Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 68, Issue 8, Pages 2393-2405Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.9b07687
Keywords
casein hydrolysate; oxidative stress; Nrf2; diabetes mellitus; peptidomic
Funding
- National Key R&D Program of China [2018YFD0901102]
- National Natural Science Foundation of China [31801478]
- National Postdoctoral Program for Innovative Talents of China [BX201700081]
- Fundamental Research Funds for the Central Universities [2018MS91]
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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.
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