{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:32:47Z","timestamp":1790555567473,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T00:00:00Z","timestamp":1510185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Sinaloa","award":["PROFAPI 2015\/049"],"award-info":[{"award-number":["PROFAPI 2015\/049"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Alcalase is the enzyme of choice to release antihypertensive peptides from amaranth proteins, but the hydrolysis conditions have not been optimized yet. Furthermore, in vivo assays are needed to confirm such a hypotensive effect. Our aim was to optimize the hydrolysis of amaranth protein with alcalase and to test in vivo the hypotensive effect of the hydrolysates. A response surface analysis was carried out to optimize the hydrolysis reaction. The response variable was the Angiotensin Converting Enzyme (ACE-I) inhibition. The hydrolysis degree was determined (free alpha-amino groups measurement). The optimized hydrolysate bioavailability was assessed in the sera of mice and the hypotensive effect was assessed in spontaneously hypertensive rats. Control groups were administered captopril or water. The optimized hydrolysis conditions were: pH = 7.01, temperature = 52 \u00b0C, enzyme concentration 0.04 mU\/mg, and time = 6.16 h. The optimized hydrolysate showed a 93.5% of ACE-I inhibition and a hydrolysis degree of 74.77%. After supplementation, the hydrolysate was bioavailable in mice from 5 to 60 min, and the hypotensive effect started at 4 h in spontaneously hypertensive rats (p &lt; 0.05 vs. water group). This effect was similar to the captopril hypotensive effect for the next 3 h (p &gt; 0.05). The use of amaranth-optimized hydrolysates as hypotensive supplements or ingredient for functional foods seems feasible.<\/jats:p>","DOI":"10.3390\/molecules22111905","type":"journal-article","created":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T11:33:02Z","timestamp":1510227182000},"page":"1905","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Amaranth Protein Hydrolysates Efficiently Reduce Systolic Blood Pressure in Spontaneously Hypertensive Rats"],"prefix":"10.3390","volume":"22","author":[{"given":"Giovanni","family":"Ram\u00edrez-Torres","sequence":"first","affiliation":[{"name":"Nutritional Sciences, Department of Chemical and Biological Sciences, University of Sonora, Hermosillo, Sonora 83000, Mexico"},{"name":"Faculty of Physical Education and Sport, University of Sinaloa, Culiac\u00e1n, Sinaloa 80019, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9","family":"Ontiveros","sequence":"additional","affiliation":[{"name":"Nutrition Sciences Academic Unit, University of Sinaloa, Culiac\u00e1n, Sinaloa 80019, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1429-4911","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"Lopez-Teros","sequence":"additional","affiliation":[{"name":"Nutritional Sciences, Department of Chemical and Biological Sciences, University of Sonora, Hermosillo, Sonora 83000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Ibarra-Diarte","sequence":"additional","affiliation":[{"name":"Nutrition Sciences Academic Unit, University of Sinaloa, Culiac\u00e1n, Sinaloa 80019, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuauht\u00e9moc","family":"Reyes-Moreno","sequence":"additional","affiliation":[{"name":"Faculty of Chemical and Biological Sciences, University of Sinaloa, Culiac\u00e1n, Sinaloa 80199, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Cuevas-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Faculty of Chemical and Biological Sciences, University of Sinaloa, Culiac\u00e1n, Sinaloa 80199, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4985-9169","authenticated-orcid":false,"given":"Francisco","family":"Cabrera-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Faculty of Physical Education and Sport, University of Sinaloa, Culiac\u00e1n, Sinaloa 80019, Mexico"},{"name":"Nutrition Sciences Academic Unit, University of Sinaloa, Culiac\u00e1n, Sinaloa 80019, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/5584_2016_99","article-title":"Hypertension is a risk factor for several types of heart disease: Review of prospective studies","volume":"956","author":"Kokubo","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1161\/01.STR.0000177495.45580.f1","article-title":"Is prehypertension a risk factor for cardiovascular diseases?","volume":"36","author":"Qureshi","year":"2005","journal-title":"Stroke"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.talanta.2012.12.041","article-title":"Vegetable foods: A cheap source of proteins and peptides with antihypertensive, antioxidant, and other less occurrence bioactivities","volume":"106","author":"Puchalska","year":"2013","journal-title":"Talanta"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.cofs.2014.09.005","article-title":"Bioactive peptides and protein hydrolysates: Research trends and challenges for application as nutraceuticals and functional food ingredients","volume":"1","year":"2015","journal-title":"Curr. Opin. Food Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1021\/jf072911z","article-title":"Bioactive peptides in amaranth (Amaranthus hypochondriacus) seed","volume":"56","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.foodchem.2010.11.065","article-title":"Amaranth seed protein hydrolysates have in vivo and in vitro antihypertensive activity","volume":"126","author":"Fritz","year":"2011","journal-title":"Food Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1007\/s12010-012-0024-y","article-title":"Review on the angiotensin-i-converting enzyme (ACE) inhibitor peptides from marine proteins","volume":"169","author":"He","year":"2013","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1039\/c2fo10192k","article-title":"Antihypertensive peptides from food proteins: A review","volume":"3","author":"Miralles","year":"2012","journal-title":"Food Funct."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1002\/jsfa.3946","article-title":"Potential of amaranthus cruentus BRS alegria in the production of flour, starch and protein concentrate: Chemical, thermal and rheological characterization","volume":"90","author":"Sobral","year":"2010","journal-title":"J. Sci. Food Agric."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s11130-004-0033-3","article-title":"Comparison of the chemical composition and nutritional value of amaranthus cruentus flour and its protein concentrate","volume":"59","author":"Escudero","year":"2004","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_11","first-page":"1619","article-title":"Pharmacokinetics study on mesoporous silica-captopril controlled release systems","volume":"6","author":"Popovici","year":"2011","journal-title":"Dig. J. Nano"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.foodchem.2009.02.062","article-title":"Angiotensin i-converting enzyme-inhibitory peptide fractions from albumin 1 and globulin as obtained of amaranth grain","volume":"116","year":"2009","journal-title":"Food Chem."},{"key":"ref_13","unstructured":"Soriano, S.J., and Tovar, P.E.G. (2017, September 30). M\u00e9todo de Obtenci\u00f3n de Hidrolizados de Prote\u00ednas del Grano de Amaranto con Actividad Antihipertensiva. Available online: https:\/\/patentscope.wipo.int\/search\/es\/detail.jsf?docId=WO2010071391."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/0076-6879(70)19014-8","article-title":"[11] the subtilisins","volume":"19","author":"Ottesen","year":"1970","journal-title":"Methods Enzymol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11869","DOI":"10.1021\/jf5035256","article-title":"Bioavailability and kinetics of the antihypertensive casein-derived peptide hlplp in rats","volume":"62","author":"Ares","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.foodres.2015.12.007","article-title":"Peptide fragments from \u03b2-casein f (134\u2013138), HLPLP, generated by the action of rat blood plasma peptidases show potent antihypertensive activity","volume":"88","author":"Santos","year":"2016","journal-title":"Food Res. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0149-7634(80)90027-5","article-title":"The role of endorphins in stress: Evidence and speculations","volume":"4","author":"Amir","year":"1980","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1146\/annurev.pa.22.040182.000421","article-title":"Angiotensin converting enzyme (ACE) inhibitors","volume":"22","author":"Antonaccio","year":"1982","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S1572-557X(05)02015-5","article-title":"Antihypertensive peptides from natural resources","volume":"2","author":"Matsui","year":"2006","journal-title":"Adv. Phytomed."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Li, B., Qiao, L., Li, L., Zhang, Y., Li, K., Wang, L., and Qiao, Y. (2017). A novel antihypertensive derived from adlay (coix larchryma-jobi l. Var. Ma-yuen stapf) glutelin. Molecules, 22.","DOI":"10.3390\/molecules22010123"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1111\/bph.13608","article-title":"Potential role of bioactive peptides in prevention and treatment of chronic diseases: A narrative review","volume":"174","author":"Cicero","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_22","unstructured":"Association of Official Analytical Chemists (1990). Official Methods of Analysis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1021\/jf60226a042","article-title":"Determination of the degree of hydrolysis of food protein hydrolysates by trinitrobenzenesulfonic acid","volume":"27","year":"1979","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"H121","DOI":"10.1111\/j.1750-3841.2009.01145.x","article-title":"Characterization and ACE-inhibitory activity of amaranth proteins","volume":"74","author":"Tiengo","year":"2009","journal-title":"J. Food Sci."},{"key":"ref_25","first-page":"2134","article-title":"Anti-hypertensive effect of total flavonoids of cydonia oblonga leaves and its mechanism based on anti-inflammatory function","volume":"38","author":"Zhou","year":"2015","journal-title":"J. Chin. Med. Mater."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/S1056-8727(97)00076-7","article-title":"Protective effects of a small dose of captopril on the reduction of glomerular basement membrane anionic sites in spontaneously hypertensive rats with streptozotocin-induced diabetes","volume":"12","author":"Isogai","year":"1998","journal-title":"J. Diabetes Complic."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.jep.2014.01.018","article-title":"Effect of cydonia oblonga mill. Fruit and leaf extracts on blood pressure and blood rheology in renal hypertensive rats","volume":"152","author":"Zhou","year":"2014","journal-title":"J. Ethnopharmacol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/11\/1905\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:48:47Z","timestamp":1760208527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/11\/1905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,9]]},"references-count":27,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2017,11]]}},"alternative-id":["molecules22111905"],"URL":"https:\/\/doi.org\/10.3390\/molecules22111905","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,9]]}}}