Network pharmacology-based exploration of the mechanism of Wenweishu granule in treating chronic atrophic gastritis with spleen-stomach cold deficiency syndrome
Jia Zheng , Zhiyong Jiao , Xinyu Yang , Qing Ruan , Yuzhe Huang , Cheng Jin , Shuangying Gui , Zihua Xuan , Xiaoyi Jia
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引用次数: 0
Abstract
Ethnopharmacological relevance
Wenweishu (WWS) is a traditional Chinese medicine compound formulated for chronic atrophic gastritis (CAG) treatment by warming the stomach and alleviating pain. However, its pharmacological mechanisms remain underexplored.
Aim of the study
This study investigated the therapeutic effects and potential mechanisms of WWS on CAG with spleen-stomach cold deficiency syndrome (SSCDS).
Methods
To achieve this, an SSCDS-CAG rat model and a human gastric mucosal epithelial cells (GES-1) cell model were established using multi-factor modeling and N-Methyl-N′-nitro-N-nitrosoguanidine (MNNG) induction, respectively. WWS's effects on gastric injury were evaluated through pathology, inflammation, serum biomarkers, and apoptosis. Additionally, MNNG's effects on GES-1 cells were analyzed. Network pharmacology, involving protein-protein interaction networks, GO/KEGG enrichment, and molecular docking, was employed to predict WWS's potential targets and mechanisms in SSCDS-CAG. Mechanistic insights were further validated using immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and western blotting.
Results
In vivo results showed that WWS alleviated symptoms in SSCDS-CAG rats, lowering symptom scores and improving gastric histopathology. It modulated serum biomarkers and reduced inflammation and apoptosis in both in vivo and in vitro studies. Network pharmacology results revealed 263 overlapping targets between WWS and SSCDS-CAG, associated with apoptosis, inflammation, and the PI3K/AKT pathway. Molecular docking revealed strong binding affinity between the core target and active WWS components. In SSCDS-CAG rats and GES-1 cells, WWS inhibited PI3K/AKT phosphorylation, increased PTEN expression, and regulated Bcl-2, Bax, and cleaved caspase-3 levels.
Conclusion
WWS reduces inflammation and apoptosis in multi-factor CAG rats and MNNG-induced GES-1 cells by modulating the PTEN/PI3K/AKT signaling pathway and apoptosis-related proteins.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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