Exploring the mechanism of acupuncture for Chronic Atrophic Gastritis based on bioinformatics and network topology strategies.

BACKGROUND: Chronic atrophic gastritis (CAG) is a progressive gastric disorder with the potential for malignant transformation. Conventional treatments primarily focus on Helicobacter pylori eradication and symptom management; however, long-term use may be associated with hepatic or renal adverse effects. Although acupuncture has demonstrated therapeutic benefits in CAG, its underlying mechanisms remain insufficiently understood. This study aimed to investigate the multi-target mechanisms of acupuncture in CAG through an integrated strategy combining network pharmacology and experimental validation.

METHODS: An integrative approach involving bioinformatics, text mining, and network analysis was employed, followed by in vivo validation in a rat model of CAG. Bioactive compounds generated following acupuncture intervention were identified through literature retrieval, and their potential targets were predicted using Search Tool for Interacting Chemicals (STITCH) and SwissTargetPrediction. CAG-related targets were collected from the GeneCards, OMIM, and UniProt databases. The overlapping targets were used to construct a protein-protein interaction network in Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DAVID. For experimental validation, CAG was induced in rats, followed by acupuncture treatment. Gastric antral tissues were evaluated by histological staining, including hematoxylin-eosin and Prussian blue staining, as well as molecular assays, including western blotting, immunohistochemistry, immunofluorescence, and ELISA, to assess the expression of IL-6, TNF-α, IL-1β, GSH, mTOR, GPX4, FTH1, TP53, and Fe3+.

RESULTS: A total of 98 potential therapeutic targets and 159 signaling pathways associated with acupuncture treatment for CAG were identified, with TP53- and mTOR-related signaling pathways emerging as key regulatory pathways. In the rat model, CAG induced marked gastric pathological injury, iron accumulation, and increased inflammatory cytokine levels, accompanied by reduced levels of GSH, TP53, mTOR, GPX4, and FTH1. Acupuncture treatment significantly alleviated gastric mucosal atrophy and inflammation, reduced Fe3+ deposition and pro-inflammatory cytokine levels, and upregulated ferroptosis-related proteins.

CONCLUSION: Acupuncture may ameliorate CAG by modulating the TP53 and mTOR signaling pathways, regulating ferroptosis, attenuating mucosal injury, and improving gastric pathological alterations.