Study On The Effect And Mechanism Of Penthorum Chinense Pursh Treating Nephrotic Syndrome Based On Network Pharmacology

Objective: To study on the effect and mechanism of Penthorum chinense pursh treating nephrotic syndrome by using network pharmacology method.Methods: Based on literature search,the chemical constituents of the Penthorum chinense pursh were obtained.By the TCMSP database,combined with oral bioavailability(>30%)analysis and resistance(>0.10),screening of active ingredients in Penthorum chinense pursh.Retrieve the protein targets of the compounds from the TCMSP and PharmMapper database.Associated Proteins and Gene Names were received via UniProt database.The protein interaction network(PPI)was constructed by Cytoscape software,and the core targets was screened and submitted to the OMIM,DisGeNET,PharmGKB,NCBI and GeneCards databases for diseases information collection.All diseases were classified by ICD-10 classification and the frequency of occurrence of single diseases was ranked,and new indications were predicted,scientific hypothesis was proposed,experimental animal model was established to verify the effect of Penthorum chinense pursh on viscera index,urine protein,serum biochemical index and histopathology of rat model.Finally,the intersection target between the constituents and new indications was found by using the network pharmacology method,as the main target for the treatment of new indications of Penthorum chinense pursh.The active “compound-target” network was established by Cytoscape software,the components with higher degree were used as the main components of the new indications on the treatment of Penthorum chinense pursh.Associated high degree target were received via String database was used as the main target.The molecular docking of key active components and key targets was carried out by Systems dock Web Site,which was used to verify the results of network analysis.gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the action targets of Penthorum chinense pursh by biological information annotation database(DAVID).Results: There were 119 active compounds in Penthorum chinense pursh,and 22 active ingredients were screened.541 corresponding targets were obtained after imported TCMSP database and PharmMapper database,and 472 standard human targets were converted after the transformation of Uniprot database.144 core targets were obtained through PPI network analysis and 401 corresponding disease information were obtained based on disease database.According to the ICD-10 classification,401 diseases were classified into 18 diseases category,with tumor diseases,blood,hematopoietic organ and immune diseases,and urogenital diseases as the most important diseases type.The frequency of mono-type diseases was ranked,and the results showed that 26 mono-type diseases with isolated proteinuria accompanied by(diffuse)membranous glomerular lesion,prostate cancer,and inflammation were the mono-type diseases with higher frequency.it was speculated that nephrotic syndrome might be a new indication for Penthorum chinense pursh,and the scientific hypothesis that “Nephrotic syndrome may be treated by Penthorum chinense pursh” have been proposed.In animal experiments,after the intervention of Penthorum chinense pursh,there was a significant difference in viscera index in the model of nephrotic syndrome rat,urine protein was decreased,and the serum TP,TC,TG levels and pathological state of renal fibrosis in the rats were improved.Finally,32 targets were identified by network pharmacology for the intersection of components of Penthorum chinense pursh and nephrotic syndrome,which were divided into 18 components.and the “compound-target” interaction network were built using Cytoscape software,the results showed that the degree of quercetin,luteolin,baicalin,Pinocembrin,kaempferol and(+)-catechin were high,that was the main active components.the results of String database showed that the degree of tumor necrosis factor(TNF),vascular endothelial growth factor(VEGF),chemokine 2(CXCL2),Prostaglandin-endoperoxide synthase 2(PTGS2),chemokine 8(CXCL8),interleukin-1 cytokines(IL-1)and interleukin-4(IL-4)had high degree,that was the main targets.Docking results showed that the key active components had good binding activity to the key targets.Gene enrichment analysis showed that there are 131 GO biological function items,including 93 biological process items,15 cell component entries,23 molecular function items,and 55 KEGG signaling pathways,in which immune response signaling pathways and inflammatory response signaling pathways.Conclusion: Penthorum chinense pursh has the effect of treating nephrotic syndrome,and the mechanism may be related to the pharmacological action of immune suppression and anti-inflammatory.