Deciphering the Anticancer Mechanism of Naringenin and Berberine in Breast Cancer via Network Pharmacology and Molecular Docking

Abstract

Breast cancer is one of the most frequent malignancies affecting women globally, and it remains a leading source of cancer-related morbidity and death. Despite major advances in conventional therapy, obstacles such as drug resistance, systemic toxicity, and poor therapeutic selectivity continue to restrict their effectiveness. As a result, the discovery of safer multitarget therapeutic molecules from natural sources has sparked significant scientific interest. The current study used an integrated network pharmacology and molecular docking technique to examine the therapeutic potential of Naringenin and Berberine against breast cancer. SwissTargetPrediction and PubChem were used to identify potential phytochemical targets, while the GeneCards database was searched for breast cancer-associated genes. Protein-protein interaction analysis and pathway enrichment studies revealed critical targets such as SRC, PIK3CA, PIK3CB, PIK3CD, CYP3A4, IGF1R, ESR1, and KDR, which are implicated in oxidative stress control, cell proliferation, endocrine resistance, and cancer progression pathways. Molecular docking research revealed that Naringenin and Berberine had favorable binding interactions with SRC (7A3D) and PIK3CA (2V1Y). Berberine had docking scores of -6.6 kcal/mol against SRC and -6.2 kcal/mol against PIK3CA, whereas Naringenin had scores of -5.8 kcal/mol and -6.9 kcal/mol, respectively, compared to the reference medication Alpelisib. These data point to the multitarget anticancer potential of these phytochemicals against breast cancer.