Resveratrol alleviated heart failure abnormalities and inhibited cardiomyocyte apoptosis in zebrafish and human AC16 cells by regulating foxo3a expression to counteract oxidative stress.
Does resveratrol improve heart failure phenotypes in preclinical models?
Resveratrol confers cardioprotection in preclinical heart failure models by activating foxo3a to counteract oxidative stress and apoptosis.
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.
Liu et al. (Sun,) conducted a other in Heart failure. Resveratrol was evaluated on Heart failure abnormalities, oxidative stress, and apoptosis. Resveratrol alleviated heart failure abnormalities and inhibited cardiomyocyte apoptosis in zebrafish and human AC16 cells by regulating foxo3a expression to counteract oxidative stress.