Mechanism of Jianpi Shugan Guben Formula for diarrhea-predominant irritable bowel syndrome based on network pharmacology and animal experiment
Objective To explore the mechanism of Jianpi Shugan Guben Decoction for diarrhea irritable bowel syndrome(IBS-D) based on network pharmacology and animal experiments. Methods The active components and potential targets of Jianpi Shugan Guben Decoction were obtained from the TCMSP database with disease targets of IBS-D identified from databases of diseases. The "Herbs-Active Ingredients-Targets"network was constructed by Cytoscape 3.9.1 software. String database was utilized for the protein-protein interaction (PPI) network where the core targets were screened. The core targets were introduced into Metascape platform for analysis of GO functional enrichment and KEGG pathway enrichment. Finally,the results of network pharmacology were validated by animal experiments. Results There were 108 active components,563 herb targets,and 1285 disease targets for Jianpi Shugan Guben Decoction and IBS-D,respectively. The "Herbs-Active Ingredients-Targets" network diagram suggested that the core components of Jianpi Shugan Guben Decoction for IBS-D include quercetin,kaempferol,isoflavone,β-sitosterol and so on. The construction of the PPI network and core targets screening showed that TP53,EGFR,AKT1,IL6,TNF,IL1B,and JUN were the core targets of Jianpi Shugan Guben Decoction for IBS-D. An analysis of GO functional enrichment and KEGG pathway enrichment demonstrated that the JAK-STAT signal pathway,p53 signal pathway,NF-KappaB signal pathway,and calcium signal pathway were potential pathways. Animal experiments showed that Jianpi Shugan Guben Decoction reduced visceral hypersensitivity and fecal water content. Quantitative real-time PCR (qRT-PCR) indicated that the relative expression of PIK3CA,AKT1,and JAK2mRNA decreased in varying degrees. Conclusion Jianpi Shugan Guben Decoction could treat IBS-D through multiple targets and pathways,and one of its potential mechanisms was related to down-regulating the expression of PIK3CA,AKT1,and JAK2,inhibiting intestinal inflammation and regulating intestinal immune function.
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