Mechanism Exploration of Astaxanthin in the Treatment of Adriamycin-induced Cardiotoxicity Based on Network Pharmacology and Experimental Validation.

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yu Zhu, Mengyao Chen, Lin Xie, Yijun Pan, Yuntian Yang, Guoxing Wan
{"title":"Mechanism Exploration of Astaxanthin in the Treatment of Adriamycin-induced Cardiotoxicity Based on Network Pharmacology and Experimental Validation.","authors":"Yu Zhu, Mengyao Chen, Lin Xie, Yijun Pan, Yuntian Yang, Guoxing Wan","doi":"10.2174/0109298673329567241014071914","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Astaxanthin (AXT), a natural antioxidant recognized for its therapeutic potential in cancer and cardiovascular diseases, holds promise in mitigating adriamycin-induced cardiotoxicity (AIC). Nevertheless, the underlying mechanisms of AXT in AIC mitigation remain to be elucidated. Consequently, this study endeavors to elucidate the mechanism of AXT against AIC, employing an integrated approach.</p><p><strong>Methods: </strong>Network pharmacology, molecular docking, and molecular dynamics simulations were harnessed to explore the molecular mechanism underlying AXT's action against AIC. Furthermore, the in-vitro AIC model was established with the H9c2 cell to generate transcriptome data for validation.</p><p><strong>Results: </strong>A total of 533 putative AXT targets and 1478 AIC-related genes were initially screened by database retrieval and bioinformatics analysis. A total of 248 potential targets of AXT against AIC and several signaling pathways were identified by network pharmacology and enrichment analysis. Two core genes (CCL2 and NOS3) and the AGE-RAGE signaling pathway in diabetic complications were further highlighted by transcriptome validation based on the AIC in-vitro model. Additionally, molecular docking and dynamics analyses supported the robust binding affinity of AXT with the core targets.</p><p><strong>Conclusion: </strong>The study suggested that AXT might ameliorate AIC through the inhibition of CCL2 and NOS3 as well as AGE-RAGE signaling, which provide a theoretical basis for the development of a strategy against AIC.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0109298673329567241014071914","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: Astaxanthin (AXT), a natural antioxidant recognized for its therapeutic potential in cancer and cardiovascular diseases, holds promise in mitigating adriamycin-induced cardiotoxicity (AIC). Nevertheless, the underlying mechanisms of AXT in AIC mitigation remain to be elucidated. Consequently, this study endeavors to elucidate the mechanism of AXT against AIC, employing an integrated approach.

Methods: Network pharmacology, molecular docking, and molecular dynamics simulations were harnessed to explore the molecular mechanism underlying AXT's action against AIC. Furthermore, the in-vitro AIC model was established with the H9c2 cell to generate transcriptome data for validation.

Results: A total of 533 putative AXT targets and 1478 AIC-related genes were initially screened by database retrieval and bioinformatics analysis. A total of 248 potential targets of AXT against AIC and several signaling pathways were identified by network pharmacology and enrichment analysis. Two core genes (CCL2 and NOS3) and the AGE-RAGE signaling pathway in diabetic complications were further highlighted by transcriptome validation based on the AIC in-vitro model. Additionally, molecular docking and dynamics analyses supported the robust binding affinity of AXT with the core targets.

Conclusion: The study suggested that AXT might ameliorate AIC through the inhibition of CCL2 and NOS3 as well as AGE-RAGE signaling, which provide a theoretical basis for the development of a strategy against AIC.

基于网络药理学和实验验证的虾青素治疗阿霉素诱发的心脏毒性的机制探索。
简介:虾青素(AXT)是一种天然抗氧化剂,具有治疗癌症和心血管疾病的潜力,有望减轻阿霉素诱导的心脏毒性(AIC)。然而,AXT 在减轻 AIC 方面的潜在机制仍有待阐明。因此,本研究采用综合方法,努力阐明 AXT 抗 AIC 的机制:方法:利用网络药理学、分子对接和分子动力学模拟来探索 AXT 对 AIC 起作用的分子机制。此外,还利用 H9c2 细胞建立了体外 AIC 模型,以生成转录组数据进行验证:结果:通过数据库检索和生物信息学分析,初步筛选出 533 个 AXT 潜在靶点和 1478 个 AIC 相关基因。通过网络药理学和富集分析,共确定了 248 个 AXT 对抗 AIC 的潜在靶点和多个信号通路。通过基于 AIC 体外模型的转录组验证,进一步突出了糖尿病并发症中的两个核心基因(CCL2 和 NOS3)和 AGE-RAGE 信号通路。此外,分子对接和动力学分析也证明了 AXT 与核心靶点的强大结合亲和力:研究表明,AXT 可通过抑制 CCL2 和 NOS3 以及 AGE-RAGE 信号转导来改善 AIC,这为开发抗 AIC 的策略提供了理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
×
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