Zanthoxyli pericarpium Effects on Gastrointestinal Motility: Network and Validation

Background Zanthoxyli pericarpium is a medicinal herb that has attracted attention for its diverse pharmacological effects and potential therapeutic uses. Purpose Th purpose of this study was to predict the potential of Z. pericarpium as a treatment for gastrointestinal motility disorder. Materials and Methods Using a network pharmacological approach, we searched traditional Chinese medicine database for Z. pericarpium and identified and analyzed the constituents and target genes for gastrointestinal motility disorder. The effects of Z. pericarpium extract on the pacemaking activity of the interstitial cells of Cajal and the intestinal transit rate were investigated. Results Using traditional Chinese medicine database, we identified 260 potential active compounds in Z. pericarpium and 131 active compounds. These compounds were associated with target genes, such as acetylcholinesterase, DPP-4, and SLC6A4. Z. pericarpium extract depolarized the pacemaker activity in interstitial cells of Cajal in murine small intestines. Pretreatment with the muscarinic M3 receptor antagonist 4-DAMP or intracellular perfusion of GDP-β-S blocked Z. pericarpium -induced interstitial cells of Cajal depolarization. In addition, Z. pericarpium -induced interstitial cells of Cajal depolarization was inhibited in the presence of various inhibitors. Moreover, in a loperamide-induced gastrointestinal motility disorder mouse model, oral administration of Z. pericarpium extract restored intestinal transit rate via motilin. Conclusion Our study confirmed the relationship between Z. pericarpium and gastrointestinal motility through network pharmacological analysis and investigated the regulation of gastrointestinal motility by Z. pericarpium through electrophysiological and animal experiments. Taken together, Z. pericarpium may have therapeutic potential for treating gastrointestinal motility disorders.