Berberine improves mitochondrial dysfunction in cells with atrophic gastritis via AMPK/PINK1/PRKN-dependent mitophagy

This study investigated the mechanisms of berberine (BBR) in chronic atrophic gastritis (CAG). In MNNG-treated GES-1 cells, BBR ameliorated mitochondrial dysfunction, enhanced cell viability and ATP production, restored mitochondrial membrane potential, and reduced mtROS levels. BBR activated PINK1/Parkin-mediated mitophagy and the AMPK/PGC-1α signaling pathway, effects that were reversed by the AMPK inhibitor Compound C. In a CAG mouse model, BBR improved gastric secretory function, alleviated histopathological damage, reduced inflammatory cytokine levels, and restored PINK1 and Parkin expression in gastric mucosa. BBR also restored AMPK phosphorylation and downstream PGC-1α expression, thereby enhancing mitophagy. Collectively, these findings demonstrate that BBR enhances PINK1/Parkin-mediated mitophagy and PGC-1α-mediated mitochondrial biogenesis by activating AMPK, ultimately restoring mitochondrial function in CAG.