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Calenduloside E Ameliorates Myocardial Ischemia-Reperfusion Injury through Regulation of AMPK and Mitochondrial OPA1

Calenduloside E (CE) is a natural triterpenoid saponin isolated from Aralia elata (Miq.) Seem., a well-known traditional Chinese medicine. Our previous studies have shown that CE exerts cardiovascular protective effects both in vivo and in vitro. However, its role in myocardial ischemia/reperfusion...

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Autores principales: Wang, Min, Wang, Rui-ying, Zhou, Jia-hui, Xie, Xue-heng, Sun, Gui-bo, Sun, Xiao-bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479459/
https://www.ncbi.nlm.nih.gov/pubmed/32934760
http://dx.doi.org/10.1155/2020/2415269
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author Wang, Min
Wang, Rui-ying
Zhou, Jia-hui
Xie, Xue-heng
Sun, Gui-bo
Sun, Xiao-bo
author_facet Wang, Min
Wang, Rui-ying
Zhou, Jia-hui
Xie, Xue-heng
Sun, Gui-bo
Sun, Xiao-bo
author_sort Wang, Min
collection PubMed
description Calenduloside E (CE) is a natural triterpenoid saponin isolated from Aralia elata (Miq.) Seem., a well-known traditional Chinese medicine. Our previous studies have shown that CE exerts cardiovascular protective effects both in vivo and in vitro. However, its role in myocardial ischemia/reperfusion injury (MIRI) and the mechanism involved are currently unknown. Mitochondrial dynamics play a key role in MIRI. This study investigated the effects of CE on mitochondrial dynamics and the signaling pathways involved in myocardial ischemia/reperfusion (MI/R). The MI/R rat model and the hypoxia/reoxygenation (H/R) cardiomyocyte model were established in this study. CE exerted significant cardioprotective effects in vivo and in vitro by improving cardiac function, decreasing myocardial infarct size, increasing cardiomyocyte viability, and inhibiting cardiomyocyte apoptosis associated with MI/R. Mechanistically, CE restored mitochondrial homeostasis against MI/R injury through improved mitochondrial ultrastructure, enhanced ATP content and mitochondrial membrane potential, and reduced mitochondrial permeability transition pore (MPTP) opening, while promoting mitochondrial fusion and preventing mitochondrial fission. However, genetic silencing of OPA1 by siRNA abolished the beneficial effects of CE on cardiomyocyte survival and mitochondrial dynamics. Moreover, we demonstrated that CE activated AMP-activated protein kinase (AMPK) and treatment with the AMPK inhibitor, compound C, abolished the protective effects of CE on OPA1 expression and mitochondrial function. Overall, this study demonstrates that CE is effective in mitigating MIRI by modulating AMPK activation-mediated OPA1-related mitochondrial fusion.
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spelling pubmed-74794592020-09-14 Calenduloside E Ameliorates Myocardial Ischemia-Reperfusion Injury through Regulation of AMPK and Mitochondrial OPA1 Wang, Min Wang, Rui-ying Zhou, Jia-hui Xie, Xue-heng Sun, Gui-bo Sun, Xiao-bo Oxid Med Cell Longev Research Article Calenduloside E (CE) is a natural triterpenoid saponin isolated from Aralia elata (Miq.) Seem., a well-known traditional Chinese medicine. Our previous studies have shown that CE exerts cardiovascular protective effects both in vivo and in vitro. However, its role in myocardial ischemia/reperfusion injury (MIRI) and the mechanism involved are currently unknown. Mitochondrial dynamics play a key role in MIRI. This study investigated the effects of CE on mitochondrial dynamics and the signaling pathways involved in myocardial ischemia/reperfusion (MI/R). The MI/R rat model and the hypoxia/reoxygenation (H/R) cardiomyocyte model were established in this study. CE exerted significant cardioprotective effects in vivo and in vitro by improving cardiac function, decreasing myocardial infarct size, increasing cardiomyocyte viability, and inhibiting cardiomyocyte apoptosis associated with MI/R. Mechanistically, CE restored mitochondrial homeostasis against MI/R injury through improved mitochondrial ultrastructure, enhanced ATP content and mitochondrial membrane potential, and reduced mitochondrial permeability transition pore (MPTP) opening, while promoting mitochondrial fusion and preventing mitochondrial fission. However, genetic silencing of OPA1 by siRNA abolished the beneficial effects of CE on cardiomyocyte survival and mitochondrial dynamics. Moreover, we demonstrated that CE activated AMP-activated protein kinase (AMPK) and treatment with the AMPK inhibitor, compound C, abolished the protective effects of CE on OPA1 expression and mitochondrial function. Overall, this study demonstrates that CE is effective in mitigating MIRI by modulating AMPK activation-mediated OPA1-related mitochondrial fusion. Hindawi 2020-08-31 /pmc/articles/PMC7479459/ /pubmed/32934760 http://dx.doi.org/10.1155/2020/2415269 Text en Copyright © 2020 Min Wang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Min
Wang, Rui-ying
Zhou, Jia-hui
Xie, Xue-heng
Sun, Gui-bo
Sun, Xiao-bo
Calenduloside E Ameliorates Myocardial Ischemia-Reperfusion Injury through Regulation of AMPK and Mitochondrial OPA1
title Calenduloside E Ameliorates Myocardial Ischemia-Reperfusion Injury through Regulation of AMPK and Mitochondrial OPA1
title_full Calenduloside E Ameliorates Myocardial Ischemia-Reperfusion Injury through Regulation of AMPK and Mitochondrial OPA1
title_fullStr Calenduloside E Ameliorates Myocardial Ischemia-Reperfusion Injury through Regulation of AMPK and Mitochondrial OPA1
title_full_unstemmed Calenduloside E Ameliorates Myocardial Ischemia-Reperfusion Injury through Regulation of AMPK and Mitochondrial OPA1
title_short Calenduloside E Ameliorates Myocardial Ischemia-Reperfusion Injury through Regulation of AMPK and Mitochondrial OPA1
title_sort calenduloside e ameliorates myocardial ischemia-reperfusion injury through regulation of ampk and mitochondrial opa1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479459/
https://www.ncbi.nlm.nih.gov/pubmed/32934760
http://dx.doi.org/10.1155/2020/2415269
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