en Medical Biology Medical Biology مقاله پژوهشی Original Research Article <p style="text-align: justify;"><span style="font-size:16px;"><span style="font-family:Times New Roman;"><b><span style="background:#2d7f8f"><span style="color:white">Background & Objective:</span></span><b> </b></b><span style="color:black">Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. In this regard, Chinese herbal medicines, including <i>Brucea javanica (BJ)</i>, <i>Centipeda minima (CM)</i>, and <i>Lithospermum erythrorhizon (LE)</i> 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.</span><br> <b><span style="background:#2d7f8f"><span style="color:white"><span style="letter-spacing:-.1pt">&nbsp;Materials & Methods:</span></span></span></b> &nbsp;<span style="color:black"><span style="letter-spacing:-.1pt">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.</span></span><br> <b><span lang="EN-IN"><span style="background:#2d7f8f"><span style="color:white">Results: </span></span></span>&nbsp;</b><span style="color:black"><span style="letter-spacing:-.1pt">The AGE-RAGE signaling pathway in diabetic complications was identified as the top key signaling pathway. The therapeutic effects of <i>CM</i>, <i>BJ</i>, and <i>LE</i> 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 <i>CM</i>, acetylshikonin for <i>LE</i>, and beta-sitosterol for <i>BJ</i>, 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.</span></span><br> <b><span style="background:#2d7f8f"><span style="color:white">Conclusion: </span></span>&nbsp;</b><i><span style="color:black">CM</span></i><span style="color:black">, <i>BJ</i>, and <i>LE</i> can treat TNBC through a multi-target and multi-pathway 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.</span></span></span></p> Network Pharmacology, Docking, Brucea javanica, Centipeda minima, Lithospermum erythrorhizon, Triple Negative Breast Neoplasms 274 290 http://journal.zums.ac.ir/browse.php?a_code=A-10-7183-1&slc_lang=en&sid=1 Reyhaneh Farrokhi Yekta rfyekta83@gmail.com 5200319475328460085804 5200319475328460085804 No Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran Nasrin Amiri-Dashatan nasrinamiri91@gmail.com 5200319475328460085805 5200319475328460085805 No Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran Afsaneh Arefi Oskouie dr.afsaneh.arefi@gmail.com 5200319475328460085806 5200319475328460085806 Yes Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran