Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Angelicae Pubescentis Radix in the treatment of rheumatoid arthritis

Abstract

Purpose:To explore the potential target proteins underlying the effect of Angelicae Pubescentis Radix(APR) on rheumatoid arthritis (RA) using a network pharmacology and molecular docking approach .Methods:First, the active components and target proteins of APR and RA related disease targets were obtained from the TCMSP, Gene Card,OMIM,DisGeNET and STRING databases. Then the active ingredient target in the RA network diagram was drawn using Cytoscape 3.7.1 software. Protein-protein interaction analysis, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analyses were carried out using the STRING and David databases. The crystal structures of RA related targets were retrieved from the RCSB PDB database. Finally, the potential active compounds and their related targets were validated using molecular docking technology.Results: Five active components of Angelicae Pubescentis Radix(APR) were screened out, including ammidin, isoimperatorin, beta-sitosterol, O-acetylcolumbianetin and angelicone and 80 key targets including MAPK8,EGFR,PTGS2,CASPASE3,MTOR,SRC,KDR,MAPK1,NOS3 and MAPK14, etc were obtained. GO enrichment analysis showed that 222 biological processes, 34 cell components and 72 molecular functions were identified; KEGG analysis showed that the targets of APR in the treatment of RA were significantly enriched in pathways in cancer, the PI3K−Akt signaling pathway, Proteoglycans in cancer, osteoclast differentiation, neuroactive ligand−receptor interaction, tuberculosis,TNF signaling pathway, serotonergic synapse, Rap1 signaling pathway,cAMP signaling pathway. The results of molecular docking showed that ammidin, isoimperatorin, beta-sitosterol, O-acetylcolumbianetin and angelicone had strong affinity for PTGS2, EGFR and MAPK8.Conclusion: APR treats RA through the characteristics of multi-component, multi-target and multi-pathway regulation.