{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:02:59Z","timestamp":1791201779949,"version":"4.2.0"},"reference-count":48,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovational Fund for Scientific and Technological Personnel of Hainan Province","award":["KJRC2023L03"],"award-info":[{"award-number":["KJRC2023L03"]}]},{"name":"Innovational Fund for Scientific and Technological Personnel of Hainan Province","award":["BK20240195"],"award-info":[{"award-number":["BK20240195"]}]},{"name":"Outstanding Youth Science Fund Project of the Natural Science Foundation of Jiangsu Province","award":["KJRC2023L03"],"award-info":[{"award-number":["KJRC2023L03"]}]},{"name":"Outstanding Youth Science Fund Project of the Natural Science Foundation of Jiangsu Province","award":["BK20240195"],"award-info":[{"award-number":["BK20240195"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This study explores the identification, characterization, and biological evaluation of angiotensin I-converting enzyme (ACE)-inhibitory peptides derived from enzymatic hydrolysates of crucian carp swim bladders. Following sequential purification by size-exclusion and reversed-phase chromatography, two bioactive peptides\u2014Hyp-Gly-Ala-Arg (Hyp-GAR) and Gly-Ala-Hyp-Gly-Ala-Arg (GA-Hyp-GAR)\u2014were identified using ultra-high-performance liquid chromatography coupled with linear ion trap\u2013Orbitrap tandem mass spectrometry. The synthetic peptides demonstrated potent ACE-inhibitory activity in vitro, with IC\u2085\u2080 values of 12.2 \u03bcM (Hyp-GAR) and 4.00 \u03bcM (GA-Hyp-GAR). Molecular docking and enzyme kinetics confirmed competitive inhibition through key interactions with ACE active site residues and zinc coordination. In vivo antihypertensive activity was evaluated in spontaneously hypertensive rats, revealing that GA-Hyp-GAR significantly reduced systolic blood pressure in a dose-dependent manner. At a dose of 36 mg\/kg, GA-Hyp-GAR reduced systolic blood pressure by 60 mmHg\u2014an effect comparable in magnitude and timing to that of captopril. Mechanistically, GA-Hyp-GAR modulated levels of angiotensin II, bradykinin, endothelial nitric oxide synthase, and nitric oxide. A 90-day subchronic oral toxicity study in mice indicated no significant hematological, biochemical, or histopathological alterations, supporting the peptide\u2019s safety profile. These findings suggest that GA-Hyp-GAR is a promising natural ACE inhibitor with potential application in functional foods or as a nutraceutical for hypertension management.<\/jats:p>","DOI":"10.3390\/molecules30132812","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T11:37:51Z","timestamp":1751283471000},"page":"2812","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Crucian Carp-Derived ACE-Inhibitory Peptides with In Vivo Antihypertensive Activity: Insights into Bioactivity, Mechanism, and Safety"],"prefix":"10.3390","volume":"30","author":[{"given":"Runxi","family":"Han","sequence":"first","affiliation":[{"name":"College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingshan","family":"Tian","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingge","family":"Han","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Experimental Teaching Center of Life Science, College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghong","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Meat Quality Control and Cultured Meat Development; Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Dai","sequence":"additional","affiliation":[{"name":"Experimental Teaching Center of Life Science, College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Meat Quality Control and Cultured Meat Development; Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"},{"name":"Sanya Institute of Nanjing Agricultural University, Sanya 572024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Boateng, E.B., and Ampofo, A.G. 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