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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.
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BACKGROUND: Previous studies have suggested that the Wuda granule (WDG) could promote the recovery of gastrointestinal (GI) function after gynecologic abdominal surgery. This trial aimed to investigate the efficacy and safety of WDG in the rapid recovery of GI function in patients after laparoscopic intestinal resection in the setting of enhanced recovery after surgery (ERAS)-based perioperative care. METHODS: We performed a randomized, double-blind, placebo-controlled pilot trial. Thirty patients who met the inclusion criteria were randomly assigned to either the WDG group or the placebo group in a 1:1 ratio. The patients received WDG or placebo twice a day in addition to ERAS-based perioperative care, starting on post-operative Day 1 until Day 3. The primary outcomes were time to first bowel movement and time to first tolerance of solid food. The secondary outcomes were time to first flatus, length of hospital stay (LOS), and post-operative ileus-related morbidity. Adverse events were also recorded. RESULTS: There were no statistically significant differences in baseline characteristics between the two groups. The median time to first bowel movement was significantly decreased in the WDG group compared with the control group (27.6 vs 50.1 h; P < 0.001), but the median times to first flatus (22.9 vs 25.1 h; P > 0.05) and LOS (5.0 vs 5.0 days; P > 0.05) were not statistically different. The occurrence rates of post-operative nausea, vomiting, abdominal distension, and abdominal pain were similar in the two groups. No adverse events occurred in any patients. CONCLUSIONS: The addition of WDG to ERAS post-operative care after laparoscopic intestinal resection can safely promote the rapid recovery of GI function.
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BACKGROUND: Postoperative ileus (POI) is a temporary disturbance in gastrointestinal motility following surgery, and intestinal inflammatory response plays a critical role in the pathogenesis of POI. Wuda granule (WDG), a gastrointestinal prokinetic Chinese herbal medicine, is prescribed to promote recovery of gastrointestinal function after abdominal surgery. However, it has remained unclear whether WDG shows anti-inflammatory effects in POI. In the present study, we investigated the effects of WDG in a rat POI model and attempted to clarify the detailed mechanisms of action. METHOD: Experimental POI was induced in adult male SD rats by intestinal manipulation (IM). WDG were orally administered after surgery at the same points (6 h, 12 h, 18 h, 24 h). Histological changes of mesenterium, levels of cytokines, and CD68 and iNOS expression were determined in rats treated or not with WDG. We also investigated the transcriptome profile of rats treated with WDG in a POI model. RESULTS: Experimental POI in rats was characterized by a marked intestinal and systemic inflammatory response. WDG significantly inhibited the infiltration of neutrophils and macrophages, reduced the levels of IL-6, and CRP, and inhibited protein expressions of CD68 and iNOS in mesentery. Comparison analysis showed that there are 1432 differentially expressed genes (DEGs) between the POI and CON sample, whereas 331 DEGs between the WDG -treated sample and the POI group. And 16 DEGs were shared by the POI vs CON and WDG vs POI groups, among which 6 hub genes associated with immune system processes were identified and verified. CONCLUSIONS: WDG treatment ameliorates the impaired gastrointestinal motility in the rat model of POI through inhibiting the inflammatory response of mesentery.