Cargando…

Icariside II, a Naturally Occurring SIRT3 Agonist, Protects against Myocardial Infarction through the AMPK/PGC-1α/Apoptosis Signaling Pathway

Myocardial infarction (MI) refers to the death of cardiomyocytes triggered by a lack of energy due to myocardial ischemia and hypoxia, and silent mating type information regulation 2 homolog 3 (SIRT3) plays an essential role in protecting against myocardial oxidative stress and apoptosis, which are...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Yeli, Feng, Linying, Xie, Dianyou, Lin, Mu, Li, Yiqi, Chen, Nana, Yang, Danli, Gao, Jianmei, Zhu, Yizhun, Gong, Qihai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405218/
https://www.ncbi.nlm.nih.gov/pubmed/36009184
http://dx.doi.org/10.3390/antiox11081465
_version_ 1784773827024125952
author Li, Yeli
Feng, Linying
Xie, Dianyou
Lin, Mu
Li, Yiqi
Chen, Nana
Yang, Danli
Gao, Jianmei
Zhu, Yizhun
Gong, Qihai
author_facet Li, Yeli
Feng, Linying
Xie, Dianyou
Lin, Mu
Li, Yiqi
Chen, Nana
Yang, Danli
Gao, Jianmei
Zhu, Yizhun
Gong, Qihai
author_sort Li, Yeli
collection PubMed
description Myocardial infarction (MI) refers to the death of cardiomyocytes triggered by a lack of energy due to myocardial ischemia and hypoxia, and silent mating type information regulation 2 homolog 3 (SIRT3) plays an essential role in protecting against myocardial oxidative stress and apoptosis, which are deemed to be the principal causes of MI. Icariside II (ICS II), one of the main active ingredients of Herbal Epimedii, possesses extensive pharmacological activities. However, whether ICS II can protect against MI is still unknown. Therefore, this study was designed to investigate the effect and possible underlying mechanism of ICS II on MI both in vivo and in vitro. The results showed that pretreatment with ICS II not only dramatically mitigated MI-induced myocardial damage in mice but also alleviated H9c2 cardiomyocyte injury elicited by oxygen and glucose deprivation (OGD), which were achieved by suppressing mitochondrial oxidative stress and apoptosis. Furthermore, ICS II elevated the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) expression, thereby activating SIRT3. However, these protective effects of ICS II on MI injury were largely abolished in SIRT3-deficient mice, manifesting that ICS II-mediated cardioprotective effects are, at least partly, due to the presence of SIRT3. Most interestingly, ICS II directly bound with SIRT3, as reflected by molecular docking, which indicated that SIRT3 might be a promising therapeutic target for ICS II-elicited cardioprotection in MI. In conclusion, our findings illustrate that ICS II protects against MI-induced oxidative injury and apoptosis by targeting SIRT3 through regulating the AMPK/PGC-1α pathway.
format Online
Article
Text
id pubmed-9405218
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-94052182022-08-26 Icariside II, a Naturally Occurring SIRT3 Agonist, Protects against Myocardial Infarction through the AMPK/PGC-1α/Apoptosis Signaling Pathway Li, Yeli Feng, Linying Xie, Dianyou Lin, Mu Li, Yiqi Chen, Nana Yang, Danli Gao, Jianmei Zhu, Yizhun Gong, Qihai Antioxidants (Basel) Article Myocardial infarction (MI) refers to the death of cardiomyocytes triggered by a lack of energy due to myocardial ischemia and hypoxia, and silent mating type information regulation 2 homolog 3 (SIRT3) plays an essential role in protecting against myocardial oxidative stress and apoptosis, which are deemed to be the principal causes of MI. Icariside II (ICS II), one of the main active ingredients of Herbal Epimedii, possesses extensive pharmacological activities. However, whether ICS II can protect against MI is still unknown. Therefore, this study was designed to investigate the effect and possible underlying mechanism of ICS II on MI both in vivo and in vitro. The results showed that pretreatment with ICS II not only dramatically mitigated MI-induced myocardial damage in mice but also alleviated H9c2 cardiomyocyte injury elicited by oxygen and glucose deprivation (OGD), which were achieved by suppressing mitochondrial oxidative stress and apoptosis. Furthermore, ICS II elevated the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) expression, thereby activating SIRT3. However, these protective effects of ICS II on MI injury were largely abolished in SIRT3-deficient mice, manifesting that ICS II-mediated cardioprotective effects are, at least partly, due to the presence of SIRT3. Most interestingly, ICS II directly bound with SIRT3, as reflected by molecular docking, which indicated that SIRT3 might be a promising therapeutic target for ICS II-elicited cardioprotection in MI. In conclusion, our findings illustrate that ICS II protects against MI-induced oxidative injury and apoptosis by targeting SIRT3 through regulating the AMPK/PGC-1α pathway. MDPI 2022-07-27 /pmc/articles/PMC9405218/ /pubmed/36009184 http://dx.doi.org/10.3390/antiox11081465 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Yeli
Feng, Linying
Xie, Dianyou
Lin, Mu
Li, Yiqi
Chen, Nana
Yang, Danli
Gao, Jianmei
Zhu, Yizhun
Gong, Qihai
Icariside II, a Naturally Occurring SIRT3 Agonist, Protects against Myocardial Infarction through the AMPK/PGC-1α/Apoptosis Signaling Pathway
title Icariside II, a Naturally Occurring SIRT3 Agonist, Protects against Myocardial Infarction through the AMPK/PGC-1α/Apoptosis Signaling Pathway
title_full Icariside II, a Naturally Occurring SIRT3 Agonist, Protects against Myocardial Infarction through the AMPK/PGC-1α/Apoptosis Signaling Pathway
title_fullStr Icariside II, a Naturally Occurring SIRT3 Agonist, Protects against Myocardial Infarction through the AMPK/PGC-1α/Apoptosis Signaling Pathway
title_full_unstemmed Icariside II, a Naturally Occurring SIRT3 Agonist, Protects against Myocardial Infarction through the AMPK/PGC-1α/Apoptosis Signaling Pathway
title_short Icariside II, a Naturally Occurring SIRT3 Agonist, Protects against Myocardial Infarction through the AMPK/PGC-1α/Apoptosis Signaling Pathway
title_sort icariside ii, a naturally occurring sirt3 agonist, protects against myocardial infarction through the ampk/pgc-1α/apoptosis signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405218/
https://www.ncbi.nlm.nih.gov/pubmed/36009184
http://dx.doi.org/10.3390/antiox11081465
work_keys_str_mv AT liyeli icarisideiianaturallyoccurringsirt3agonistprotectsagainstmyocardialinfarctionthroughtheampkpgc1aapoptosissignalingpathway
AT fenglinying icarisideiianaturallyoccurringsirt3agonistprotectsagainstmyocardialinfarctionthroughtheampkpgc1aapoptosissignalingpathway
AT xiedianyou icarisideiianaturallyoccurringsirt3agonistprotectsagainstmyocardialinfarctionthroughtheampkpgc1aapoptosissignalingpathway
AT linmu icarisideiianaturallyoccurringsirt3agonistprotectsagainstmyocardialinfarctionthroughtheampkpgc1aapoptosissignalingpathway
AT liyiqi icarisideiianaturallyoccurringsirt3agonistprotectsagainstmyocardialinfarctionthroughtheampkpgc1aapoptosissignalingpathway
AT chennana icarisideiianaturallyoccurringsirt3agonistprotectsagainstmyocardialinfarctionthroughtheampkpgc1aapoptosissignalingpathway
AT yangdanli icarisideiianaturallyoccurringsirt3agonistprotectsagainstmyocardialinfarctionthroughtheampkpgc1aapoptosissignalingpathway
AT gaojianmei icarisideiianaturallyoccurringsirt3agonistprotectsagainstmyocardialinfarctionthroughtheampkpgc1aapoptosissignalingpathway
AT zhuyizhun icarisideiianaturallyoccurringsirt3agonistprotectsagainstmyocardialinfarctionthroughtheampkpgc1aapoptosissignalingpathway
AT gongqihai icarisideiianaturallyoccurringsirt3agonistprotectsagainstmyocardialinfarctionthroughtheampkpgc1aapoptosissignalingpathway