Gualou Xiebai Banxia Decoction suppresses cardiomyocyte apoptosis in mice after myocardial infarction through activation of acetaldehyde dehydrogenase 2.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiac apoptosis has been reported to be involved in the development of Heart failure (HF) after Myocardial infarction (MI). As a traditional Chinese medicine with cardioprotective properties, Gualou Xiebai Banxia Decoction (GXBD) is therapeutically effective in treating MI. However, whether GXBD regulates cardiac apoptosis in HF after MI remains unknown, and the underlying mechanisms still unclear.

AIM OF THE STUDY: This study aimed to explore the effects and potential mechanisms of GXBD on cardiac apoptosis after MI.

MATERIALS AND

METHODS

The MI model was constructed by ligating the left anterior descending coronary artery (LAD) in mice. The cardioprotective effects of GXBD were determined by echocardiography, masson staining, and haematoxylin and eosin (HE) staining. Bioinformatics analysis and network Pharmacology were used to explore the underlying molecular mechanisms of GXBD in MI. The effects of GXBD on cardiomyocyte apoptosis as well as the ALDH2 were examined by TUNEL staining, Immunohistochemistry (IHC), and Western blot (WB). Additionally, the effects of GXBD on oxidative stress, apoptosis and the ALDH2 in H9c2 cells were investigated using reactive oxygen species (ROS) detection, Hoechst33342/PI stainingand and WB. Moreover, the effects of suppressing and overexpressing ALDH2 in H9c2 cells were further examined.

RESULTS

Target prediction analysis showed that ALDH2 was a key target of GXBD which could ameliorate myocardial infarction. GXBD dose-dependently reduced cardiomyocyte apoptosis and ventricular dysfunction. In vivo experiments, GXBD activated ALDH2 enzymatic activity and inhibited the expression levels of Bax, Bcl-2, Cleaved Caspase 3, and Caspase 9. In vitro experiments, GXBD inhibited apoptosis in H9c2 cells. The inhibitory effects of GXBD on these were at least partially attributed to ALDH2 activation while silencing of ALDH2 significantly reversed these inhibitory effects of GXBD.

CONCLUSION

GXBD exerts inhibitory effects on cardiomyocyte apoptosis in mice after MI and suppresses H9c2 cells oxidative stress and apoptosis through activation of the enzyme activity of ALDH2.