Improvement effect and mechanism of XuanFuDaiZhe tang on rats with diarrheal irritable bowel syndrome induced by colorectal dilation

• Published in: Journal of ethnopharmacology 2025-01, Vol.337 (Pt 3), p.118938, Article 118938
• Main Authors: Wang, Shasha, Jing, Weiliang, Gu, Guanliang, Li, Shile, Pang, Jie, Cong, Huan, Zhang, Kuo, Yang, Jingyu, Wu, Chunfu
• Format: Article
• Language: English
• Subjects: Animals; Aquaporin; Colon - drug effects; Colon - metabolism; Colon - pathology; Diarrhea - drug therapy; Diarrhoea-predominant irritable bowel syndrome; Disease Models, Animal; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Irritable Bowel Syndrome - drug therapy; Irritable Bowel Syndrome - metabolism; Male; MLCK–MLC pathway; Protein Interaction Maps; Rats; Rats, Sprague-Dawley; Tight junction protein; XuanFuDaiZhe tang
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2024.118938

XuanFuDaiZhe Tang (XFDZT) is used in traditional Chinese medicine (TCM) to treat diarrhoea-predominant irritable bowel syndrome (IBS-D). Our laboratory has demonstrated that XFDZT remarkably improves various gastrointestinal motility disorders in animal models. However, previous studies have only focused on one or several protein targets without systematically investigating dynamic changes and protein interrelations. To explore the mechanisms underlying the therapeutic action of XFDZT in IBS-D using a network pharmacology approach and in vivo experiments. The active compounds of XFDZT were selected from TCM Systems Pharmacology and TCM Integrated databases, and potential targets were identified using the Swiss Target Prediction databases. Targets related to IBS-D were mined from the DisGeNet, Drug Bank, and Therapeutic Target databases. The intersecting protein–protein interactions (PPIs) of the drug–disease crossover genes were analysed, and a central PPI network was constructed using the STRING database and Cytoscape 3.7.2. Following Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, a gene pathway network was constructed to identify key target genes and pathways. Using haematoxylin and eosin staining and western blotting, we validated how XFDZT controls water expression in the body to treat IBS-D infection. First, the results showed that XFDZT contained 1037 active ingredients and 1458 corresponding targets. After intersecting the 252 IBS targets, 108 targets were identified. The main targets of XFDZT were albumin, aquaporins such as AQP1 and AQP3, calmodulin, and the cellular enzyme CYP2C9. GO and KEGG enrichment predicted that the action pathways were the neuroactive ligand–receptor interaction, calcium signalling pathway, serotonergic synapse signalling pathway, cGMP–PKG signalling pathway, cAMP signalling pathway, and MLCK–MLC signalling pathway. Second, an IBS-D rat model was constructed using colorectal dilation (CRD). CRD can significantly induce IBS-D symptoms such as diarrhoea, abdominal pain, and anxiety and depression-like behaviour in rats. XFDZT (10, 20, and 40 g/kg) administered for 14, 21, and 28 days significantly reversed these changes in IBS-D rats in a time- and dose-dependent manner, suggesting that XFDZT significantly improved IBS-D. Finally, the mechanism by which XFDZT improves IBS-D was explored from the perspective of AQPs, tight junction proteins, and motility-related proteins in colon tissu