Network Pharmacology and Experimental Validation of Effective Components of Panacis Quinquefolii Radix and Carthamus tinctorius in Treatment of Early Diabetic Nephropathy
Objective:To investigate the mechanism of effective components of Panacis Quinquefolii Radix and Carthamus tinctori-us in the treatment of early diabetic nephropathy(DN)through network pharmacology,molecular docking,and cell experiments.Methods:The interference targets of the active components of Panacis Quinquefolii Radix and Carthamus tinctorius were obtained by using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and then mapped with the early DN gene targets in GeneCards,TTD,and other databases to form intersection targets.The protein-protein interaction(PPI)network was constructed by the STRING database,and the core targets were selected by Cytoscape 3.8.2 software.Gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis were performed by the DA-VID database,and then the network diagram of"effective component-key target-pathway-disease"was presented by Cytoscape 3.8.2 software.Molecular docking was carried out using Autodock Tools.MTT assay was used to detect the activity of effective components on LPS-induced human mesangial cells(HMCs),and ELISA was used to detect the effect of effective components on inflammatory factors.Results:There were 24 active components and 207 corresponding drug targets of early DN treated with Pana-cis Quinquefolii Radix and Carthamus tinctorius,of which 72 were associated with early DN.Network topological parameter analysis yielded 15 key targets such as TNF,IL-6,and IL-1 β,and KEGG pathway analysis selected 20 signaling pathways such as AGE-RAGE,TNF,HIF-1,IL-17,and NF-κB;molecular docking indicated that IL-6 stably bound to quercetin,luteolin,baicalein,and ginsenoside rh2.Cell experiments found that quercetin,luteolin,and baicalein could significantly inhibit the expression of IL-6,TNF-α,and IL-1 β.Conclusion:The effective components of Panacis Quinquefolii Radix and Carthamus tinctorius can effectively inhibit the inflammation of early DN and protect the kidney.These results provide a basis for subsequent in-depth study.