Orientin Reduces Myocardial Infarction Size via eNOS/NO Signaling and Thus Mitigates Adverse Cardiac Remodeling

Orientin is a flavonoid extracted from Chinese traditional herb, Polygonum orientale L. Previous study has reported that orientin protected myocardial from ischemia reperfusion injury. However, whether orientin could protect against cardiac remodeling after myocardial injury remains unclear. The aim...

Full description

Bibliographic Details
Main Authors: Fangfang Li, Jing Zong, Hao Zhang, Peijie Zhang, Luhong Xu, Kai Liang, Lu Yang, Hui Yong, Wenhao Qian
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-12-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fphar.2017.00926/full
_version_ 1818311365165580288
author Fangfang Li
Fangfang Li
Jing Zong
Jing Zong
Hao Zhang
Hao Zhang
Peijie Zhang
Luhong Xu
Luhong Xu
Kai Liang
Kai Liang
Lu Yang
Lu Yang
Hui Yong
Hui Yong
Wenhao Qian
Wenhao Qian
author_facet Fangfang Li
Fangfang Li
Jing Zong
Jing Zong
Hao Zhang
Hao Zhang
Peijie Zhang
Luhong Xu
Luhong Xu
Kai Liang
Kai Liang
Lu Yang
Lu Yang
Hui Yong
Hui Yong
Wenhao Qian
Wenhao Qian
author_sort Fangfang Li
collection DOAJ
description Orientin is a flavonoid extracted from Chinese traditional herb, Polygonum orientale L. Previous study has reported that orientin protected myocardial from ischemia reperfusion injury. However, whether orientin could protect against cardiac remodeling after myocardial injury remains unclear. The aim of our study is to investigate the effects of orientin in the progression of cardiac remodeling after myocardial infarction (MI). Mice cardiac remodeling model was established by left coronary artery ligation surgery. Experimental groups were as follows: vehicle-sham, orientin-sham, vehicle-MI, and orientin-MI. Animals were treated with vehicle or orientin (40 mg/kg) for 25 days starting 3 days after surgery. After 4 weeks of MI, mice with orientin treatment had decreased mortality and improved cardiac function. Significantly, at 4 weeks post-MI, orientin treatment decreased fibrosis, inflammatory response, and cardiomyocyte apoptosis. Furthermore, orientin treatment attenuated the hypoxia-induced neonatal rat cardiomyocyte apoptosis and increased cell viability. Additionally, orientin supplementation mitigated oxidative stress in remodeling heart tissue and cardiomyocytes exposed to hypoxia as measured by 2′,7′-dichlorodihydrofluorescein diacetate fluorescent probe. Mechanistically, orientin promotes cardioprotection by activating the eNOS/NO signaling cascades, which was confirmed by eNOS inhibitor (L-NAME) in vitro and in vivo. Inhibition of oxidative stress by orientin via eNOS/NO signaling cascades in the heart may represent a potential therapy for cardiac remodeling.
first_indexed 2024-12-13T08:00:48Z
format Article
id doaj.art-d5ba33069fa14bb192748b9aa8e1aa15
institution Directory Open Access Journal
issn 1663-9812
language English
last_indexed 2024-12-13T08:00:48Z
publishDate 2017-12-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Pharmacology
spelling doaj.art-d5ba33069fa14bb192748b9aa8e1aa152022-12-21T23:54:26ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-12-01810.3389/fphar.2017.00926314138Orientin Reduces Myocardial Infarction Size via eNOS/NO Signaling and Thus Mitigates Adverse Cardiac RemodelingFangfang Li0Fangfang Li1Jing Zong2Jing Zong3Hao Zhang4Hao Zhang5Peijie Zhang6Luhong Xu7Luhong Xu8Kai Liang9Kai Liang10Lu Yang11Lu Yang12Hui Yong13Hui Yong14Wenhao Qian15Wenhao Qian16Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaInstitute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaInstitute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaInstitute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, ChinaEmergency Department, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaInstitute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaInstitute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaInstitute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaInstitute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaInstitute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, ChinaOrientin is a flavonoid extracted from Chinese traditional herb, Polygonum orientale L. Previous study has reported that orientin protected myocardial from ischemia reperfusion injury. However, whether orientin could protect against cardiac remodeling after myocardial injury remains unclear. The aim of our study is to investigate the effects of orientin in the progression of cardiac remodeling after myocardial infarction (MI). Mice cardiac remodeling model was established by left coronary artery ligation surgery. Experimental groups were as follows: vehicle-sham, orientin-sham, vehicle-MI, and orientin-MI. Animals were treated with vehicle or orientin (40 mg/kg) for 25 days starting 3 days after surgery. After 4 weeks of MI, mice with orientin treatment had decreased mortality and improved cardiac function. Significantly, at 4 weeks post-MI, orientin treatment decreased fibrosis, inflammatory response, and cardiomyocyte apoptosis. Furthermore, orientin treatment attenuated the hypoxia-induced neonatal rat cardiomyocyte apoptosis and increased cell viability. Additionally, orientin supplementation mitigated oxidative stress in remodeling heart tissue and cardiomyocytes exposed to hypoxia as measured by 2′,7′-dichlorodihydrofluorescein diacetate fluorescent probe. Mechanistically, orientin promotes cardioprotection by activating the eNOS/NO signaling cascades, which was confirmed by eNOS inhibitor (L-NAME) in vitro and in vivo. Inhibition of oxidative stress by orientin via eNOS/NO signaling cascades in the heart may represent a potential therapy for cardiac remodeling.http://journal.frontiersin.org/article/10.3389/fphar.2017.00926/fullorientinmyocardial infarctioncardiac remodelingeNOSnitric oxidereactive oxygen species
spellingShingle Fangfang Li
Fangfang Li
Jing Zong
Jing Zong
Hao Zhang
Hao Zhang
Peijie Zhang
Luhong Xu
Luhong Xu
Kai Liang
Kai Liang
Lu Yang
Lu Yang
Hui Yong
Hui Yong
Wenhao Qian
Wenhao Qian
Orientin Reduces Myocardial Infarction Size via eNOS/NO Signaling and Thus Mitigates Adverse Cardiac Remodeling
Frontiers in Pharmacology
orientin
myocardial infarction
cardiac remodeling
eNOS
nitric oxide
reactive oxygen species
title Orientin Reduces Myocardial Infarction Size via eNOS/NO Signaling and Thus Mitigates Adverse Cardiac Remodeling
title_full Orientin Reduces Myocardial Infarction Size via eNOS/NO Signaling and Thus Mitigates Adverse Cardiac Remodeling
title_fullStr Orientin Reduces Myocardial Infarction Size via eNOS/NO Signaling and Thus Mitigates Adverse Cardiac Remodeling
title_full_unstemmed Orientin Reduces Myocardial Infarction Size via eNOS/NO Signaling and Thus Mitigates Adverse Cardiac Remodeling
title_short Orientin Reduces Myocardial Infarction Size via eNOS/NO Signaling and Thus Mitigates Adverse Cardiac Remodeling
title_sort orientin reduces myocardial infarction size via enos no signaling and thus mitigates adverse cardiac remodeling
topic orientin
myocardial infarction
cardiac remodeling
eNOS
nitric oxide
reactive oxygen species
url http://journal.frontiersin.org/article/10.3389/fphar.2017.00926/full
work_keys_str_mv AT fangfangli orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT fangfangli orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT jingzong orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT jingzong orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT haozhang orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT haozhang orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT peijiezhang orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT luhongxu orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT luhongxu orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT kailiang orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT kailiang orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT luyang orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT luyang orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT huiyong orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT huiyong orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT wenhaoqian orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling
AT wenhaoqian orientinreducesmyocardialinfarctionsizeviaenosnosignalingandthusmitigatesadversecardiacremodeling