVIER GMBH
ISSN	0944-7113
EISSN	1618-095X
卷号	121
DOI	10.1016/j.phymed.2023.155105
页数	14
WOS类目	Plant Sciences ; Chemistry, Medicinal ; Integrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS研究方向	Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
WOS记录号	WOS:001088826800001
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2023-10
URL	查看原文
PubMed ID	37801893
SCOPUSEID	2-s2.0-85173027410
通讯作者地址	[Su, Lan]Key Laboratory of Cardiovascular Disease of Wenzhou,Department of Cardiology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Molecular Medicine;Pharmacology;Pharmaceutical Science;Drug Discovery;Complementary and Alternative Medicine
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/183326
专题	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	Su, Lan
作者单位	1.The Key Laboratory of Cardiovascular Disease of Wenzhou,Department of Cardiology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,China; 2.The Key Laboratory of Emergency and Disaster Medicine of Wenzhou,Department of Emergency,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,China; 3.Department of Cardiology,The Second Affiliated Hospital of Jiaxing University,Zhejiang,Jiaxing,China; 4.The First School of Medicine,Wenzhou Medical University,Zhejiang,Wenzhou,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
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	Dai, Shanshan,Chen, Yunxuan,Fan, Xiaoxi,et al. Emodin attenuates cardiomyocyte pyroptosis in doxorubicin-induced cardiotoxicity by directly binding to GSDMD[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology,2023,121.
APA	Dai, Shanshan., Chen, Yunxuan., Fan, Xiaoxi., Han, Jibo., Zhong, Lingfeng., ... & Ye, Bozhi. (2023). Emodin attenuates cardiomyocyte pyroptosis in doxorubicin-induced cardiotoxicity by directly binding to GSDMD. Phytomedicine : international journal of phytotherapy and phytopharmacology, 121.
MLA	Dai, Shanshan,et al."Emodin attenuates cardiomyocyte pyroptosis in doxorubicin-induced cardiotoxicity by directly binding to GSDMD".Phytomedicine : international journal of phytotherapy and phytopharmacology 121(2023).