{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T18:15:36Z","timestamp":1770228936277,"version":"3.49.0"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T00:00:00Z","timestamp":1557705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011002","name":"National Natural Science Foundation of China-Yunnan Joint Fund","doi-asserted-by":"publisher","award":["31360381"],"award-info":[{"award-number":["31360381"]}],"id":[{"id":"10.13039\/501100011002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The peptide QAGLSPVR, which features high angiotensin-I-converting enzyme (ACE) inhibitory activity, was identified in our previous study. In this study, the in vivo antihypertensive effect of QAGLSPVR was evaluated. Results showed that QAGLSPVR exerts a clear antihypertensive effect on spontaneously hypertensive rats (SHRs), and the systolic and diastolic blood pressures of the rats remarkably decreased by 41.86 and 40.40 mm Hg, respectively, 3 h after peptide administration. The serum ACE activities of SHRs were determined at different times, and QAGLSPVR was found to decrease ACE activities in serum; specifically, minimal ACE activity was found 3 h after administration. QAGLSPVR could be completely absorbed by the Caco-2 cell monolayer, and its transport percentage was 3.5% after 2 h. The transport route results of QAGLSPVR showed that Gly-Sar and wortmannin exert minimal effects on the transport percentage of the peptide (p&gt; 0.05), thus indicating that QAGLSPVR transport through the Caco-2 cell monolayer is not mediated by peptide transporter 1 or transcytosis. By contrast, cytochalasin D significantly increased QAGLSPVR transport (p&lt; 0.05); thus, QAGLSPVR may be transported through the Caco-2 cell monolayer via the paracellular pathway.<\/jats:p>","DOI":"10.3390\/md17050288","type":"journal-article","created":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T11:00:57Z","timestamp":1557745257000},"page":"288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Antihypertensive Effect in Vivo of QAGLSPVR and Its Transepithelial Transport Through the Caco-2 Cell Monolayer"],"prefix":"10.3390","volume":"17","author":[{"given":"Liping","family":"Sun","sequence":"first","affiliation":[{"name":"Yunnan Institute of Food Safety, Kunming University of Science and Technology, No. 727 South Jingming Road, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beiyi","family":"Wu","sequence":"additional","affiliation":[{"name":"Yunnan Institute of Food Safety, Kunming University of Science and Technology, No. 727 South Jingming Road, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyan","family":"Yan","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Biochemical Engineering, College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao 266042, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hu","family":"Hou","sequence":"additional","affiliation":[{"name":"Food Science and Technology, Ocean University of China, No 5, Yushan Road, Qingdao 266005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongliang","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Yunnan Institute of Food Safety, Kunming University of Science and Technology, No. 727 South Jingming Road, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.foodchem.2017.06.112","article-title":"In silico analysis and molecular docking study of angiotensin I-converting enzyme inhibitory peptides from smooth-hound viscera protein hydrolysates fractionated by ultrafiltration","volume":"239","author":"Abdelhedi","year":"2018","journal-title":"Food Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1016\/j.procbio.2016.07.006","article-title":"Angiotensin-I-converting enzyme (ACE) inhibitory peptides from Pacific cod skin gelatin using ultrafiltration membranes","volume":"51","author":"Ngo","year":"2016","journal-title":"Process Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1007\/s11947-010-0439-9","article-title":"Production of the angiotensin-I-converting enzyme (ACE)-inhibitory peptide from hydrolysates of jellyfish (Rhopilemaesculentum) collagen","volume":"5","author":"Zhuang","year":"2012","journal-title":"Food Bio. Technol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"417","DOI":"10.3390\/md10020417","article-title":"Antihypertensive effect of long-term oral administration of jellyfish (Rhopilemaesculentum) collagen peptides on renovascular hypertension","volume":"10","author":"Zhuang","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.procbio.2017.08.009","article-title":"Angiotensin I-converting enzyme inhibitory peptides from Sipuncula (Phascolosoma esculenta): Purification, identification, molecular docking and antihypertensive effects on spontaneously hypertensive rats","volume":"63","author":"Guo","year":"2017","journal-title":"Process Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3945\/jn.109.116228","article-title":"Current in vitro testing of bioactive peptides is not valuable","volume":"140","author":"Foltz","year":"2010","journal-title":"J. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.foodchem.2016.10.087","article-title":"Identification, functional gastrointestinal stability and molecular docking studies of lentil peptides with dual antioxidant and angiotensin I converting enzyme inhibitory activities","volume":"221","author":"Bonache","year":"2017","journal-title":"Food Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1021\/jf405639w","article-title":"Transport of egg white ACE-inhibitory peptide, Gln-Ile-Gly-Leu-Phe, in human intestinal Caco-2 cell monolayers with cytoprotective effect","volume":"62","author":"Ding","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.jff.2018.04.023","article-title":"Behavior of three hypocholesterolemic peptides from soy protein in an intestinal model based on differentiated Caco-2 cell","volume":"45","author":"Aiello","year":"2018","journal-title":"J. Func. Food."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5251","DOI":"10.1039\/C8FO00569A","article-title":"Preparation and identification of novel inhibitory angiotensin-I-converting enzyme peptides from tilapia skin gelatin hydrolysates: Inhibition kinetics and molecular docking","volume":"9","author":"Yuan","year":"2018","journal-title":"Food Func."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.foodchem.2013.03.091","article-title":"Nine novel angiotensin I-converting enzyme (ACE) inhibitory peptides from cuttlefish (Sepia officinalis) muscle protein hydrolysates and antihypertensive effect of the potent active peptide in spontaneously hypertensive rats","volume":"170","author":"Balti","year":"2015","journal-title":"Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/j.1365-2621.2000.tb16049.x","article-title":"Classification and antihypertensive activity of angiotensin I-converting enzyme inhibitory peptides derived from food proteins","volume":"65","author":"Fujita","year":"2000","journal-title":"J. Food Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.peptides.2009.03.002","article-title":"A novelACE inhibitory peptide isolated from Acaudina molpadioidea hydrolysate","volume":"30","author":"Zhao","year":"2009","journal-title":"Peptides"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1161\/01.HYP.23.1.74","article-title":"Angiotensin converting enzyme inhibition prevents the increase in aortic collagen in rats","volume":"23","author":"Albaladejo","year":"1994","journal-title":"Hypertension"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5783","DOI":"10.3390\/nu7075252","article-title":"Peptides-derived from thai rice bran improves endothelial function in 2K-1C renovascular hypertensive rats","volume":"7","author":"Boonla","year":"2015","journal-title":"Nutrients"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.foodres.2017.12.080","article-title":"Hydrolysis and transepithelial transport of two corn gluten derived bioactive peptides in human Caco-2 cell monolayers","volume":"106","author":"Ding","year":"2018","journal-title":"Food Res. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1042\/bj2840595","article-title":"A survey of membrane peptidases in two human colonic cell lines, Caco-2 and HT-29","volume":"284","author":"Howell","year":"1992","journal-title":"Biochem. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3109\/09637486.2016.1144722","article-title":"Digestion and absorption of an egg white ACE-inhibitory peptide in human intestinal Caco-2 cell monolayers","volume":"67","author":"Ding","year":"2016","journal-title":"Int. J. Food Sci. Nut."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jfca.2017.01.011","article-title":"Transepithelial transport of lunasin and derived peptides: Inhibitory effects on the gastrointestinal cancer cells viability","volume":"68","author":"Recio","year":"2018","journal-title":"J. Food Comp. Ana."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11956","DOI":"10.1021\/jf202890e","article-title":"Transport across Caco-2 cell monolayer and sensitivity to hydrolysis of two anxiolytic peptides from alpha(s1)-casein, alpha-casozepine, and alpha(s1)-casein-(f91\u221297): Effect of bile salts","volume":"59","author":"Miclo","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_21","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 Func."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.ifset.2012.07.009","article-title":"The effect of molecular weights on the survivability of caseinderived antioxidant peptides after the simulated gastrointestinal digestion","volume":"16","author":"Chen","year":"2012","journal-title":"Innov. Food Sci. Emer. Technol."},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2174\/1389200043489153","article-title":"(Section A: Molecular, structural, and cellular biology of drug transporters) Peptide transporters: Structure, function, regulation and application for drug delivery","volume":"5","author":"Terada","year":"2004","journal-title":"Curr. Drug Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8143","DOI":"10.1021\/acs.jafc.5b01824","article-title":"Transport of antihypertensive peptide RVPSL, ovotransferrin 328\u2013332, in human intestinal Caco-2 cell monolayers","volume":"63","author":"Ding","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1271\/bbb.100015","article-title":"Molecular size of collagen peptide reverses the permeability of Caco-2 cells","volume":"74","author":"Shimizu","year":"2010","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1016\/j.peptides.2009.06.031","article-title":"Stability to gastrointestinal enzymes and structure\u2013activity relationship of b-casein peptides with antihypertensive properties","volume":"30","author":"Contreras","year":"2009","journal-title":"Peptides"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1002\/jsfa.8545","article-title":"Transepithelial transport of milk-derived angiotensin I-converting enzyme inhibitory peptide with the RLSFNP sequence","volume":"98","author":"Guo","year":"2017","journal-title":"J. Sci. Food Agric."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1021\/acs.jafc.7b04196","article-title":"Purification and characterization of peptides inhibiting MMP-1 activity with C-terminate of Gly-Leu from simulated gastrointestinal digestion hydrolysates of tilapia (Oreochromis niloticus) skin gelatin","volume":"66","author":"Sun","year":"2018","journal-title":"J. Agric. Food Chemi."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/17\/5\/288\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:51:26Z","timestamp":1760187086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/17\/5\/288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,13]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["md17050288"],"URL":"https:\/\/doi.org\/10.3390\/md17050288","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,13]]}}}