{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:10:14Z","timestamp":1790295014181,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ift.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Food Science"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>ABSTRACT<\/jats:title>\n                    <jats:p>\n                      Angiotensin\u2010converting enzyme\u2010inhibitory (ACE\u2010I) peptides derived from marine proteins have received widespread attention for their high efficiency and safety in the management of hypertension. In this study, the mackerel (\n                      <jats:italic>Scomber japonicus<\/jats:italic>\n                      ) muscle papain hydrolysate (MMPH) was isolated via ultrafiltration and gel chromatography. Then peptides with ACE\u2010I activity were screened using LC\u2010MS\/MS and virtual screening. Ten novel ACE\u2010I peptides were identified from MMPH. In which, APFLAG showed the greatest inhibitory effects in vitro with an IC\n                      <jats:sub>50<\/jats:sub>\n                      value of 69.45 \u00b1 2.93 \u00b5M, followed by FDHKKFF (212.85 \u00b1 3.19 \u00b5M) and LFPKFA (259.05 \u00b1 3.72 \u00b5M). Molecular docking studies revealed that all these three peptides bind to S\n                      <jats:sub>1<\/jats:sub>\n                      and S\n                      <jats:sub>2<\/jats:sub>\n                      pockets, while APFLAG and LFPKFA interacted with the zinc (Zn)\u2010binding domain residues and only FDHKKFF interacted with the S\n                      <jats:sub>1<\/jats:sub>\n                      \u2019 pocket of ACE. Furthermore, the best peptide, APFLAG, inhibited ACE competitively and noncompetitively. Network pharmacology analysis suggested that APFLAG regulates blood pressure by targeting the renin\u2010angiotensin system (RAS) and modulating renin secretion via ACE and renin. Additionally, APFLAG promotes vasodilation and lowers blood pressure by regulating vascular smooth muscle cells through the activation of tyrosine\u2010protein kinase SRC (SRC) and signal transducer and activator of transcription 3 (STAT3). These findings underscore the multifaceted anti\u2010hypertensive mechanisms of APFLAG and highlight its potential for therapeutic management of hypertension.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>Practical Application<\/jats:bold>\n                      : Preparation of mackerel muscle hydrolysate with strong ACE\u2010I activity by papain hydrolysis, ultrafiltration, and gel chromatography. The oligopeptides APFLAG, FDHKKFF, and LFPKFA exhibited excellent ACE\u2010I activity. Producing bioactive peptides is a promising strategy to realize high\u2010value applications of mackerel muscle protein.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1750-3841.70767","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:36:27Z","timestamp":1765791387000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Revealing Novel Angiotensin\u2010Converting Enzyme (ACE)\u2010Inhibitory Peptides From Mackerel Hydrolysates and Potential Antihypertensive Mechanism Using Virtual Screening and Network Pharmacology Analysis"],"prefix":"10.1111","volume":"90","author":[{"given":"Hui","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Coastal Marine Biotechnology for Universities in Fujian Province, College of Oceanology and Food Science Quanzhou Normal University  Quanzhou China"},{"name":"College of Food Science Fujian Agriculture and Forestry University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxu","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Coastal Marine Biotechnology for Universities in Fujian Province, College of Oceanology and Food Science Quanzhou Normal University  Quanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food Science Fujian Agriculture and Forestry University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Coastal Marine Biotechnology for Universities in Fujian Province, College of Oceanology and Food Science Quanzhou Normal University  Quanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Coastal Marine Biotechnology for Universities in Fujian Province, College of Oceanology and Food Science Quanzhou Normal University  Quanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youping","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Biological Science and Engineering Fuzhou University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7573-8921","authenticated-orcid":false,"given":"Baobei","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Coastal Marine Biotechnology for Universities in Fujian Province, College of Oceanology and Food Science Quanzhou Normal University  Quanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zong\u2010Ping","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Coastal Marine Biotechnology for Universities in Fujian Province, College of Oceanology and Food Science Quanzhou Normal University  Quanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfutfo.2024.07.017"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.0c00925"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2021.131070"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1fo02830h"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tifs.2021.08.017"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2023.137074"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00343\u2010022\u20102012\u20106"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods11131889"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fbio.2025.106438"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/md21100516"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.13386\/j.issn1002\u20100306.2015.18.051"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22084068"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2020.128719"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fbio.2024.105235"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2022.133897"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13020\u2010021\u201000507\u20101"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","unstructured":"Li R. 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