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Objective <p>To investigate the cardioprotective effects of Wenyang Zhenshuai granules (WYZSG) against doxorubicin (DOX)-induced cardiotoxicity and elucidate the underlying molecular mechanisms.</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月21日

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  • Xu Deng,
  • Xiaoping Li,
  • Jialuo Cai,
  • Zelin Xu,
  • Xinyu Chen,
  • Kunpeng Yao,
  • Yuntao Luo

摘要

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.