<i>Tricholoma matsutake</i> heptapeptide prevents gastric mucosa injury by regulating oxidative stress‐related mitochondrial function and mucous layer integrity

Abstract Short‐term excessive alcohol consumption easily leads to ethanolic gastric injury. Recent research on bioactive functional factors in preventing and treating ethanol‐induced acute gastric injury has garnered attention. This study explored the direct protective effects of the Tricholoma matsutake ‐derived peptide Ser–Ala–Pro–Trp–Gly–Leu–Ala (SAPWGLA) on ethanol‐induced acute gastric damage. The results showed that SAPWGLA showed dose‐dependent protection against gastric mucosal injury, including the regulation of oxidative stress and mitochondrial function, as well as the enhancement of mucosal barrier integrity. SAPWGLA maintained normal mitochondrial metabolism by alleviating intracellular reactive oxygen species (ROS) accumulation; 400 mg/mL SAPWGLA reduced ROS levels by 81.72 ± 1.55% and reversed the decrease of MMP by ethanol to 1.22 ± 0.01 (J‐aggregates/monomer) in GES‐1 cells. Also, SAPWGLA enhanced the tight junctions between GES‐1 cells. In addition, SAPWGLA improved the integrity of the mucosal barrier by maintaining the balance of the mucus layer and regulating the expression of TJ proteins. Daily oral administration of SAPWGLA (50 mg/kg) exhibited a restoration in hexosamine to 10.76 ± 0.73 mg/g prot, a regulation in claudin‐1, occludin, and ZO‐1 (1.21‐, 1.39‐, and 0.73‐fold of the control group). These findings suggest that SAPWGLA can be a potential novel therapeutic approach to dealing with acute gastric injury caused by ethanol.