Round Scad-Derived Octapeptide WCPFSRSF Confers Neuroprotection by Regulating Akt/Nrf2/NFκB Signaling

Abstract

We previously identified peptides derived from round scad as potential Nrf2 activators. However, the neuroprotection of these peptides is still unclear. In this study, we aimed to investigate the neuroprotective effect of WCPFSRSF against glutamateinduced neurotoxicity, and the memory-improving effects of WCPFSRSF in mice were also explored. Results showed that WCPFSRSF ameliorated oxidative stress by improving the activities of antioxidant enzymes and promoting the Nrf2-mediated endogenous defense system. Moreover, there is an interaction between the up-regulation of Nrf2 and the down-regulation of NFκB induced by the peptide, which was related to the generation of reactive oxygen species (ROS) and could be abolished by the Akt inhibitor LY294002. Further analysis demonstrated that WCPFSRSF may act as a radical scavenger and Nrf2 activator. The antioxidant and anti-inflammatory effects might be related to the Cys and Trp in WCPFSRSF. Moreover, WCPFSRSF could improve spatial memory impairment in sleep-deprived mice. Thus, this work provided evidence for WCPFSRSF as a potential candidate against neurotoxicity and memory deficits.

In Vitro Simulated Gastrointestinal Digestion Stability of a Neuroprotective Octapeptide WCPFSRSF and Prediction of Potential Bioactive Peptides in Its Digestive Fragments by Multiple Bioinformatics Tools

“…Our previous transcriptome study suggested that WCPFSRSF altered the inflammatory-related pathways including TNF, NFκB, IL-17, and IL-6 pathways in the hippocampus of mice . WCPFSRSF also acted as a Keap1 inhibitor to modulate the Nrf2-related endogenous antioxidant system in cells . Therefore, Keap1 protein and other 10 inflammatory-related biomacromolecules were selected.…”

“…Lactate dehydrogenase (LDH) and reactive oxygen species (ROS) were measured as previously described . Briefly, the cells were seeded at a density of 2 × 10 5 cells/mL on 96-well plates for 24 h; then, peptides dissolved in the medium were added to the culture for 24 h in the presence of glutamate, and the levels of LDH and ROS were measured by analysis kits (Beyotime Biotechnology Institute).…”

“…13 Moreover, WCPFSRSF could inhibit oxidative stress by promoting endogenous antioxidant defense systems via the Nrf2 signaling pathway. 5 In addition, the amino acid composition and specific sequences or positions may be associated with the neuroprotective potential of peptides in the cellular system. 25,26…”

“…Maintaining the biological ability of peptides after gastrointestinal digestion is a prerequisite for reaching target organs to exert their capabilities . Our previous studies have shown that the round scad-derived peptide Trp-Cys-Pro-Phe-Ser-Arg-Ser-Phe (WCPFSRSF) could improve memory impairment in mice . However, whether WCPFSRSF exerted memory improvement in vivo through its intact form or new peptides produced during digestion has not yet been explored.…”

Food Protein-Derived Antioxidant Peptides: Molecular Mechanism, Stability and Bioavailability

“…However, due to its relatively small size, dark colour, susceptibility to spoilage, and poor taste, it is not suitable for commercial fish consumption [ 66 ]. In this regard, the biological antioxidant capacity and mechanism of Round scad protein-derived peptides WCPFSRSF and ILGATIDNSK have been confirmed [ 43 , 67 ]. Thus, a broad range of marine organisms or by-products can be exploited as raw materials for the elaboration of natural antioxidants, meaning that it has the potential to be used as a functional ingredient in the food, cosmetic, and pharmaceutical industries.…”