{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:16:16Z","timestamp":1790140576928,"version":"4.0.1"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T00:00:00Z","timestamp":1557964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology","award":["MOST105-2320-B-039-017-MY3"],"award-info":[{"award-number":["MOST105-2320-B-039-017-MY3"]}]},{"name":"Ministry of Science and Technology","award":["MOST107-2320-B-039-029-MY3"],"award-info":[{"award-number":["MOST107-2320-B-039-029-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Corn silk tea has been used in folk medicine for anti-hypertensive healthcare. Angiotensin-converting enzyme (ACE) plays a crucial role on the homeostasis of blood pressure. However, effects of corn silk tea on ACE activity and the presence of ACE inhibitory constituents in corn silk are still unknown. Here we applied proteomics and bioinformatics approaches to identify corn silk bioactive peptides (CSBps) that target ACE from the boiling water extract of corn silk (CSE). CSE significantly reduced systolic blood pressure (SBP) levels in spontaneously hypertensive rats and inhibited the ACE activity. By proteomics coupled with bioinformatics analyses, we identified a novel ACE inhibitory peptide CSBp5 in CSE. CSBp5 significantly inhibited the ACE activity and decreased SBP levels in a dose-dependent manner. Docking analysis showed that CSBp5 occupied the substrate-binding channel of ACE and interacted with ACE via hydrogen bonds. In conclusion, we identified that CSE exhibited anti-hypertensive effects in SHRs via the inhibition of ACE, the target of most anti-hypertensive drugs. In addition, an ACE inhibitory phytopeptide CSBp5 that decreased SBP levels in rats was newly identified. Our findings supported the ethnomedical use of corn silk tea on hypertension. Moreover, the identification of ACE inhibitory phytopeptide in corn silk further strengthened our findings.<\/jats:p>","DOI":"10.3390\/molecules24101886","type":"journal-article","created":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T11:21:22Z","timestamp":1558005682000},"page":"1886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Antihypertensive Effects of Corn Silk Extract and Its Novel Bioactive Constituent in Spontaneously Hypertensive Rats: The Involvement of Angiotensin-Converting Enzyme Inhibition"],"prefix":"10.3390","volume":"24","author":[{"given":"Chia-Cheng","family":"Li","sequence":"first","affiliation":[{"name":"Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9510-3146","authenticated-orcid":false,"given":"Yu-Chen","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Chinese Medicine, China Medical University Hospital, Taichung 40447, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Yi","family":"Lo","sequence":"additional","affiliation":[{"name":"Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Wen","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6507-8015","authenticated-orcid":false,"given":"Chien-Yun","family":"Hsiang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2390-1461","authenticated-orcid":false,"given":"Tin-Yun","family":"Ho","sequence":"additional","affiliation":[{"name":"Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,16]]},"reference":[{"key":"ref_1","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. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1146\/annurev.pharmtox.010909.105610","article-title":"Tissue renin-angiotensin-aldosterone systems: Targets for pharmacological therapy","volume":"50","author":"Bader","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"134","DOI":"10.2174\/157340809789071155","article-title":"Angiotensin converting enzyme\u2014New insights into structure, biological significance and prospects for domain-selective inhibitors","volume":"5","author":"Watermeyer","year":"2009","journal-title":"Curr. Enzym. Inhib."},{"key":"ref_4","first-page":"CD001841","article-title":"First-line drugs for hypertension","volume":"4","author":"Wright","year":"2008","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1080\/10408398.2014.898241","article-title":"Antihypertensive peptides of animal origin: A review","volume":"57","author":"Bhat","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Daskaya-Dikmen, C., Yucetepe, A., Karbancioglu-Guler, F., Daskaya, H., and Ozcelik, B. (2017). Angiotensin-I-converting enzyme (ACE)-inhibitory peptides from plants. Nutrients, 9.","DOI":"10.3390\/nu9040316"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Joel, C.H., Sutopo, C.C.Y., Prajitno, A., Su, J.H., and Hsu, J.L. (2018). Screening of angiotensin-I converting enzyme inhibitory peptides derived from Caulerpa lentillifera. Molecules, 23.","DOI":"10.3390\/molecules23113005"},{"key":"ref_8","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_9","doi-asserted-by":"crossref","unstructured":"Ram\u00edrez-Torres, G., Ontiveros, N., Lopez-Teros, V., Ibarra-Diarte, J., Reyes-Moreno, C., Cuevas-Rodr\u00edguez, E.O., and Cabrera-Ch\u00e1vez, F. (2017). Amaranth protein hydrolysates efficiently reduce systolic blood pressure in spontaneously hypertensive rats. Molecules, 22.","DOI":"10.3390\/molecules22111905"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13473","DOI":"10.3390\/molecules190913473","article-title":"Hypotensive effects and angiotensin-converting enzyme inhibitory peptides of reishi (Ganoderma lingzhi) auto-digested extract","volume":"19","author":"Tran","year":"2014","journal-title":"Molecules"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3168\/jds.S0022-0302(95)76689-9","article-title":"Purification and characterization of angiotensin I-converting enzyme inhibitors from sour milk","volume":"78","author":"Nakamura","year":"1995","journal-title":"J. Dairy Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1271\/bbb.100560","article-title":"Effect of an excess intake of casein hydrolysate containing Val-Pro-Pro and Ile-Pro-Pro in subjects with normal blood pressure, high-normal blood pressure, or mild hypertension","volume":"75","author":"Ishida","year":"2011","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2915498","DOI":"10.1155\/2019\/2915498","article-title":"Corn silk tea for hypertension: A systematic review and meta-analysis of randomized controlled trials","volume":"2019","author":"Shi","year":"2019","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_14","first-page":"5097","article-title":"Beneficial effects of corn silk on metabolic syndrome","volume":"23","author":"Wang","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wu, L., Ma, Z., Cheng, J., and Liu, J. (2016). Anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of flavonoids from corn silk on STZ-induced diabetic mice. Molecules, 21.","DOI":"10.3390\/molecules21010007"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"22102","DOI":"10.3390\/molecules201219835","article-title":"Safety evaluation, in vitro and in vivo antioxidant activity of the flavonoid-rich extract from Maydis stigma","volume":"20","author":"Peng","year":"2015","journal-title":"Molecules"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2016.02.024","article-title":"Kinetics of \u03b1-amylase and \u03b1-glucosidase inhibitory potential of Zea mays Linnaeus (Poaceae), Stigma maydis aqueous extract: An in vitro assessment","volume":"183","author":"Sabiu","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.carbpol.2017.01.092","article-title":"Physicochemical properties and antidiabetic effects of a polysaccharide from corn silk in high-fat diet and streptozotocin-induced diabetic mice","volume":"164","author":"Pan","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1021\/acs.jafc.6b03327","article-title":"Corn silk extract and its bioactive peptide ameliorated lipopolysaccharide-induced inflammation in mice via the nuclear factor-\u03baB signaling pathway","volume":"65","author":"Ho","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/cxo.12240","article-title":"Corn silk aqueous extracts and intraocular pressure of systemic and non-systemic hypertensive subjects","volume":"98","author":"George","year":"2015","journal-title":"Clin. Exp. Optom."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9697","DOI":"10.3390\/molecules17089697","article-title":"Corn silk (Stigma maydis) in healthcare: A phytochemical and pharmacological review","volume":"17","author":"Hasanudin","year":"2012","journal-title":"Molecules"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1161\/HYPERTENSIONAHA.107.097865","article-title":"Angiotensin-converting enzyme C-terminal catalytic domain is the main site of angiotensin I cleavage in vivo","volume":"51","author":"Fuchs","year":"2008","journal-title":"Hypertension"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/srep00717","article-title":"Molecular recognition and regulation of human angiotensin-I converting enzyme (ACE) activity by natural inhibitory peptides","volume":"2","author":"Masuyer","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/0378-8741(91)90010-B","article-title":"Hemodynamic effects of a boiling water dialysate of maize silk in normotensive anaesthetized dogs","volume":"31","author":"Pantoja","year":"1991","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.phymed.2003.12.010","article-title":"Zea mays L. extracts modify glomerular function and potassium urinary excretion in conscious rats","volume":"12","author":"Velazquez","year":"2005","journal-title":"Phytomedicine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1046\/j.1440-1681.2001.03531.x","article-title":"Comparison of telemetric and tail-cuff blood pressure monitoring in adrenocorticotrophic hormone-treated rats","volume":"28","author":"Fraser","year":"2001","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7891","DOI":"10.1021\/jf0705670","article-title":"Peptide with angiotensin I-converting enzyme inhibitory activity from hydrolyzed corn gluten meal","volume":"55","author":"Yang","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/j.1749-6632.1995.tb19990.x","article-title":"Production of bioactive peptides from corn endosperm proteins by some proteases","volume":"750","author":"Miyoshi","year":"1995","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1039\/C5FO00815H","article-title":"Isolation and identification of a novel peptide from zein with antioxidant and antihypertensive activities","volume":"6","author":"Wang","year":"2015","journal-title":"Food Funct."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1177\/1470320313489206","article-title":"C domain-selective inhibition of angiotensin-converting enzyme","volume":"14","author":"Ehlers","year":"2013","journal-title":"J. Renin Angiotensin Aldosterone Syst."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/jmr.905","article-title":"Studies on the molecular recognition between bioactive peptides and angiotensin-converting enzyme","volume":"22","author":"Pina","year":"2009","journal-title":"J. Mol. Recognit."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.drudis.2014.10.003","article-title":"Peptide therapeutics: Current status and future directions","volume":"20","author":"Fosgerau","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"36617","DOI":"10.1038\/srep36617","article-title":"PEPlife: A repository of the half-life of peptides","volume":"6","author":"Mathur","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1161\/01.HYP.7.2.244","article-title":"An improved fluorometric assay of rat serum and plasma converting enzyme","volume":"7","author":"Santos","year":"1985","journal-title":"Hypertension"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4142\/jvs.2011.12.1.21","article-title":"Determination of angiotensin I-converting enzyme activity in equine blood: Lack of agreement between methods of analysis","volume":"12","author":"Costa","year":"2011","journal-title":"J. Vet. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1021\/jf3042402","article-title":"Momordica charantia and its novel polypeptide regulate glucose homeostasis in mice via binding to insulin receptor","volume":"61","author":"Lo","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s10238-012-0217-2","article-title":"Clarithromycin modulates Helicobacter pylori-induced activation of nuclear factor-\u03baB through classical and alternative pathways in gastric epithelial cells","volume":"14","author":"Peng","year":"2014","journal-title":"Clin. Exp. Med."},{"key":"ref_38","unstructured":"(2019, April 01). Access Mascot for free - Protein identification software. Available online: http:\/\/www.matrixscience.com."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mooney, C., Haslam, N.J., Pollastri, G., and Shields, D.C. (2012). Towards the improved discovery and design of functional peptides: Common features of diverse classes permit generalized prediction of bioactivity. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045012"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1093\/jaoac\/91.4.965","article-title":"BIOPEP database and other programs for processing bioactive peptide sequences","volume":"91","author":"Minkiewicz","year":"2008","journal-title":"J. AOAC Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1093\/nar\/gki481","article-title":"PatchDock and SymmDock: Servers for rigid and symmetric docking","volume":"33","author":"Inbar","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_42","unstructured":"(2019, April 01). PEPstrMOD: Peptide Tertiary Structure Prediction with Natural, Non-Natural and Modified Residues. Available online: http:\/\/osddlinux.osdd.net\/raghava\/pepstrmod\/ multiseq.php."},{"key":"ref_43","unstructured":"(2019, April 01). UCSF Chimera. Available online: https:\/\/www.cgl.ucsf.edu\/chimera\/."},{"key":"ref_44","unstructured":"(2019, April 01). LIGPLOT. Available online: https:\/\/www.ebi.ac.uk\/thornton-srv\/software\/ LIGPLOT\/."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jep.2011.03.021","article-title":"Subchronic toxicity study of corn silk with rats","volume":"137","author":"Wang","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jep.2016.07.012","article-title":"Toxicological evaluation of the flavonoid-rich extract from Maydis stigma: Subchronic toxicity and genotoxicity studies in mice","volume":"192","author":"Peng","year":"2016","journal-title":"J. Ethnopharmacol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/10\/1886\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:52:32Z","timestamp":1760187152000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/10\/1886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,16]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["molecules24101886"],"URL":"https:\/\/doi.org\/10.3390\/molecules24101886","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,16]]}}}