Mechanism of Codonopsis Radix in treatment of intestinal mucositis based on network pharmacology and cell experiments
Objective To investigate the potential mechanism of Codonopsis Radix(CR)in the treatment of intestinal mucositis(IM)using network pharmacology and verify it in cell experiments.Methods The chemical constituents of Codonopsis Radix were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database,the targets corresponding to the chemical components of Codonopsis Radix were obtained from UniProt and SwissTargetPrediction database,the disease-related genes were obtained from online Mendelian Inheritance in Man(OMIM)and GeneCards database,and the Codonopsis Radix and IM intersection targets were screened by bioinformatics data analysis platform,and the action targets of Codonopsis Radix for IM were obtained.Cytoscape software was used to construct the chemical compositional-target-disease interaction network,the STRING database was used to obtain PPI network,and the Database for Annotation,Visualization and Integrated Discovery(DA VID)database was used for gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Small intestinal epithelial cells IEC-6 stimulated by 5-fluorouracil(5-FU,10 μg/mL)were treated with different concentrations of Codonopsis Radix alcohol extract(0,50,100 μg/mL).Inflammatory cytokines were detected by enzyme-linked immunosorbent assay(ELISA),the expressions of PI3K and AKT were detected by immunohistochemistry,and the reactive oxygen species(ROS)content was detected by fluorescence method.Results A total of 21 active ingredients of Codonopsis Radix were selected,corresponding to 401 targets.There were 2 210 targets related to intestinal mucositis and 197 targets of Codonopsis Radix-intestinal mucositis intersection.GO and KEGG enrichment analysis showed that Codonopsis Radix treated intestinal mucositis mainly via PI3K/AKT signaling pathway,etc.The alcohol extract of Codonopsis Radix(100 μg/mL)decreased the contents of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)(P＜0.05),and upregulated the contents of IL-4 and IL-10(P＜0.01).The alcohol extract of Codonopsis Radix(50 μg/mL)had no significant effect on the reduction of inflammatory factors(TNF-α and IL-6),and reduced the contents of IL-4 and IL-10(P＜0.05).The alcohol extract of Codonopsis Radix(100 μg/mL)decreased the level of ROS(P＜0.01),and downregulated the expres-sions of PI3K and AKT(P＜0.01).The alcohol extract of Codonopsis Radix(50 μg/mL)decreased the levels of AKT and PI3K(P＜0.05),but had no significant effect on ROS.Conclusion Codonopsis Radix may play a role in the treatment of intestinal mucositis by regulating PI3K/AKT signaling pathway.
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