Can Epimedii herba treat periodontitis? A prediction based on network pharmacology, molecular docking, and dynamics analysis

Epimedii herba (EH) showed numerous activities and has the potential to treat periodontitis. However, the pharmacological mechanism has not been exhaustively elucidated. This study predicted the specific targets and mechanisms of EH to prevent and treat periodontitis. A traditional Chinese medicine system pharmacology database and analysis platform was used to screen key compounds of EH and their corresponding targets. Therapeutic Target Database and Comparative Toxicogenomics Database were used to identify targets related to periodontitis. Intersection targets were observed using a Venn diagram. The key components and corresponding protein targets of EH were searched. The intersection targets were obtained and then they were imported into the STRING database to construct a PPI network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Molecular docking between the screened chemical components of EH and key targets was performed using Discovery Studio 2019. The binding stability between components and target proteins was confirmed using molecular dynamics simulations. The binding stability between components and target proteins was confirmed using molecular dynamics simulations. Through network pharmacological analysis, 23 active compounds of EH were identified, including kaempferol and icariin. Based on GeneCards, GEO, and other databases, 3291 periodontitis-related genes were obtained. Venn diagram analysis revealed 137 intersection targets of EH and periodontitis, and Protein kinase B (AKT1) and Tumor necrosis factor (TNF) were identified as the key targets of EH for periodontitis treatment. GO and KEGG analyses revealed that the primary pathways mediating the therapeutic effects of EH were related to cancer, lipid, and atherosclerosis. Molecular docking showed that 8-isopentenyl-kaempferol had the best binding ability to ESR1, which was confirmed by dynamics simulations. This study demonstrated that EH can be used for periodontitis treatment, and the corresponding targets and potential mechanisms were investigated based on network pharmacology, molecular docking, and dynamics simulation analysis. Notably, 8-isopentenyl-kaempferol exhibited good binding affinity and stability to ESR1, which may partially explain the molecular mechanisms of EH for treating periodontitis. Hence, EH can be a novel choice for the clinical treatment of periodontitis in the future.