Tabersonine alleviates obesity-induced cardiomyopathy by binding to Transforming growth factor activated kinase 1 (TAK1) and inhibiting TAK1-mediated inflammation.

doi:10.1002/ptr.7666

科研成果详情

题名	Tabersonine alleviates obesity-induced cardiomyopathy by binding to Transforming growth factor activated kinase 1 (TAK1) and inhibiting TAK1-mediated inflammation.
作者	Chen, Yanghao1,2; Lin, Wante1,2; Chen, Pan2; Ye, Bozhi1,2; Luo, Wu2; Wang, Xu 2; Huang, Weijian1; Wu, Gaojun1; Liang, Guang1,2,3
发表日期	2023-03
发表期刊	Phytotherapy research : PTR 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	TAK1 Tabersonine inflammation obesity-induced cardiomyopathy
摘要	Obesity-induced cardiomyopathy (OIC) is an increasingly serious global disease caused by obesity. Chronic inflammation greatly contributes to the pathogenesis of OIC. This study aimed to explore the role and mechanism of tabersonine (Tab), a natural alkaloid with antiinflammatory activity, in the treatment of OIC. High fat diet (HFD)-induced obese mice were administered with Tab. The results showed that Tab significantly inhibit inflammation, myocardial fibrosis, and hypertrophy to prevent heart dysfunction, without the alteration of body weight and hyperlipidemia, in HFD-induced obese mice. H9c2 cells and primary cardiomyocytes stimulated by palmitic acid (PA) were used to explore the molecular mechanism and target of Tab. We examined the effect of Tab on key proteins involved in HFD/PA-induced inflammatory signaling pathway and found that Tab significantly inhibits TAK1 phosphorylation in cardiomyocytes. We further detected the direct interaction between Tab and TAK1 at the cellular, animal, and molecular levels. We found that Tab directly binds to TAK1 to inhibit TAK1 phosphorylation, which then blocks TAK1-TAB2 interaction and then NF-κB pro-inflammatory pathway in cultured cardiomyocytes. Our results indicate that Tab is a potential agent for the treatment of OIC, and TAK1 is an effective therapeutic target for this disease.
资助项目	National Natural Science Foundation of China; Zhejiang Provincial Key Scientific Project; [21961142009]; [82000793]; [2021C03041]; [2019C03012]
出版者	WILEY
出版地	HOBOKEN
ISSN	0951-418X
EISSN	1099-1573
卷号	37 期号:3 页码:860-871
DOI	10.1002/ptr.7666
页数	12
WOS类目	Chemistry, Medicinal ; Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000889268100001
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2022-11
URL	查看原文
PubMed ID	36420902
SCOPUSEID	2-s2.0-85142643075
通讯作者地址	[Wu, Gaojun]Department of Cardiology and Medical Research Center,the First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325035,China ; [Liang, Guang]Department of Cardiology,the First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
Scopus学科分类	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/171454
专题	附属第一医院药学院（分析测试中心）_生物有机与药物化学研究中心
通讯作者	Wu, Gaojun; Liang, Guang
作者单位	1.Department of Cardiology and The Key Laboratory of Cardiovascular Disease of Wenzhou,the First Affiliated Hospital,Wenzhou Medical University,Wenzhou,China; 2.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,China; 3.School of Pharmaceutical Sciences,Hangzhou Medical College,Hangzhou,China
第一作者单位	附属第一医院; 药学院（分析测试中心）; 生物有机与药物化学研究中心
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	Chen, Yanghao,Lin, Wante,Chen, Pan,et al. Tabersonine alleviates obesity-induced cardiomyopathy by binding to Transforming growth factor activated kinase 1 (TAK1) and inhibiting TAK1-mediated inflammation.[J]. Phytotherapy research : PTR,2023,37(3):860-871.
APA	Chen, Yanghao., Lin, Wante., Chen, Pan., Ye, Bozhi., Luo, Wu., ... & Liang, Guang. (2023). Tabersonine alleviates obesity-induced cardiomyopathy by binding to Transforming growth factor activated kinase 1 (TAK1) and inhibiting TAK1-mediated inflammation.. Phytotherapy research : PTR, 37(3), 860-871.
MLA	Chen, Yanghao,et al."Tabersonine alleviates obesity-induced cardiomyopathy by binding to Transforming growth factor activated kinase 1 (TAK1) and inhibiting TAK1-mediated inflammation.".Phytotherapy research : PTR 37.3(2023):860-871.