Mechanism and experimental verification of Sijunzi Decoction in treatment of ulcerative colitis based on network pharmacology / 中国中药杂志

ABSTRACT

To explore the mechanism of Sijunzi Decoction in the treatment of ulcerative colitis(UC) based on network pharmacology. The active components and corresponding targets of Sijunzi Decoction were extracted with Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets were standardized with the help of Uniprot database. The related targets of UC were obtained through GeneCards database and Disgenet database, and the intersection targets of drugs and diseases were screened by R language. The visual regulation network of "active ingredient-disease target" of Sijunzi Decoction was constructed by Cytoscape software, and the protein-protein interaction network was constructed by STRING database. The functional enrichment analysis of gene ontology(GO) and the enrichment analysis of Kyoto encyclopedia of genes and genomes(KEGG) pathway were carried out on Bioconductor platform, and some of the targets were verified by animal experiments. Through database analysis, a total of 135 active components of Sijunzi Decoction, 114 predicted targets and 80 common targets with UC were obtained. The core target proteins included interleukin 6(IL-6), caspase-3(CASP3), vascular endothelial growth factor A(VEGFA), epidermal growth factor receptor(EGFR) and so on. GO functional enrichment analysis involved 102 items, which mainly affected transcription factor activity, enzyme activity, receptor activity and biochemical process regulation. KEGG pathway enrichment analysis showed that 120 items were involved in human cytomegalovirus infection, cancer, apoptosis, inflammation and other pathways. Mouse experiments showed that Sijunzi Decoction could down-regulate the expression of target proteins IL-6 and caspase-3 and inhibit intestinal epithelial cell apoptosis. The treatment of UC with Sijunzi Decoction is the result of the interaction among multi-components, multi-targets and multi-pathways. It is proved by experiments that Sijunzi Decoction may play an effective role by regulating the expression of IL-6 and caspase-3, and getting involved in apoptosis, inflammation and other pathways.