引言：以往的研究表明，乌达颗粒（WDG）已经用于治疗胃肠道运动障碍（GMD），但其作用和潜在机制尚未阐明。本研究旨在通过网络分析、动物实验和临床实验验证，探索WDG治疗GMD的机制和药理作用。方法：根据口服生物利用度（OB）≥20%和药物样性（DL）≥0.10，从中医系统药理数据库（TCMSP，http://lsp.nwu.edu.cn/index.php）和中华传统医药百科全书（ETCM，http://www.tcmip.cn/ETCM/index.php/Home/Index/）中确定了WDG的化学成分。从GeneCards数据库（https://www.genecards.org/）中检索与GMD相关的靶点，并从Swiss Target Prediction数据库（http://www.swisstargetprediction.ch/）中检索WDG化合物的靶点。进行网络分析以筛选WDG的关键活性化合物和关键靶点。然后通过大鼠体内实验和临床实验验证WDG的药理作用。结果：结果显示筛选出117个WDG的有效活性化合物，并选择了494个针对GMD的WDG化合物的靶点。这些靶点参与了炎症调控和胃肠道运动的生物过程。机制主要涉及PI3K-Akt信号通路和Rap1信号通路的调控。此外，分子对接分析表明，WDG的八个关键活性化合物可能主要通过靶向HARS、AKT和PIK3CA等靶点发挥对GMD的作用。动物实验和临床试验均显示，WDG通过抑制炎症和促进胃肠道运动可以发挥治疗GMD的效果，还可以改善腹腔镜结直肠癌手术后的消化功能。结论：本研究首次证明WDG通过抑制炎症水平和促进胃肠道运动来改善GMD，为理解WDG治疗GMD提供了新的见解，对未来的研究提供了启示，并对临床治疗GMD的策略提供了参考。版权 © 2023 Jiang, Zou, Chen, Zhang, Tang, Chen, Qin, Yang, Chen, and Cao.

Introduction: Previous studies indicated that Wuda Granule (WDG) has been applied in the treatment of gastrointestinal motility disorder (GMD), but the effect and underlying mechanisms is yet to be elucidated. This study aimed to explore the mechanism and pharmacological effect of WDG for GMD via network analysis, verification of animal experiments and clinical experiments. Methods: The chemical components of WDG were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP, http://lsp.nwu.edu.cn/index.php), and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/Index/) according to oral bioavailability (OB) ≥ 20% and drug-likeness (DL) ≥ 0.10. The targets of WDG compounds were retrieved from the Swiss Target Prediction database (http://www.swisstargetprediction.ch/) and targets related to GMD were retrieved from GeneCards database (https://www.genecards.org/). Network analysis were performed to screen the key active compounds of WDG and its hub targets. Then the pharmacological effect of WDG were verified via vivo experiments in rats and clinical experiments. Results: The results showed that 117 effective active compounds of WDG were screened and 494 targets of WDG compounds targeting GMD were selected. These targets were involved in the biological process of inflammatory regulation and the regulation of gastrointestinal motility. The mechanism was mainly involved in the regulation of PI3K-Akt signaling pathway and Rap1 signaling pathway. In addition, molecular docking analysis suggested that eight key active compounds of WDG may be mainly responsible for the effect of WDG on GMD by targeting HARS, AKT, and PIK3CA, respectively. Animal experiments and clinical trials both suggested that WDG could exert therapeutical effect on GMD via inhibiting inflammation and promoting gastrointestinal motility, it could also improve digestive function of patients with laparoscopic colorectal cancer after surgery. Conclusion: This study was the first to demonstrate that WDG improved GMD mainly via inhibiting inflammatory level and promoting gastrointestinal motility, providing new insights for the understanding of WDG for GMD, inspiration for future research and reference for clinical strategy in terms of the treatment of GMD.Copyright © 2023 Jiang, Zou, Chen, Zhang, Tang, Chen, Qin, Yang, Chen and Cao.