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

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 tradition...

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Autores principales: Tsai, Chin-Feng, Su, Hsing-Hui, Chen, Ke‐Min, Liao, Jiuan-Miaw, Yao, Yi-Ting, Chen, Yi-Hung, Wang, Meilin, Chu, Ya-Chun, Wang, Yi-Hsin, Huang, Shiang-Suo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858273/
https://www.ncbi.nlm.nih.gov/pubmed/33551799
http://dx.doi.org/10.3389/fphar.2020.586498
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author Tsai, Chin-Feng
Su, Hsing-Hui
Chen, Ke‐Min
Liao, Jiuan-Miaw
Yao, Yi-Ting
Chen, Yi-Hung
Wang, Meilin
Chu, Ya-Chun
Wang, Yi-Hsin
Huang, Shiang-Suo
author_facet Tsai, Chin-Feng
Su, Hsing-Hui
Chen, Ke‐Min
Liao, Jiuan-Miaw
Yao, Yi-Ting
Chen, Yi-Hung
Wang, Meilin
Chu, Ya-Chun
Wang, Yi-Hsin
Huang, Shiang-Suo
author_sort Tsai, Chin-Feng
collection PubMed
description 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.
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spelling pubmed-78582732021-02-05 Paeonol Protects Against Myocardial Ischemia/Reperfusion-Induced Injury by Mediating Apoptosis and Autophagy Crosstalk Tsai, Chin-Feng Su, Hsing-Hui Chen, Ke‐Min Liao, Jiuan-Miaw Yao, Yi-Ting Chen, Yi-Hung Wang, Meilin Chu, Ya-Chun Wang, Yi-Hsin Huang, Shiang-Suo Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2021-01-21 /pmc/articles/PMC7858273/ /pubmed/33551799 http://dx.doi.org/10.3389/fphar.2020.586498 Text en Copyright © 2021 Tsai, Su, Chen, Liao, Yao, Chen, Wang, Chu, Wang and Huang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Tsai, Chin-Feng
Su, Hsing-Hui
Chen, Ke‐Min
Liao, Jiuan-Miaw
Yao, Yi-Ting
Chen, Yi-Hung
Wang, Meilin
Chu, Ya-Chun
Wang, Yi-Hsin
Huang, Shiang-Suo
Paeonol Protects Against Myocardial Ischemia/Reperfusion-Induced Injury by Mediating Apoptosis and Autophagy Crosstalk
title Paeonol Protects Against Myocardial Ischemia/Reperfusion-Induced Injury by Mediating Apoptosis and Autophagy Crosstalk
title_full Paeonol Protects Against Myocardial Ischemia/Reperfusion-Induced Injury by Mediating Apoptosis and Autophagy Crosstalk
title_fullStr Paeonol Protects Against Myocardial Ischemia/Reperfusion-Induced Injury by Mediating Apoptosis and Autophagy Crosstalk
title_full_unstemmed Paeonol Protects Against Myocardial Ischemia/Reperfusion-Induced Injury by Mediating Apoptosis and Autophagy Crosstalk
title_short Paeonol Protects Against Myocardial Ischemia/Reperfusion-Induced Injury by Mediating Apoptosis and Autophagy Crosstalk
title_sort paeonol protects against myocardial ischemia/reperfusion-induced injury by mediating apoptosis and autophagy crosstalk
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858273/
https://www.ncbi.nlm.nih.gov/pubmed/33551799
http://dx.doi.org/10.3389/fphar.2020.586498
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