Persistent inflammation and oxidative stress are two biological processes that reinforce each other and can inhibit tissue repair. Long-term conventional antiinflammatory therapy can cause side effects; therefore, safer, natural-based therapies are needed. One approach that has the potential to support the tissue repair process is the use of bioactive peptides from Spirulina platensis, which are known to possess various physiological activities. This study aims to identify the bioactive peptide profile of Spirulina platensis and to evaluate its antioxidant and antiinflammatory activities, as well as its potential to support regeneration, using a zebrafish (Danio rerio) model in vivo. Spirulina platensis protein was extracted using phosphate buffer and sonication, purified via ammonium sulfate fractionation, and then gradually hydrolyzed using papain and Flavorzyme to obtain low-molecular-weight peptides. Protein concentration was determined using the Bradford method, while the peptide profile was analyzed using SDS-PAGE. Antioxidant activity was evaluated using the ABTS assay to determine the EC50 value. Regenerative support activity was tested using a zebrafish caudal fin amputation model, both with and without oxidative stress induction via UVB radiation. The results showed that bioactive peptides from crude protein (PK) had a protein concentration of 1.00 ± 0.08 mg/mL, while the 40% ammonium sulfate fraction (AS40) had the highest protein content at 2.10 ± 0.17 mg/mL. SDS-PAGE analysis showed that the hydrolysis process produced peptides with a dominant molecular weight of <10 kDa, which falls within the general range of low-molecular-weight bioactive peptides. Antioxidant assays for protein hydrolysates revealed EC50 values of 14.789 ?g/mL for PK and 29.578 ?g/mL for AS40, which are classified as having strong antioxidant activity. Regeneration test results indicated potential regenerative support, with the protein hydrolysate exhibiting significantly better regenerative support activity compared to the protein extract. In contrast, observations of macrophage migration showed no significant differences compared to the control group. Based on these results, bioactive peptides from Spirulina platensis have the potential to support tissue regeneration, primarily through antioxidant activity, which is thought to play a role in suppressing the accumulation of reactive oxygen species. However, a direct antiinflammatory effect based on macrophage migration could not be demonstrated in this study. These findings support the potential of bioactive peptides from Spirulina platensis as candidates for bioactive compounds that support tissue regeneration and provide a basis for further research on the molecular mechanisms involved.
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