Foxiangsan Modulates Dopaminergic and Motilin Pathways to Improve Gastrointestinal Motility in Diabetic Gastroparesis

INTRODUCTION: Diabetic gastroparesis (DGP) is a severe diabetic complication with limited therapeutic options. This study investigates the effects of Foxiangsan on DGP and elucidates its molecular mechanisms. METHODS: A rat model of DGP was established and divided into 5 groups: model (MG), western medicine (WMG, domperidone), and 3 Foxiangsan dose groups (LDG, MDG, HDG). Serum dopamine (DA) and motilin levels, along with striatal DA receptor D2 (DRD2) expression, were measured. Network pharmacology identified bioactive compounds and targets, and pathway enrichment and molecular docking were used to evaluate mechanistic interactions. RESULTS: Foxiangsan significantly improved gastrointestinal motility, increased motilin levels, reduced DA levels, and enhanced DRD2 expression in the striatum. Network pharmacology identified DRD2, AKT1, and MAPK3 as key targets, while molecular docking confirmed strong binding affinities of bioactive compounds such as β-sitosterol and baicalein with DRD2. The therapeutic effects of Foxiangsan involve modulation of the cAMP, serotonin, and DA pathways. CONCLUSION: Foxiangsan exerts multicomponent, multi-target, and multi-pathway actions in DGP by modulating neuroendocrine function, suggesting its potential as a novel therapeutic approach. Further investigations are needed to confirm its clinical efficacy.