{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T03:49:52Z","timestamp":1777002592290,"version":"3.51.4"},"reference-count":36,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["AGL2016-77105-R"],"award-info":[{"award-number":["AGL2016-77105-R"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The peptide AVFQHNCQE demonstrated to produce nitric oxide-mediated antihypertensive effect. This study investigates the bioavailability and the opioid-like activity of this peptide after its oral administration. For this purpose, in silico and in vitro approaches were used to study the peptide susceptibility to GI digestion. In addition, AVFQHNCQE absorption was studied both in vitro by using Caco-2 cell monolayers and in vivo evaluating peptide presence in plasma from Wistar rats by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS\/MS) and by ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Both in vivo and in vitro experiments demonstrated that peptide AVFQHNCQE was not absorbed. Thus, the potential involvement of opioid receptors in the BP-lowering effect of AVFQHNCQE was studied in the presence of opioid receptors-antagonist Naloxone. No changes in blood pressure were recorded in rats administered Naloxone, demonstrating that AVFQHNCQE antihypertensive effect is mediated through its interaction with opioid receptors. AVFQHNCQE opioid-like activity would clarify the antihypertensive properties of AVFQHNCQE despite its lack of absorption.<\/jats:p>","DOI":"10.3390\/biom10070992","type":"journal-article","created":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T05:00:08Z","timestamp":1593666008000},"page":"992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Implication of Opioid Receptors in the Antihypertensive Effect of a Novel Chicken Foot-Derived Peptide"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0416-7102","authenticated-orcid":false,"given":"Anna","family":"Mas-Capdevila","sequence":"first","affiliation":[{"name":"Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0768-0611","authenticated-orcid":false,"given":"Lisard","family":"Iglesias-Carres","sequence":"additional","affiliation":[{"name":"Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6529-1345","authenticated-orcid":false,"given":"Anna","family":"Arola-Arnal","sequence":"additional","affiliation":[{"name":"Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8657-5726","authenticated-orcid":false,"given":"Gerard","family":"Aragon\u00e8s","sequence":"additional","affiliation":[{"name":"Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7384-8588","authenticated-orcid":false,"given":"Bego\u00f1a","family":"Muguerza","sequence":"additional","affiliation":[{"name":"Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain"},{"name":"EURECAT-Technology Centre of Catalonia, Technological Unit of Nutrition and Health, 43204 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6468-3088","authenticated-orcid":false,"given":"Francisca Isabel","family":"Bravo","sequence":"additional","affiliation":[{"name":"Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.peptides.2015.07.013","article-title":"Bioactive peptides derived from natural proteins with respect to diversity of their receptors and physiological effects","volume":"72","author":"Yoshikawa","year":"2015","journal-title":"Peptides"},{"key":"ref_2","first-page":"223","article-title":"Bioactive peptides: A review","volume":"15","author":"Sharma","year":"2011","journal-title":"Int. J. Bioautomation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/fqs\/fyx006","article-title":"Bioactive peptides: A review","volume":"1","year":"2017","journal-title":"Food Qual. Saf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.peptides.2008.02.005","article-title":"The antihypertensive effect of peptides: A novel alternative to drugs?","volume":"29","author":"Hong","year":"2008","journal-title":"Peptides"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Andrade, P., Valentao, P., and Pereira, D.M. (2017). Natural angiotensin converting enzyme (ACE) inhibitors with antihypetensive properties. Natural Products Targeting Clinically Relevant Enzymes, Wiley-VCH Verlag GmbH & Co.","DOI":"10.1002\/9783527805921"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18014","DOI":"10.1038\/nrdp.2018.14","article-title":"Hypertension","volume":"4","author":"Oparil","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/j.1524-6175.2004.02866.x","article-title":"Angiotensin-converting enzyme inhibitors side effects\u2014physiologic and non-physiologic considerations","volume":"6","author":"Sica","year":"2004","journal-title":"J. Clin. Hypertens."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jff.2014.03.002","article-title":"Mechanisms of food protein-derived antihypertensive peptides other than ACE inhibition","volume":"8","author":"Udenigwe","year":"2014","journal-title":"J. Funct. Foods"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.niox.2010.04.006","article-title":"Tryptic amaranth glutelin digests induce endothelial nitric oxide production through inhibition of ACE: Antihypertensive role of amaranth peptides","volume":"23","year":"2010","journal-title":"Nitric Oxide Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.fshw.2015.11.004","article-title":"Bioactive peptides on endothelial function","volume":"5","author":"Chakrabarti","year":"2016","journal-title":"Food Sci. Hum. Wellness"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1079\/BJN20041189","article-title":"Bioavailability of angiotensin I converting enzyme inhibitory peptides","volume":"92","author":"Vermeirssen","year":"2004","journal-title":"Br. J. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1002\/mnfr.200700503","article-title":"Transepithelial transport across Caco-2 cell monolayers of antihypertensive egg-derived peptides. PepT1-mediated flux of Tyr-Pro-Ile","volume":"52","author":"Miguel","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.cis.2010.11.001","article-title":"Antihypertensive peptides: Production, bioavailability and incorporation into foods","volume":"165","author":"Recio","year":"2011","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1017\/S0954422414000225","article-title":"Are intact peptides absorbed from the healthy gut in the adult human?","volume":"27","author":"Stevens","year":"2014","journal-title":"Nutr. Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.regpep.2009.03.012","article-title":"Opioid receptors in the gastrointestinal tract","volume":"155","author":"Holzer","year":"2009","journal-title":"Regul. Pept."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1017\/S0954422413000206","article-title":"Food-derived bioactive peptides\u2014A new paradigm","volume":"27","author":"Moughan","year":"2014","journal-title":"Nutr. Res. Rev."},{"key":"ref_18","first-page":"347","article-title":"Bioactive peptides derived from bovine whey proteins: Opioid and ace-inhibitory peptides","volume":"11","year":"2001","journal-title":"Trends Food Sci. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1016\/S0024-3205(00)00471-9","article-title":"Alpha-lactorphin lowers blood pressure measured by radiotelemetry in normotensive and spontaneously hypertensive rats","volume":"66","author":"Nurminen","year":"2000","journal-title":"Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/0196-9781(86)90124-5","article-title":"Endogenous opioids and opiate antagonists modulate the blood pressure of the spontaneously hypertensive rat","volume":"7","author":"Levin","year":"1986","journal-title":"Peptides"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/S0024-3205(02)01793-9","article-title":"Alpha-lactorphin and beta-lactorphin improve arterial function in spontaneously hypertensive rats","volume":"71","author":"Sipola","year":"2002","journal-title":"Life Sci."},{"key":"ref_22","unstructured":"Bravo, F.I., Arola, L., and Muguerza, B. (2017). Procedure for Obtaining a Hydrolyzate Claw Chicken Leg with Antihypertensive Activity, and Peptides Obtained Hydrolyzate Containing. (ES2606954A1), Spain Patent."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mas-Capdevila, A., Iglesias-Carres, L., Arola-Arnal, A., Aragon\u00e8s, G., Aleixandre, A., Bravo, F.I., and Muguerza, B. (2019). Evidence that Nitric Oxide is Involved in the Blood Pressure Lowering Effect of the Peptide AVFQHNCQE in Spontaneously Hypertensive Rats. Nutrients, 11.","DOI":"10.3390\/nu11020225"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mas-Capdevila, A., Pons, Z., Aleixandre, A., Bravo, F.I., and Muguerza, B. (2018). Dose-Related Antihypertensive Properties and the Corresponding Mechanisms of a Chicken Foot Hydrolysate in Hypertensive Rats. Nutrients, 10.","DOI":"10.3390\/nu10091295"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5640","DOI":"10.1021\/jf904538w","article-title":"Egg white ovalbumin digestion mimicking physiological conditions","volume":"58","author":"Martos","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1161\/01.HYP.4.6.898","article-title":"Tail-cuff blood pressure measurement without external preheating in awake rats","volume":"4","author":"Butterfield","year":"1982","journal-title":"Hypertension"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1146\/annurev-food-022814-015520","article-title":"Antihypertensive Peptides from Food Proteins","volume":"6","author":"Aluko","year":"2015","journal-title":"Annu. Rev. Food Sci. Technol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0271-5317(04)00058-2","article-title":"Angiotensin I\u2014Converting enzyme inhibitory peptides derived from food proteins and their physiological and pharmacological effects","volume":"24","author":"Li","year":"2004","journal-title":"Nutr. Res."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.peptides.2012.10.014","article-title":"The cardiovascular effects of a chimeric opioid peptide based on morphiceptin and PFRTic-NH2","volume":"39","author":"Li","year":"2013","journal-title":"Peptides"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.idairyj.2003.08.002","article-title":"Antihypertensive opioid-like milk peptide \u03b1-lactorphin: Lack of effect on behavioural tests in mice","volume":"14","author":"Collin","year":"2004","journal-title":"Int. Dairy J."},{"key":"ref_32","first-page":"107","article-title":"Opioid Peptides and Central Control of Blood Pressure","volume":"6","author":"Reid","year":"1984","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1097\/ALN.0b013e31819146a9","article-title":"Modulation of Opioid Actions by Nitric Oxide Signaling","volume":"110","author":"Toda","year":"2009","journal-title":"Anesthesiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/1541-4337.12051","article-title":"Food-originating ACE inhibitors, including antihypertensive peptides, as preventive food components in blood pressure reduction","volume":"13","author":"Iwaniak","year":"2014","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/S0140-6736(79)92186-X","article-title":"Captopril in the Treatment of Clinical Hypertension and Cardiac Failure","volume":"314","author":"Atkinson","year":"1979","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.idairyj.2007.09.006","article-title":"Bioavailability of the antihypertensive peptide LHLPLP: Transepithelial flux of HLPLP","volume":"18","author":"Da","year":"2008","journal-title":"Int. Dairy J."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/7\/992\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:46:15Z","timestamp":1760175975000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/7\/992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,2]]},"references-count":36,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["biom10070992"],"URL":"https:\/\/doi.org\/10.3390\/biom10070992","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,2]]}}}