Formononetin Alleviates MNNG-Triggered Chronic Atrophic Gastritis: Its Potential Mechanisms

Area of Science:

• Gastroenterology
• Molecular Biology
• Pharmacology

Background:

• Chronic atrophic gastritis (CAG) is a precursor to gastric cancer (GC).
• Formononetin (FMN), an isoflavone, shows potential for treating gastric ulcers and GC.
• The protective effects of FMN against CAG and its mechanisms remain uninvestigated.

Purpose of the Study:

• To investigate the therapeutic effects of FMN on CAG in vitro.
• To elucidate the underlying molecular mechanisms of FMN in treating CAG.

Main Methods:

• Network pharmacology identified core targets of FMN in CAG.
• A CAG cell model was established using MNNG-induced GES-1 cells.
• Cell viability, inflammatory cytokines, apoptosis, and protein expression (NCOA1, c-Jun, c-Fos) were assessed.

Main Results:

• Network pharmacology identified c-Jun as a core target, regulating apoptosis and inflammation.
• FMN treatment reversed MNNG-induced decreases in cell viability and increases in inflammation and apoptosis.
• FMN reduced NCOA1, c-Jun, and c-Fos protein levels; an AP-1 inhibitor enhanced FMN's effects.

Conclusions:

• FMN ameliorates MNNG-induced cell damage in GES-1 cells.
• FMN exerts anti-inflammatory and anti-apoptotic effects by modulating the NCOA1/AP-1 signaling pathway.
• FMN demonstrates potential therapeutic efficacy against CAG.