{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:04:57Z","timestamp":1791828297186,"version":"4.3.4"},"reference-count":48,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T00:00:00Z","timestamp":1613520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>It is well established that maintaining healthy blood pressure is fundamental in order to avoid disorders to the heart and blood vessels. In prevention, and alongside pharmacological therapy, the use of natural substances has been proven to be extremely helpful for pre- and mild hypertensive subjects. Our study was therefore focused on the effects, both in vitro and in humans, of a grape seed extract, Enovita (GSEe), a highly standardized extract in polyphenols of Vitis vinifera L. The in vitro human umbilical vein endothelial cells (HUVEC) model was chosen to explore the extract properties related to vascular inflammation\/vasodilation. A significant reduction of both soluble Inter-Cellular Adhesion Molecule-1 (sICAM) and endothelin-1 secretion\/release was induced by GSEe in HUVEC cells. A randomized, double-blind, placebo-controlled clinical study in healthy volunteers was further performed to investigate GSEe benefits. In healthy volunteers, both supplementations significantly modulated blood pressure, with a pronounced effect after GSEe tablets (300 mg\/day for 16 weeks) in respect to placebo. In the male gender subgroup, no placebo effect was observed as it was for the female group. As an additional outcome, an overall GSEe positive modulation emerged on mood related to stress perception. Thus, GSEe resulted in a benefit of modulating endothelial functionality and blood pressure. It was noteworthy that GSEe relieved the perceived stress, promising new future perspectives on mood comfort.<\/jats:p>","DOI":"10.3390\/nu13020654","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T21:35:42Z","timestamp":1613597742000},"page":"654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Grape Seed Extract Positively Modulates Blood Pressure and Perceived Stress: A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Volunteers"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3787-5268","authenticated-orcid":false,"given":"Christiane","family":"Sch\u00f6n","sequence":"first","affiliation":[{"name":"BioTeSys GmbH, Schelztorstr. 54\u201356, 73728 Esslingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Allegrini","sequence":"additional","affiliation":[{"name":"Research and Development Department, Indena SpA, 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Engelhart-Jentzsch","sequence":"additional","affiliation":[{"name":"BioTeSys GmbH, Schelztorstr. 54\u201356, 73728 Esslingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2819-943X","authenticated-orcid":false,"given":"Antonella","family":"Riva","sequence":"additional","affiliation":[{"name":"Research and Development Department, Indena SpA, 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6681-7329","authenticated-orcid":false,"given":"Giovanna","family":"Petrangolini","sequence":"additional","affiliation":[{"name":"Research and Development Department, Indena SpA, 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,17]]},"reference":[{"key":"ref_1","first-page":"52","article-title":"Guide of Hypertensive Crisis Pharmacotherapy","volume":"17","author":"Mendez","year":"2017","journal-title":"Cardiovasc. 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