Scholarlink

<p>Sepsis-induced cardiomyopathy represents a life-threatening complication arising from severe sepsis and septic shock. Hydroxysafflor yellow A (HSYA), a major quinone chalcone constituent, protects cardiac function in this disease. This study explored the detailed mechanisms of HSYA in mitigating sepsis-related cardiomyopathy. Potential targets of HSYA against sepsis-induced cardiomyopathy were identified by integrating sepsis-related genes (GSE131761), genes associated with myocardial damage (GeneCards), and potential targets of HSYA (CTD, GeneCards, SwissTargetPrediction). GO and KEGG pathway enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed. Hub genes were identified by machine learning and WGCNA. An in vitro cellular model was generated by stimulating AC16 cardiomyocytes with LPS. Cell viability and apoptosis were determined by CCK-8 assay and flow cytometry, respectively. KEGG pathway enrichment analysis revealed the potential involvement of NF-κB, TNF, IL-17, and MAPK signaling pathways in the protective role of HSYA against sepsis-induced cardiomyopathy. HSYA attenuated LPS-induced pro-inflammatory cytokine expression, ROS generation, and cell apoptosis in AC16 cardiomyocytes. Mechanistically, HSYA upregulated GATA3 expression in LPS-stimulated AC16 cardiomyocytes. Moreover, downregulation of GATA3 enhanced pro-inflammatory cytokine expression, ROS generation, and cell apoptosis in HSYA-treated AC16 cardiomyocytes under LPS. Our in vitro findings suggest that GATA3 may serve as a potential mediator through which HSYA attenuates LPS‑induced cardiomyocyte injury by concurrently dampening inflammation, oxidative stress, and apoptosis.</p> Graphical abstract <p>This study integrated network pharmacology, machine learning algorithms, and WGCNA approaches to systematically investigate the mechanisms through which HSYA alleviates sepsis-induced myocardial damage. Using an LPS-induced AC16 cardiomyocyte cytotoxicity model, the cardioprotective effect of HSYA is validated and mechanistically linked to its regulatory action on the transcription factor GATA3.</p> <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

GATA3 mediates the cardioprotective effect of hydroxysafflor yellow a against septic cardiomyopathy: insights from integrated machine learning, WGCNA, and experimental validation

  • 期刊论文

  • 发表日期：

    2026年5月9日

查看全文
  • Lihong Lou,
  • Lin Yuan,
  • Chunli Zeng,
  • Yaoguo Han,
  • Ming Lu,
  • Ming Lei

摘要

Sepsis-induced cardiomyopathy represents a life-threatening complication arising from severe sepsis and septic shock. Hydroxysafflor yellow A (HSYA), a major quinone chalcone constituent, protects cardiac function in this disease. This study explored the detailed mechanisms of HSYA in mitigating sepsis-related cardiomyopathy. Potential targets of HSYA against sepsis-induced cardiomyopathy were identified by integrating sepsis-related genes (GSE131761), genes associated with myocardial damage (GeneCards), and potential targets of HSYA (CTD, GeneCards, SwissTargetPrediction). GO and KEGG pathway enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed. Hub genes were identified by machine learning and WGCNA. An in vitro cellular model was generated by stimulating AC16 cardiomyocytes with LPS. Cell viability and apoptosis were determined by CCK-8 assay and flow cytometry, respectively. KEGG pathway enrichment analysis revealed the potential involvement of NF-κB, TNF, IL-17, and MAPK signaling pathways in the protective role of HSYA against sepsis-induced cardiomyopathy. HSYA attenuated LPS-induced pro-inflammatory cytokine expression, ROS generation, and cell apoptosis in AC16 cardiomyocytes. Mechanistically, HSYA upregulated GATA3 expression in LPS-stimulated AC16 cardiomyocytes. Moreover, downregulation of GATA3 enhanced pro-inflammatory cytokine expression, ROS generation, and cell apoptosis in HSYA-treated AC16 cardiomyocytes under LPS. Our in vitro findings suggest that GATA3 may serve as a potential mediator through which HSYA attenuates LPS‑induced cardiomyocyte injury by concurrently dampening inflammation, oxidative stress, and apoptosis.

Graphical abstract

This study integrated network pharmacology, machine learning algorithms, and WGCNA approaches to systematically investigate the mechanisms through which HSYA alleviates sepsis-induced myocardial damage. Using an LPS-induced AC16 cardiomyocyte cytotoxicity model, the cardioprotective effect of HSYA is validated and mechanistically linked to its regulatory action on the transcription factor GATA3.