Protein hydrolysates and peptides from animal by-products as a preventive strategy for local inflammation and neuroinflammation

Identifier:  TDX:4438

Handle: https://hdl.handle.net/20.500.11797/TDX4438

Authors:  Ibarz Blanch, Néstor

Abstract:
Bioactive peptides obtained from food and agri-food by-products have emerged as good candidates as functional ingredients for the prevention of many inflammation-associated diseases. In this context, this doctoral thesis focused on developing protein hydrolysates from animal by-products with anti-inflammatory or neuroprotective properties and identifying their bioactive peptides. In the first part of the study, hydrolysate H8 from pigskin collagen showed the highest cyclooxygenase-2 (COX-2) inhibitory activity, which was selective for COX-2. The peptide fraction <10 kDa of H8 prevented localized acute inflammation in a carrageenan-induced paw edema model and exhibited antinociceptive capacity in an acute pain model after topical application to rats. This peptide fraction reduced nitric oxide production, COX-2 activity, and COX-2 and inducible nitric oxide synthase protein expression in lipopolysaccharide-stimulated RAW 264.7 cells. Moreover, the anti-inflammatory peptides AGERGEQ and GSKGRPG were identified in the hydrolysate H8. In the second part of this thesis, twelve hydrolysates were obtained from an animal protein-rich by-product using different enzymatic hydrolysis conditions. The hydrolysates CFH3 and CFH5 showed good prolyl oligopeptidase (POP) inhibitory activity and their neuroprotective effects were studied in the Caenorhabditis elegans strain CL4176, a model of Alzheimer’s disease. CFH3 delayed paralysis induced by amyloid-ß aggregation in C. elegans in a dose-dependent manner, demonstrating its neuroprotective effects. Twenty-three novel peptides were identified in CFH3, nine of them with potential activity according to the PeptideRanker score. The results obtained support the potential of these hydrolysates as preventive tools for localized inflammation and neuroprotection, as well as for promoting sustainability and circular economy in the agri-food sector. The developed hydrolysates and the identified peptides could be useful for food and pharmacological industries to develop anti-inflammatory and neuroprotective products.