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Peer-reviewedCC BY-NC-ND 4.0Journal of Cardiothoracic Surgery

Mechanistic exploration of Wenyang Zhenshuai granules in doxorubicin-induced cardiotoxicity: integrating network pharmacology and experimental validation

  • Xu Deng1
  • Xiaoping Li1
  • Jialuo Cai1
  • Zelin Xu1
  • Xinyu Chen1
  • Kunpeng Yao2
  • Yuntao Luo3,4
4 affiliations
  1. 1Center of Preventive Treatment of Disease, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007 Hunan China
  2. 2Hunan University of Chinese Medicine, Changsha, 410208 Hunan China
  3. 3Department of Health Management, The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007 Hunan China
  4. 4The First Hospital of Hunan University of Chinese Medicine, No. 95 Shaoshan Middle Road, Changsha, Hunan Province China
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Abstract

Objective: To investigate the cardioprotective effects of Wenyang Zhenshuai granules (WYZSG) against doxorubicin (DOX)-induced cardiotoxicity and elucidate the underlying molecular mechanisms.

Methods: Network pharmacology was performed to identify the potential therapeutic targets of WYZSG against doxorubicin (DOX)-induced cardiac injury. Protein–protein interaction (PPI) network construction, hub gene analysis, and molecular docking were conducted to identify key targets and validate the interactions between the major active compounds and core targets. In vivo, a rat model of DOX-induced cardiac injury was established to evaluate the effects of WYZSG on cardiac injury, histopathological changes, apoptosis, and serpin family E member 1 (SERPINE1) expression. The role of SERPINE1 in the protective effects of WYZSG was further validated through SERPINE1 overexpression experiments.

Results: A total of 65 bioactive compounds and 1,057 putative targets were identified, with 49 overlapping targets associated with cardiac injury. Network analysis highlighted genistein, L-phenylalanine, daidzein, nobiletin, and isoliquiritigenin as the major active constituents, while SERPINE1 emerged as a central hub gene. Molecular docking confirmed strong binding affinities between these core compounds and SERPINE1. In vivo, WYZSG attenuated DOX-induced cardiac injury, reduced serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) levels, alleviated myocardial histopathological damage, inhibited cardiomyocyte apoptosis, and dose-dependently downregulated SERPINE1 expression in DOX-treated rats. Notably, SERPINE1 overexpression partially abolished the cardioprotective effects of WYZSG against DOX-induced cardiac injury.

Conclusion: WYZSG protects against DOX-induced cardiac injury by suppressing SERPINE1 expression, providing mechanistic insight into its cardioprotective effects and supporting its potential therapeutic application in DOX-induced cardiac injury.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13019-026-04631-7.

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Cite

BibTeXRIS
BibTeX
@article{deng2026mechanistic,
  title = {{Mechanistic exploration of Wenyang Zhenshuai granules in doxorubicin-induced cardiotoxicity: integrating network pharmacology and experimental validation}},
  author = {Xu Deng and Xiaoping Li and Jialuo Cai and Zelin Xu and Xinyu Chen and Kunpeng Yao and Yuntao Luo},
  journal = {Journal of Cardiothoracic Surgery},
  year = {2026},
  month = jul,
  doi = {10.1186/s13019-026-04631-7},
  url = {https://doi.org/10.1186/s13019-026-04631-7},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Mechanistic exploration of Wenyang Zhenshuai granules in doxorubicin-induced cardiotoxicity: integrating network pharmacology and experimental validation
AU  - Xu Deng
AU  - Xiaoping Li
AU  - Jialuo Cai
AU  - Zelin Xu
AU  - Xinyu Chen
AU  - Kunpeng Yao
AU  - Yuntao Luo
PY  - 2026
DA  - 2026/07/21
JO  - Journal of Cardiothoracic Surgery
DO  - 10.1186/s13019-026-04631-7
UR  - https://doi.org/10.1186/s13019-026-04631-7
AB  - Objective: To investigate the cardioprotective effects of Wenyang Zhenshuai granules (WYZSG) against doxorubicin (DOX)-induced cardiotoxicity and elucidate the underlying molecular mechanisms.  Methods: Network pharmacology was performed to identify the potential therapeutic targets of WYZSG against doxorubicin (DOX)-induced cardiac injury. Protein–protein interaction (PPI) network construction, hub gene analysis, and molecular docking were conducted to identify key targets and validate the interactions between the major active compounds and core targets. In vivo, a rat model of DOX-induced cardiac injury was established to evaluate the effects of WYZSG on cardiac injury, histopathological changes, apoptosis, and serpin family E member 1 (SERPINE1) expression. The role of SERPINE1 in the protective effects of WYZSG was further validated through SERPINE1 overexpression experiments.  Results: A total of 65 bioactive compounds and 1,057 putative targets were identified, with 49 overlapping targets associated with cardiac injury. Network analysis highlighted genistein, L-phenylalanine, daidzein, nobiletin, and isoliquiritigenin as the major active constituents, while SERPINE1 emerged as a central hub gene. Molecular docking confirmed strong binding affinities between these core compounds and SERPINE1. In vivo, WYZSG attenuated DOX-induced cardiac injury, reduced serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) levels, alleviated myocardial histopathological damage, inhibited cardiomyocyte apoptosis, and dose-dependently downregulated SERPINE1 expression in DOX-treated rats. Notably, SERPINE1 overexpression partially abolished the cardioprotective effects of WYZSG against DOX-induced cardiac injury.  Conclusion: WYZSG protects against DOX-induced cardiac injury by suppressing SERPINE1 expression, providing mechanistic insight into its cardioprotective effects and supporting its potential therapeutic application in DOX-induced cardiac injury.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13019-026-04631-7.
SN  - 1749-8090
ER  -