To investigate the potential targets and molecular mechanisms of berberine in the treatment of cervical cancer via an integrated network pharmacology and molecular docking approach, providing a theoretical basis for its clinical application. Berberine-related targets were retrieved from TCMSP, PharmMapper, and SwissTargetPrediction databases, applying “Norm Fit” > 0.5 in PharmMapper. Cervical cancer–related genes were obtained from OMIM and GeneCards databases, with the top 1000 genes ranked by relevance from GeneCards. Common targets were identified using the Venny platform, and protein–protein interaction (PPI) networks were constructed via the STRING database and analyzed using Cytoscape 3.9.1 with the CytoNCA plug-in. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed via the DAVID database. Molecular docking between berberine and key proteins (HSP90AA1, MAPK14) was conducted using AutoDock Vina, with interactions visualized by PyMOL and LigPlot+. A total of 28 common targets for berberine and cervical cancer were identified, from which 12 core targets (SRC, HSP90AA1, ESR1, PTGS2, MAPK14, CDK2, etc.) were screened by topological analysis. GO enrichment revealed involvement in inflammatory response regulation, cytokine activity, and cell cycle progression. KEGG pathway analysis indicated significant enrichment in progesterone-mediated oocyte maturation, VEGF signaling, cellular senescence, and cell cycle pathways. Molecular docking demonstrated favorable binding energies between berberine and HSP90AA1 (−6.5 kcal/mol) as well as MAPK14 (−8.2 kcal/mol), stabilized by hydrogen bonds (HIS450 in HSP90AA1; SER154 in MAPK14) and hydrophobic interactions. Berberine may exert therapeutic effects on cervical cancer through multi-target and multi-pathway regulation, particularly by modulating HSP90AA1, MAPK14, and SRC, and affecting angiogenesis, hormone signaling, and cell cycle control. These findings provide a pharmacological basis for further preclinical and clinical investigation of berberine as a potential adjunctive therapy for cervical cancer.
Tan et al. (Sun,) studied this question.