Investigating the Mechanism of Astragalus in the Treatment of Periodontitis through Bioinformatics Analysis

Abstract

Abstract Background: Periodontitis, a common oral inflammatory disease which may cause premature tooth loss, was proved can be treated by Astragalus, but the detailed mechanisms are still not clear. We validated and discussed the molecular mechanism by using bioinformatics methods and cell experimental, and in order to clarify the mechanism of Astragalus during the treatment of periodontitis. Methods:The active ingredients of Astragalus and their corresponding targets were obtained using the TCMSP database, and the periodontitis-related targets were obtained from DrugBank database, GeneCards database etc., then GO and KEGG analyses were performed based on Metascape database. Astragalus active ingredients and related targets network, Astragalus-active components-targets of periodontitis network, and Astragalus-active components- periodontitis targets-signaling pathways network were constructed by using Cytoscape3.9.0 software. Thereafter, Molecular docking and molecular dynamic simulation were analyzed in Discovery Studio 2019 software and Gromacs 2021.2 software package respectively, in order to evaluate the stability of combination between active components and core targets. Results:17 compounds of Astragalus and 464 corresponding targets were obtained and 5 major active ingredients were screened from the drug active ingredients- periodontitis gene network. PPI network analysis revealed the top 10 core potential targets, 7 of them have suitable crystal structure and can be used for molecular docking, including interleukin-6 (IL6), tumor necrosis factor (TNF), RAC-α serine/threonine protein kinase (AKT1), interleukin-1β(IL1β), prostaglandin G/H synthase-2 (PTGS2), matrix metalloproteinase-9 (MMP9), and Caspase3 (CASP3). In addition, 58 GO terms and 146 KEGG pathways were identified. 5 major active ingredients and 7 core targets which mentioned above were docked molecularly in Discovery Studio 2019 software. Molecular dynamics simulations confirmed that there has a stable combination between Caspase3 and Kaempferol ligand system. Conclusions: Based on the results of network pharmacology, molecular docking and molecular dynamics, it can be concluded that Astragalus has multiple active ingredients, and targets different signaling pathways to regulate the inflammatory response, immune response and oxidative stress in order to play a beneficial role in the treatment of periodontitis, especially Kaempferol can combine with Caspase3 stably to inhibit the cell apoptosis, our data provide solid evidences and enlightenment for the clinical application of Astragalus in future.