{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:31:28Z","timestamp":1791261088852,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Xinjiang Uygur Autonomous Region Tianshan Yingcai Young Talent in Scientific and Technological Innovation","award":["2023TSYCCX0073"],"award-info":[{"award-number":["2023TSYCCX0073"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Hypertension represents a leading contributor to cardiovascular disorders and premature mortality. Given the pervasive nature of adverse effects associated with current angiotensin-converting enzyme inhibitors (ACEIs), there is a significant interest in identifying novel bioactive lead compounds from natural sources. This study identifies, for the first time, three novel angiotensin-converting enzyme (ACE) inhibitory peptides released from Bungarus multicinctus (BM) via simulated gastrointestinal digestion (SGD). Methods: Active fractions were enriched by ultrafiltration and subjected to stability assessment. The peptide sequences were then determined using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS\/MS) and bioinformatics tools, followed by chemical synthesis. Finally, the inhibitory mechanism was investigated using kinetic analysis and molecular docking. Results: The intestinal digest exhibited potent ACE inhibition, with the &lt;5 kDa fraction achieving 79% inhibition at 1 mg\/mL and demonstrating favorable stability under varying temperatures, pH, and ionic strengths. Molecular docking revealed strong binding (affinity &lt; \u22129.9 kcal\/mol) of the peptides PPSPPRW, WGFTKF, and PSLFPPRL to key ACE residues\u2014Tyr523, His513, and Arg522\u2014via hydrogen and hydrophobic interactions. Enzyme kinetics characterized PPSPPRW and WGFTKF as competitive inhibitors, and PSLFPPRL as mixed type. The peptides demonstrated acceptable cell viability at lower concentrations, establishing a preliminary safety window for therapeutic application. Conclusions: These findings establish BM as a valuable source of stable, bioactive ACE-inhibitory peptides (ACEIPs) acting as promising lead compounds for antihypertensive therapies.<\/jats:p>","DOI":"10.3390\/ph19010096","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T16:07:07Z","timestamp":1767629227000},"page":"96","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel Angiotensin-Converting Enzyme Inhibitory Peptides from Bungarus multicinctus: Simulated Gastrointestinal Digestion, Identification and Antihypertensive Mechanism"],"prefix":"10.3390","volume":"19","author":[{"given":"Yingying","family":"Ren","sequence":"first","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Pharmacy College of Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6039-1735","authenticated-orcid":false,"given":"Han","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2902-7834","authenticated-orcid":false,"given":"Yubin","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyan","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayzohra","family":"Ablat","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2823-4664","authenticated-orcid":false,"given":"Qiang","family":"Yin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Pharmacy College of Shihezi University, Shihezi 832003, China"},{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Mu","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,4]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024). 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