| Abstrak/Abstract |
Research background. Chronic and uncontrolled inflammation can precipitate a range of diseases within the body. Inflammation is mainly linked to cyclooxygenase-2 (COX-2) upregulation and overexpression. Several bioactive peptides from marine organisms have been demonstrated to inhibit COX-2. The peptide derived from peanut worm (Siphonosoma australe) collagen has not exhibited COX-2 inhibitory activity. This study aimed to know the COX-2 inhibitory activity of peanut worm collagen utilizing pepsin-pancreatin during in vitro simulated digestion.
Experimental approach. During simulated in vitro digestion, commercial pepsin (at pH 3) and pancreatin (at pH 7.5) were applied for 240 min at 37 °C to evaluate the degree of hydrolysis, peptide concentration, and COX-2 inhibitory activity. Samples showing the most significant COX-2 inhibitory activity were subsequently separated into fractions and identified.
Results and conclusions. The 210 min in vitro simulated digestion showed the highest COX-2 inhibitory activity (64.31 %). This finding was confirmed by the elevated degree of hydrolysis (DH) and peptide concentrations observed during the in vitro simulated digestion. The peptide fraction of <1 kDa exhibited the highest inhibitory activity (89.05 %), followed by peptide sequencing. Three novel peptides, ADIAGQAAQVLR, LNNEITTLR, and VGTVEK, were identified and contain crucial amino acids, confirming them as COX-2 inhibitors. VGTVEK has the most potent interaction, as shown by the lowest binding energy (−4.41 kcal/mol). The molecular docking revealed that VGTVEK (631.35 Da) binds to the active side of COX-2, forming hydrogen bonds with Gln178, Leu338, Ser339, Tyr371, Ile503, Phe504, Val509, and Ser516 and hydrophobic interactions with Met99, Val102, Val330, Ile331, Tyr334, Val335, Leu345, Trp373, Leu517, and Leu520. Other biological activities of the produced peptides included ACE inhibitors, DPP-IV inhibitors, and α-glucosidase inhibitors. According to the toxicity prediction, peptides have been classified as non-toxic.
Novelty and scientific contribution. This research found that consuming peanut worm collagen contributed to producing more potent COX-2 inhibitory peptides during the digestion process in the gastrointestinal tract. Peanut worm peptide, which has the lowest molecular weight, has shown significant effectiveness as a COX-2 inhibitor and is safe to consume. |
