Pharmacological targets and mechanism of baicalein in treating breast cancer: a study based on network pharmacology, molecular docking, and bioinformatics analysis

Breast cancer (BC) is the leading malignancy affecting women globally, underscoring the urgent need for novel therapeutic strategies. Baicalein, a bioactive flavonoid derived from Scutellaria baicalensis, has shown promising antitumor properties in preclinical studies, yet its precise molecular targets and mechanisms in BC remain inadequately characterized. This study integrates network pharmacology, molecular docking, transcriptomic profiling, and microbiomics to systematically elucidate the therapeutic potential and clinical relevance of baicalein in BC. We identified 37 baicalein-related targets (BRTs) through network pharmacology, narrowing these to four hub targets (HSP90AA1, CCNB1, NCOA2, TDRD7) via differential expression analysis and prognostic validation. Molecular docking and molecular dynamics simulations revealed strong binding affinities (≤ − 5.0 kJ/mol) between baicalein and these targets. A baicalein-related prognostic signature (BRPS) was constructed via multivariate Cox regression, stratifying patients into high- and low-risk groups. The high-risk group exhibited significantly worse overall survival (P < 0.001), elevated immunosuppression (e.g., M2 macrophage enrichment), and reduced chemotherapy sensitivity. Functional enrichment analyses revealed divergent pathways between the risk groups: the high-risk group was enriched in extracellular matrix remodeling and PI3K-AKT signaling, whereas the low-risk group presented activation of cytokine interactions and B-cell receptor pathways. Notably, intratumor microbiome (IM) profiling revealed 125 differentially abundant microbial taxa, with Succinimonas and Acidibacillus correlating positively with high-risk BRT expression. Immune landscape analysis further demonstrated that low-risk patients presented increased CD8 + T/NK cell infiltration, elevated immune checkpoint expression (PD-1/CTLA-4), and greater predicted responsiveness to immunotherapy. Drug sensitivity analysis linked the BRPS to chemotherapeutic efficacy, with high-risk patients showing susceptibility to methotrexate and docetaxel. This study accurately identified the four core targets of baicalein in treating BC. The BRPS could predict patient prognosis and guide personalized therapeutic strategies, positioning baicalein as a potential adjunct to conventional therapies. These findings bridge traditional pharmacology with systems biology, offering actionable insights for precision oncology in BC management.