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Abstract

Introduction

Chronic atrophic gastritis (CAG) is the initial phase in the carcinogenesis of gastric cancer (GC). Therefore, effective treatment for CAG is important in reducing the risk of GC progression. As an isoflavone compound, formononetin (FMN) has been identified as a potential therapeutic agent for acute gastric ulcers and GC. However, no study has reported the protective effect of FMN against CAG and its underlying mechanism. This study aimed to explore the therapeutic effects of FMN on CAG and its underlying mechanisms

Methods

Network pharmacology was applied to predict the core targets of FMN therapy in CAG. The CAG cell model was developed using N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-triggered human gastric epithelial cells (GES-1). The CCK-8 assay was applied to estimate cellular viability. The expression of inflammatory cytokines in cell supernatant was detected by ELISA. The protein levels and localization of nuclear receptor coactivator 1 (NCOA1), c-Jun, and c-Fos were evaluated using western blotting and immunofluorescence staining. Cell apoptosis was measured using flow cytometry.

Results

Network pharmacology analysis identified c-Jun as the core target of FMN in the treatment of CAG, with biological processes primarily involving the regulation of apoptosis and inflammation. , MNNG exposure reduced GES-1 cell viability as well as increased inflammation and cellular apoptosis, and these effects were reversed by FMN treatment. In detail, FMN decreased the protein levels of NCOA1, c-Jun, and c-Fos in MNNG-triggered GES-1 cells. The activator protein-1 (AP-1) inhibitor T-5224 enhanced the effects of FMN treatment on cell viability, inflammatory response, and apoptosis in MNNG-triggered GES-1 cells.

Discussion

This study employed network pharmacology analysis to identify FMN's therapeutic targets for CAG and validated the underlying mechanisms in vitro. While these results are promising, in vivo validation is required to confirm the efficacy of FMN. A comparative pharmacological evaluation against existing therapeutic agents and bioactive compounds would further elucidate FMN's therapeutic potential for CAG treatment.

Conclusion

FMN ameliorated the cell damage that MNNG triggered in GES-1 cells. The mechanism involved the anti-inflammatory and anti-apoptotic effects of FMN modulation of the NCOA1/AP-1 signaling axis. The present preliminary study found FMN to exhibit a potential therapeutic effect against CAG.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2025-07-03
2025-09-14

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Formononetin Alleviates MNNG-Triggered Chronic Atrophic Gastritis: Its Potential Mechanisms
Bentham Science Publishers ; https://doi.org/10.2174/0113862073409559250618212035
/content/journals/cchts/10.2174/0113862073409559250618212035
/content/journals/cchts/10.2174/0113862073409559250618212035
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  • Article Type:     Research Article
Keywords: apoptosis ; chronic atrophic gastritis ; nuclear receptor coactivator 1 ; Formononetin ; activator protein-1 ; inflammation

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