BACKGROUND: Irritable bowel syndrome (IBS) is a chronic intestinal disorder characterized by abdominal discomfort, stool characteristics, and changes in bowel habits. Among them, diarrhea-type (diarrhea-predominant irritable bowel syndrome, abbreviated as IBS-D) is the most common. Because its pathogenesis is not understood, symptomatic treatment is currently used in clinical practice, and its long-term effect is still unclear. Decoction of Angelica sinensis, Zingiberis Rhizoma Recens, and Mutton (DAZM) is a famous traditional Chinese medicine recipe created by Zhang Zhongjing, a famous doctor in the Eastern Han Dynasty 2000 years ago, and is still in use today. Our research team has previously investigated the clinical study of DAZM in the treatment of IBS-D and conducted animal experiment research, indicating that DAZM has a significant effect on improving IBS-D. Yet, there are few reports on the specific mechanism of action of DAZM in improving the treatment of IBS and related types. Most studies discuss and verify its efficacy and protection from a clinical perspective. For this reason, this research will explore the constituent targets and mechanisms of DAZM to improve the treatment of IBS-D, provide relevant scientific evidence, and also provide reference evidence for the efficacy of food therapy decoction in improving the treatment of diseases and mechanism to open up new experimental research ideas.
METHODS: Identification of drug ingredients and collection of targets for DAZM using ultra-performance liquid chromatography with linear ion trap-electrostatic field orbitrap mass spectrometry and the Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine database, active ingredients were selected based on their oral bioavailability and drug-like properties. Obtained IBS-D targets using the GeneCards database, took the intersection of IBS-D targets and DAZM targets and obtained potential targets of DAZM for the treatment of IBS-D. Using Cytoscape software to draw a network diagram of "Food therapy decoction-ingredient-target-disease" and selected the ingredients with larger parameter values by topological analysis. Correlation analysis of the selected active and parametric ingredients with prominent symptoms of IBS-D using SymMap database, and selection of potential core ingredients. The construction of protein interaction networks from the String database and the selection of potential core targets. Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analyses using the Metascape database, establishing the bioinformatic processes and signaling pathways involved. Molecular docking of core ingredients and potential core targets was performed using AutoDock Vina, and the results were visualized using Python molecule (PyMOL) and LigPlus+. Finally, based on the results of this research combined with previous literature reports, the discussion section of this paper summarizes in detail the key core ingredients, targets, and signaling pathways of DAZM in improving IBS-D.
RESULTS: DAZM may act on eight potential core targets (threonine kinase 1, insulin, tumour necrosis factor, tumour protein p53, interleukin 6, epidermal growth factor receptor, connexin β1, and interleukin 1β) through eight core ingredients (Zingiberone, Shyobunone, Palmitic acid, Sebiferic acid, β-Bisabolene, β-Sitosterol, Stigmasterol, and Oleic acid). inhibit pro-inflammatory factors through Advanced Glycation End Products-Receptor (AGE-RAGE) signaling pathway, Cyclic Adenosine Monophosphate (cAMP) signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, Calmodulin (CaM) signaling pathway, and other pathways. It can alleviate the inflammatory response, enhance the intestinal mucosal barrier and regulate intestinal motility, and play a role in the treatment and improvement of IBS-D.
CONCLUSIONS: This research mainly found the mechanism of DAZM on IBS-D, which may involve multiple ingredients, multiple targets, and multiple pathways. DAZM with medicinal and edible functions can effectively improve the treatment of IBS-D. This kind of dietary therapy is suitable for long-term treatment and is worthy of promotion.