Discussion on the mechanism of action of Dabuyin Pills in treating IgA nephropathy based on network pharmacology
Objective To explore the mechanism of action of Dabuyin Pills in treating IgA nephropathy(IgAN)based on network pharmacology,and to verify it with animal experiments.Methods Taking"Radix Rehmanniae Preparata"and"Rhizoma Anemarrhenae"as keywords,respectively,the active components and corresponding target proteins were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(BATMAN-TCM),and"IgAN"was searched in GeneCards database to screen out the intersection targets of Dabuyin Pills and IgAN.Protein-protein interaction(PPI)network was constructed by using STRING database.Gene ontology(GO)analysis and enrichment analysis of Kyoto encyclopedia of genes and genomes(KEGG)were carried out in Bioinformatics.The network diagram of"drug-component-target"was constructed by Cytoscape.The molecular docking of protein kinase B1(Akt1),mitogen-activated protein kinase 1(MAPK1)and tumor suppressor protein(TP53)was carried out by using AutoDockTools.The model of IgAN was established,and then Dabuyin Pills was given for intervention.The kidney,urine and serum of mice in each group were collected,and the serum blood urea nitrogen(BUN)and 24-hour urine protein quantification(24h-UTP)were measured,and the slices were prepared and the IgA deposition intensity of slices was observed.Results There were 180 intersection targets between Dabuyin Pills and IgAN.GO enrichment analysis involved 923 items of biological process,81 items of cell components and 157 items of molecular function;KEGG analysis screened out the first 20 signal pathways,including interleukin-17(IL-17)pathway,phosphatidyl inositol 3-kinase/protein kinase B(PI3K/Akt)pathway,etc.The results of molecular docking showed that quercetin in Dabuyin Pills had good binding ability with key targets such as Akt1 and MAPK1.Compared with the model group,the 24h-UTP and serum BUN were improved(P<0.01),and the IgA deposition in the mesangial area of kidney tissue was significantly reduced in IgAN mice after treatment of Dabuyin Pills.Conclusion Dabuyin Pills has a certain therapeutic effect on IgAN,and its mechanism of action may be related to IL-17 and PI3K/Akt pathways.
Dabuyin PillsIgA nephropathyNetwork pharmacologyMolecular dockingMechanism of action