Network Pharmacology and Molecular Docking: Exploring the Mechanism of Peppermint in Mastitis Prevention and Treatment in Dairy Cows.

Abstract

In order to elucidate the active ingredients, potential targets, and mechanisms of action of peppermint in treating bovine mastitis, this study utilized network pharmacology analysis and molecular docking to conduct an exploratory, prospective investigation. Using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, all compounds and targets of peppermint were retrieved. After removing duplicates, a total of 133 compounds and 272 targets were obtained. Targets were then standardized to gene names using the UniProt database to construct a drug-component-target network. A total of 183 disease targets related to bovine mastitis were retrieved from the GeneCards database. We obtained 28 cross targets of peppermint targets and bovine mastitis targets, and constructed a protein-protein interaction (PPI) network using the STRING database. A visual network was built using Cytoscape 3.10.0 software, and seven core targets were analyzed and obtained. GO and KEGG pathway enrichment analysis was performed using the Metascape database. Molecular docking was conducted using AutoDockTools-1.5.6 software on some small-molecule compounds and the seven targets to evaluate the stability of binding between peppermint and core targets. Apigenin, luteolin, and ursolic acid are the three main components in peppermint. Core targets (TNF, IL-6, STAT-3, IL-1β, FGF-2, IFNG, and ESR-1) were selected based on the PPI network. The enrichment analysis suggested that the major signaling pathways in network pharmacology may include AGEs-RAGE, IL-17, NF-κB, TLRs, HIF-1, TGF-β, PI3K-Akt, and MAPK. The molecular docking results showed that one of the main components of mint, ursolic acid, exhibited good binding activity with all core targets of bovine mastitis. Other constituents also produced favorable binding with some core targets. This study elucidates the mechanisms of mint in treating bovine mastitis, providing data to support the potential development of new therapies for bovine mastitis using mint and its constituents.