The Multi-Target Action Mechanism for the Anti-Periodontitis Effect of Astragali radix Based on Bioinformatics...

Background:Astragali radix is a traditional Chinese medicine with potential therapeutic effects on periodontitis; however, its underlying mechanisms require further investigation. Methods: We employed network pharmacology, molecular docking, molecular dynamics simulations, and in vitro experiments to explore the potential actions and mechanisms of Astragali radix in treating periodontitis. Results: A total of 17 compounds (including the most prevalent one, Kaempferol) from Astragali radix and 464 corresponding targets were identified, from which five major active ingredients were selected based on the drug-active ingredient and periodontitis gene network. Protein-protein interaction (PPI) network analysis identified the top ten core potential targets, seven of which possess suitable crystal structures for molecular docking. These include interleukin-6 (IL6), tumor necrosis factor (TNF), AKT serine/threonine kinase 1 (AKT1), interleukin-1β (IL1β), prostaglandin G/H synthase-2 (PTGS2), matrix metalloproteinase-9 (MMP9), and caspase-3 (CASP3). Additionally, 58 Gene Ontology (GO) terms and 146 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified. The five major active ingredients and seven core targets mentioned above were subjected to molecular docking analysis using Discovery Studio 2019 software. Molecular dynamic simulations confirmed a stable interaction between the CASP3 and the Kaempferol ligand system. In vitro experiments indicated that Kaempferol significantly inhibited lipopolysaccharide (LPS)-induced apoptosis in human periodontal ligament stem cells and reduced the expression levels of IL6, CASP3 and MMP9. Conclusions: This study systematically elucidates that the primary active ingredients derived from Astragali radix exert their pharmacological effects (including anti-inflammation and anti-apoptosis) primarily by interacting with multiple targets. These findings establish a promising foundation for the targeted application of Astragali radix in the treatment of periodontitis.