Danlou Tablet Protects Against Cardiac Remodeling and Dysfunction after Myocardial Ischemia/Reperfusion Injury
Lin Li1,2, Weitong Qi1,2, Yujiao Zhu1,2
1Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China.
Insights
Danlou tablet effectively prevents cardiac remodeling and dysfunction following myocardial ischemia/reperfusion injury (I/RI). This Chinese medicine protects heart cells by inhibiting apoptosis through the AKT and FoxO3a pathways.
Area of Science:
- Cardiovascular Biology
- Pharmacology
- Cellular Pathology
Background:
- Myocardial ischemia/reperfusion injury (I/RI) and subsequent ventricular remodeling are key drivers of heart failure.
- Danlou tablet (Dan) is a Chinese medicine used for angina pectoris, but its cardioprotective effects against I/RI are not well understood.
Purpose of the Study:
- To investigate the protective effects of Danlou tablet against cardiac remodeling and dysfunction after myocardial I/RI.
- To elucidate the underlying molecular mechanisms of Danlou tablet's cardioprotection.
Main Methods:
- Administration of Danlou tablet preventively and therapeutically in a rat model of myocardial I/RI.
- Assessment of ventricular remodeling and cardiac function at 3 weeks post-I/RI.
- Evaluation of apoptosis markers (Bax/Bcl2 ratio, Caspase3 cleavage) and signaling pathways (AKT, FoxO3a, BIM, PUMA) in heart tissue and cultured cardiomyocytes.
Main Results:
- Danlou tablet administration attenuated ventricular remodeling and improved cardiac function post-I/RI.
- Danlou tablet significantly inhibited myocardial apoptosis in vivo and in vitro.
- Mechanistically, Danlou tablet promoted AKT and FoxO3a phosphorylation, leading to reduced BIM and PUMA expression.
Conclusions:
- Danlou tablet demonstrates significant cardioprotective effects against cardiac remodeling and dysfunction following myocardial I/RI.
- The cardioprotection is mediated by the inhibition of apoptosis via the AKT/FoxO3a signaling pathway.
- These findings support the clinical application of Danlou tablet for ischemic heart diseases.
Abstract:
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.
