Network pharmacology insights into the mechanistic basis of Taohe Chengqi Decoction in the treatment of constipation.
Constipation is a common gastrointestinal disorder associated with impaired motility, inflammation, and altered neuro-intestinal regulation. Taohe Chengqi Decoction, a classical prescription from Shang Han Lun, has been widely applied in the treatment of constipation, yet its pharmacological mechanisms remain insufficiently understood. We integrated systems pharmacology and network analysis to elucidate the therapeutic mechanisms of Taohe Chengqi Decoction against constipation. Active compounds and their putative targets were retrieved from traditional Chinese medicine systems pharmacology and PubChem, while constipation-related genes were collected from GeneCards and OMIM. Shared targets were identified and subsequently analyzed using STRING to construct a protein-protein interaction network. Hub proteins were ranked by degree centrality. A drug-disease-target network was built to map the interactions between Taohe Chengqi Decoction and constipation. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed to uncover functional modules and signaling pathways. A total of 188 common targets were identified. Protein-protein interaction network analysis highlighted AKT1, interleukin-6 (IL6), IL1B, and JUN as hub proteins, suggesting central roles in regulating inflammation, apoptosis, and signal transduction. Additional nodes with high connectivity, such as caspase-3, PTGS2, signal transducer and activator of transcription 3, hypoxia-inducible factor-1α, estrogen receptor 1, and epidermal growth factor receptor, were implicated in apoptosis, oxidative stress, and transcriptional regulation. The drug-disease-target network revealed a dense and highly interconnected structure, reflecting the multicomponent, multi-target nature of Taohe Chengqi Decoction. Kyoto encyclopedia of genes and genomes enrichment indicated significant involvement of the advanced glycation end-product binding to their receptor signaling pathway, along with IL-17, TNF, and HIF-1 pathways, underscoring the contribution of inflammatory and oxidative stress-related processes. This study, based on computational pharmacology analysis, predicts that Taohe Chengqi Decoction may exert therapeutic effects on constipation through an integrated regulation involving multiple components, targets, and pathways. The potential mechanisms are likely associated with the modulation of inflammatory responses, apoptosis, and oxidative stress, with the advanced glycation end-product binding to their receptor signaling pathway possibly acting as a key mediator. These findings provide theoretical insights and future directions for elucidating the molecular mechanisms underlying the therapeutic effects of Taohe Chengqi Decoction against constipation.