Sequential Hydrolysis of Jellyfish Cotylorhiza tuberculata Reveals Tissue-Specific Bioactivities

The increasing incidence of jellyfish blooms and the consequent accumulation of jellyfish bycatch impose the need to explore new strategies for the valorization of this marine biomass. Jellyfish are attracting growing interest as sustainable sources of proteins, collagen, and bioactive peptides with potential applications in food, nutraceutical, and biotechnological fields. In this work, the Mediterranean jellyfish Cotylorhiza tuberculata was investigated as a source of proteinaceous fractions and enzymatic hydrolysates. Umbrella and oral arms were processed separately by phosphate-buffered saline (PBS) extraction, followed by sequential enzymatic digestion of the insoluble material with pepsin and collagenase. The resulting extracts were fractionated by membrane ultrafiltration and characterized for protein content. The fractions were then tested for antioxidant activity, angiotensin-I-converting enzyme (ACE) inhibition, effects on A2058 melanoma and HaCaT keratinocyte viability, and modulation of IL-6 response in intestinal Caco-2 cells. Collagenase-derived fractions showed the highest antioxidant activity, while ACE-inhibitory activity was mainly associated with pepsin-derived samples. Selected umbrella-derived fractions differentially affected A2058 and HaCaT cell viability. Finally, preliminary Caco-2 experiments indicated limited, fraction-dependent modulation of IL-6 levels. Overall, these results suggest that C. tuberculata may represent a useful source of protein-derived fractions with in vitro antioxidant and ACE-inhibitory activities, supporting further investigation of jellyfish bycatch as a resource for functional ingredients.