Protective effect of Xinmai'an tablets via mediation of the AMPK/SIRT1/ PGC-1a signaling pathway on myocardial ischemia-reperfusion injury in rats

Background: Xinmai'an tablets are a compound Chinese medicine comprising six traditional Chinese medicines that have been clinically applied to treat cardiovascular diseases such as premature ventricular contractions for many years. However, pharmacological effects and underlying mechanisms of Xinmai'an tablet in protecting against myocardial ischemia-reperfusion injury (MIRI) were barely ever studied. Purpose: To investigate the cardioprotective properties of Xinmai'an tablet against MIRI and the underlying molecular mechanism in rats. Methods: We initially established the UHPLC-QTRAP-MS/MS analysis method to ensure the controllable quality of Xinmai'an tablet. We further identified the cardioprotective effects of Xinmai'an tablet against MIRI using TTC staining, hematoxylin and eosin, echocardiography, the transmission electron microscope analysis, biochemical analysis, and ELISA. We then investigated whether the safeguarding effect of Xinmai'an tablet on MIRI model rats was related to AMPK/SIRT1/PGC-1 alpha pathway via western blotting. Results: Xinmai'an tablet decreased myocardial infarct size; ameliorated cardiac function; alleviated myocardial and mitochondrial damage; and suppressed oxidative stress injury, vascular endothelial damage, and apoptosis response in MIRI model rats. Mechanistically, our results showed that Xinmai'an tablet can dramatically activate the AMPK/SIRT1/PGC-1 alpha pathway and subsequently diminish mitochondrial oxidative stress damage. This was evidenced by increased ATP, Na+-K+-ATPase, and Ca2+-Mg2+-ATPase levels, upregulation of GLUT4, p-AMPK, SIRT1, and PGC-1 alpha protein levels; and reduced GLUT1 protein level. Conclusion: To the knowledge of the author of this article, this study is the first report of Xinmai'an tablet attenuating MIRI, potentially associated with the activation of the AMPK/SIRT1/PGC-1 alpha pathway and subsequent reduction of mitochondrial oxidative stress damage. These findings reveal a novel pharmacological effect and mechanism of action of Xinmai'an tablet and highlight a promising therapeutic drug for ischemic cardiovascular diseases.