Jiang Zhi, Zou Qiuping, Chen Qicheng, Zhang Junhong, Tang Hailin, Chen Jingbao, Qin You, Yang Liming, Chen Zhiqiang, Cao Lixing
Department of Perioperative Research Centre of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Emergency Department, Dongguan People's Hospital, Dongguan, China.
Front Pharmacol. 2023 Aug 21;14:1237686. doi: 10.3389/fphar.2023.1237686. eCollection 2023.
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. 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. 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. 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.
先前的研究表明，乌达颗粒（WDG）已被应用于治疗胃肠动力障碍（GMD），但其效果和潜在机制尚待阐明。本研究旨在通过网络分析、动物实验验证和临床实验，探索WDG治疗GMD的机制和药理作用。根据口服生物利用度（OB）≥20%和类药性（DL）≥0.10，从中药系统药理学数据库（TCMSP，http://lsp.nwu.edu.cn/index.php）和《中药大辞典》（ETCM，http://www.tcmip.cn/ETCM/index.php/Home/Index/）中鉴定WDG的化学成分。从瑞士靶点预测数据库（http://www.swisstargetprediction.ch/）中检索WDG化合物的靶点，从基因卡片数据库（https://www.genecards.org/）中检索与GMD相关的靶点。进行网络分析以筛选WDG的关键活性化合物及其核心靶点。然后通过大鼠体内实验和临床实验验证WDG的药理作用。结果表明，筛选出WDG的117种有效活性化合物，选择了WDG化合物针对GMD的494个靶点。这些靶点参与炎症调节和胃肠动力调节的生物学过程。其机制主要涉及PI3K-Akt信号通路和Rap1信号通路的调节。此外，分子对接分析表明，WDG的8种关键活性化合物可能分别通过靶向HARS、AKT和PIK3CA，主要负责WDG对GMD的作用。动物实验和临床试验均表明，WDG可通过抑制炎症和促进胃肠动力对GMD发挥治疗作用，还可改善腹腔镜结直肠癌术后患者的消化功能。本研究首次证明WDG主要通过抑制炎症水平和促进胃肠动力改善GMD，为理解WDG治疗GMD提供了新的见解，为未来研究提供了启示，并为GMD治疗的临床策略提供了参考。
