{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T16:58:17Z","timestamp":1789923497962,"version":"4.0.1"},"reference-count":28,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:00:00Z","timestamp":1622419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Key R &amp; D Project of Shanxi Province","award":["201903D221032"],"award-info":[{"award-number":["201903D221032"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The areca (Areca catechu L.) nut kernel (ANK) is a good potential protein source for its high protein content of 9.89\u201314.62 g\/100 g and a high yield of around 300,000 tons per year in China. However, utilization of the areca nut kernel is limited. To expand the usage of ANK in pharmaceutical or foods industries, areca nut kernel globulin was extracted and angiotensin-I converting enzyme (ACE) inhibition peptides were prepared and identified using gel chromatography, reversed phase HPLC separation, UPLC-ESI-MS\/MS analysis and in silico screening. Finally, a novel ACE-inhibitory heptapeptide (Ala\u2013Pro\u2013Lys\u2013Ile\u2013Glu\u2013Glu\u2013Val) was identified and chemically synthesized. The combination pattern between APKIEEV and ACE, and the inhibition kinetics, antihypertensive effect and endothlein-1 inhibition activity of APKIEEV were studied. The results of the molecular docking demonstrated that APKIEEV could bind to four active sites (not the key active sites) of ACE via short hydrogen bonds and demonstrated high ACE-inhibitory activity (IC50: 550.41 \u03bcmol\/L). Moreover, APKIEEV exhibited a significantly lowering effect on both the systolic blood pressure and diastolic blood pressure of spontaneously hypertensive rats, and had considerable suppression ability on intracellular endothelin-1. These results highlight the potential usage of APKIEEV as ingredients of antihypertensive drugs or functional foods.<\/jats:p>","DOI":"10.3390\/molecules26113308","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T21:42:06Z","timestamp":1622497326000},"page":"3308","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Identification, Characterization and Antihypertensive Effect In Vivo of a Novel ACE-Inhibitory Heptapeptide from Defatted Areca Nut Kernel Globulin Hydrolysates"],"prefix":"10.3390","volume":"26","author":[{"given":"Xing","family":"Liu","sequence":"first","affiliation":[{"name":"College of Medicine and Food Engineering, Shanxi University of Chinese Medicine, Taiyuan 030619, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanwen","family":"Li","sequence":"additional","affiliation":[{"name":"College of Medicine and Food Engineering, Shanxi University of Chinese Medicine, Taiyuan 030619, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Medicine and Food Engineering, Shanxi University of Chinese Medicine, Taiyuan 030619, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Qin","sequence":"additional","affiliation":[{"name":"College of Medicine and Food Engineering, Shanxi University of Chinese Medicine, Taiyuan 030619, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Medicine and Food Engineering, Shanxi University of Chinese Medicine, Taiyuan 030619, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Medicine and Food Engineering, Shanxi University of Chinese Medicine, Taiyuan 030619, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang","family":"Shen","sequence":"additional","affiliation":[{"name":"Yunnan Institute of Food Safety, Kunming University of Science and Technology, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"128867","DOI":"10.1016\/j.foodchem.2020.128867","article-title":"Purification and identification of novel ACE inhibitory and ACE2 upregulating peptides from spent hen muscle proteins","volume":"345","author":"Fan","year":"2021","journal-title":"Food Chem."},{"key":"ref_2","unstructured":"(2019). Global Burden of Disease (GBD) 2017 Diet Collaborators. Health effects of dietary risks in 195 countries, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet, 393, 1958\u20131972."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.foodchem.2017.02.039","article-title":"Antihypertensive peptides from animal products, marine organisms, and plants","volume":"228","author":"Lee","year":"2017","journal-title":"Food Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"103488","DOI":"10.1016\/j.jff.2019.103488","article-title":"ACE inhibitory activity in vitro and antihypertensive effect in vivo of LSGYGP and its transepithelial transport by Caco-2 cell monolayer","volume":"61","author":"Zhao","year":"2019","journal-title":"J. Funct. Food"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jff.2016.11.021","article-title":"Purification, characterization, synthesis, in vivo ACE inhibition and in vitro antihypertensive activity of bioactive peptides derived from palm kernel expeller glutelin-2 hydrolysates","volume":"28","author":"Zheng","year":"2017","journal-title":"J. Funct. Food"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zheng, Y.J., Zhang, Y.F., and San, S. (2020). Efficacy of a Novel ACE-Inhibitory Peptide from Sargassum maclurei in Hypertension and Reduction of Intracellular Endothelin-1. Nutrients, 12.","DOI":"10.3390\/nu12030653"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.1007\/s00216-018-0852-x","article-title":"Recent trends and analytical challenges in plant bioactive peptide separation, identification and validation","volume":"410","author":"Piovesana","year":"2018","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_8","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":"Contreras","year":"2011","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.foodchem.2016.12.039","article-title":"Identification and quantification of ACE-inhibiting peptides in enzymatic hydrolysates of plant proteins","volume":"224","author":"Rudolph","year":"2017","journal-title":"Food Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.foodchem.2017.09.152","article-title":"A novel calcium-binding peptide from Antarctic krill protein hydrolysates and identification of binding sites of calcium-peptide complex","volume":"243","author":"Hou","year":"2018","journal-title":"Food Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1021\/acs.jafc.6b05140","article-title":"Analysis of alkaloids in areca nut-containing products by liquid chromatography\u2013tandem mass spectrometry","volume":"65","author":"Jain","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"123872","DOI":"10.1016\/j.jhazmat.2020.123872","article-title":"Evaluation of cytotoxicity of areca nut and its commercial products on normal human gingival fibroblast and oral squamous cell carcinoma cell lines","volume":"403","author":"Adil","year":"2021","journal-title":"J. Hazard. Mater."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jclepro.2014.02.025","article-title":"Characterization of physical, mechanical, thermal and morphological properties of agro-waste betel nut (Areca catechu) husk fibre","volume":"72","author":"Yusriah","year":"2014","journal-title":"J. Clean. Prod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.jep.2015.02.010","article-title":"Areca catechu L. (Arecaceae): A review of its traditional uses, botany, phytochemistry, pharmacology and toxicology","volume":"164","author":"Peng","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"104548","DOI":"10.1016\/j.yrtph.2019.104548","article-title":"Chemistry, metabolism and pharmacology of carcinogenic alkaloids present in areca nut and factors affecting their concentration","volume":"110","author":"Gupta","year":"2019","journal-title":"Regul. Toxicol. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"128855","DOI":"10.1016\/j.foodchem.2020.128855","article-title":"Identification of post-digestion angiotensin-I converting enzyme (ACE) inhibitory peptides from soybean protein Isolate: Their production conditions and in silico molecular docking with ACE","volume":"345","author":"Xu","year":"2021","journal-title":"Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.lwt.2018.12.059","article-title":"Purification, identification, and characterization of novel angiotensin I converting enzyme (ACE) inhibitory peptides from Alcalase digested horse gram flour","volume":"103","author":"Bhaskar","year":"2019","journal-title":"LWT Food Sci. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.foodchem.2018.02.107","article-title":"Identification of a novel ACE-inhibitory peptide from casein and evaluation of the inhibitory mechanisms","volume":"256","author":"Tu","year":"2018","journal-title":"Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"109908","DOI":"10.1016\/j.foodres.2020.109908","article-title":"Novel antioxidant and ACE inhibitory peptide identified from Arthrospira platensis protein and stability against thermal\/pH treatments and simulated gastrointestinal digestion","volume":"139","author":"Wang","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_20","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":"Ling","year":"2018","journal-title":"Food Funct."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.foodchem.2017.06.112","article-title":"Peptidomic analysis of antioxidant and ACE-inhibitory peptides obtained from tomato waste proteins fermented using Bacillus subtilis","volume":"239","author":"Abdelhedi","year":"2018","journal-title":"Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"92688","DOI":"10.1039\/C6RA19971B","article-title":"Purification, characterization, synthesis, in vivo and in vitro antihypertensive activity of bioactive peptides derived from coconut (Cocos nucifera L.) cake globulin hydrolysates","volume":"6","author":"Li","year":"2016","journal-title":"RSC Adv."},{"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":"9388","DOI":"10.1021\/ac901775h","article-title":"Colorimetric, high-throughput assay for screening angiotensin I-converting enzyme inhibitors","volume":"81","author":"Jimsheena","year":"2009","journal-title":"Anal. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1111\/1750-3841.15115","article-title":"Isolation of novel ACE-inhibitory peptide from naked oat globulin hydrolysates in silico approach: Molecular docking, in vivo antihypertension and effects on renin and intracellular endothelin-1","volume":"85","author":"Zheng","year":"2020","journal-title":"J. Food Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"D956","DOI":"10.1093\/nar\/gku1141","article-title":"AHTPDB: A comprehensive platform for analysis and presentation of antihypertensive peptides","volume":"43","author":"Kumar","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Alcaide-Hidalgo, J.M., Romero, M., Duarte, J., and L\u00f3pez-Huertas, E. (2020). Antihypertensive effects of virgin olive oil (unfiltered) low molecular weight peptides with ACE inhibitory activity in spontaneously hypertensive rats. Nutrients, 12.","DOI":"10.3390\/nu12010271"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"C1","DOI":"10.1111\/1750-3841.12269","article-title":"Purification, identification, and in vivo activity of angiotensin I-converting enzyme inhibitory peptide, from ribbon fish (Trichiurus haumela) backbone","volume":"79","author":"Zou","year":"2014","journal-title":"J. Food Sci."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/11\/3308\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:09:28Z","timestamp":1760162968000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/11\/3308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,31]]},"references-count":28,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["molecules26113308"],"URL":"https:\/\/doi.org\/10.3390\/molecules26113308","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,31]]}}}