Study On The Mechanism Of Action Of Kunxian Capsule In The Treatment Of Membranous Nephropathy Based On Bioinformatics

Objective:Membranous nephropathy(MN)is an autoimmune disease and the main pathological type of nephrotic syndrome in adults.Traditional Chinese medicine is a treasure in traditional Chinese medicine.The treatment of membranous nephropathy shows the advantages of multiple pathways,multiple targets,and high safety.Its mechanism of action is the focus of current research.Among them,Kunxian Capsule,as the result of the national key project,is composed of Kunming Mountain Begonia,Epimedium,Dodder and Lycium Barbarum.At present,there have been clinical trials of Kunxian Capsules in the treatment of membranous nephropathy,but its active ingredients and mechanism of action need to be further studied.Methods:Through literature research and HERB,BATMAN-TCM,and TCMSP databases,the active compounds in Kunxian Capsules were obtained,and compound targets were obtained,and KEGG pathway enrichment analysis was performed using metascape database;obtained from CTD,Gene Card,and OMIM databases The prediction target of membranous nephropathy is the intersection target with Kunxian Capsule.The core genes were obtained using Cytohubba,and the pathway analysis results with significant differences(P<0.05)were selected by KEGG enrichment again.Based on literature and pathway enrichment results,it was determined that PI3K-Akt signaling pathway,JAK-STAT signaling pathway,TGF-β signaling pathway,and chemokine signaling pathway were collected by Pub Chem Bio Assay to collect key target active ligand compound data sets.Based on the RDKit module,the Tanimoto coefficient was used to calculate the compound similarity between the active compound of Kunxian Capsule and the active ligand compound of the target,and the compound pair with a similarity of more than 0.7 was initially selected to obtain the potential active compound.The three-dimensional structures of the target proteins and potential active compounds were obtained from the PDB and Pub Chem databases,respectively,and the AKT1,STAT1/3,CXCR2/4,SMAD3,MAPK1/3/8/14 targets and the active ingredients of Kunxian Capsule were analyzed by Auto Dock Vina software.Molecular docking simulation experiments were performed..Results:Virtual drug screening is an important method to explain the pharmacological mechanism.In this paper,the active compounds of Kunxian Capsules were collected through the database,and a total of 152 active ingredients were obtained by screening the drug-like index and oral bioavailability index.According to the results of enrichment analysis and literature search,the key targets of Kunxian Capsule in the treatment of membranous nephropathy were obtained through PI3K-AKT signaling pathway,JAK-STAT signaling pathway,chemokine signaling pathway and TGF-β signaling pathway.Obtained 19,980 cases of high-throughput screening of active ligand compound data.The 152 known active ingredients and active ligand compounds in Kunxian Capsules were calculated.Finally,a total of 562 pairs of compounds with a similarity of more than 0.7 were obtained.The top 10 compound pairs in each pathway were selected for molecular docking simulation experiments.The active ingredients in Kunxian Capsules with better binding activity to related targets were oxychelerythrine,abrusgenic acid),triptotriterpenic acid A’(triptotriterpenic acid a’),quercetin(quercetin),glycitein(glycitein),diflucoronate valerate(DFV),chryseriol,Hyperin,isorhamnetin,sesamin,etc.Conclusion:With the advancement of technology and data mining methods and the continuous growth of drug target information,the study of compound polypharmacology has become fast and efficient.In this study,multiple databases were used to analyze the molecular similarity and molecular docking.Finally,the active ingredients in Kunxian Capsules with better binding activity to related targets were oxychelerythrine,oxychelerythrine,and acacia.abrusgenic acid,triptotriterpenic acid A’(triptotriterpenic acid a’),etc.,mainly through PI3K-AKT signaling pathway,JAK-STAT signaling pathway,chemokine signaling pathway and TGF-β signaling pathway to play a role in the treatment of membranous nephropathy.