Peptidomic and in silico screening of six novel antioxidant and hepatoprotective peptides in Musculus senhousei hydrolysate

Abstract

Studies have shown that Musculus senhousei is an ideal source of bioactive peptides that exhibit antioxidant and hepatoprotective properties. However, the structural features of their active peptide sequences are not yet clear. Hence, in this study, a peptidomic strategy was applied to reveal 6 novel antioxidant peptides (CVKWML, WWL, WDRW, WWWV, RSPWR, and WPRCQL) from the 2077 peptides identified in a hepatoprotective Musculus senhousei hydrolysate. Results from quantum chemical calculations and molecular docking suggested that these peptides might scavenge free radicals by donating electrons via Trp residues and non-covalent interactions with the key antioxidative target of Keap1. Validation of the antioxidant activity suggested that all the peptides exhibited stronger ABTS radical-scavenging activity than that of Trolox and could reduce the reactive oxygen species (ROS) and aminotransferase (AST and ALT) levels in hepatocytes, protecting against alcoholic hepatocyte injury. Notably, the peptides with a Trp residue at the N-terminus (WWL, WDRW, WWWV, and WPRCQL) tended to be more bioactive regardless of the strategy applied (in silico, in vitro, or in cellular). Overall, the results indicated that the N-terminus Trp residue plays a vital role on the antioxidant and hepatoprotective activities of the Musculus senhousei peptides, providing valuable insights for further establishing the structure–activity relationship of antioxidant peptides and guiding the targeted preparation of peptides as hepatoprotective functional food ingredients.