Two Antihypertensive and Antioxidant Peptides Derived from Alaska Pollack (Theragra chalcograma) Skin: In Silico, In Vitro, and In Vivo Investigation

• DOI: 10.1021/acs.jafc.5c00166
• Publication Date: 2025-04-10T12:18:00Z
• Authors: Jing Li; Duo Cai; Yong-Nian Zhai; Chen-Xi Wu; Hai-Lin Zhang; Jian Zhang; Cheng-Lin Liu; Shi-Hai Liu; Jian-Bo Qu

This study aimed to identify and characterize two novel dual-functional peptides with antihypertensive antioxidant activities from byproducts of Alaska pollock skin (APS). Results showed that fifty-nine were identified APS, which peptides, GP1 (GSAGPAGPSGPRGP) GP2 (LGDARNSPAPP), predicted exhibit the highest angiotensin-converting enzyme (ACE) inhibitory activities. demonstrated favorable ACE (IC50 values 0.166 0.177 mmol/L, respectively) significantly reduced blood pressure in hypertensive rats. Additionally, both effectively scavenged 2,2'-casino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, EC50 0.273 0.629 mg/mL protected HepG2 cells against H2O2-induced damage. Molecular docking revealed interacted amino acid residues within active pocket at entrance channel ACE, displaying mixed-competitive inhibition patterns. These could also bind Kelch domain Kelch-like ECH associating protein (Keap1), thereby promoting nuclear factor erythroid 2-related 2 (Nrf2)-mediated transcriptional activation enzymes through Keap1-Nrf2 pathway. The dual properties APS coupled high gastrointestinal stability, validated their utilization as multifunctional ingredients functional foods, nutraceuticals, peptide-based hydrogel development.