Metabolomics reveals the mechanism of Zhilong Huoxue Tongyu capsule in the treatment of heart failure

Abstract Energy deprivation in cardiomyocytes is a pivotal factor in the progression of heart failure (HF). Zhilong Huoxue Tongyu capsule (ZL) is a widely used Chinese patent medicine that has been employed in the treatment of various cardiovascular diseases. However, its effects on HF and its impac...

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Main Authors: Li Chen, Dingshan Zhang, Yu Zheng, Jinyi Xue, Quanrong Zhang, Ziwen Deng, Maryam Mazhar, Yuan Zou, Ping Liu, Mingtai Chen, Gang Luo, Mengnan Liu
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-00088-1
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author Li Chen
Dingshan Zhang
Yu Zheng
Jinyi Xue
Quanrong Zhang
Ziwen Deng
Maryam Mazhar
Yuan Zou
Ping Liu
Mingtai Chen
Gang Luo
Mengnan Liu
author_facet Li Chen
Dingshan Zhang
Yu Zheng
Jinyi Xue
Quanrong Zhang
Ziwen Deng
Maryam Mazhar
Yuan Zou
Ping Liu
Mingtai Chen
Gang Luo
Mengnan Liu
author_sort Li Chen
collection DOAJ
description Abstract Energy deprivation in cardiomyocytes is a pivotal factor in the progression of heart failure (HF). Zhilong Huoxue Tongyu capsule (ZL) is a widely used Chinese patent medicine that has been employed in the treatment of various cardiovascular diseases. However, its effects on HF and its impact on cardiac metabolism remain to be elucidated. This study aims to validate the therapeutic effects of ZL on heart failure and analyze its influence on human cardiac metabolism through clinical trials and untargeted metabolomics research. A cohort of 80 HF patients was enrolled, all of whom received conventional treatment (CT) in conjunction with ZL. Primary therapeutic endpoints included left ventricular ejection fraction, brain natriuretic peptide levels, 6-min walking distance, the Minnesota Living with Heart Failure Questionnaire score, and traditional Chinese medicine (TCM) syndrome scores. Ultra-high performance liquid chromatography-tandem mass spectrometry was utilized to identify key compounds, core targets, and pathways implicated in the anti-HF effects of CT combined with ZL. Seventy-six subjects completed the clinical study. Post-treatment, significant improvements were observed in heart function, exercise endurance, quality of life, and TCM syndrome scores. Untargeted metabolomics screening identified 57 differential metabolites in the serum of subjects pre- and post-treatment, including PC 20:2_20:2 and cyclic acid, among others. Of these, 25 metabolites were upregulated, while 32 were downregulated. Pathway analysis indicated that these differential metabolites were involved in riboflavin metabolism, the citrate cycle, alanine, aspartate and glutamate metabolism, arginine biosynthesis, butanoate metabolism, lipoic acid metabolism, and fatty acid biosynthesis. The combination of CT and ZL for HF treatment exhibits promising clinical efficacy, potentially mediated through the optimization of cardiac energy metabolism.
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spelling doaj-art-53002fccff08433ab30086381de5b3ec2025-08-20T02:55:29ZengNature PortfolioScientific Reports2045-23222025-04-0115111310.1038/s41598-025-00088-1Metabolomics reveals the mechanism of Zhilong Huoxue Tongyu capsule in the treatment of heart failureLi Chen0Dingshan Zhang1Yu Zheng2Jinyi Xue3Quanrong Zhang4Ziwen Deng5Maryam Mazhar6Yuan Zou7Ping Liu8Mingtai Chen9Gang Luo10Mengnan Liu11Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityDepartment of Cardiovascular Disease, Shenzhen Traditional Chinese Medicine HospitalAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAffiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAbstract Energy deprivation in cardiomyocytes is a pivotal factor in the progression of heart failure (HF). Zhilong Huoxue Tongyu capsule (ZL) is a widely used Chinese patent medicine that has been employed in the treatment of various cardiovascular diseases. However, its effects on HF and its impact on cardiac metabolism remain to be elucidated. This study aims to validate the therapeutic effects of ZL on heart failure and analyze its influence on human cardiac metabolism through clinical trials and untargeted metabolomics research. A cohort of 80 HF patients was enrolled, all of whom received conventional treatment (CT) in conjunction with ZL. Primary therapeutic endpoints included left ventricular ejection fraction, brain natriuretic peptide levels, 6-min walking distance, the Minnesota Living with Heart Failure Questionnaire score, and traditional Chinese medicine (TCM) syndrome scores. Ultra-high performance liquid chromatography-tandem mass spectrometry was utilized to identify key compounds, core targets, and pathways implicated in the anti-HF effects of CT combined with ZL. Seventy-six subjects completed the clinical study. Post-treatment, significant improvements were observed in heart function, exercise endurance, quality of life, and TCM syndrome scores. Untargeted metabolomics screening identified 57 differential metabolites in the serum of subjects pre- and post-treatment, including PC 20:2_20:2 and cyclic acid, among others. Of these, 25 metabolites were upregulated, while 32 were downregulated. Pathway analysis indicated that these differential metabolites were involved in riboflavin metabolism, the citrate cycle, alanine, aspartate and glutamate metabolism, arginine biosynthesis, butanoate metabolism, lipoic acid metabolism, and fatty acid biosynthesis. The combination of CT and ZL for HF treatment exhibits promising clinical efficacy, potentially mediated through the optimization of cardiac energy metabolism.https://doi.org/10.1038/s41598-025-00088-1Heart failureZhilong Huoxue Tongyu capsuleClinical effectUntargeted metabolomicsCardiac energy metabolism
spellingShingle Li Chen
Dingshan Zhang
Yu Zheng
Jinyi Xue
Quanrong Zhang
Ziwen Deng
Maryam Mazhar
Yuan Zou
Ping Liu
Mingtai Chen
Gang Luo
Mengnan Liu
Metabolomics reveals the mechanism of Zhilong Huoxue Tongyu capsule in the treatment of heart failure
Scientific Reports
Heart failure
Zhilong Huoxue Tongyu capsule
Clinical effect
Untargeted metabolomics
Cardiac energy metabolism
title Metabolomics reveals the mechanism of Zhilong Huoxue Tongyu capsule in the treatment of heart failure
title_full Metabolomics reveals the mechanism of Zhilong Huoxue Tongyu capsule in the treatment of heart failure
title_fullStr Metabolomics reveals the mechanism of Zhilong Huoxue Tongyu capsule in the treatment of heart failure
title_full_unstemmed Metabolomics reveals the mechanism of Zhilong Huoxue Tongyu capsule in the treatment of heart failure
title_short Metabolomics reveals the mechanism of Zhilong Huoxue Tongyu capsule in the treatment of heart failure
title_sort metabolomics reveals the mechanism of zhilong huoxue tongyu capsule in the treatment of heart failure
topic Heart failure
Zhilong Huoxue Tongyu capsule
Clinical effect
Untargeted metabolomics
Cardiac energy metabolism
url https://doi.org/10.1038/s41598-025-00088-1
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