Shenmai injection revives cardiac function in rats with hypertensive heart failure: involvement of microbial-host co-metabolism

Abstract Heart failure (HF) is a complex syndrome marked by considerable expenditures and elevated mortality and morbidity rates globally. Shenmai injection (SMI), a form of Traditional Chinese Medicine-based therapy, has demonstrated effectiveness in treating HF. Recent research suggests that Tradi...

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Main Authors: Lin Li, Senjie Zhong, Jiahao Ye, Siyuan Hu, Xiajun Xiong, Guangyu Chen, Zhixi Hu
Format: Article
Language:English
Published: BMC 2025-01-01
Series:BMC Complementary Medicine and Therapies
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Online Access:https://doi.org/10.1186/s12906-024-04737-2
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author Lin Li
Senjie Zhong
Jiahao Ye
Siyuan Hu
Xiajun Xiong
Guangyu Chen
Zhixi Hu
author_facet Lin Li
Senjie Zhong
Jiahao Ye
Siyuan Hu
Xiajun Xiong
Guangyu Chen
Zhixi Hu
author_sort Lin Li
collection DOAJ
description Abstract Heart failure (HF) is a complex syndrome marked by considerable expenditures and elevated mortality and morbidity rates globally. Shenmai injection (SMI), a form of Traditional Chinese Medicine-based therapy, has demonstrated effectiveness in treating HF. Recent research suggests that Traditional Chinese Medicine (TCM) may induce beneficial changes in microbial-host co-metabolism, potentially providing cardiovascular protection. This study used a rat model of hypertensive heart failure (H-HF) to explore the mechanism of SMI. The possible compounds and key targets of SMI against H-HF were investigated using network pharmacology. The pharmacodynamics of SMI were validated using the H-HF animal model, with analysis of fecal gut microbiota integrating metabolomics and 16S rRNA sequencing. Metorigin metabolite traceability analysis and the MetaboAnalyst platform were utilized to explore the action mechanism. To evaluate changes in serum TMAO levels, targeted metabolomics was performed. Finally, the study looked at the intrinsic relationships among modifications in the intestinal flora, metabolite profile changes, and the targets of SMI compounds to clarify how they might be used to treat H-HF. According to metabolomics and 16S rRNA sequencing, by reestablishing homeostasis in the gut microbiota, SMI affects vital metabolic pathways, such as energy metabolism, amino acid metabolism, and bile acid metabolism. Increased serum TMAO levels were identified to be a risk factor for H-HF, and SMI was able to downregulate the levels of TMAO-related metabolites. Network pharmacology analysis identified 13 active components of SMI targeting 46 proteins, resulting in differential expression changes in 8 metabolites and 24 gut microbes. In conclusion, this study highlights the effectiveness of SMI in alleviating H-HF and its potential to modulate microbial-host co-metabolism. Through a comprehensive discussion of the interconnected relationships among the components, targets, metabolites, and gut microbiota, it provided fresh light on the therapeutic mechanism of SMI on H-HF.
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spelling doaj-art-71e1e35a4d5d4e86965b2a88753b30022025-01-26T12:15:09ZengBMCBMC Complementary Medicine and Therapies2662-76712025-01-0125112110.1186/s12906-024-04737-2Shenmai injection revives cardiac function in rats with hypertensive heart failure: involvement of microbial-host co-metabolismLin Li0Senjie Zhong1Jiahao Ye2Siyuan Hu3Xiajun Xiong4Guangyu Chen5Zhixi Hu6The Domestic First-class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese MedicineThe First Affiliated Hospital of Guangzhou University of Chinese MedicineThe Domestic First-class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese MedicineThe Domestic First-class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese MedicineProvincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese MedicineProvincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese MedicineThe Domestic First-class Discipline Construction Project of Chinese Medicine, Hunan University of Chinese MedicineAbstract Heart failure (HF) is a complex syndrome marked by considerable expenditures and elevated mortality and morbidity rates globally. Shenmai injection (SMI), a form of Traditional Chinese Medicine-based therapy, has demonstrated effectiveness in treating HF. Recent research suggests that Traditional Chinese Medicine (TCM) may induce beneficial changes in microbial-host co-metabolism, potentially providing cardiovascular protection. This study used a rat model of hypertensive heart failure (H-HF) to explore the mechanism of SMI. The possible compounds and key targets of SMI against H-HF were investigated using network pharmacology. The pharmacodynamics of SMI were validated using the H-HF animal model, with analysis of fecal gut microbiota integrating metabolomics and 16S rRNA sequencing. Metorigin metabolite traceability analysis and the MetaboAnalyst platform were utilized to explore the action mechanism. To evaluate changes in serum TMAO levels, targeted metabolomics was performed. Finally, the study looked at the intrinsic relationships among modifications in the intestinal flora, metabolite profile changes, and the targets of SMI compounds to clarify how they might be used to treat H-HF. According to metabolomics and 16S rRNA sequencing, by reestablishing homeostasis in the gut microbiota, SMI affects vital metabolic pathways, such as energy metabolism, amino acid metabolism, and bile acid metabolism. Increased serum TMAO levels were identified to be a risk factor for H-HF, and SMI was able to downregulate the levels of TMAO-related metabolites. Network pharmacology analysis identified 13 active components of SMI targeting 46 proteins, resulting in differential expression changes in 8 metabolites and 24 gut microbes. In conclusion, this study highlights the effectiveness of SMI in alleviating H-HF and its potential to modulate microbial-host co-metabolism. Through a comprehensive discussion of the interconnected relationships among the components, targets, metabolites, and gut microbiota, it provided fresh light on the therapeutic mechanism of SMI on H-HF.https://doi.org/10.1186/s12906-024-04737-2Heart failureShenmai injectionGut microbiotaFecal metabolomicsTMAO
spellingShingle Lin Li
Senjie Zhong
Jiahao Ye
Siyuan Hu
Xiajun Xiong
Guangyu Chen
Zhixi Hu
Shenmai injection revives cardiac function in rats with hypertensive heart failure: involvement of microbial-host co-metabolism
BMC Complementary Medicine and Therapies
Heart failure
Shenmai injection
Gut microbiota
Fecal metabolomics
TMAO
title Shenmai injection revives cardiac function in rats with hypertensive heart failure: involvement of microbial-host co-metabolism
title_full Shenmai injection revives cardiac function in rats with hypertensive heart failure: involvement of microbial-host co-metabolism
title_fullStr Shenmai injection revives cardiac function in rats with hypertensive heart failure: involvement of microbial-host co-metabolism
title_full_unstemmed Shenmai injection revives cardiac function in rats with hypertensive heart failure: involvement of microbial-host co-metabolism
title_short Shenmai injection revives cardiac function in rats with hypertensive heart failure: involvement of microbial-host co-metabolism
title_sort shenmai injection revives cardiac function in rats with hypertensive heart failure involvement of microbial host co metabolism
topic Heart failure
Shenmai injection
Gut microbiota
Fecal metabolomics
TMAO
url https://doi.org/10.1186/s12906-024-04737-2
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