Jichuan decoction alleviates constipation by inhibiting the PI3K/Akt/mTOR signaling pathway: an integrated network pharmacology and experimental study

Chronic constipation affects approximately 15% of the global population and substantially reduces patients' quality of life. Jichuan Decoction (JCD), a traditional Chinese medicine (TCM) formulation, has demonstrated clinical efficacy in the treatment of constipation; however, its underlying molecular mechanisms remain poorly understood. This study integrated network pharmacology, molecular docking, and in vivo experiments to systematically elucidate the anti-constipation mechanisms of JCD. Network pharmacology analysis identified 41 bioactive compounds in JCD and 20 overlapping therapeutic targets associated with constipation, among which MTOR and PTGS2 were identified as core targets. Molecular docking analysis revealed strong binding affinities (ΔG < - 5 kcal/mol) between key JCD constituents and these targets. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the PI3K/Akt signaling pathway plays a central role in JCD-mediated effects. In a loperamide-induced rat model of constipation, JCD treatment increased fecal water content, shortened the first black stool expulsion time, restored intestinal propulsion, mitigated colonic mucosal damage, and regulated enteric nervous system activity. Mechanistically, JCD suppressed the phosphorylation of key proteins in the PI3K/Akt/mTOR signaling pathway. This study unveils JCD's multi-target action via modulation of the PI3K/Akt/mTOR pathway, bridging TCM's empirical use with modern pharmacological insights. Further clinical translation and mechanistic studies are warranted.