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

Chinese Medicine

Yuhong Sun¹  Feng Liu²  Shuxian Lu³  Zhaojie Lyu³  Zhihao Wang³  Hongkai Liu³  Peirong Liu³  Mengyan Hu³  Jing Tian⁴ 

[1] Shaanxi Buchang Pharmaceutical Co. Ltd., 710075, Xi’an, China;Shaanxi Buchang Pharmaceutical Co. Ltd., 710075, Xi’an, China;Shaanxi Institute of International Trade and Commence, 712046, Xi’an, China;Western China Zebrafish Research Center for Human Diseases and Drug Screening, The College of Life Sciences, Northwest University, 710069, Xi’an, China;Western China Zebrafish Research Center for Human Diseases and Drug Screening, The College of Life Sciences, Northwest University, 710069, Xi’an, China;Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, 710069, Xi’an, China;

关键词: Cardiomyopathy;    Naoxintong (NXT);    Zebrafish;    Transcriptome;    HEG1;   

DOI  :  10.1186/s13020-021-00532-0

来源: Springer

【 摘 要 】

BackgroundCardiomyopathy 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.MethodsThe 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.ResultsIn 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.ConclusionNXT presented myocardial protective effect and could restore myocardial injury and cardiac dysfunction in zebrafish; the action mechanism was involved in HEG1-CCM signaling.

【 授权许可】

CC BY