Molecular mechanism of gambogic acid in the treatment of periodontitis based on network pharmacology

CAO Xiao; FENG Yanqing; FU Zibo; CHEN Shan

doi:10.13276/j.issn.2097-1656.2024.10.008

Abstract：Objective To investigate the role and molecular mechanism of gambogic acid(GA)in the treatment of periodontitis by network pharmacology and molecular docking.Methods SwissTargetPredicton,SEA and SuperPred databases were used to obtain the related targets of GA.The related targets of periodontitis were retrieved from GeneCards,DisGeNET and CTD databases.Common targets for drugs and diseases were obtained by constructing Venn diagrams.The common targets were uploaded to the STRING online platform to construct"protein-protein interaction(PPI)network"of common targets,and the PPI network was visualized by Cytoscape 3.10.0 software to screen out key targets.Metascape database was used to conduct GO enrichment analysis and KEGG enrichment analysis for key targets,and the"KEGG pathway-key target"network diagram was constructed.The pdb files of the top 10 key targets were obtained from the PDB database.Molecular docking was performed using AutoDock4 software.Results A total of 185"drug-disease"common targets were obtained,including STAT3,CASP3,TLR4,HIF1-α,MTOR,STAT1,ITGB1,HDAC1,ITGB3,CASP8 and other core targets.A total of 141 signaling pathways were obtained by KEGG analysis,including neutrophil extracellular traps(NETs)formation,PI3K-AKT signaling pathway,Toll-like receptor signaling pathway and other signaling pathways.Molecular docking results showed that the binding energies of GA and corresponding key targets were ≤-5 kJ/mol,and drug-target binding ability was good.Conclusion GA can regulate immune response,inflammatory response,and tissue repair by participating in NETs formation,PI3K-AKT signaling pathway,Toll-like receptor signaling pathway and other signaling pathways,and play a therapeutic role in periodontitis.