Columbianadin通过Sirt1/FOXO1信号通路减弱阿霉素诱导的心脏损伤、氧化应激和细胞凋亡。

IF 1.1 4区 医学 Q3 SURGERY
Bo Peng, Li Rao, Jiaolong Yang, Xiaowei Ku, Bin Kong, Wei Shuai, He Huang
{"title":"Columbianadin通过Sirt1/FOXO1信号通路减弱阿霉素诱导的心脏损伤、氧化应激和细胞凋亡。","authors":"Bo Peng,&nbsp;Li Rao,&nbsp;Jiaolong Yang,&nbsp;Xiaowei Ku,&nbsp;Bin Kong,&nbsp;Wei Shuai,&nbsp;He Huang","doi":"10.1590/acb382223","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Oxidative stress and apoptosis contribute to the pathological basis of doxorubicin (DOX)-induced cardiotoxicity. Columbianadin (CBN) is one of the main bioactive constituents isolated from the root of Angelica pubescens. Herein, we intended to explore the potential role and molecular basis of CBN in DOX-induced cardiotoxicity.</p><p><strong>Methods: </strong>C57BL/6 mice were subjected to DOX (15 mg/kg/day, i.p.) to generate DOX-induced cardiotoxicity. CBN (10 mg/kg/day, i.p.) was administered for four week following DOX injection.</p><p><strong>Results: </strong>DOX administered markedly dampened cardiac function, increased cardiac injury, excessive reactive oxygen species (ROS) production, and cardiomyocyte loss. These alterations induced by DOX significantly alleviated by CBN treatment. Mechanistically, our results demonstrated that the CBN exerts cardioprotection role against DOX by up-regulating silent information regulator 1 (Sirt1) and decreasing acetylation of forkhead box O1 (FOXO1). Moreover, Sirt1 inhibition with Ex-527 significantly blunt the beneficial effect of CBN on DOX-induced cardiotoxicity, including cardiac dysfunction, ROS, and apoptosis.</p><p><strong>Conclusion: </strong>Collectively, CBN attenuated oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity through maintaining Sirt1/FOXO1 signaling pathway. Our results demonstrated that CBN might be used to treat DOX-related cardiotoxicity.</p>","PeriodicalId":6992,"journal":{"name":"Acta cirurgica brasileira","volume":"38 ","pages":"e382223"},"PeriodicalIF":1.1000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10292807/pdf/","citationCount":"1","resultStr":"{\"title\":\"Columbianadin attenuates doxorubicin-induced cardiac injury, oxidative stress, and apoptosis via Sirt1/FOXO1 signaling pathway.\",\"authors\":\"Bo Peng,&nbsp;Li Rao,&nbsp;Jiaolong Yang,&nbsp;Xiaowei Ku,&nbsp;Bin Kong,&nbsp;Wei Shuai,&nbsp;He Huang\",\"doi\":\"10.1590/acb382223\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Oxidative stress and apoptosis contribute to the pathological basis of doxorubicin (DOX)-induced cardiotoxicity. Columbianadin (CBN) is one of the main bioactive constituents isolated from the root of Angelica pubescens. Herein, we intended to explore the potential role and molecular basis of CBN in DOX-induced cardiotoxicity.</p><p><strong>Methods: </strong>C57BL/6 mice were subjected to DOX (15 mg/kg/day, i.p.) to generate DOX-induced cardiotoxicity. CBN (10 mg/kg/day, i.p.) was administered for four week following DOX injection.</p><p><strong>Results: </strong>DOX administered markedly dampened cardiac function, increased cardiac injury, excessive reactive oxygen species (ROS) production, and cardiomyocyte loss. These alterations induced by DOX significantly alleviated by CBN treatment. Mechanistically, our results demonstrated that the CBN exerts cardioprotection role against DOX by up-regulating silent information regulator 1 (Sirt1) and decreasing acetylation of forkhead box O1 (FOXO1). Moreover, Sirt1 inhibition with Ex-527 significantly blunt the beneficial effect of CBN on DOX-induced cardiotoxicity, including cardiac dysfunction, ROS, and apoptosis.</p><p><strong>Conclusion: </strong>Collectively, CBN attenuated oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity through maintaining Sirt1/FOXO1 signaling pathway. Our results demonstrated that CBN might be used to treat DOX-related cardiotoxicity.</p>\",\"PeriodicalId\":6992,\"journal\":{\"name\":\"Acta cirurgica brasileira\",\"volume\":\"38 \",\"pages\":\"e382223\"},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10292807/pdf/\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta cirurgica brasileira\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1590/acb382223\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"SURGERY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta cirurgica brasileira","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1590/acb382223","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"SURGERY","Score":null,"Total":0}
引用次数: 1

摘要

目的:氧化应激和细胞凋亡参与了多柔比星(DOX)诱导心脏毒性的病理基础。Columbianadin (CBN)是从短毛当归(Angelica pubescens)根中分离得到的主要活性成分之一。在此,我们打算探索CBN在dox诱导的心脏毒性中的潜在作用和分子基础。方法:C57BL/6小鼠灌胃DOX (15 mg/kg/d, ig),产生DOX诱导的心脏毒性。在DOX注射后给予CBN (10 mg/kg/天,i.p) 4周。结果:DOX显著抑制心功能,增加心脏损伤,过量活性氧(ROS)产生和心肌细胞损失。经CBN处理后,DOX诱导的这些改变明显减轻。在机制上,我们的研究结果表明,CBN通过上调沉默信息调节因子1 (Sirt1)和降低forkhead box 1 (FOXO1)的乙酰化来发挥抗DOX的心脏保护作用。此外,用Ex-527抑制Sirt1显著减弱了CBN对dox诱导的心脏毒性的有益作用,包括心功能障碍、ROS和细胞凋亡。结论:综上所述,CBN通过维持Sirt1/FOXO1信号通路,减轻dox诱导的心脏毒性中氧化应激和心肌细胞凋亡。我们的研究结果表明,CBN可能用于治疗dox相关的心脏毒性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Columbianadin attenuates doxorubicin-induced cardiac injury, oxidative stress, and apoptosis via Sirt1/FOXO1 signaling pathway.

Purpose: Oxidative stress and apoptosis contribute to the pathological basis of doxorubicin (DOX)-induced cardiotoxicity. Columbianadin (CBN) is one of the main bioactive constituents isolated from the root of Angelica pubescens. Herein, we intended to explore the potential role and molecular basis of CBN in DOX-induced cardiotoxicity.

Methods: C57BL/6 mice were subjected to DOX (15 mg/kg/day, i.p.) to generate DOX-induced cardiotoxicity. CBN (10 mg/kg/day, i.p.) was administered for four week following DOX injection.

Results: DOX administered markedly dampened cardiac function, increased cardiac injury, excessive reactive oxygen species (ROS) production, and cardiomyocyte loss. These alterations induced by DOX significantly alleviated by CBN treatment. Mechanistically, our results demonstrated that the CBN exerts cardioprotection role against DOX by up-regulating silent information regulator 1 (Sirt1) and decreasing acetylation of forkhead box O1 (FOXO1). Moreover, Sirt1 inhibition with Ex-527 significantly blunt the beneficial effect of CBN on DOX-induced cardiotoxicity, including cardiac dysfunction, ROS, and apoptosis.

Conclusion: Collectively, CBN attenuated oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity through maintaining Sirt1/FOXO1 signaling pathway. Our results demonstrated that CBN might be used to treat DOX-related cardiotoxicity.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
1.90
自引率
9.10%
发文量
60
审稿时长
3-8 weeks
期刊介绍: Information not localized
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信