The aim of this study was to investigate the target and and molecular mechanism of action of berberine (BBR) against Staphylococcus aureus (S. aureus) infection. This experiment first screened common targets of BBR and S. aureus infection based on network pharmacology, constructed a PPI network, and performed GO/KEGG enrichment analysis. The binding activity of BBR and core targets was verified through molecular docking. Finally, a mouse infection model was constructed to observe pathological changes in the liver and spleen using tissue sections, and qPCR was used to validate the expression levels of the selected target genes’ mRNA. The results showed that: 1) A total of 109 common target points between BBR and S. aureus were successfully screened. Through network pharmacology analysis, 251 GO entries and 62 KEGG entries were ultimately obtained, mainly enriched in the MAPK, PI3K-Akt, and GnRH pathways. Molecular docking results showed that BBR had good binding energy with six proteins, including Casp3 and Jun, among the intersection targets. 2) BBR can alleviate liver tissue lesions caused by S. aureus infection; at the same time, it can significantly upregulate the expression of Casp3 mRNA and Jun mRNA in mouse liver. In summary, this study preliminarily identified Casp3 and Jun as potential targets for BBR’s anti-S. aureus activity. Additionally, a mouse model of S. aureus infection was established to further confirm that BBR can alleviate liver and spleen lesions by regulating the mRNA expression of Casp3 and Jun. The findings of this study provide a theoretical basis for the development and application of BBR as an anti-S. aureus infection drug.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |