Exploration of Liuwei Dihuang Pill on periodontitis based on network pharmacology and molecular docking

This study explores the mechanism of Liuwei Dihuang Pill (LWDHP) in the treatment of periodontitis using network pharmacology and molecular docking. The active ingredients and targets of LWDHP were obtained from databases such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Databases such as GeneCards, OMIM, and DisGeNET were used to obtain the relevant targets related to periodontitis. The intersection of these 2 groups of targets was taken and imported into STRING to facilitate the acquisition of protein-protein interaction data, which was then imported into Cytoscape 3.10.2 to perform topological analysis to obtain the core targets. Gene ontology and Kyoto encyclopedia of genes and genomes bioinformatics enrichment analyses of the intersecting targets were performed using the DAVID database. Validation of molecular docking matching between key active ingredients with top 5 degree values and key targets with top 5 degree values in the treatment of periodontitis with LWDHP using AutoDockTools-1.5.6. A total of 69 active ingredients were discerned in LWDHP, implicating 198 periodontitis-relevant targets. Thirty-four core targets were obtained by protein-protein interaction network topology analysis, among which the key targets with the top 5 values of degree were tumor necrosis factor (TNF), serine/threonine protein kinase AKT1, sarcoma, epidermal growth factor receptor, and matrix metallopeptidase 9. Topological analysis revealed that the key active ingredients with the top 5 values of degree in LWDHP were Polyporenic acid C, Alisol B, Hydroxygenkwanin, Denudatin B, and Kadsurenone. The molecular docking results demonstrated that the binding energies of the above molecules with targets were all <-5 kcal/mol, indicating a good binding ability between these molecules. The gene ontology enrichment results indicated that the treatment of periodontitis by LWDHP was mainly related to the inflammatory response, positive regulation of phosphatidylinositol-3-kinase-Akt (PI3K-Akt) signal transduction and other processes. Analysis of the Kyoto encyclopedia of genes and genomes signaling pathway showed that the TNF signaling pathway, the PI3K-Akt signaling pathway, and so on are important signaling pathways. In conclusion, the mechanism of action of LWDHP in the treatment of periodontitis is characterized by multicomponents, multi-targets, and multi-pathways. TNF, serine/threonine protein kinase AKT1, sarcoma, epidermal growth factor receptor, and matrix metallopeptidase 9 are the key targets and the TNF signaling pathway, the PI3K-Akt signaling pathway are the key pathways. LWDHP treats periodontitis through actions such as anti-inflammatory and regulation of the balance between osteogenesis and bone destruction.