Yunweiling alleviates functional constipation: integrating network pharmacology and experimental study

Abstract

Background: This study investigated the impacts and mechanisms of yunweiling in the management of Functional Constipation (FC) using network pharmacology and experimental research.

Methods: Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Genecard, and Online Mendelian Inheritance in Man (OMIM) databases, a potential gene target for yunweiling in treating FC was found. A pharmacological network was built and viewed in Cytoscape. A protein interaction map was created with STRING and Cytoscape. ‘clusterProfiler’ helped uncover its mechanism. Molecular docking was done with AutoDock Vina. In a constipation mouse model, Western blot was used to assess yunweiling's effectiveness.

Results: To investigate yunweiling's therapeutic effects on FC, we employed a loperamide-induced constipation model. Successful model establishment was confirmed by first black stool time, reduced stool output, and impaired gastrointestinal motility. Yunweiling treatment, especially at high and medium doses, significantly alleviated constipation symptoms by reducing first black stool time, increasing stool output, and enhancing gastrointestinal motility. HE staining revealed yunweiling's ability to restore colon tissue structure. Yunweiling modulated the expression of key proteins TP53, P-AKT, P-PI3K, RET, and Rai, implicating its involvement in the PI3K-Akt signaling pathway. Comparative analysis showed yunweiling to be more effective than its individual components (shionone, β-sitosterol, and daucosterol) in improving constipation. The combination of yunweiling with TP53 and PI3K-Akt inhibitors further enhanced its therapeutic effects, suggesting a synergistic mechanism.

Conclusions: The integration of network pharmacology and experimental investigations indicated the effectiveness of yunweiling in managing FC, offering essential theoretical support for clinical application.

Keywords

functional constipation / mouse model / network pharmacology / yunweiling

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