Network pharmacology-based study on the mechanism of Yiwei Decoction in chronic atrophic gastritis and experimental assessment

Abstract

Objective: Yiwei Decoction (YWD) is an ancient TCM formula with historical use in treating chronic atrophic gastritis (CAG). However, its pharmacodynamic mechanisms remain poorly understood. This study aims to study the effect of YWD on CAG through network pharmacology and experimental verification. Methods: UPLC/MS and the SwissADME database were employed to identify active compounds in YWD. YWD targets were screened by SwissTargetPrediction databases, CAG targets were screened by databases, and the two were intersected for PPI network analysis. The target prediction was performed by GO and KEGG analysis. H2O2-induced injury models were established in zebrafish and GES-1 ​cells, which were subsequently treated with varying doses of YWD. Oxidative stress indicators and apoptosis and inflammation levels in zebrafish and GES-1 ​cells were assessed using fluorescence microscopy, flow cytometry, and microplate reader assays. The binding capabilities of the core components and core targets were examined using molecular docking. Q-PCR and Western blot were employed to analyze the expression levels of Nrf2, Keap1, and HO-1, respectively. Results: Forty-nine compounds were identified from YWD. Network pharmacological analysis suggested that YWD may treat CAG by modulating redox-related signaling pathways, inhibiting apoptosis, and reducing inflammation. Subsequent in vitro and in vivo experiments validated these predictions. YWD effectively mitigated H2O2-induced oxidative stress in zebrafish and GES-1 ​cells, suppressing ROS and decreasing apoptosis. YWD reduced inflammation in gastric epithelial cells. Molecular docking results suggested that methylophiopogonanone A and imperatorin may play a key role in the treatment of YWD. Mechanistically, YWD activated the Nrf2 signaling pathway, downregulated Keap1 expression, and upregulated HO-1 and Bcl2 expression. Conclusion: YWD could improve oxidative stress indicators, inhibiting cell apoptosis, reducing inflammation, and its molecular mechanism of the CAG treatment may be through the Keap1/Nrf2/HO-1 pathways, and to promote the body's antioxidant system.

Keywords

• Yiwei Decoction
• Chronic atrophic gastritis
• Network pharmacology
• Zebrafish
• GES-1
• Oxidative stress