Buyang Huanwu decoction inhibits cardiomyocyte apoptosis after myocardial infarction by enhancing aldehyde dehydrogenase-2 activity and protein expression

Abstract

ObjectiveTo investigate the potential mechanisms of the protective effects of Buyang Huanwu decoction (BYHWD) on cardiomyocyte apoptosis after myocardial infarction (MI) and to provide the foundation for the clinical application of BYHWD in preventing and treating cardiomyocyte apoptosis-related disorders after MI. MethodsThe MI rat model was established by ligation of the left anterior descending (LAD) coronary artery. After the 20-week treatment with BYHWD, the following parameters were assessed to investigate the protective effects of BYHWD on cardiomyocyte apoptosis after MI, both in vivo and in vitro: mortality rate; heart weight/body weight (HW/BW); transthoracic echocardiography measurements; histopathological analysis; immunohistochemistry (IHC) analysis; TUNEL apoptosis assay; caspase-3 activity assay; aldehyde dehydrogenase-2 (ALDH2) enzymatic activity assay; malondialdehyde (MDA) content analysis; western blot analysis; MTT assay; and Hoechst 33342/PI apoptosis assay. ResultsThe mortality of the MI rats was significantly reduced by BYHWD treatment. Furthermore, BYHWD treatment significantly improved the heart function and significantly reduced the HW/BW ratio. Histopathological analysis showed that BYHWD treatment significantly relieved MI-induced cardiac injury and significantly decreased collagen formation. The TUNEL apoptosis assay showed that treatment with BYHWD reduced the cardiomyocyte apoptosis of MI rats in a dose-dependent manner. Moreover, BYHWD treatment could significantly inhibit oxidative stress-induced neonatal cardiomyocyte apoptosis, which is consistent with the results of animal experiments in vivo. Interestingly, the ALDH2 activity and protein expression was significantly reduced in the MI model group, while the content of toxic aldehydes, including 4-HNE and MDA, was increased. Importantly, BYHWD enhanced the activity of ALDH2 and the expression of ALDH2 protein and attenuated the content of toxic aldehydes in a dose-dependent manner. Furthermore, we found that co-treatment with an ALDH2 inhibitor, disulfiram, partially inhibited the cardiomyocyte protective effects of BYHWD. ConclusionsCollectively, our results suggest that BYHWD exerted anti-apoptotic effects in cardiomyocytes after MI by enhancing the ALDH2 activity and protein expression and decreasing the toxic aldehyde content.