Therapeutic Effect of Wenweishu Granules on Functional Dyspepsia Rats with Spleen-stomach Deficiency Cold Syndrome Based on Bioinformatics Analysis and Experimental Validation
10.13422/j.cnki.syfjx.20250608
- VernacularTitle:基于生物信息分析及实验验证探讨温胃舒颗粒对脾胃虚寒证功能性消化不良大鼠的治疗作用
- Author:
Xinyu YANG
1
;
Xiaoyi JIA
1
;
Zihua XUAN
1
;
Shuangying GUI
1
;
Yanfang WU
2
;
Yuhan MA
2
;
Qin RUAN
1
;
Jia ZHENG
1
;
Zhiyong JIAO
1
Author Information
1. School of Pharmacy， Anhui University of Chinese Medicine， Hefei 230012，China
2. Hefei China Resources Shenlu Pharmaceutical Co. Ltd.，Hefei 231200，China
- Publication Type:Journal Article
- Keywords:
Wenweishu granules;
spleen-stomach deficiency cold syndrome;
functional dyspepsia;
stem cell factor （SCF）/receptor tyrosine kinase（c-Kit）;
network pharmacology
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(18):30-40
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveThis study aims to investigate the therapeutic effects of Wenweishu granule （WWSG） on functional dyspepsia （FD） with spleen-stomach deficiency cold syndrome in rats by integrating network pharmacology， molecular docking， and animal experiments. MethodsActive components and corresponding targets of WWSG were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Disease-related targets for FD with spleen-stomach deficiency cold syndrome were screened using GeneCards and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Core therapeutic targets were identified via Cytoscape and validated by molecular docking. A rat model of FD with spleen-stomach deficiency cold syndrome was established using vinegar gavage combined with tail-clamping. The rats were randomly divided into a model group， low-， medium-， and high-dose WWSG groups （2.0， 4.0， 8.0 g·kg-1）， a domperidone group （3.0 mg·kg-1）， a Fuzi Lizhong pillwan （0.8 g·kg-1）， and a normal control group （n=10 per group）. Drugs were administered once daily by gavage for 14 consecutive days. After treatment， body weight， symptom scores， and gastrointestinal motility indices were recorded. Gastric and duodenal pathologies changes were observed via hematoxylin-eosin （HE） staining. Brain-gut peptides were measured in serum and tissue using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot were performed to assess stem cell factor （SCF） and receptor tyrosine kinase （c-Kit） protein expression in gastric tissues. ResultsA total of 305 drug targets， 1 140 disease targets， and 116 overlapping targets were identified. Cytoscape analysis revealed 104 core targets. Enrichment analysis indicated that the SCF/c-Kit signaling pathway was the key mechanism. Molecular docking confirmed a strong binding affinity between active components of WWSG and SCF/c-Kit proteins （binding energy<-5.1 kcal·mol-1）. Compared with the normal group， model rats exhibited slower weight gain （P<0.05）， reduced gastric emptying and intestinal propulsion （P<0.01）， mild gastric mucosal shedding， duodenal inflammatory cell infiltration， decreased levels of gastrin （GAS）， 5-hydroxytryptamine （5-HT）， and vasoactive intestinal peptide （VIP） （P<0.05， P<0.01）， and elevated somatostatin （SS） expression （P<0.05， P<0.01）. WWSG treatment ameliorated weight gain， symptom scores， and low-grade inflammation in gastric/duodenal tissues. High-dose WWSG significantly improved gastric emptying and intestinal propulsion， upregulated GAS， 5-HT， and VIP， and downregulated SS expression in serum and tissues （P<0.05， P<0.01）. Immunohistochemistry and Western blot demonstrated that SCF and c-Kit protein expression was decreased in the model group （P<0.05， P<0.01）， which was reversed by WWSG intervention （P<0.05）. ConclusionWWSG exerts therapeutic effects on FD with spleen-stomach deficiency cold syndrome in rats， potentially by regulating the SCF/c-Kit signaling pathway to enhance gastrointestinal motility.
