Tricholoma matsutake-Derived Peptides Show Gastroprotective Effects against Ethanol-Induced Acute Gastric Injury

Acute gastric injury caused by ethanol is a frequent disorder of the gastrointestinal tract. In this study, we investigated the potential gastroprotective effects of Tricholoma matsutake-derived peptides against ethanol-triggered acute gastric injury and the associated mechanisms. Peptides SDLKHFPF and SDIKHFPF significantly attenuated the ethanol-induced decrease in GES-1 cell survival (82.39 ± 1.93 and 80.10 ± 1.08% vs 56.58 ± 1.86%), inhibited GES-1 cell apoptosis, and alleviated the ethanol-induced gastric mucosal injury (64.76 ± 3.98 and 49.29 ± 3.25%), ulcer index (3.33 ± 0.47 and 4.67 ± 0.47 vs 6.67 ± 0.47), and histopathological changes in mice. Peptide treatment inhibited the phosphorylation and nuclear translocation of nuclear factor kappa B (NF-κB), the secretion of tumor necrosis factor-α, interleukin-6, and endothelin-1. In addition, T. matsutake peptide pretreatment increased growth factor secretion, upregulated B-cell lymphoma-2, downregulated Bcl-2-associated X (Bax), and cleaved cysteinyl aspartate specific proteinase 3, thereby promoting gastric cell survival. These findings strongly suggest that T. matsutake peptides attenuate ethanol-induced inflammatory responses and apoptosis by suppressing NF-κB signaling activation, thereby enhancing gastric epithelial barrier functions.