Coptisine alleviates MNNG-induced GES-1 cell damage and chronic atrophic gastritis in rats by modulating apoptosis-related proteins, amino acid metabolism, and the PI3K/Akt signaling pathway

Chronic atrophic gastritis (CAG) progression is driven by dysregulated apoptosis. Coptisine (COPT), a natural alkaloid, shows potential in gastrointestinal diseases, but its mechanisms for targeting apoptosis in CAG remain unclear. This study examined COPT’s effects on MNNG-induced GES-1 cells (MCs, GES-1 cells injured by 40 μM N-methyl-N'-nitro-N-nitrosoguanidine for 24 h) damage and CAG in rats, focusing on apoptosis-related proteins. In vitro , 5 μM COPT reduced apoptosis in MNNG-injured MC cells (25.6%→15.1%, P <0.05) by modulating apoptosis-related proteins, and caused G0/G1 cell cycle arrest ( P <0.05). In vivo , COPT alleviated mucosal atrophy and inflammation in rat CAG, decreased the gastric mucosal apoptotic index ( P <0.05), normalized PGA/PGC and GAST, and downregulated IL-6/IL-1β/TNF-α ( P <0.05), similar to Vitaco. COPT reversed amino acid metabolism disorders, docked with AKT1, and suppressed the PI3K/Akt pathway ( P <0.05), a key Pathway in apoptosis regulation. Overall, COPT may alleviate MNNG-induced MCs damage and mitigate CAG in rats, potentially by targeting apoptotic pathways via modulation of the PI3K/Akt pathway. This provides preliminary evidence for its potential as a candidate for clinical application in CAG. Schematic diagram shows Coptisine alleviates CAG by targeting apoptosis via PI3K/Akt pathway, reducing MNNG-induced cell damage. CAG: Chronic atrophic gastritis; PI3K: phosphatidylinositol-4,5-bisphosphate 3-kinase; Akt: protein kinase B.