Abstract
Acute myocardial infarction (AMI) results in irreversible cardiac cell damage or death because of decreased blood flow to the heart. Apoptosis plays an important role in the process of tissue damage after myocardial infarction (MI), which has pathological and therapeutic implications. Ferulic acid (FA) is a phenolic acid endowed with strong antioxidative and cytoprotective activities. The present study aimed to investigate whether FA protects cardiomyocytes from apoptosis by regulating autophagy, which is a cellular self-digestion process, and one of the first lines of defense against oxidative stress. Apoptosis was induced by TNF-α (10 ng/mL) and cycloheximide (CHX, 5 μg/mL) in rat H9c2 cardiomyocytes. FA-inhibited TNF-α/CHX-induced apoptosis was determined by the quantification of TUNEL-positive cells, and the effect was associated with decreased ROS production and inhibited caspase3 activation. FA treatment enhanced autophagy and increased autophagy-associated protein expression, leading to an inhibition of mTOR signaling. When co-treated with 3-methyladenine (3-MA), an autophagy inhibitor, the anti-apoptotic effect of FA was attenuated. In an in vivo mouse MI model, FA treatment decreased the apoptotic cell number, reduced infarct size, and improved cardiac performance, as determined by histological and echocardiographic assessments. Taken collectively, these results suggest that FA could protect cardiomyocytes from apoptosis by enhancing autophagy.
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Acknowledgements
This study was supported by the National Natural Science Foundation of China [Grant number: 81603329], and Program of International S&T Cooperation Project of China [Grant number: 2015DFA30430].
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Li, C., Chen, L., Song, M. et al. Ferulic acid protects cardiomyocytes from TNF-α/cycloheximide-induced apoptosis by regulating autophagy. Arch. Pharm. Res. 43, 863–874 (2020). https://doi.org/10.1007/s12272-020-01252-z
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DOI: https://doi.org/10.1007/s12272-020-01252-z