Kuang Liu , Yihao Zhu , Wenjie Gao , Xuhui Han , Qinghua Zhang , Yanbin Zhao , Yao Zu
{"title":"Resveratrol alleviates heart failure by activating foxo3a to counteract oxidative stress and apoptosis","authors":"Kuang Liu , Yihao Zhu , Wenjie Gao , Xuhui Han , Qinghua Zhang , Yanbin Zhao , Yao Zu","doi":"10.1016/j.biopha.2024.117716","DOIUrl":null,"url":null,"abstract":"<div><div>Resveratrol has been extensively studied for its multifaceted health benefits. Nonetheless, the pharmacological mechanisms of resveratrol for heart failure remain elusive, especially the cardioprotective effects. To address this knowledge gap, we performed high-throughput drug screening using zebrafish and discovered that resveratrol significantly alleviated heart failure, including rescuing abnormalities in heart rate, blood flow, cardiac output, and <em>nppb</em> overexpression. Mechanically, calcium optical mapping revealed that resveratrol diminished the prolongation of calcium duration at 90 % repolarization (CaD90). Membrane potential assay demonstrated that resveratrol alleviated mitochondrial damage, subsequently relieved the excessive accumulation of reactive oxygen species (ROS). Tunel staining further showed that resveratrol inhibited cardiomyocyte apoptosis both in zebrafish and human AC16 cell. Given the close relationship between the Forkhead Box O (<em>foxo</em>) family and oxidative stress and apoptosis, we used qPCR and noted that resveratrol could regulate the heart failure-induced expressions of <em>foxo1b</em> and <em>foxo3a</em> to normal levels. Furthermore, we conducted in situ hybridization to confirm the effective down-regulation patterns of <em>foxo3a</em> after resveratrol treatment. To investigate whether resveratrol’s effects are mediated via <em>foxo3a</em>, we used gardenoside to inhibit <em>foxo3a</em> expression, noting that resveratrol’s cardioprotective effects were reduced with <em>foxo3a</em> inhibition. Overall, our study underscores the molecular mechanisms by which resveratrol confers cardioprotection and provides a reference for heart failure therapeutic approaches.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117716"},"PeriodicalIF":6.9000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedicine & Pharmacotherapy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0753332224016020","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Resveratrol has been extensively studied for its multifaceted health benefits. Nonetheless, the pharmacological mechanisms of resveratrol for heart failure remain elusive, especially the cardioprotective effects. To address this knowledge gap, we performed high-throughput drug screening using zebrafish and discovered that resveratrol significantly alleviated heart failure, including rescuing abnormalities in heart rate, blood flow, cardiac output, and nppb overexpression. Mechanically, calcium optical mapping revealed that resveratrol diminished the prolongation of calcium duration at 90 % repolarization (CaD90). Membrane potential assay demonstrated that resveratrol alleviated mitochondrial damage, subsequently relieved the excessive accumulation of reactive oxygen species (ROS). Tunel staining further showed that resveratrol inhibited cardiomyocyte apoptosis both in zebrafish and human AC16 cell. Given the close relationship between the Forkhead Box O (foxo) family and oxidative stress and apoptosis, we used qPCR and noted that resveratrol could regulate the heart failure-induced expressions of foxo1b and foxo3a to normal levels. Furthermore, we conducted in situ hybridization to confirm the effective down-regulation patterns of foxo3a after resveratrol treatment. To investigate whether resveratrol’s effects are mediated via foxo3a, we used gardenoside to inhibit foxo3a expression, noting that resveratrol’s cardioprotective effects were reduced with foxo3a inhibition. Overall, our study underscores the molecular mechanisms by which resveratrol confers cardioprotection and provides a reference for heart failure therapeutic approaches.
期刊介绍:
Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.