Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish

Abstract Background Cardiomyopathy is a kind of cardiovascular diseases, which makes it more difficult for the heart to pump blood to other parts of the body, eventually leading to heart failure. Naoxintong (NXT), as a traditional Chinese Medicine (TCM) preparation, is widely used in the treatment o...

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Autores principales:	Mengyan Hu, Peirong Liu, Shuxian Lu, Zhihao Wang, Zhaojie Lyu, Hongkai Liu, Yuhong Sun, Feng Liu, Jing Tian
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Cardiomyopathy Naoxintong (NXT) Zebrafish Transcriptome HEG1 Other systems of medicine RZ201-999
Acceso en línea:	https://doaj.org/article/1918274c7e6748c899f4155b1f80a11d
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spelling	oai:doaj.org-article:1918274c7e6748c899f4155b1f80a11d2021-11-21T12:06:46ZMyocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish10.1186/s13020-021-00532-01749-8546https://doaj.org/article/1918274c7e6748c899f4155b1f80a11d2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13020-021-00532-0https://doaj.org/toc/1749-8546Abstract Background Cardiomyopathy is a kind of cardiovascular diseases, which makes it more difficult for the heart to pump blood to other parts of the body, eventually leading to heart failure. Naoxintong (NXT), as a traditional Chinese Medicine (TCM) preparation, is widely used in the treatment of cardiovascular diseases, including cardiomyopathy, while its underlying mechanism has not been fully elucidated. The purpose of this study is to investigate the therapeutic effect of NXT on cardiomyopathy and its molecular mechanism in zebrafish model. Methods The zebrafish cardiomyopathy model was established using terfenadine (TFD) and treated with NXT. The therapeutic effect of NXT on cardiomyopathy was evaluated by measuring the heart rate, the distance between the sinus venosus and bulbus arteriosus (SV-BA), the pericardial area, and the blood flow velocity of zebrafish. Then, the zebrafish hearts were isolated and collected; transcriptome analysis of NXT on cardiomyopathy was investigated. Moreover, the heg1 mutant of zebrafish congenital cardiomyopathy model was used to further validate the therapeutic effect of NXT on cardiomyopathy. Additionally, UPLC analysis combined with the zebrafish model investigation was performed to identify the bioactive components of NXT. Results In the TFD-induced zebrafish cardiomyopathy model, NXT treatment could significantly restore the cardiovascular malformations caused by cardiac dysfunction. Transcriptome and bioinformatics analyses of the TFD and TFD + NXT treated zebrafish developing hearts revealed that the differentially expressed genes were highly enriched in biological processes such as cardiac muscle contraction and heart development. As a cardiac development protein associated with cardiomyopathy, HEG1 had been identified as one of the important targets of NXT in the treatment of cardiomyopathy. The cardiovascular abnormalities of zebrafish heg1 mutant could be recovered significantly from NXT treatment, including the expanded atrial cavity and blood stagnation. qRT-PCR analysis further showed that NXT could restore cardiomyopathy phenotype in zebrafish through HEG1-CCM signaling. Among the seven components identified in NXT, paeoniflorin (PF) and salvianolic acid B (Sal B) were considered to be the main bioactive ones with myocardial protection. Conclusion NXT presented myocardial protective effect and could restore myocardial injury and cardiac dysfunction in zebrafish; the action mechanism was involved in HEG1-CCM signaling.Mengyan HuPeirong LiuShuxian LuZhihao WangZhaojie LyuHongkai LiuYuhong SunFeng LiuJing TianBMCarticleCardiomyopathyNaoxintong (NXT)ZebrafishTranscriptomeHEG1Other systems of medicineRZ201-999ENChinese Medicine, Vol 16, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cardiomyopathy Naoxintong (NXT) Zebrafish Transcriptome HEG1 Other systems of medicine RZ201-999
spellingShingle	Cardiomyopathy Naoxintong (NXT) Zebrafish Transcriptome HEG1 Other systems of medicine RZ201-999 Mengyan Hu Peirong Liu Shuxian Lu Zhihao Wang Zhaojie Lyu Hongkai Liu Yuhong Sun Feng Liu Jing Tian Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish
description	Abstract Background Cardiomyopathy is a kind of cardiovascular diseases, which makes it more difficult for the heart to pump blood to other parts of the body, eventually leading to heart failure. Naoxintong (NXT), as a traditional Chinese Medicine (TCM) preparation, is widely used in the treatment of cardiovascular diseases, including cardiomyopathy, while its underlying mechanism has not been fully elucidated. The purpose of this study is to investigate the therapeutic effect of NXT on cardiomyopathy and its molecular mechanism in zebrafish model. Methods The zebrafish cardiomyopathy model was established using terfenadine (TFD) and treated with NXT. The therapeutic effect of NXT on cardiomyopathy was evaluated by measuring the heart rate, the distance between the sinus venosus and bulbus arteriosus (SV-BA), the pericardial area, and the blood flow velocity of zebrafish. Then, the zebrafish hearts were isolated and collected; transcriptome analysis of NXT on cardiomyopathy was investigated. Moreover, the heg1 mutant of zebrafish congenital cardiomyopathy model was used to further validate the therapeutic effect of NXT on cardiomyopathy. Additionally, UPLC analysis combined with the zebrafish model investigation was performed to identify the bioactive components of NXT. Results In the TFD-induced zebrafish cardiomyopathy model, NXT treatment could significantly restore the cardiovascular malformations caused by cardiac dysfunction. Transcriptome and bioinformatics analyses of the TFD and TFD + NXT treated zebrafish developing hearts revealed that the differentially expressed genes were highly enriched in biological processes such as cardiac muscle contraction and heart development. As a cardiac development protein associated with cardiomyopathy, HEG1 had been identified as one of the important targets of NXT in the treatment of cardiomyopathy. The cardiovascular abnormalities of zebrafish heg1 mutant could be recovered significantly from NXT treatment, including the expanded atrial cavity and blood stagnation. qRT-PCR analysis further showed that NXT could restore cardiomyopathy phenotype in zebrafish through HEG1-CCM signaling. Among the seven components identified in NXT, paeoniflorin (PF) and salvianolic acid B (Sal B) were considered to be the main bioactive ones with myocardial protection. Conclusion NXT presented myocardial protective effect and could restore myocardial injury and cardiac dysfunction in zebrafish; the action mechanism was involved in HEG1-CCM signaling.
format	article
author	Mengyan Hu Peirong Liu Shuxian Lu Zhihao Wang Zhaojie Lyu Hongkai Liu Yuhong Sun Feng Liu Jing Tian
author_facet	Mengyan Hu Peirong Liu Shuxian Lu Zhihao Wang Zhaojie Lyu Hongkai Liu Yuhong Sun Feng Liu Jing Tian
author_sort	Mengyan Hu
title	Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish
title_short	Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish
title_full	Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish
title_fullStr	Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish
title_full_unstemmed	Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish
title_sort	myocardial protective effect and transcriptome profiling of naoxintong on cardiomyopathy in zebrafish
publisher	BMC
publishDate	2021
url	https://doaj.org/article/1918274c7e6748c899f4155b1f80a11d
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Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish

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