title: Skin extracts from 2 Italian table grapes (Italia and Palieri) inhibit tissue factor expression by human blood mononuclear cells.
abstract: Grape and its products such as red wine and grape juice have well-known 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 (Palieri and Italia) inhibited TF expression in lipopolysaccharide (LPS)-stimulated MNC in a concentration-dependent manner with ≥90% inhibition of TF activity and antigen at 6 μg/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-inhibiting 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-mediated clotting activation, if confirmed by in vivo studies, might represent an important antithrombotic mechanism.
  
  
  CONCLUSIONS
  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 in vitro method on whole blood that allows the evaluation of one of the most important antithrombotic activities of food and food-derived products. The simplicity of the method makes it suitable also for screening purposes in large-scale studies.
authors.affiliation: Research Unit for Grape and Wine Growing in the Mediterranean Environment, CRA-UTV Agricultural Research Council, Turi, Bari, Italy.
authors.forename: Rosa Anna
authors.initials: RA
authors.lastname: Milella
authors.forename: Donato
authors.initials: D
authors.lastname: Antonacci
authors.forename: Pasquale
authors.initials: P
authors.lastname: Crupi
authors.forename: Francesca
authors.initials: F
authors.lastname: Incampo
authors.forename: Cosimo
authors.initials: C
authors.lastname: Carrieri
authors.forename: Nicola
authors.initials: N
authors.lastname: Semeraro
authors.forename: Mario
authors.initials: M
authors.lastname: Colucci
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000473:pathology; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D027843:Vitis / Q000737:chemistry*
chemical_list: D008070:Lipopolysaccharides; D010936:Plant Extracts; D059808:Polyphenols; D013925:Thromboplastin