Mechanism of Huangqi Jianzhong Decoction in Treating Diarrhea Predominant Irritable Bowel Syndrome Based on Network Pharmacology and Molecular Docking Technology

Abstract

Background Clinical treatment often achieves unsatisfactory effect for irritable bowel syndrome (IBS) , a common complex functional gastrointestinal disease. Huangqi Jianzhong Decoction is widely used for diarrhea IBS (IBS-D) , and its efficacy has been recognized, but the mechanism is unclear and relevant studies are rare. Objective To explore the potential mechanism of Huangqi Jianzhong Decoction in the treatment of IBS-D based on network pharmacology and molecular docking. Methods TCMSP database was adopted to acquire the active ingredients and corresponding targets of all herbals in Huangqi Jianzhong Decoction. And targets related to IBS-D were identified using GeneCards, OMIM, TTD, Drug Bank and PharmGKB databases. Then the intersection of herbal targets and IBS-D-related targets were selected to obtain the potential therapeutic targets of Huangqi Jianzhong Decoction for IBS-D. Cytoscape, String and Metascape were used to construct an "herbals-active ingredients-target" network map, draw the protein-protein interaction network (PPI) , and conduct genetic ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. AutoDock Vina and PyMOL were used for the visualization of molecular docking results. Results Finally, we obtained 123 active ingredients and 247 potential targets of Huangqi Jianzhong Decoction, 3 486 IBS-D related targets, and 180 intersected herbals targets and IBS-D-related targets. A total of 2 376 items of biological process, 194 items of molecular function and 115 items of cellular component were identified through GO enrichment analysis. Enrichment analysis of KEGG signaling pathway revealed MAPK, NF-κB, cAMP, estrogen and other related signal pathways. The molecular docking results showed that the main active ingredients of Huangqi Jianzhong Decoction in the treatment of IBS-D are quercetin, kaempferol, β-sitosterol, isorhamnetin, formononetin, stigmasterol, calycosin, 7-O-methylisomucronulatol, and they showed good binding to core proteins AKT1, TP53, TNF, IL-6, CASP3, IL-1B, EGFR and CTNNB1. Conclusion Therefore, we speculated that Huangqi Jianzhong Decoction may plays a role in the treatment of IBS-D by enhancing intestinal barrier function, reducing visceral hypersensitivity, reducing inflammatory response and regulating intestinal flora.

Keywords

• diarrhea irritable bowel syndrome|huangqi jianzhong decoction|network pharmacology|molecular docking