{"title":"p-Coumaric acid modulates PGC1-α and TFAM expression to protect cardiomyocytes from doxorubicin toxicity via mitochondrial biogenesis","authors":"Kottayath Govindan Nevin, Sunitha Mary Chacko, DhanyaKrishnan Radhakrishnan, Sini Hariharan, 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.
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.