ABSTRACT
Objective:To explore the potential mechanism of Bianketong tablet （BKT） in the treatment of constipation-predominant irritable bowel syndrome （C-IBS） based on network pharmacology and bioinformatics. Method:The BKT-meridian network was constructed for analyzing the combined effect of the nine Chinese herbs in BKT. The active components and targets of BKT were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and then screened according to the oral bioavailability （OB） and drug likeness （DL） criteria. Following the acquisition of C-IBS target set from GeneCards， Online Mendelian Inheritance in Man （OMIM）， Drugbank and DisGeNet， the protein-protein interaction （PPI） network was constructed. Cytoscape 3.7.2 was utilized for network visualization. The screened key targets were subjected to gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis using DAVID platform. The C-IBS mouse model was established via intragastric administration of ice water， and the key targets of BKT against C-IBS were verified by enzyme linked immunosorbent assay （ELISA） and immunohistochemistry. Result:The large intestinal meridian was the main site where BKT acted. There were 70 potential active components in BKT， which acted on 227 intersection targets. Through T helper cell 17（Th17） differentiation， Toll-like receptor （TLR）， tumor necrosis factor and other signaling pathways， BKT participated in inflammatory response， immune regulation， intestinal nerve regulation， hormonal regulation， and oxidative stress response， thus exerting the therapeutic effects against C-IBS. As reveled by <italic>in vivo</italic> experiments， BKT significantly improved the small intestinal propulsion rate， up-regulated the expression of vasoactive intestinal peptide （VIP） in serum and colon tissue of C-IBS mice， and down-regulated the expression of nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B）， interleukin（IL）-6， and TLR2 in serum and colon tissue， which confirmed the reliability of integration analysis. Conclusion:BKT inhibits C-IBS via multiple components， multiple targets， and multiple pathways. This study has provided ideas for further clinical research and experimental verification of BKT in the treatment of C-IBS.
ABSTRACT
Integrated pharmacological approach was used to predict the target genes and signal pathways of Xiaoer Fupi granules in the treatment of functional dyspepsia(FD), and the possible mechanism was discussed. The disease target information was collected by the DISEASES and UniProt databases, integrated pharmacological platform of traditional Chinese medicine(TCM-IP) was used to predict chemical composition, target, protein gene ontology(GO) function and Kyoto encyclopedia of genes and genomes(KEGG) pathway, and the networks of candidate target and TCMs-chemical components-core targets-key pathways were constructed. A total of 2 882 potential targets and 96 candidate target pathways were predicted, and β-1,4-galactosyltransferase(β-1,4-GalT) subtypes(B4GALT4, B4GALT2, B4GALT1) and phosphorylated protein kinase C subtype D(PRKCD), adenylate cyclase 2(ADCY2) and other targets were predicted. Some pathways were enriched, such as nervous system, endocrine system, thyroid hormone signaling pathway, long-term depression and other pathways related to FD. It was predicted that Xiaoer Fupi granules for treating FD by regulating gastrointestinal hormones, anti-depression, and regulating nerves and endocrine system. This study provides a basis for the precise clinical application and positioning of Xiaoer Fupi granules, and helps to clarify the mechanism of this drug.