| Objective To systematically characterize the main chemical components of total flavonoids in propolis (TFP), and to ex-plore the mechanism of action of TFP in the treatment of periodontitis.Methods Ultra-high performance liquid chromatography-quad-rupole time-of-flight tandem mass spectrometer (UPLC-Q-TOF/MS) was used to determine the chemical composition of TFP. Using Pub-chem and Swiss Target Prediction databases to search the potential targets of TFP. In addition, periodontitis-related targets werescreened through the online human Mendelian genetic database (OMIM) and GeneCards databases, and the intersection targets of TFPand periodontitis were obtained by Venny 2.1 platform. Cytoscape 3.7.2 software and STRING database were used to construct the"component-target" network diagram and intersection target interaction network diagram, GO function and KEGG pathway enrichmentanalysis of intersection targets were performed using the DAVID database. Autodock vina1.1.2 software was used to perform moleculardocking of the screened potential pharmacodynamic components of TFP with the core target. LPS-induced inflammatory model of hu-man periodontal ligament stem cells (hPDLSCs) was established in vitro, and the anti-inflammatory activity of TFP was verified. Re.sults Thirteen components were identified from TFP. A total of 90 intersections of TFP and periodontitis were obtained. Among them,serine/threonine-protein kinase 1 (AKT1), prostaglandin-endoperoxide synthase (PTGS2), Epidermal growth factor receptor (EGFR)were the core targets of TFP in the treatment of periodontitis. GO function analysis yielded 1 496 items, involving antibacterial, anti-in-flammatory, and regulation of excessive immune response, etc. The KEGG pathway was enriched with 134 entries, involving key signal-ing pathways such as PI3K-AKT signaling pathway, estrogen signaling pathway, relaxin pathway, etc. It showed the treatment of peri-odontitis through anti-inflammatory, promoting osteogenic differentiation, inhibiting lipogenic differentiation and reducing the level ofoxidative stress. The docking conformation suggested that 5, 7, 4'-trihydroxy-3, 6-dimethoxy flavone, genistein, luteolin-5-methyl ether,and xanthophyllin in TFP had more stable conformation and stronger affinity with the core target of PTGS2 and EGFR. It is suggestedthat it is a potential pharmacodynamic component of TFP in the treatment of periodontitis. In vitro experiments further confirmed that TFP could inhibit the levels of inflammatory factors (TNF-α, IL-6, IL-17) in the supernatant of hPDLSCs induced by LPS, indicating that TFP has good anti-inflammatory activity.Conclusion Various components of TFP plays a role in treating periodontitis through an-ti-inflammation, alleviating oxidative stress injury and promoting bone formation. |
