| Sumario: | Background & Objective: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. In this regard, Chinese herbal medicines, including Brucea javanica (BJ), Centipeda minima (CM), and Lithospermum erythrorhizon (LE) have exhibited anti-TNBC effects in both cell culture and mouse models, yet, a comprehensive understanding of their mechanisms of action remains elusive. Our study employed a network pharmacology approach and molecular docking to elucidate the potential pivotal pathways, drug targets, and most efficacious active constituents of these medications in the treatment of TNBC. Materials & Methods: The active compounds and their corresponding target genes were obtained from the TCMSP database. The potential target genes associated with TNBC were also collected from DisGENet. The PPI network was established in the STRING database. The gene ontology and pathway enrichment analyses were conducted using the DAVID platform. AutoDock Vina was used for molecular docking. Results: The AGE-RAGE signaling pathway in diabetic complications was identified as the top key signaling pathway. The therapeutic effects of CM, BJ, and LE involved a variety of biological processes, primarily the positive regulation of gene expression and cell proliferation, as well as the negative regulation of the apoptotic process. It has previously been observed that AGEs promote and increase the proliferation, invasion, and migration of breast cancer cell lines. The top target proteins included AKT1, TP53, CASP3, and VEGFA. The top active ingredients identified were stigmasterol, beta-sitosterol, nobiletin, and quercetin for CM, acetylshikonin for LE, and betasitosterol for BJ, as determined by the disease-drug-compound-target network analysis. The docking results showed good binding affinities ranging from -9 to -6 kcal/mol for all the docked complexes. Conclusion: CM, BJ, and LE can treat TNBC through a multi-target and multipathway mechanism, regulating key cancer signaling pathways and the apoptotic process. This network pharmacology approach provided a new basis for subsequent experimental validation and further exploration of the role of these herbal drugs in treating TNBC.
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