{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:36:43Z","timestamp":1777869403910,"version":"3.51.4"},"reference-count":63,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009110","name":"Natural Science Foundation of Xinjiang Uygur Autonomous Region","doi-asserted-by":"publisher","award":["2022D01C680"],"award-info":[{"award-number":["2022D01C680"]}],"id":[{"id":"10.13039\/100009110","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Research and Development Program of Xinjiang Uygur Autonomous Region","award":["2023B02034-1"],"award-info":[{"award-number":["2023B02034-1"]}]},{"name":"Key Research and Development Program of Xinjiang Uygur Autonomous Region","award":["2025B04032-001"],"award-info":[{"award-number":["2025B04032-001"]}]},{"name":"Xin Jiang Agriculture Research System Fund project","award":["XJARS-11"],"award-info":[{"award-number":["XJARS-11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Hypertension is a severe global public health issue. Food-derived angiotensin-converting enzyme (ACE)-inhibitory peptides have shown great potential as safe and effective alternatives to synthetic antihypertensive drugs. Camel milk is rich in bioactive peptides. This study aimed to screen for ACE-inhibitory peptides from hydrolyzed camel casein, explore their inhibitory mechanisms and endothelial protective effects in vitro, and reveal their potential antihypertensive pathways using network pharmacology. This study screened three peptides with angiotensin-converting enzyme (ACE) inhibitory activity from enzymatically hydrolyzed camel casein components: MVPFLQPK, VPFLQPKVM, and QKWKFL, with IC50 values of 277.1, 396.9, and 486.9 \u03bcmol\/L, respectively. Enzyme inhibition kinetics analysis indicated that MVPFLQPK exhibited a non-competitive inhibition pattern, VPFLQPKVM exhibited a mixed inhibition pattern, and QKWKFL exhibited a competitive inhibition pattern. Molecular docking revealed that all three peptides formed hydrogen bond interactions with ACE, and QKWKFL and VPFLQPKVM directly bound to the enzyme\u2019s active site to inhibit substrate catalysis. Molecular dynamics simulation further confirmed the high stability of the three peptide\u2013ACE complexes, with binding free energies from \u221234.24 to \u221251.19 kcal\/mol. The primary contributing forces include hydrogen bonds, van der Waals interactions, electrostatic forces, and nonpolar solvation effects. Network pharmacology analysis suggested that these peptides may exert synergistic antihypertensive effects by regulating multiple blood pressure-related pathways, including the renin\u2013angiotensin system, renin secretion, and calcium signaling pathways, by acting on key targets such as ACE, REN, SRC, and MMP9. Cell experiments demonstrated that all three peptides exhibited no cytotoxicity in the Ang II-induced HUVEC injury model, significantly promoted NO release, inhibited ET-1 secretion, and possessed endothelial protective potential. This study investigated the in vitro ACE-inhibitory mechanism of peptides derived from camel milk and their potential role in blood pressure regulation, providing experimental evidence for subsequent in vivo activity validation and the development of functional camel milk protein products.<\/jats:p>","DOI":"10.3390\/nu18091436","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:32:21Z","timestamp":1777555941000},"page":"1436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition Mechanism, Multi-Target Regulation, and Protective Effects of Camel Casein ACE-Inhibitory Peptide on HUVECs Cells"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5112-0303","authenticated-orcid":false,"given":"Fei","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Smart Agriculture (Research Institute), Xinjiang University, Urumqi 830017, China"},{"name":"Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science & Technology, Urumqi 830017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Miao","sequence":"additional","affiliation":[{"name":"College of Smart Agriculture (Research Institute), Xinjiang University, Urumqi 830017, China"},{"name":"Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science & Technology, Urumqi 830017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenkun","family":"Huo","sequence":"additional","affiliation":[{"name":"College of Smart Agriculture (Research Institute), Xinjiang University, Urumqi 830017, China"},{"name":"Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science & Technology, Urumqi 830017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruiqi","family":"He","sequence":"additional","affiliation":[{"name":"College of Smart Agriculture (Research Institute), Xinjiang University, Urumqi 830017, China"},{"name":"Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science & Technology, Urumqi 830017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Qin","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science & Technology, Urumqi 830017, China"},{"name":"Xinjiang Camel Industry Engineering Technology Research Center, Urumqi 830046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science & Technology, Urumqi 830017, China"},{"name":"Xinjiang Camel Industry Engineering Technology Research Center, Urumqi 830046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongkai","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Smart Agriculture (Research Institute), Xinjiang University, Urumqi 830017, China"},{"name":"Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science & Technology, Urumqi 830017, China"},{"name":"Xinjiang Camel Industry Engineering Technology Research Center, Urumqi 830046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s11906-013-0340-9","article-title":"Muntner, High blood pressure: The leading global burden of disease risk factor and the need for worldwide prevention programs","volume":"15","author":"Bromfield","year":"2013","journal-title":"Curr. 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