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To assess the safety of tuna peptides, cells were treated with 200 µM of peptide S1–8, which maintained viability above 90%, comparable to the blank control (100.00 ± 18.18%) and non-toxic relative to the positive control (134.31 ± 10.75%) (Figure 1B).

In the CSE-induced injury model (cell viability: 50.89 ± 2.68% vs. control), pretreatment with tuna peptides S1, S5, S6, and S7 significantly restored viability... (Figure 1B).

pretreatment with S1, S5, S6, and S7 significantly reduced ROS levels in a concentration-dependent manner. (Figure 2A,B)

In comparison to the model group, all tuna peptide treatment groups at a concentration of 200 μM demonstrated enhanced cellular antioxidant capacity, characterized by increased CAT and SOD activities, elevated GSH levels, and reduced MDA levels (p < 0.001). (Figure 3)

At a concentration of 200 μM, the tuna peptide treatment groups (S1, S6, and S7) showed a significant reduction in these inflammatory markers compared to the model group. (Figure 4)

At a concentration of 200 µM, the apoptosis rate in the peptide-treated groups was significantly lower than that in the model group (p < 0.001). (Figure 5)

treatment with tuna peptides S1, S5, S6, and S7, resulted in a significant reduction in green fluorescence and a notable increase in red fluorescence (p < 0.001), suggesting that these peptides effectively restored MMP and inhibited CSE-induced apoptosis. (Figure 6)

tuna peptides S1, S5, S6, and S7 significantly promote the migration of MLE-12 cells and accelerate wound closure in a concentration-dependent manner. (Figure 7)

pretreatment with 200 μM tuna peptides S1, S5, S6, and S7 significantly increased Nrf2 mRNA expression and decreased Keap1 mRNA expression in MLE-12 cells compared to the model group. (Figure 8)

At a concentration of 200 μM, the nuclear Nrf2 levels in the S1 and S6 peptide-treated groups showed significant higher compared to the model group (p < 0.05). (Figure 9)

treatment with 200 µM tuna peptides S1, S5, S6, and S7 significantly reduced p65 mRNA expression and increased IκBα mRNA expression (p < 0.001). (Figure 11A,B)

pretreatment with 200 μM tuna peptides S1, S5, S6, and S7 significantly increased the Bcl-2/Bax mRNA expression ratio compared to the model group, with highly significant differences (p < 0.001). (Figure 11C)