Corn Protein-Derived Bioactive Peptides Protect Gastric Epithelial Cells from Helicobacter pylori-Induced Injury by Alleviating Oxidative Stress, Mitochondrial Dysfunction, and Inflammation

H. pylori infection induces oxidative stress and inflammatory responses in gastric epithelial cells, which are key factors in the pathogenesis of gastritis and ulcers. Given the increasing threat of antibiotic resistance, non-antibiotic approaches that target host cell injury mechanisms are gaining considerable interest. While peptides derived from corn protein are known for their antioxidant and anti-inflammatory activities, whether they can alleviate H. pylori-induced gastric epithelial injury remains unclear. In this study, we evaluated the preventive effects of corn protein-derived bioactive peptides (CPDP-N), prepared by neutral protease hydrolysis, against H. pylori-triggered injury in human GES-1 cells. CPDP-N exhibited no cytotoxic effects, reduced H. pylori-induced intracellular ROS accumulation in a dose-dependent manner, and markedly increased the activities of intracellular antioxidant enzymes. Flow cytometry and fluorescence imaging demonstrated that CPDP-N attenuated the loss of mitochondrial membrane potential and relieved G0/G1 cell cycle arrest. CPDP-N markedly suppressed the secretion of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-8, attenuated LDH release, and upregulated the anti-inflammatory cytokine IL-10. Moreover, CPDP-N markedly lowered the H. pylori-induced elevation of nuclear factor kappa-B (NF-κB) p65 protein, a key regulator of inflammatory signaling. These protective effects were accompanied by reduced intracellular ROS levels and lower NF-κB p65 abundance, suggesting the involvement of oxidative stress and NF-κB pathways. Collectively, these findings demonstrate that corn protein-derived peptides can protect gastric epithelial cells from H. pylori-induced oxidative and inflammatory injury, highlighting their potential as a dietary intervention for H. pylori-associated gastric diseases.