Paeonol Protects Against Myocardial Ischemia/Reperfusion-Induced Injury by Mediating Apoptosis and Autophagy Crosstalk.

Abstract

Many studies have shown that crosstalk exists between apoptosis and autophagy, despite differences in mechanisms between these processes. Paeonol, a major phenolic compound isolated from Moutan Cortex Radicis, the root bark of Paeonia × suffruticosa Andrews (Paeoniaceae), is widely used in traditional Chinese medicine as an antipyretic, analgesic and anti-inflammatory agent. In this study, we investigated the detailed molecular mechanisms of the crosstalk between apoptosis and autophagy underlying the cardioprotective effects of paeonol in rats subjected to myocardial ischemia/reperfusion (I/R) injury. Myocardial I/R injury was induced by occlusion of the left anterior descending coronary artery (LAD) for 1 h followed by 3 h of reperfusion. Paeonol was intravenously administered 15 min before LAD ligation. We found that paeonol significantly improved cardiac function after myocardial I/R injury and significantly decreased myocardial I/R-induced arrhythmia and mortality. Paeonol also significantly decreased myocardial infarction and plasma LDH activity and Troponin-I levels in carotid blood after I/R. Compared with vehicle treatment, paeonol significantly upregulated Bcl-2 protein expression and significantly downregulated the cleaved forms of caspase-8, caspase-9, caspase-3 and PARP protein expression in the I/R injured myocardium. Myocardial I/R-induced autophagy, including the increase of Beclin-1, p62, LC3-I, and LC3-II protein expression in the myocardium was significantly reversed by paeonol treatment. Paeonol also significantly increased the Bcl-2/Bax and Bcl-2/Beclin-1 ratios in the myocardium after I/R injury. The cardioprotective role of paeonol during I/R injury may be due to its mediation of crosstalk between apoptotic and autophagic signaling pathways, which inhibits apoptosis and autophagic cell death.

• Authors: Chin-Feng Tsai, Hsing-Hui Su, Ke-Min Chen, Jiuan-Miaw Liao, Yi-Ting Yao, Yi-Hung Chen, Meilin Wang, Ya-Chun Chu, Yi-Hsin Wang, Shiang-Suo Huang
• Journal: Frontiers in pharmacology (Front Pharmacol) Vol. 11 Pg. 586498 ( 2020) ISSN: 1663-9812 [Print] Switzerland
• PMID: 33551799 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Tsai, Su, Chen, Liao, Yao, Chen, Wang, Chu, Wang and Huang.