Objective:To explore the mechanism of total flavonoids of Rhizoma Drynariae(TFRD)in the treatment of rheumatoid arthritis(RA)based on network pharmacology.Methods:The active components of TFRD were identified from the...Objective:To explore the mechanism of total flavonoids of Rhizoma Drynariae(TFRD)in the treatment of rheumatoid arthritis(RA)based on network pharmacology.Methods:The active components of TFRD were identified from the Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform(TCMSP).Relevant targets of TFRD were predicted by TCMSP,PubChem,SwissTargetPrediction and STITCH database,and standard target names were obtained from Uniprot database.RA-related targets were retrieved from GenBank,GeneCards,DisGeNet and OMIM databases.The intersection genes were imported into STRING database to construct a protein-protein interaction(PPI)network,in order to predict the core proteins.GO functional annotation analysis and KEGG pathway enrichment analysis were then performed.A“drug-component-target-disease”regulatory network was constructed using Cytoscape 3.8.2,and the active components of TFRD were molecularly docked with the predicted core targets.Results:A total of 10 active compounds,including luteolin,naringenin and kaempferol,were screened out from TCMSP database,and 210 relevant targets were predicted.A total of 2009 RA-related targets were screened out,and 123 targets of TFRD-RA intersection targets were obtained.STAT3,MAPK1,MAPK3,AKT1,MAPK8,IL-6,TNF,MAPK14,IL-4,IL-2,VEGFA,IL-1β and MAPK9 may be the key targets of TFRD in the treatment of RA.GO functional enrichment analysis suggested that transcriptional regulation and cytokine activity regulation may play an important role in TFRD in RA treatment.KEGG pathway enrichment analysis suggested that PI3K/AKT,IL-17,TNF-α,T cell receptor transduction and regulation of Th17 cell differentiation may play an important role in the treatment of RA by TFRD.The regulatory network suggested that luteolin and naringenin may be the key components of TFRD in the treatment of RA,which also had good affinity with the core targets AKT1,PI3K and STAT3 by molecular docking,which may further affect their phosphorylation by changing the molecular conformation.Conclusion:TFRD may inhibit the inflammatory response of RA by regulating inflammationrelated cytokines and related conduction pathways,and PI3K/AKT pathway may be an important pathway of TFRD in the treatment of RA.Luteolin is the key component of TFRD in the treatment of RA,and may play a vital role in the downstream pathway by inhibiting the conformation of related core proteins and thereby regulating phosphorylation.展开更多
基金National Key Clinical Specialty Capacity Building Project(No.2011-ZDZK-001)National Natural Science Foundation of China(No.81673941)。
文摘Objective:To explore the mechanism of total flavonoids of Rhizoma Drynariae(TFRD)in the treatment of rheumatoid arthritis(RA)based on network pharmacology.Methods:The active components of TFRD were identified from the Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform(TCMSP).Relevant targets of TFRD were predicted by TCMSP,PubChem,SwissTargetPrediction and STITCH database,and standard target names were obtained from Uniprot database.RA-related targets were retrieved from GenBank,GeneCards,DisGeNet and OMIM databases.The intersection genes were imported into STRING database to construct a protein-protein interaction(PPI)network,in order to predict the core proteins.GO functional annotation analysis and KEGG pathway enrichment analysis were then performed.A“drug-component-target-disease”regulatory network was constructed using Cytoscape 3.8.2,and the active components of TFRD were molecularly docked with the predicted core targets.Results:A total of 10 active compounds,including luteolin,naringenin and kaempferol,were screened out from TCMSP database,and 210 relevant targets were predicted.A total of 2009 RA-related targets were screened out,and 123 targets of TFRD-RA intersection targets were obtained.STAT3,MAPK1,MAPK3,AKT1,MAPK8,IL-6,TNF,MAPK14,IL-4,IL-2,VEGFA,IL-1β and MAPK9 may be the key targets of TFRD in the treatment of RA.GO functional enrichment analysis suggested that transcriptional regulation and cytokine activity regulation may play an important role in TFRD in RA treatment.KEGG pathway enrichment analysis suggested that PI3K/AKT,IL-17,TNF-α,T cell receptor transduction and regulation of Th17 cell differentiation may play an important role in the treatment of RA by TFRD.The regulatory network suggested that luteolin and naringenin may be the key components of TFRD in the treatment of RA,which also had good affinity with the core targets AKT1,PI3K and STAT3 by molecular docking,which may further affect their phosphorylation by changing the molecular conformation.Conclusion:TFRD may inhibit the inflammatory response of RA by regulating inflammationrelated cytokines and related conduction pathways,and PI3K/AKT pathway may be an important pathway of TFRD in the treatment of RA.Luteolin is the key component of TFRD in the treatment of RA,and may play a vital role in the downstream pathway by inhibiting the conformation of related core proteins and thereby regulating phosphorylation.
