Identification and in silico analysis of novel antioxidant peptides from Grifola frondosa hydrolysates: Cytoprotective effects in H2O2-induced Caco-2 cells.

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Citation abstract

This study sought to extract and characterize novel antioxidant peptides from Grifola frondosa, assessing their protective effects on Caco-2 cells exposed to H 2 O 2 -induced oxidative stress. Through LC-MS/MS and molecular docking simulations targeting the Keap1-Nrf2 (PDB ID: 2FLU), four peptides FDWFK, DWFK, EPYPLP, and WDYH were identified with the highest binding affinity. In H₂O₂-stressed Caco-2 cells, these peptides showed dose-dependent cytoprotection. Among them, WDYH demonstrated superior cytoprotection, maintaining 87.52 % ± 2.46 % cellular viability when administered at 0.5 mg/mL during oxidative challenge. Furthermore, these peptides significantly reduced intracellular MDA levels while enhancing the activity of SOD and CAT (P < 0.05). Specifically, WDYH increased CAT activity by 3.18-fold and SOD activity by 1.53-fold compared to the oxidative stress-injured group. These outcomes provide perspectives on the processes behind antioxidants and structural basis of bioactive peptides derived from Grifola frondosa, supporting their potential as functional food ingredients against oxidative stress.