Marine Fish-Derived ACE-Inhibitory Peptides: Preparation via Enzymatic Hydrolysis and Their In Vitro Activity

Hypertension constitutes a major global public health burden. Although angiotensin-converting enzyme (ACE) inhibitors are beneficial, their adverse effects have prompted the search for safer natural alternatives. ACE-inhibitory peptides have drawn extensive research attention, attributed to their low toxicity and high bioavailability. This article reviews current advances regarding the preparation, separation, purification, and in vitro activity evaluation of these peptides obtained from different marine fish species. Raw material sources are classified into major commercial species and minor or cultured species, highlighting the influence of species and tissue origin on peptide bioactivity. Enzymatic hydrolysis, particularly single-enzyme and dual-enzyme approaches, is the main preparation method. Subsequent separation and purification, involving ultrafiltration, gel filtration chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC), are crucial for enriching bioactive fractions and identifying novel peptide sequences. Also, the classical hippuryl-histidyl-leucine (HHL)-high-performance liquid chromatography (HPLC) assay remains the standard for the evaluation of in vitro activity using IC₅₀ values. Future work emphasizes integrated in vitro and in vivo validation, AI-assisted screening, and the sustainable utilization of processing by-products to advance marine peptides as novel antihypertensive agents.