{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T18:37:34Z","timestamp":1762195054069,"version":"build-2065373602"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,8,3]],"date-time":"2012-08-03T00:00:00Z","timestamp":1343952000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Food Science"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:p>\n                    <jats:bold>Abstract:\u2003<\/jats:bold>\n                    Grape and its products such as red wine and grape juice have well\u2010known antithrombotic properties, which have been attributed to their high content in polyphenolic compounds. Most studies on the mechanisms underlying these beneficial effects, among which the suppression of tissue factor (TF) synthesis in blood mononuclear cells (MNC) and vascular endothelium is a prominent one, have been performed with purified polyphenols, while little is known about the effect of fresh grapes which contain a multitude of phytochemicals whose interaction may lead to different cell responses. In this study, we investigated the effect of grape skin extracts (GSEs) on TF expression in isolated blood MNC and in whole blood. Alcoholic extracts from skins of 2 grape varieties (\n                    <jats:italic>Palieri<\/jats:italic>\n                    and\n                    <jats:italic>Italia<\/jats:italic>\n                    ) inhibited TF expression in lipopolysaccharide (LPS)\u2010stimulated MNC in a concentration\u2010dependent manner with \u226590% inhibition of TF activity and antigen at 6 \u03bcg\/mL of gallic acid equivalents. Noteworthy, GSEs were also able to inhibit the appearance of TF in whole blood challenged with LPS. The 2 grape varieties displayed a fairly similar TF\u2010inhibiting capacity despite marked differences in phenolic profile. When selected purified polyphenols were tested, their ability to inhibit TF expression was markedly lower as compared to grape extracts, whereas a mixture of some representative polyphenols was much more efficient, supporting the occurrence of a synergistic effect. Given the key role of cell TF in thrombotic diseases, the inhibition of MNC\u2010mediated clotting activation, if confirmed by\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies, might represent an important antithrombotic mechanism.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Practical Application:\u2003<\/jats:bold>\n                    Our data indicate that the combination of different polyphenols, as in grape extracts, is much more efficient than the single constituents, a finding that might be useful as starting point for the development of new antithrombotic nutraceutics. In addition, our study validated a simple, inexpensive, and physiologically relevant\n                    <jats:italic>in vitro<\/jats:italic>\n                    method on whole blood that allows the evaluation of one of the most important antithrombotic activities of food and food\u2010derived products. The simplicity of the method makes it suitable also for screening purposes in large\u2010scale studies.\n                  <\/jats:p>","DOI":"10.1111\/j.1750-3841.2012.02818.x","type":"journal-article","created":{"date-parts":[[2012,8,3]],"date-time":"2012-08-03T16:26:03Z","timestamp":1344011163000},"source":"Crossref","is-referenced-by-count":18,"title":["Skin Extracts from 2 Italian Table Grapes (\n                    <i>Italia<\/i>\n                    and\n                    <i>Palieri<\/i>\n                    ) Inhibit Tissue Factor Expression by Human Blood Mononuclear Cells"],"prefix":"10.1111","volume":"77","author":[{"given":"Rosa Anna","family":"Milella","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donato","family":"Antonacci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Crupi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Incampo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cosimo","family":"Carrieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Semeraro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Colucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,8,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1318.2006.01158.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.177402"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2003.00217.x"},{"key":"e_1_2_6_5_1","first-page":"37","article-title":"The grape phenolic determination","volume":"49","author":"Di Stefano R","year":"1991","journal-title":"Riv Vitic Enol"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114510001522"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.109.107474"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf0302207"},{"key":"e_1_2_6_9_1","first-page":"611","article-title":"Bioactivity of grape chemicals for human health","volume":"4","author":"Iriti M","year":"2009","journal-title":"Nat Prod Commun"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2006.01.020"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2008.08.007"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf0111209"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3841.2010.01662.x"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-042210-121137"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.2761"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.1982.tb00580.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms11041679"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.19.2.419"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/72.5.1150"},{"key":"e_1_2_6_20_1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1055\/s-0037-1614044","article-title":"Fibrin down\u2010regulates LPS and PMA\u2010induced tissue factor expression by blood mononuclear cells","volume":"87","author":"Rossiello MR","year":"2000","journal-title":"Thromb Haemost"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2008.01.004"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04318.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1657625"},{"key":"e_1_2_6_24_1","first-page":"443","volume-title":"Thrombosis. 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