Ellagic acid protects against angiotensin II‐induced hypertrophic responses through ROS‐mediated MAPK pathway in H9c2 cells

Abstract

AbstractThe early myocardial response of hypertension is an elevation of angiotensin‐II (Ang‐II) concentration, leading to heart failure and cardiac hypertrophy. This hypertrophic event of the heart is mediated by the interaction of Ang type 1 receptors (AT‐R1), thereby modulating NADPH oxidase activity in cardiomyocytes, which alters redox status in cardiomyocytes. Ellagic acid (EA) has anti‐inflammatory and anti‐oxidative capacities. Thus, EA has potential preventive effects on cardiovascular diseases and diabetes. In the last decades, because the protective effect of EA on Ang‐II‐induced hypertrophic responses is unclear, this study aims to investigate the protective effect of EA in cardiomyocytes. H9c2 cells were treated to Ang‐II 1 μM for 24 h to induce cellular damage. We found that EA protected against Ang‐II‐increased cell surface area and pro‐hypertrophic gene expression in H9c2. EA reduced Ang‐II‐caused AT‐R1 upregulation, thereby inhibiting oxidative stress NADPH oxidase activation. EA mitigated Ang‐II‐enhanced p38 and extracellular‐signal‐regulated kinase (ERK) phosphorylation. Moreover, EA treatment under Ang‐II stimulation also reversed NF‐κB activity and iNOS expression. This study shows that EA protects against Ang‐II‐induced myocardial hypertrophy and attenuates oxidative stress through reactive oxygen species‐mediated mitogen‐activated protein kinase signaling pathways in H9c2 cells. Thus, EA may be an effective compound for preventing Ang‐II‐induced myocardial hypertrophy.