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The objective of this research is to study the mechanism of Xiaoyao pill in the treatment of breast hyperplasia by using network pharmacological formula. The active components of Xiaoyao pill were collected and screened in the Pharmacological Database and Analysis Platform of Chinese Medicine (TCMSP), and the included compounds were predicted by TCMSP database. GeneCards database, NCBI gene database and OMIM database were used for screening of breast hyperplasia disease targets. The drug targets and disease targets were selected to make a Venn diagram, and the common targets were used to make a PPI network diagram in the String database. Topological analysis and MCODE cluster analysis were used to screen the core targets and core genes. The key active ingredients were screened in Cytoscape 3.8.0 software. The STRING database was used for GO analysis and KEGG analysis for key targets, and the relevant results were imported into Cytoscape 3.8.0 to draw the component-disease-path path-target network diagram. The active components and targets of Xiaoyao Pills were screened, among which 169 targets were related to breast hyperplasia. Stat3, Akt1, MAPK1, Jun, MAPK3 and other 20 targets were the key targets of this drug in the treatment of breast hyperplasia, and HTR2A, IL2, TOP2A, PCNA, MMP1 were the core genes of this drug in the treatment of breast hyperplasia. Quercetin, Kaempferol, luteolin, naringenin, licochalcone A, 7-methoxy-2-methyl isoflavone, formononetin, and acacetin may be the main active components of Xiaoyao Pill in the treatment of breast hypertrophy. A total of 2328 biological processes were enriched by GO enrichment analysis, with 160 molecular function correlations and 47 cell composition correlations. Enrichment analysis showed that it was associated with 166 pathways, including AGE-RAGE signaling pathway, TNF signaling pathway, IL-17 signaling pathway, Th17 cell differentiation, fluid shear stress and atherosclerosis signaling pathway. The molecular docking verification results showed that the key active ingredients and core targets were well docking. From the perspective of network pharmacology, the potential mechanism and pharmacological substance basis of Xiaoyao pill in the treatment of breast hyperplasia are preliminarily revealed, providing ideas for the follow-up research on Xiaoyao pill in the treatment of gynecological diseases.

RuXian-I has traditionally been used as a remedy for breast hyperplasia in the Inner Mongolia Autonomous Region of China. As a first step toward the investigation of biomarkers associated with RuXian-I treatment, a proteome-wide analysis of rat breast tissue was conducted. First, rat breast hyperplasia was induced by injection of estradiol and progesterone. After treatment with RuXian-I, there is a marked decrease in the hyperplasia, as can be shown by decreases in the nipple diameter and the pathological changes in breast. Subsequently, we used an approach that integrates size-based 2D-DIGE, MALDI-TOF/TOF-MS, and bioinformatics to analyze data from the control group, the model group and the RuXian-I treatment group. Using this approach, seventeen affected proteins were identified. Among these, 15 (including annexin A1, annexin A2, superoxide dismutase [Mn], peroxiredoxin-1, translationally-controlled tumor protein and a B-crystallin) were significantly up-regulated in the model group and down-regulated upon treatment with RuXian-I, and two (Tpil protein and myosin-4) have the opposite change trend. The expression of annexin A1 was confirmed using immunohistochemistry. The expression of superoxide dismutase (SOD) activity was confirmed biochemically. These results indicated that RuXian-I treats rat breast hyperplasia through regulation of cell cycle, immune system, metabolic, signal transduction, etc. The differential expressions of these proteins (annexin A1, superoxide dismutase [Mn], alpha B-crystallins and translationally controlled tumor protein, among others) were associated with occurrence and metastasis of breast cancer. These findings might provide not only far-reaching valuable insights into the mechanism of RuXian-I action, but also leads for prognosis and diagnosis of breast hyperplasia and breast cancer.