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Baihe Dihuang-Danshen Decoction in Myocardial Ischemia-reperfusion Injury: Network Pharmacology and Experimental
Ling Huang1, Lei Zhang2, Qiang Xu2
1Third-Grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, College of Medicine and Health Sciences, China Three Gorges University, Yichang, China.
Introduction:
Myocardial ischemia-reperfusion injury (MIRI) significantly impairs the prognosis of cardiac surgery. Baihe Dihuang-Danshen Decoction (BDDSD), a Chinese herbal formula, has shown efficacy against MIRI. This study combined network pharmacology and experimental validation to identify the core compounds and mechanisms of BDDSD.
Methods:
The compounds of BDDSD were identified through the TCMSP and BATMAN databases. Potential targets were determined by intersecting MIRI-related differential genes with BDDSD compound targets. A protein-protein interaction (PPI) network was constructed using the STING platform. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed using the Metascape database. A TF-gene network and a gene-miRNA network were generated using the NetworkAnalyst platform. Immune infiltration analysis was conducted using CIBERSORT. In vivo verification was then performed, followed by molecular docking analysis.
Results:
The analysis revealed that BDDSD's cardioprotective effects against MIRI are mediated by six core compounds (e.g., Tanshinone IIA, Cryptotanshinone), which synergistically modulate key targets (e.g., IL6, HMOX1). In rats, BDDSD treatment reduced myocardial structural damage. Notably, MIRI-induced upregulation of mRNA expression of all six core targets was significantly suppressed by BDDSD. Molecular docking confirmed strong compound-target binding, further validating BDDSD's efficacy in MIRI.
Discussion:
Our study elucidated the mechanisms underlying BDDSD's action in MIRI treatment. However, given that BDDSD operates through multiple components and targets, the complex interactions between these compounds require further investigation. Additionally, comprehensive toxicity assessments in preclinical models are needed to establish its safety profile.
Conclusion:
This study provides a comprehensive overview of the core compounds, potential targets, and mechanisms of BDDSD in MIRI treatment, offering a foundation for further research into the pathological mechanisms of MIRI and the therapeutic potential of traditional Chinese herbal decoctions.
