Evaluation and Exploration of Potentially Bioactive Peptides in Casein Hydrolysates against Liver Oxidative Damage in STZ/HFD-Induced Diabetic Rats

Hyperglycemia-induced oxidative stress can cause liver damage in diabetes, and protein hydrolysates with antidiabetic and antioxidant properties are emerging as a potential therapy. In this study, protective effects of casein hydrolysates against live oxidative damage in streptozotocin/high-fat-induced diabetic rats were studied and potentially bioactive peptides were explored by an integrated approach of differential peptide and in silico analysis. Results showed that different casein hydrolysates significantly alleviated liver oxidative damage (p < 0.05) via different mechanisms. Particularly, casein hydrolyzed by a papain-flavourzyme combination (P-FCH) treatment significantly improved liver antioxidant enzyme activities by enhancing nuclear factor erythroid 2-related factor 2 (Nrf2) transcription (p < 0.05). Furthermore, 18 peptides were screened as potential bioactive peptides by analyzing differential peptides among different hydrolysates combined with in silico prediction. Among them, the dipeptide WM might directly inhibit the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 interaction as potential Nrf2 activators. These results suggested that P-FCH might be an alternative way to treat liver damage in diabetes.