Abstract: Objective To optimize the matrix formulation, prepare a breast nodule pain-alleviating gel plaster (BNPGP), and explore its potential mechanism for the treatment of breast hyperplasia via network pharmacology and molecular docking technology. Methods With the “initial adhesion, cohesive strength and comprehensive sensory organs” as evaluation indexes, the matrix prescription of BNPGP was optimized by orthogonal design, and its formability was investigated. All the targets of the active components and breast hyperplasia were retrieved from such databases as TCMSP, Targetnet, Genecards, OMIM with network pharmacology. The Venny tool was used to screen the intersection targets. The drug-active component-target network was established with Cytoscape software, and protein-protein interaction (PPI) analysis was performed on the intersection targets using String database. KEGG and GO pathway enrichment analysis was performed on the intersection targets using Metascape database. Finally, molecular docking verification was carried out with AutoDockTool and PyMoL software. Results Orthogonal test optimized the matrix prescription of BNPGP as follows: carbomer 20 mL at a swelling ratio of 1 : 40, 20 mL drug solution of 3 g·mL^-1, 7 mL glycerol, and 1.5 mL methyl p-hydroxybenzoate of 0.1 g·mL^-1. Based on network pharmacology, 45 effective components of BNPGP and 49 intersection targets between active components and breast hyperplasia were screened, including ESR1 and EGFR, which were involved in regulating Pathways in cancer, Proteoglycans in cancer, and Chemical carcinogenesis-receptor activation in the treatment of breast hyperplasia. Molecular docking showed that the main active components-luteolin and kaempferol-had strong binding ability to core targets EGFR and AR. Conclusion BNPGP prepared according to this optimal process has uniform appearance, good adhesion and formability, which can provide reference for the development of processes. BNPGP may play a role in the treatment of breast hyperplasia by regulating hormone levels and cell cycle, inhibiting angiogenesis by regulating key targets such as EGFR, AR, STAT3, and intervening in EGFR/PI3K/Akt, JAK/STAT signaling pathways.

Key words: breast nodule pain-alleviating gel plaster, breast hyperplasia, matrix prescription, orthogonal design, network pharmacology, molecular docking, mechanism