{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:35Z","timestamp":1787028515170,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T00:00:00Z","timestamp":1688428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Marine Biodiversity Institute of Korea (MABIK) Research Program","award":["2023M00500"],"award-info":[{"award-number":["2023M00500"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Angiotensin I-converting enzyme (ACE) is an important blood pressure regulator. In this study, we aimed to investigate the ACE-inhibitory effects of meroterpenoids isolated from the brown alga, Sargassum macrocarpum, and the molecular mechanisms underlying ACE inhibition. Four fractions of S. macrocarpum were prepared using hexane, chloroform, ethyl acetate, and water as solvents and analyzed for their potential ACE-inhibitory effects. The chloroform fraction showed the strongest ACE-inhibitory effect, with an IC50 value of 0.18 mg\/mL. Three meroterpenoids, sargachromenol, 7-methyl sargachromenol, and sargaquinoic acid, were isolated from the chloroform fraction. Meroterpenoids isolated from S. macrocarpum had IC50 values of 0.44, 0.37, and 0.14 mM. The molecular docking study revealed that the ACE-inhibitory effect of the isolated meroterpenoids was mainly attributed to Zn-ion, hydrogen bonds, pi-anion, and pi\u2013alkyl interactions between the meroterpenoids and ACE. These results suggest that S. macrocarpum could be a potential raw material for manufacturing antihypertensive nutraceutical ingredients.<\/jats:p>","DOI":"10.3390\/ijms241311065","type":"journal-article","created":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:33:42Z","timestamp":1688517222000},"page":"11065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Angiotensin I-Converting Enzyme (ACE) Inhibition and Molecular Docking Study of Meroterpenoids Isolated from Brown Alga, Sargassum macrocarpum"],"prefix":"10.3390","volume":"24","author":[{"given":"Seok-Chun","family":"Ko","sequence":"first","affiliation":[{"name":"National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Yul","family":"Kim","sequence":"additional","affiliation":[{"name":"National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Min","family":"Lee","sequence":"additional","affiliation":[{"name":"National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Jin","family":"Yim","sequence":"additional","affiliation":[{"name":"National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gun-Woo","family":"Oh","sequence":"additional","affiliation":[{"name":"National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalae","family":"Kang","sequence":"additional","affiliation":[{"name":"Jeju Marine Research Center, Korea Institute of Ocean Science and Technology (KIOST), Jeju 63349, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Jin","family":"Heo","sequence":"additional","affiliation":[{"name":"Jeju Marine Research Center, Korea Institute of Ocean Science and Technology (KIOST), Jeju 63349, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyunghwa","family":"Baek","sequence":"additional","affiliation":[{"name":"National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0627-1402","authenticated-orcid":false,"given":"Dae-Sung","family":"Lee","sequence":"additional","affiliation":[{"name":"National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"129521","DOI":"10.1016\/j.foodchem.2021.129521","article-title":"Identification of water-soluble peptides in distilled spent grain and its angiotensin converting enzyme (ACE) inhibitory activity based on UPLC-Q-TOF-MS and proteomics analysis","volume":"353","author":"Wei","year":"2021","journal-title":"Food Chem."},{"key":"ref_2","unstructured":"Alper, A.B., Calhoun, D.A., and Oparil, S. (2011). Encyclopedia of Life Sciences, Nature Publishing Group."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0002-9149(01)02321-9","article-title":"The role of rennin\u2013angiotensin system in the development of cardiovascular disease","volume":"89","author":"Unger","year":"2022","journal-title":"Am. J. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.foodchem.2004.05.028","article-title":"Isolation of angiotensin I converting enzyme (ACE) inhibitor from fermented oyster sauce, Crassostrea gigas","volume":"90","author":"Je","year":"2005","journal-title":"Food Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1161\/HYPERTENSIONAHA.115.06892","article-title":"Angiotensin converting enzyme 2 metabolizes and partially inactivates pyrapelin-13 and apelin-17: \u201cPhysiological effects in the cardiovascular system\u201d","volume":"68","author":"Wang","year":"2016","journal-title":"Hypertension"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/j.biortech.2005.01.001","article-title":"Angiotensin I converting enzyme (ACE) inhibitory peptide derived from the sauce of fermented blue mussel Mytilus edulis","volume":"96","author":"Je","year":"2005","journal-title":"Bioresour. Technol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3390\/nu9040316","article-title":"Angiotensin I-converting enzyme (ACE) inhibitory peptides from plants","volume":"9","author":"Yuceteoe","year":"2017","journal-title":"Nutrients"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1016\/j.procbio.2012.07.015","article-title":"A novel angiotensin I-converting enzyme (ACE) inhibitory peptide from a marine Chlorella ellipsoidea and its antihypertensive effect in spontaneously hypertensive rats","volume":"47","author":"Ko","year":"2012","journal-title":"Process Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.procbio.2011.10.005","article-title":"Purification of characterization of angiotensin I-converting enzyme inhibitory peptide from enzymatic hydrolysates of Styela clava flesh tissue","volume":"47","author":"Ko","year":"2012","journal-title":"Process Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/0041-0101(72)90023-2","article-title":"Bradykinin-potentiating peptides from the venom of Agkistrodon halys blomhoffii: Isolation of five bradykinin potentiators B and C","volume":"10","author":"Kato","year":"1972","journal-title":"Toxicon"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/S0002-9343(03)00090-1","article-title":"Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on blood pressure and the kidney","volume":"114","author":"Thurman","year":"2003","journal-title":"Am. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.joim.2021.09.006","article-title":"Angiotensin-converting enzyme inhibitors from plants: A review of their diversity, modes of action, prospects, and concerns in the management of diabetes-centric complications","volume":"19","author":"Chakrabortya","year":"2021","journal-title":"J. Integr. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.fct.2016.02.022","article-title":"Octaphlorethol A, a marine algae product, exhibits antidiabetic effects in type 2 diabetic mice by activating AMP-activated kinase and upregulating the expression of glucose transporter 4","volume":"91","author":"Lee","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1002\/ptr.6266","article-title":"Bromophenol (5-bromo-3,4-dihydroxybenzaldehyde) isolated from red alga Polysiphonia morrowii inhibits adipogenesis by regulating expression of adipogenic transcription factors and AMP-activated protein kinase activation in 3T3-L1 adipocytes","volume":"33","author":"Ko","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.fct.2013.07.011","article-title":"Octaphlorethol A, a novel phenolic compound isolated from Ishige foliacea, protects against streptozotocin-induced pancreatic \u03b2 cell damage by reducing oxidative stress and apoptosis","volume":"59","author":"Lee","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.bbrc.2012.03.036","article-title":"Octaphlorethol A, a novel phenolic compound isolated from a brown alga, Ishige foliacea, increases glucose transporter 4-mediated glucose uptake in skeletal muscle cells","volume":"420","author":"Lee","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"200","DOI":"10.3390\/biomedicines9020200","article-title":"Antiviral effects of polyphenols from marine algae","volume":"9","author":"Besednova","year":"2021","journal-title":"Biomedicines"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.fct.2016.01.023","article-title":"Anti-obesity effects of seaweeds of Jeju Island on the differentiation of 3T3-L1 preadipocytes and obese mice fed a high-fat diet","volume":"90","author":"Kang","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.jff.2015.07.003","article-title":"Angiotensin I-converting enzyme (ACE) inhibition and nitric oxide (NO)-mediated antihypertensive effect of octaphlorethol A isolated from Ishige sinicola: In vitro molecular mechanism and in vivo SHR model","volume":"18","author":"Ko","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"24951","DOI":"10.1039\/D0RA03576A","article-title":"Pharmacological and natural products diversity of the brown algae genus Sargassum","volume":"10","author":"Rushdi","year":"2020","journal-title":"RSC Adv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.jff.2018.10.030","article-title":"Tuberatolide B is isolated from Sargassum macrocarpum inhibited LPS-stimulated infammatory response via MAPKs and NF-\u03baB signaling pathway in RAW 264.7 cells and zebrafsh model","volume":"52","author":"Kim","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Choi, Y.K., Kim, J., Lee, K.M., Choi, Y.J., Ye, B.R., Kim, M.S., Ko, S.G., Lee, S.H., Kang, D.H., and Heo, S.J. (2017). Tuberatolide B suppresses cancer progression by promoting ROS\u2013mediated inhibition of STAT3 signaling. Mar. Drugs, 15.","DOI":"10.3390\/md15030055"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/ja.2009.25","article-title":"The novel anti-Propiobacterium acnes compound, Sargafuran, found in the marine brown alga Sargassum macrocarpum","volume":"62","author":"Kamei","year":"2009","journal-title":"J. Antibiot."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1007\/s11418-020-01449-y","article-title":"Macrocarquinoids A\u2013C, new meroterpenoids from Sargassum macrocarpum","volume":"75","author":"Niwa","year":"2021","journal-title":"J. Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ejphar.2004.01.033","article-title":"Sargaquinoic acid supports the survival of neuronal PC12D cells in a growth factor-independent manner","volume":"488","author":"Tsang","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1134\/S1063074021050035","article-title":"Comparative studies on antioxidant, angiotensin-converting enzyme inhibitory and anticoagulant activities of the methanol extracts from two brown algae (Sargassum horneri and Sargassum thunbergii)","volume":"47","author":"Caijiao","year":"2021","journal-title":"Russ. J. Mar. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"93","DOI":"10.4162\/nrp.2011.5.2.93","article-title":"Effect of phlorotannins isolated from Ecklonia cava on angiotensin I-converting enzyme (ACE) inhibitory activity","volume":"5","author":"Wijesinghe","year":"2021","journal-title":"Nutr. Res. Pract."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"113024","DOI":"10.1016\/j.phytochem.2021.113024","article-title":"Spirornatas A-C from brown alga Turbinaria ornata: Anti-hypertensive spiroketals attenuate angiotensin-I converting enzyme","volume":"195","author":"Chakraborty","year":"2022","journal-title":"Phytochemistry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.5012\/bkcs.2007.28.10.1831","article-title":"Isolation of a new chromene from the brown alga Sargassum thunbergii","volume":"28","author":"Seo","year":"2007","journal-title":"Bull. Korean Chem. Soc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.phytochem.2008.12.007","article-title":"Meroditerpenoids from the southern Australian marine brown alga Sargassum fallax","volume":"70","author":"Reddy","year":"2009","journal-title":"Phytochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11832","DOI":"10.1021\/jf404641v","article-title":"Angiotensin-converting enzyme inhibitory effects by plant phenolic compounds: A study of structure activity relationships","volume":"61","author":"Shukor","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1002\/bab.1321","article-title":"Chebulin: Terminalia Chebula Retz. Fruit-derived peptide with angiotensin-Iconverting enzyme inhibitory activity","volume":"62","author":"Sornwatana","year":"2015","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.lwt.2016.08.047","article-title":"A novel antioxidant and ACE-inhibitory peptide from rice bran protein: Biochemical characterization and molecular docking study","volume":"75","author":"Wang","year":"2017","journal-title":"LWT-Food Sci. Technol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.jprot.2015.08.018","article-title":"Screening, discovery, and characterization of angiotensin-I converting enzyme inhibitory peptides derived from proteolytic hydrolysate of bitter melon seed Proteins","volume":"128","author":"Priyanto","year":"2015","journal-title":"J. Proteom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3774","DOI":"10.1016\/j.foodchem.2013.06.095","article-title":"The impact of fermentation and in vitro digestion on formation angiotensin converting enzyme (ACE) Inhibitory peptides from pea proteins","volume":"141","author":"Jakubczyk","year":"2013","journal-title":"Food Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4532","DOI":"10.3390\/molecules28114532","article-title":"Is it still relevant to discover new ACE inhibitors from natural products? YES, but only with comprehensive approaches to address the patients\u2019 real problems: Chronic dry cough and angioedema","volume":"28","author":"Manoharan","year":"2023","journal-title":"Molecules"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.jprot.2013.10.006","article-title":"A novel angiotensin converting enzyme inhibitory peptide derived from proteolytic digest of Chinese soft-shelled turtle egg white proteins","volume":"94","author":"Rawendra","year":"2013","journal-title":"J. Proteom."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jff.2014.01.021","article-title":"Antihypertensive effect of novel angiotensin I converting enzyme inhibitory peptide from chum salmon (Oncorhynchus keta) skin in spontaneously hypertensive rats","volume":"7","author":"Lee","year":"2014","journal-title":"J. Funct. Foods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.peptides.2014.07.026","article-title":"A novel angiotensin-I converting enzyme (ACE) inhibitory peptide from gastro intestinal protease hydrolysate of silkworm pupa (Bombyx mori) protein: Biochemical characterization and molecular docking study","volume":"68","author":"Wu","year":"2015","journal-title":"Peptides"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.procbio.2016.12.023","article-title":"Purification and molecular docking study of angiotensin I-converting enzyme (ACE) inhibitory peptides from hydrolysates of marine sponge Stylotella aurantium","volume":"54","author":"Ko","year":"2017","journal-title":"Process Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1016\/j.molimm.2005.10.020","article-title":"Biological and molecular docking studies on coagulin-H: Human IL-2 novel natural inhibitor","volume":"43","author":"Mesaik","year":"2006","journal-title":"Mol. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1089\/jmf.2019.4415","article-title":"Structural evidence for antihypertensive effect of an antioxidant peptide purified from the edible marine animal styela clava","volume":"23","author":"Kang","year":"2020","journal-title":"J. Med. Food"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/11065\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:05:49Z","timestamp":1760126749000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/13\/11065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,4]]},"references-count":42,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241311065"],"URL":"https:\/\/doi.org\/10.3390\/ijms241311065","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,4]]}}}