Intracellular ethanol‐mediated oxidation and apoptosis in HepG2/CYP2E1 cells impaired by two active peptides from seahorse (Hippocampus kuda bleeler) protein hydrolysates via the Nrf2/HO‐1 and akt pathways

Seahorse (Hippocampus kuda Bleeler) are representative marine species in aquaculture, with special value of medicine and food. In this study, the protective effects of two peptides from seahorse hydrolysates (SHP‐1 and SHP‐2) against ethanol‐mediated oxidative stress in HepG2/CYP2E1 cells were investigated. Firstly, SHP‐1 and SHP‐2 presented no cytotoxicity. Compared with the ethanol‐treated groups, SHP‐1 and SHP‐2 increased cell viability in a concentration‐dependent manner. Secondly, SHP‐1 and SHP‐2 markedly reduced intracellular reactive oxygen species (ROS) generation, gamma‐glutamyltranspeptidase (GGT) activity, and tumor necrosis factor‐α (TNF‐α) levels and remarkably enhanced superoxide dismutase (SOD) and glutathione (GSH) activities. SHP‐1 and SHP‐2 also down‐regulated the expressions of GGT, bax, c‐caspase‐8/‐9/‐3, p‐Akt, p‐IκB‐α, p‐p65, p‐ERK, and p‐p38 but up‐regulated SOD, GSH, NF‐E2‐related factor 2 (Nrf2), heme oxygenase‐1 (HO‐1), and bcl‐2 levels, as revealed by Western blot analysis. Moreover, SHP‐1 and SHP‐2 increased the mitochondrial membrane potential (MMP), reduced DNA damage, and suppressed the nuclear translocation of p65. These results suggest that two peptides from seahorse hydrolysates can be considered a potential functional biomaterial and further improve the use value of seahorse in aquaculture.