Mechanism of Lajiao Fengshi Plaster in the Treatment of Arthralgia Based on Network Pharmacology
Objective To investigate the mechanism of Lajiao Fengshi Plaster in the treatment of arthralgia.Methods The active ingredients of medicinal herbs in the preparation were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and PubMed database,the targets were obtained by the SwissTargetPrediction database.The targets of arthralgia were predicted by the GeneCards,OMIM,and TTD databases,the common targets of active ingredients and disease were screened by the Venn online plotting software,and the common targets were imported into the STRING database for protein-protein interaction(PPI)analysis.The Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on common targets were performed based on the Metascape platform.The disease-active ingredient-common target-pathway network was constructed by the Cytoscape 3.9.0 software,the main active ingredients and core targets of Lajiao Fengshi Plaster in the treatment of arthralgia were screened by the Network Analyzer tool of this software,and the molecular docking was performed for verification.Results A total of 28 active ingredients,440 targets of active ingredients,1296 disease targets,105 common targets were obtained.The GO functional enrichment analysis showed 1374 biological functions,including 1184 biological processes,61 cellular components and 129 molecular functions.The KEGG pathway enrichment analysis showed 135 signaling pathways,mainly involving the calcium signaling pathway,cyclic adenosine monophosphate(cAMP)signaling pathway,and inflammatory mediator regulation of transient receptor potential(TRP)channels.Six main active ingredients[oleanolic acid,capsaicin,dihydrocapsaicin,capsiate,(-)-borneol,menthol]and 15 core targets(mTOR,ESR1,TP53,etc.)were obtained.The molecular docking showed that the TRPV1,ESR1,PTGS2,mTOR and MMP-9 target proteins had good binding activity with the above five main active ingredients except for capsiate,with the binding energy lower than-1.2 kcal/mol.Conclusion Lajiao Fengshi Plaster may regulate the expressions of mTOR,ESR1,PTGS2,TP53,TRPV1 and other genes through chemical components such as capsaicin,dihydrocapsaicin,oleanolic acid,(-)-borneol and menthol,and then regulate the calcium signaling pathway,cAMP signaling pathway to treat arthralgia.