Supplementary Material for: Foxiangsan Modulates Dopaminergic and Motilin Pathways to Improve Gastrointestinal Motility in Diabetic Gastroparesis

Background 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 five groups: model (MG), western medicine (WMG, domperidone), and three Foxiangsan dose groups (LDG, MDG, HDG). Serum dopamine (DA) and motilin levels, along with striatal dopamine 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 dopamine pathways. Conclusion Foxiangsan exerts multi-component, 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.

背景 糖尿病性胃轻瘫（Diabetic gastroparesis, DGP）是一类治疗选择有限的重症糖尿病并发症。本研究探讨香砂散（Foxiangsan）对糖尿病性胃轻瘫的干预作用，并阐明其潜在分子机制。
方法 本研究构建糖尿病性胃轻瘫大鼠模型，造模成功后将大鼠分为五组：模型组（MG）、西药组（WMG，多潘立酮）以及三个香砂散剂量组（低剂量组LDG、中剂量组MDG、高剂量组HDG）。检测各组大鼠血清多巴胺（Dopamine, DA）与胃动素水平，并测定纹状体多巴胺D2受体（Dopamine receptor D2, DRD2）的表达情况。通过网络药理学筛选活性化合物与作用靶点，结合通路富集分析与分子对接技术评估其机制互作关系。
结果 香砂散可显著改善大鼠胃肠动力，升高血清胃动素水平、降低多巴胺水平，并上调纹状体多巴胺D2受体的表达。网络药理学筛选得到DRD2、AKT1及MAPK3为核心靶点；分子对接验证显示β-谷甾醇（β-sitosterol）、汉黄芩素（baicalein）等活性成分与DRD2具有较强结合亲和力。香砂散的治疗作用涉及对cAMP通路、血清素（serotonin）通路及多巴胺通路的调控。
结论 香砂散通过调控神经内分泌功能，对糖尿病性胃轻瘫发挥多成分、多靶点、多通路的干预作用，提示其有望成为新型治疗策略。未来仍需开展进一步研究以验证其临床疗效。