Cargando…

Liquiritigenin attenuates isoprenaline-induced myocardial fibrosis in mice through the TGF-β1/Smad2 and AKT/ERK signaling pathways

Myocardial fibrosis is a pathological process characterized by excessive accumulation of extracellular matrix in myocardial interstitial spaces. Myocardial fibrosis is a fundamental process in ventricular remodeling and a primary contributor to the progression of heart failure. Liquiritigenin (LQ) i...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Li, Fang, Hui, Yu, Yong-Hong, Liu, Shan-Xin, Yang, Zhi-Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365605/
https://www.ncbi.nlm.nih.gov/pubmed/34328199
http://dx.doi.org/10.3892/mmr.2021.12326
_version_ 1783738743155326976
author Li, Li
Fang, Hui
Yu, Yong-Hong
Liu, Shan-Xin
Yang, Zhi-Qiang
author_facet Li, Li
Fang, Hui
Yu, Yong-Hong
Liu, Shan-Xin
Yang, Zhi-Qiang
author_sort Li, Li
collection PubMed
description Myocardial fibrosis is a pathological process characterized by excessive accumulation of extracellular matrix in myocardial interstitial spaces. Myocardial fibrosis is a fundamental process in ventricular remodeling and a primary contributor to the progression of heart failure. Liquiritigenin (LQ) is a flavanone compound with anti-oxidative, anti-carcinogenic, anti-inflammatory and estrogenic properties. The present study aimed to investigate the regulatory potential of LQ treatment in a mouse model of isoprenaline (ISO)-induced cardiac fibrosis and in cultured H9C2 cardiomyocytes stimulated with angiotensin II (Ang II). The treatment of ISO-induced mice with LQ significantly decreased the levels of cardiac injury-related proteins in the serum and ECM accumulation in mouse heart tissues. LQ treatment also effectively alleviated cardiac dysfunction in ISO-treated mice. Further analyses revealed that LQ inhibited ISO-induced collagen formation and activation of the transforming growth factor-β1 (TGF-β1)/Smad2 and protein kinase B (AKT)/extracellular signal-regulated kinase (ERK) signaling pathways. As a major pathological event in myocardial fibrosis, the apoptosis of cardiomyocytes has been considered a key mechanism contributing to impaired left ventricle performance. The pretreatment of rat cardiomyocytes with LQ significantly reduced the apoptosis of H9C2 cells, and inhibited Ang II-induced activation of the TGF-β1/Smad2 and AKT/ERK pathways. In conclusion, the present study revealed that LQ ameliorated ISO-induced myocardial fibrosis in mice and inhibited the apoptosis of cardiomyocytes in vitro by inhibiting the TGF-β1/Smad2 and AKT/ERK signaling pathways. These results suggested the anti-fibrotic and cardioprotective potential of LQ in fibrosis, thus supporting the use of LQ for the management of cardiomyocyte injury and myocardial fibrosis in patients with cardiac diseases.
format Online
Article
Text
id pubmed-8365605
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-83656052021-08-29 Liquiritigenin attenuates isoprenaline-induced myocardial fibrosis in mice through the TGF-β1/Smad2 and AKT/ERK signaling pathways Li, Li Fang, Hui Yu, Yong-Hong Liu, Shan-Xin Yang, Zhi-Qiang Mol Med Rep Articles Myocardial fibrosis is a pathological process characterized by excessive accumulation of extracellular matrix in myocardial interstitial spaces. Myocardial fibrosis is a fundamental process in ventricular remodeling and a primary contributor to the progression of heart failure. Liquiritigenin (LQ) is a flavanone compound with anti-oxidative, anti-carcinogenic, anti-inflammatory and estrogenic properties. The present study aimed to investigate the regulatory potential of LQ treatment in a mouse model of isoprenaline (ISO)-induced cardiac fibrosis and in cultured H9C2 cardiomyocytes stimulated with angiotensin II (Ang II). The treatment of ISO-induced mice with LQ significantly decreased the levels of cardiac injury-related proteins in the serum and ECM accumulation in mouse heart tissues. LQ treatment also effectively alleviated cardiac dysfunction in ISO-treated mice. Further analyses revealed that LQ inhibited ISO-induced collagen formation and activation of the transforming growth factor-β1 (TGF-β1)/Smad2 and protein kinase B (AKT)/extracellular signal-regulated kinase (ERK) signaling pathways. As a major pathological event in myocardial fibrosis, the apoptosis of cardiomyocytes has been considered a key mechanism contributing to impaired left ventricle performance. The pretreatment of rat cardiomyocytes with LQ significantly reduced the apoptosis of H9C2 cells, and inhibited Ang II-induced activation of the TGF-β1/Smad2 and AKT/ERK pathways. In conclusion, the present study revealed that LQ ameliorated ISO-induced myocardial fibrosis in mice and inhibited the apoptosis of cardiomyocytes in vitro by inhibiting the TGF-β1/Smad2 and AKT/ERK signaling pathways. These results suggested the anti-fibrotic and cardioprotective potential of LQ in fibrosis, thus supporting the use of LQ for the management of cardiomyocyte injury and myocardial fibrosis in patients with cardiac diseases. D.A. Spandidos 2021-10 2021-07-30 /pmc/articles/PMC8365605/ /pubmed/34328199 http://dx.doi.org/10.3892/mmr.2021.12326 Text en Copyright: © Li et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Articles
Li, Li
Fang, Hui
Yu, Yong-Hong
Liu, Shan-Xin
Yang, Zhi-Qiang
Liquiritigenin attenuates isoprenaline-induced myocardial fibrosis in mice through the TGF-β1/Smad2 and AKT/ERK signaling pathways
title Liquiritigenin attenuates isoprenaline-induced myocardial fibrosis in mice through the TGF-β1/Smad2 and AKT/ERK signaling pathways
title_full Liquiritigenin attenuates isoprenaline-induced myocardial fibrosis in mice through the TGF-β1/Smad2 and AKT/ERK signaling pathways
title_fullStr Liquiritigenin attenuates isoprenaline-induced myocardial fibrosis in mice through the TGF-β1/Smad2 and AKT/ERK signaling pathways
title_full_unstemmed Liquiritigenin attenuates isoprenaline-induced myocardial fibrosis in mice through the TGF-β1/Smad2 and AKT/ERK signaling pathways
title_short Liquiritigenin attenuates isoprenaline-induced myocardial fibrosis in mice through the TGF-β1/Smad2 and AKT/ERK signaling pathways
title_sort liquiritigenin attenuates isoprenaline-induced myocardial fibrosis in mice through the tgf-β1/smad2 and akt/erk signaling pathways
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365605/
https://www.ncbi.nlm.nih.gov/pubmed/34328199
http://dx.doi.org/10.3892/mmr.2021.12326
work_keys_str_mv AT lili liquiritigeninattenuatesisoprenalineinducedmyocardialfibrosisinmicethroughthetgfb1smad2andakterksignalingpathways
AT fanghui liquiritigeninattenuatesisoprenalineinducedmyocardialfibrosisinmicethroughthetgfb1smad2andakterksignalingpathways
AT yuyonghong liquiritigeninattenuatesisoprenalineinducedmyocardialfibrosisinmicethroughthetgfb1smad2andakterksignalingpathways
AT liushanxin liquiritigeninattenuatesisoprenalineinducedmyocardialfibrosisinmicethroughthetgfb1smad2andakterksignalingpathways
AT yangzhiqiang liquiritigeninattenuatesisoprenalineinducedmyocardialfibrosisinmicethroughthetgfb1smad2andakterksignalingpathways