Mechanistic Insights into the Therapeutic Effects of Tiaozang Shumi Mixture on Chronic Constipation

Abstract

Objective: This study aimed to investigate the therapeutic effects and underlying mechanisms of Tiaozang Shumi Mixture for treating chronic constipation. Methods: Network pharmacology identified active components of Tiaozang Shumi Mixture and their targets via the Traditional Chinese Medicine Systems Pharmacology (TCMSP). Core targets were screened through protein–protein interaction (PPI) network analysis using STRING and Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed with Database for Annotation, Visualization, and Integrated Discovery (DAVID), and molecular docking of core components with targets was validated using AutoDock and PyMOL. In animal studies, 60 male C57 mice were randomly divided into normal control, model, positive control, and low-, medium-, and high-dose Tiaozang Shumi Mixture groups. Results: A total of 151 active compounds and 924 potential targets were obtained through comprehensive database screening and target mapping, yielding 298 potential therapeutic targets and six core targets. In comparison to the model group, Tiaozang Shumi Mixture significantly reduced the time to first black stool, increased defecation frequency and fecal water content, and enhanced small intestinal propulsion in the animal model (p < 0.01). The mixture ameliorated colonic histopathological injury, elevated serum 5-hydroxytryptamine (5-HT) concentrations, and reduced vasoactive intestinal peptide (VIP), nitric oxide (NO), and aquaporin-3 (AQP3) expression levels (p < 0.05), whereas gastrin levels demonstrated no significant difference. Conclusion: Tiaozang Shumi Mixture effectively improved constipation symptoms in mice. The underlying mechanism may involve modulation of the PI3K-Akt signaling pathway and regulation of 5-HT, VIP, NO, and AQP3 expression, thereby promoting intestinal motility.