p-Coumaric acid modulates PGC1-α and TFAM expression to protect cardiomyocytes from doxorubicin toxicity via mitochondrial biogenesis

IF 1.3 Q3 PHARMACOLOGY & PHARMACY
Kottayath Govindan Nevin, Sunitha Mary Chacko, DhanyaKrishnan Radhakrishnan, Sini Hariharan, Arunkumar Gangadharan
{"title":"p-Coumaric acid modulates PGC1-α and TFAM expression to protect cardiomyocytes from doxorubicin toxicity via mitochondrial biogenesis","authors":"Kottayath Govindan Nevin,&nbsp;Sunitha Mary Chacko,&nbsp;DhanyaKrishnan Radhakrishnan,&nbsp;Sini Hariharan,&nbsp;Arunkumar Gangadharan","doi":"10.1007/s13596-024-00805-7","DOIUrl":null,"url":null,"abstract":"<div><p>At present, there are no alternatives for doxorubicin (Dox), which is associated with cardiotoxicity. Countering the negative effects of Dox with natural compounds is gaining interest among the scientific community. Prior studies demonstrated that <i>p</i>-Coumaric acid (<i>p</i>CA) decreased the toxicity caused by Dox in cardiomyocytes and is expected to work through multiple cellular mechanisms. This study aimed to clarify the fundamental mechanism of how <i>p</i>CA protects the heart. Cardiomyocyte cells (H9c2) were treated with Dox, <i>p</i>CA, and a combination of <i>p</i>CA and Dox. After 24 h of treatment, gene expression of COX 2, NF-κß, PGC1-α, cytb, and TFAM was measured. Swiss ADME analysis was conducted to assess the drug-likeness characteristics, Pro-Tox for toxicity properties of <i>p</i>CA, and in silico analysis was performed to evaluate the interaction of <i>p</i>CA with Keap 1 protein. The mRNA expressions of COX-2 and NF-κß (p65) were found to be upregulated in Dox-treated cells among the different treatment groups whereas, the activity was found to be greatly reduced in <i>p</i>CA groups before and during Dox treatment. mRNA levels of PGC1-α, TFAM, and Cyt b were found to be upregulated in the <i>p</i>CA pre and cotreated groups when compared to Dox-treated cells indicating the involvement of mitochondrial biogenesis. In silico analysis showed that <i>p</i>CA has druggable properties with no toxicity, while it interacted with keap 1 protein. The results demonstrate that Dox treatment may aggravate myocardial injury which is alleviated by <i>p</i>CA by modulating the PGC1α and keap1 pathways thereby boosting mitochondrial biogenesis.</p></div>","PeriodicalId":7613,"journal":{"name":"Advances in Traditional Medicine","volume":"25 3","pages":"653 - 663"},"PeriodicalIF":1.3000,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Traditional Medicine","FirstCategoryId":"1085","ListUrlMain":"https://link.springer.com/article/10.1007/s13596-024-00805-7","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

At present, there are no alternatives for doxorubicin (Dox), which is associated with cardiotoxicity. Countering the negative effects of Dox with natural compounds is gaining interest among the scientific community. Prior studies demonstrated that p-Coumaric acid (pCA) decreased the toxicity caused by Dox in cardiomyocytes and is expected to work through multiple cellular mechanisms. This study aimed to clarify the fundamental mechanism of how pCA protects the heart. Cardiomyocyte cells (H9c2) were treated with Dox, pCA, and a combination of pCA and Dox. After 24 h of treatment, gene expression of COX 2, NF-κß, PGC1-α, cytb, and TFAM was measured. Swiss ADME analysis was conducted to assess the drug-likeness characteristics, Pro-Tox for toxicity properties of pCA, and in silico analysis was performed to evaluate the interaction of pCA with Keap 1 protein. The mRNA expressions of COX-2 and NF-κß (p65) were found to be upregulated in Dox-treated cells among the different treatment groups whereas, the activity was found to be greatly reduced in pCA groups before and during Dox treatment. mRNA levels of PGC1-α, TFAM, and Cyt b were found to be upregulated in the pCA pre and cotreated groups when compared to Dox-treated cells indicating the involvement of mitochondrial biogenesis. In silico analysis showed that pCA has druggable properties with no toxicity, while it interacted with keap 1 protein. The results demonstrate that Dox treatment may aggravate myocardial injury which is alleviated by pCA by modulating the PGC1α and keap1 pathways thereby boosting mitochondrial biogenesis.

对香豆酸调节PGC1-α和TFAM表达,通过线粒体生物发生保护心肌细胞免受阿霉素毒性
目前,阿霉素(Dox)与心脏毒性有关,尚无替代品。用天然化合物对抗Dox的负面影响正引起科学界的兴趣。先前的研究表明,对香豆酸(pCA)降低了Dox对心肌细胞的毒性,并有望通过多种细胞机制发挥作用。本研究旨在阐明pCA保护心脏的基本机制。心肌细胞(H9c2)分别用Dox、pCA以及pCA和Dox联合治疗。治疗24 h后,检测小鼠COX 2、NF-κß、PGC1-α、cytb、TFAM基因表达。采用Swiss ADME分析评估pCA的药物相似特性,Pro-Tox分析评估pCA的毒性特性,采用in silico分析评估pCA与Keap 1蛋白的相互作用。COX-2和NF-κß (p65) mRNA表达在不同处理组的Dox处理细胞中均上调,而pCA组在Dox处理前和处理过程中活性均显著降低。与dox处理的细胞相比,pCA预处理组和共处理组的PGC1-α、TFAM和Cyt b的mRNA水平上调,表明参与了线粒体生物发生。结果表明,pCA与keap - 1蛋白相互作用,具有可药物性,无毒性。结果表明,Dox可加重心肌损伤,而pCA可通过调节PGC1α和keap1通路,促进线粒体生物发生,从而减轻心肌损伤。
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
Advances in Traditional Medicine
Advances in Traditional Medicine PHARMACOLOGY & PHARMACY-
CiteScore
4.30
自引率
0.00%
发文量
50
期刊介绍: Advances in Traditional Medicine (ADTM) is an international and peer-reviewed journal and publishes a variety of articles including original researches, reviews, short communications, and case-reports. ADTM aims to bridging the gap between Traditional knowledge and medical advances. The journal focuses on publishing valid, relevant, and rigorous experimental research and clinical applications of Traditidnal Medicine as well as medical classics. At the same time, the journal is devoted to communication among basic researcher and medical clinician interested in the advancement of Traditional Medicine. Topics covered by the journal are: Medical Classics & History; Biomedical Research; Pharmacology & Toxicology of Natural Products; Acupuncture & Moxibustion; Sasang Constitutional Medicine; Diagnostics and Instrumental Development; Clinical Research. ADTM is published four times yearly. The publication date of this journal is 30th March, June, September, and December.
×
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:604180095
Book学术官方微信