{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T21:14:56Z","timestamp":1773695696116,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,26]],"date-time":"2021-12-26T00:00:00Z","timestamp":1640476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K09273"],"award-info":[{"award-number":["17K09273"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The vasorelaxant effect of polyphenols is well known, and the mortality rate due to coronary artery disease is low in people who consume polyphenol-containing foods. We aimed to elucidate the mechanism by which polyphenols derived from persimmon juice (PJ) and persimmon leaves (PLs) induce vasorelaxation and suppress vasocontraction in the superior mesenteric arteries isolated from male Sprague Dawley rats. Vasocontraction was induced with 1 \u00b5M phenylephrine, and polyphenol-induced vasorelaxation was expressed as a percentage of the previous tone induced by phenylephrine. PJ powder (100 mg\/L) induced higher levels of vasorelaxation (mean \u00b1 standard error of the mean, 88.6% \u00b1 4.4%) than PLs powder (1 g\/L; 72.0% \u00b1 10.8%). Nitric oxide pathway inhibitors (NG-nitro-L-arginine methyl ester + carboxy-PTIO) did not affect persimmon-derived polyphenol-induced vasorelaxation, whereas potassium chloride, tetraethylammonium, and potassium-channel inhibitors did. Vasorelaxation was endothelium independent with both extracts. Phenylephrine-induced vasocontraction was suppressed by pretreatment with PJ and PLs powder, even when inositol triphosphate-mediated Ca2+ release and extracellular Ca2+ influx were inhibited. These results suggest that persimmon-derived polyphenol phytocomplex cause vasorelaxation and inhibit vasocontraction through hyperpolarization of smooth muscle cells. Persimmon-derived polyphenols may be able to prevent cardiovascular diseases caused by abnormal contraction of blood vessels.<\/jats:p>","DOI":"10.3390\/nu14010089","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T01:06:54Z","timestamp":1640567214000},"page":"89","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Endothelium-Independent Relaxation of Vascular Smooth Muscle Induced by Persimmon-Derived Polyphenol Phytocomplex in Rats"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9530-9366","authenticated-orcid":false,"given":"Risa","family":"Kudo","sequence":"first","affiliation":[{"name":"Department of Legal Medicine, Nara Medical University, 840 Shijocho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7714-5123","authenticated-orcid":false,"given":"Katsuya","family":"Yuui","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Nara Medical University, 840 Shijocho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shogo","family":"Kasuda","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Nara Medical University, 840 Shijocho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Khan, N., and Mukhtar, H. (2018). Tea Polyphenols in Promotion of Human Health. Nutrients, 11.","DOI":"10.3390\/nu11010039"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1248\/bpb.b14-00157","article-title":"Effect of short-term polyphenol treatment on endothelial dysfunction and thromboxane A2 levels in streptozotocin-induced diabetic mice","volume":"37","author":"Taguchi","year":"2014","journal-title":"Biol. Pharm. Bull."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1152\/ajpendo.00377.2013","article-title":"Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: Therapeutic implications for diabetes and its cardiovascular complications","volume":"305","author":"Munir","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1097\/MOL.0b013e32835bcdff","article-title":"Dietary flavonoids and the development of type 2 diabetes and cardiovascular diseases: Review of recent findings","volume":"24","author":"Naidoo","year":"2013","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.phrs.2012.10.018","article-title":"Beneficial effects of polyphenols on cardiovascular disease","volume":"68","author":"Miguel","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.abb.2010.04.006","article-title":"Polyphenols and health: Update and perspectives","volume":"501","author":"Sies","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1590\/S1807-59322009000500011","article-title":"Short-term red wine consumption promotes differential effects on plasma levels of high-density lipoprotein cholesterol, sympathetic activity, and endothelial function in hypercholesterolemic, hypertensive, and healthy subjects","volume":"64","author":"Andrade","year":"2009","journal-title":"Clinics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.vph.2008.08.004","article-title":"Vasoprotective endothelial effects of a standardized grape product in humans","volume":"50","author":"Chaves","year":"2009","journal-title":"Vascul. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1590\/S0100-879X2005000900008","article-title":"The action of red wine and purple grape juice on vascular reactivity is independent of plasma lipids in hypercholesterolemic patients","volume":"38","author":"Coimbra","year":"2005","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.diabres.2018.06.017","article-title":"Epigallocatechin gallate improves insulin resistance in HepG2 cells through alleviating inflammation and lipotoxicity","volume":"142","author":"Zhang","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3374","DOI":"10.1039\/C8FO00167G","article-title":"EGCG stimulates the recruitment of brite adipocytes, suppresses adipogenesis and counteracts TNF-\u03b1-triggered insulin resistance in adipocytes","volume":"9","author":"Mi","year":"2018","journal-title":"Food Funct."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.2174\/1381612825666190722100504","article-title":"Polyphenols Regulate Endothelial Functions and Reduce the Risk of Cardiovascular Disease","volume":"25","author":"Yamagata","year":"2019","journal-title":"Curr. Pharm. Des."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Li, H., Xia, N., Hasselwander, S., and Daiber, A. (2019). Resveratrol and Vascular Function. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092155"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.lfs.2013.11.016","article-title":"Epigallocatechin gallate attenuates ET-1-induced contraction in carotid artery from type 2 diabetic OLETF rat at chronic stage of disease","volume":"118","author":"Matsumoto","year":"2014","journal-title":"Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/B978-0-12-394383-5.00014-X","article-title":"Antihypertensive role of polyphenols","volume":"58","author":"Rodrigo","year":"2012","journal-title":"Adv. Clin. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1124\/jpet.108.145326","article-title":"Angiotensin II-induced hypertension is associated with a selective inhibition of endothelium-derived hyperpolarizing factor-mediated responses in the rat mesenteric artery","volume":"328","author":"Bronner","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1097\/HJH.0b013e3283186994","article-title":"Antihypertensive effect of French maritime pine bark extract (Flavangenol): Possible involvement of endothelial nitric oxide-dependent vasorelaxation","volume":"27","author":"Kwak","year":"2009","journal-title":"J. Hypertens."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1097\/FJC.0b013e31819ccfc9","article-title":"Crataegus special extract WS 1442 causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of endothelial NO synthase but not via activation of estrogen receptors","volume":"53","author":"Anselm","year":"2009","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1038\/sj.bjp.0701011","article-title":"Nitric oxide production and endothelium-dependent vasorelaxation induced by wine polyphenols in rat aorta","volume":"120","author":"Andriambeloson","year":"1997","journal-title":"Br. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.vph.2006.08.411","article-title":"Endothelium-dependent vasodilator effect of Euterpe oleracea Mart. (A\u00e7a\u00ed) extracts in mesenteric vascular bed of the rat","volume":"46","author":"Rocha","year":"2007","journal-title":"Vascul. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.cardiores.2006.08.004","article-title":"Grape juice causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of eNOS","volume":"73","author":"Anselm","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/sj.bjp.0705774","article-title":"Red wine polyphenols induce EDHF-mediated relaxations in porcine coronary arteries through the redox-sensitive activation of the PI3-kinase\/Akt pathway","volume":"142","author":"Ndiaye","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"ref_23","first-page":"2625","article-title":"Persimmon leaf flavonoid promotes brain ischemic tolerance","volume":"8","author":"Miao","year":"2013","journal-title":"Neural Regen. Res."},{"key":"ref_24","first-page":"245","article-title":"Hypoglycemic and hypocholesterolaemia effect of total flavonoids from persimmon leaf in alloxan-induced diabetic mice and its mechanism","volume":"30","author":"Gao","year":"2009","journal-title":"Taishan Yixueyuan Xuebao"},{"key":"ref_25","first-page":"49","article-title":"Extraction, separation and pharmacological effects of total flavonoids from persimmon leaf","volume":"2","author":"Xin","year":"2007","journal-title":"Zhongyiyao Xuebao"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1271\/bbb.100926","article-title":"Antihypertensive and vasorelaxant effects of water-soluble proanthocyanidins from persimmon leaf tea in spontaneously hypertensive rats","volume":"75","author":"Kawakami","year":"2011","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104","DOI":"10.5979\/cha.1962.104","article-title":"A colorimetric determination of tea tannin with ferrous tartrate","volume":"19","author":"Iwase","year":"1962","journal-title":"Tea Res. J. (Chagyo Kenkyu Hokoku)"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/dta.2390","article-title":"Direct detection of the psychoactive substance MT-45 in human tissue samples by probe electrospray ionization-tandem mass spectrometry","volume":"10","author":"Usui","year":"2018","journal-title":"Drug Test. Anal."},{"key":"ref_29","first-page":"289","article-title":"LC-MS\/MS for simultaneous determination of four major active catechins of tea polyphenols in rat plasma and its application to pharmacokinetics","volume":"2","author":"Wang","year":"2010","journal-title":"Chin. Herb. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1177\/0960327115611944","article-title":"Ethanol attenuates vasorelaxation via inhibition of inducible nitric oxide synthase in rat artery exposed to interleukin-1\u03b2","volume":"35","author":"Yuui","year":"2016","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4323\/rjlm.2017.1","article-title":"Effect of ethanol on capsaicin-induced nerve-mediated vasorelaxation in rat arteries","volume":"25","author":"Kudo","year":"2017","journal-title":"Rom. J. Legal Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1097\/00005344-199611000-00014","article-title":"The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation","volume":"28","author":"Shimokawa","year":"1996","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_33","first-page":"H1090","article-title":"Heterogeneous distribution of endothelium-dependent relaxations resistant to NG-nitro-L-arginine in rats","volume":"263","author":"Nagao","year":"1992","journal-title":"Am. J. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1007\/s00424-010-0806-4","article-title":"Nutritional improvement of the endothelial control of vascular tone by polyphenols: Role of NO and EDHF","volume":"459","author":"Auger","year":"2010","journal-title":"Pflugers. Arch."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/B978-0-12-385061-4.00006-4","article-title":"Polyphenol-induced endothelium-dependent relaxations role of NO and EDHF","volume":"60","author":"Auger","year":"2010","journal-title":"Adv. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1042\/CS20100311","article-title":"Red wine polyphenols prevent endothelial dysfunction induced by endothelin-1 in rat aorta: Role of NADPH oxidase","volume":"120","author":"Zarzuelo","year":"2011","journal-title":"Clin. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1210\/en.2009-0997","article-title":"Green tea polyphenol epigallocatechin gallate reduces endothelin-1 expression and secretion in vascular endothelial cells: Roles for AMP-activated protein kinase, Akt, and FOXO1","volume":"151","author":"Reiter","year":"2010","journal-title":"Endocrinology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1007\/s00424-009-0759-7","article-title":"Endothelium-derived contracting factors mediate the Ang II-induced endothelial dysfunction in the rat aorta: Preventive effect of red wine polyphenols","volume":"459","author":"Kane","year":"2010","journal-title":"Pflug. Arch."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"331","DOI":"10.3136\/nskkk.63.331","article-title":"Polyphenols from Persimmon Fruits as a Functional Foods Material","volume":"63","author":"Kometani","year":"2016","journal-title":"Nippon Shokuhin Kagaku Kogaku Kaishi"},{"key":"ref_40","first-page":"1637","article-title":"The chemical structure of kaki-tannin from immature fruit of the persimmon (Diospyros kaki L.)","volume":"42","author":"Matsuo","year":"1978","journal-title":"Agric. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1271\/bbb.100056","article-title":"Major water-soluble polyphenols, proanthocyanidins, in leaves of persimmon (Diospyros kaki) and their alpha-amylase inhibitory activity","volume":"74","author":"Kawakami","year":"2010","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6190","DOI":"10.1074\/jbc.M309114200","article-title":"A constituent of green tea, epigallocatechin-3-gallate, activates endothelial nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxation","volume":"279","author":"Lorenz","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/ptr.5969","article-title":"(\u2212)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels","volume":"32","author":"Marinko","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.3389\/fphar.2019.01430","article-title":"Pu-Erh Tea Relaxes the Thoracic Aorta of Rats by Reducing Intracellular Calcium","volume":"10","author":"Luo","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/ajh.2009.213","article-title":"Effect of cocoa products on blood pressure: Systematic review and meta-analysis","volume":"23","author":"Desch","year":"2010","journal-title":"Am. J. Hypertens."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1016\/j.jacc.2008.01.059","article-title":"Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial","volume":"51","author":"Balzer","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1093\/jn\/138.9.1671","article-title":"Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate","volume":"138","author":"Grassi","year":"2008","journal-title":"J. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1093\/ajcn\/88.1.38","article-title":"Flavonoids, flavonoid-rich foods, and cardiovascular risk: A meta-analysis of randomized controlled trials","volume":"88","author":"Hooper","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1002\/mnfr.200800182","article-title":"Vascular action of polyphenols","volume":"53","author":"Ghosh","year":"2009","journal-title":"Mol. Nutr. Food. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s00395-008-0759-3","article-title":"Green and black tea are equally potent stimuli of NO production and vasodilation: New insights into tea ingredients involved","volume":"104","author":"Lorenz","year":"2009","journal-title":"Basic Res. Cardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1161\/01.CIR.104.2.151","article-title":"Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease","volume":"104","author":"Duffy","year":"2001","journal-title":"Circulation"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1007\/BF00165396","article-title":"BRL 38227 (levcromakalim)-induced hyperpolarization reduces the sensitivity to Ca2+ of contractile elements in canine coronary artery","volume":"347","author":"Okada","year":"1993","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_53","first-page":"33","article-title":"K+ channel-opening action and KRN2391-induced reduction of Ca2+ sensitivity of arterial smooth muscle","volume":"326","author":"Okada","year":"1993","journal-title":"Arch. Int. Pharmacodyn. Ther."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/1\/89\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:53:45Z","timestamp":1760169225000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/1\/89"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,26]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["nu14010089"],"URL":"https:\/\/doi.org\/10.3390\/nu14010089","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,26]]}}}