Isoalantolactone Regulates the Activity of Mitogen-Activated Protein Kinases and Nuclear-Factor Erythroid 2-Related Factor 2 Pathways to Attenue Angiotensin II-Induced Cardiomyocyte Hypertrophy and Oxidative Stress

Abstract

While isoalantolactone is a sesquiterpene lactone known for its anti-inflammatory and antioxidant activities, its role in cardiac hypertrophy is unknown. This study aimed to explore the role and mechanism of isoalantolactone in cardiomyocyte hypertrophy using angiotensin II-treated H9C2 cells as a model. The Western blot analysis was used to evaluate changes in the cardiac hypertrophy marker proteins atrial natriuretic peptide and brain natriuretic peptide and the activity of nuclear-factor erythroid 2-related factor 2/mitogen-activated protein kinase signaling pathway. Rhodamine-phalloidin staining was used to measure the surface area of cardiomyocytes. Apoptosis and intracellular reactive oxygen species levels were measured by flow cytometry. The results showed that isoalantolactone inhibited angiotensin II-induced H9C2 cell hypertrophy and cardiomyocyte apoptosis and reduced intracellular reactive oxygen species and cytochrome C levels in a dose-dependent manner. Furthermore, isoalantolactone upregulated the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 and inhibited extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 (a stress-stimulated kinase) activation. Collectively, the findings suggest that isoalantolactone can enhance the antioxidant capacity of H9C2 cells, reduce apoptosis, and inhibit cardiac hypertrophy, and these protective effects may be related to the regulation of nuclear-factor erythroid 2-related factor 2 and mitogen-activated protein kinase pathway activity by isoalantolactone.