Therapeutic role of Wuda granule in gastrointestinal motility disorder through promoting gastrointestinal motility and decreasing inflammatory level

Zhi Jiang; Qiuping Zou; Qicheng Chen; Junhong Zhang; Hailin Tang; Jingbao Chen; You Qin; Liming Yang; Zhiqiang Chen; Lixing Cao

doi:10.3389/fphar.2023.1237686

Therapeutic role of Wuda granule in gastrointestinal motility disorder through promoting gastrointestinal motility and decreasing inflammatory level

Front Pharmacol. 2023 Aug 21:14:1237686. doi: 10.3389/fphar.2023.1237686. eCollection 2023.

Authors

Zhi Jiang¹, Qiuping Zou^{1

2}, Qicheng Chen¹, Junhong Zhang³, Hailin Tang⁴, Jingbao Chen¹, You Qin⁵, Liming Yang⁵, Zhiqiang Chen¹, Lixing Cao¹

Affiliations

¹ Department of Perioperative Research Centre of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
² Emergency Department, Dongguan People's Hospital, Dongguan, China.
³ Department of Research Public Service Center, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
⁴ State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
⁵ Department of Minimally Invasive Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Abstract

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.

Keywords: Chinese herb medicine; Wuda granule; gastrointestinal motility disorders; molecule docking; network analysis.

Grants and funding

This work was financially supported by the National Natural Science Foundation of China (No.82204716), Department of Science and Technology of Guangdong Province (No. 2021A1515110773, 2022A1515220198), Guangzhou Basic and Applied Basic Research Foundation (No. 2023A03J0759) and Guangzhou Municipal Science and Technology Bureau (No.202201011785), and the Traditional Chinese Medicine Bureau of Guangdong Province (No.20225012, 20231363), and also the Special Project for Clinical Research of Guangdong Provincial Hospital of Chinese Medicine (YN10101902), the Guangdong Administration for Market Regulation (Guangdong Intellectual Property Administration) [No. (2022)158].