Danlou Tablet Protects Against Cardiac Remodeling and Dysfunction after Myocardial Ischemia/Reperfusion Injury through Activating AKT/FoxO3a Pathway

Myocardial ischemia/reperfusion injury (I/RI) and ventricular remodeling are the critical pathological basis of heart failure. Danlou tablet (Dan) is a kind of Chinese patent medicine used in angina pectoris treatment in China. However, it remains unclear whether and how Dan could protect against cardiac remodeling after myocardial I/RI. In this study, both preventive and therapeutic administration of Dan attenuated ventricular remodeling and cardiac dysfunction at 3 weeks after myocardial I/RI. Dan inhibited Bax/Bcl2 ratio and Caspase3 cleavage in heart tissues and also inhibited apoptosis of human AC16 cells and neonatal rat cardiomyocytes stressed by oxygen and glucose deprivation/reperfusion. Mechanistically, Dan inhibited myocardial apoptosis through phosphorylating AKT and FoxO3a, thereby inhibiting downstream BIM and PUMA expressions. Collectively, these results demonstrate that Dan treatment is effective to protect against cardiac remodeling and dysfunction after myocardial I/RI and provide theoretical basis for its cardioprotection and clinical application in treating ischemic cardiac diseases.