The impact of plant plyphenols on platelet activation and their aggregation with endothelial, blood and malignant cels

Trombociti imaju važnu ulogu u patogenezi kardiovaskularnih i malignih bolesti. Uticaj biološki aktivnih sastojaka namirnica na aktivaciju trombocita i njihovu heterotipsku agregaciju predstavlja jedan od potencijalnih mehanizama njihove uloge u prevenciji hroničnih bolesti i promociji zdravlja. Rezultati interventnih dijetarnih studija potvrđuju uticaj polifenola na funkciju trombocita. Protočna citometrija predstavlja jednu od najoptimalnijih metoda ispitivanja uticaja dijetarnih sastojaka na trombocite. Osnovni cilj doktorske disertacije je ispitivanje uticaja biljaka koje sadrže polifenole na aktivaciju trombocita i njihovu agregaciju sa leukocitima, u in vitro eksperimentalnim uslovima, kao i nakon konzumacije namirnica biljnog porekla, koje predstavljaju dijetarni izvor polifenola. Primenom protočne citometrije pokazano je da u in vitro eksperimentalnim uslovima svi ispitivani ekstrakti (ekstrakt koprive, mirođije, šarplaninskog čaja, kelja, nara, japanske jabuke i aronije) pokazuju efekte su na neki od analiziranih parametara aktivacije trombocita i njihove agregacije sa monocitima i neutrofilima, kod zdravih ispitanika ili ispitanika sa metaboličkim sindromom. Na najveći broj parametara delovali su ekstrakti kelja i mirođije, a u tom smislu najmanje izraženo delovanje pokazao je ekstrakt nara. Ispitivanjem delovanja metabolita pokazano je da svi ispitivani metaboliti: kvercetin-3-glukuronid, 3’-metil-kvercetin-3-glukuronid, kvercetin-3’-sulfat i sulforafan-cistein-glicin pokazuju efekte na neki od parametara aktivacije trombocita i njihove agregacije sa monocitima i neutrofilima, kod zdravih ispitanika ili ispitanika sa metaboličkim sindromom. Sulforafan-cistein-glicin delovao je na veći broj parametara u odnosu na metabolite kvercetina. Delovanje 3’-metil-kvercetin-3-glukuronida bilo je izraženije u odnosu na delovanje ostalih metabolita kvercetina. Nakon ispitivanja delovanja jednokratne konzumacije namirnica koje predstavljaju dijetarni izvor polifenola pokazano je da konzumacija soka od aronije kod zdravih ispitanika dovodi do smanjenja aktivacije trombocita i to smanjenjem procenta Pselektin- pozitivnih trombocita u bazalnim uslovima, kao i smanjenjem procenta i gustine ovog adhezionog receptora nakon ex vivo delovanja adenozin-difosfata i arahidonske kiseline kao agonista...Platelets have an important role in the pathogenesis of the cardiovascular and malignant diseases. The impact of bioactive dietary compounds on platelet activation and their aggregation with leukocytes is one of the potential mechanisms of their role in health promotion and the prevention of chronic diseases. The results of dietary intervention studies confirm the effect of polyphenols on platelet function. Flow cytometry is considered to be one of the most advantageous methods in investigation of dietary compounds effects on platelets. The main aim of this study was the evaluation of potential effects of polyphenol - rich plants on platelets activation and their aggregation with leukocytes, in in vitro experimental setting and after the consumption of plant foods, as dietary sources of polyphenols. All investigated plant extracts (extracts of nettle, dill, mountain tea, kale, pomegranate, persimmon and chokeberry) affected some of the analyzed parameters of platelets activation and their aggregation with monocytes and neutrophils, in healthy subjects or subjects with metabolic syndrome The most effective were kale and dill extracts, influencing most of the parameters evaluated by flow cytometry, while the least effective was pomegranate extract. All investigated metabolites: quercetin - 3 - glucuronide, 3' - methyl - quercetin - 3 - glucuronide, quercetin - 3' - sulfate and sulforaphane - cysteine - glycine have shown the effects on some parameters of platelet activation and their aggregation with monocytes and neutrophils, in healthy subjects or subjects with metabolic syndrome. The most effective was sulforaphane - cysteine - glycine, influencing most of the analyzed parameters . 3' - methyl - quercetin - 3 - glucuronide showed more pronounced effects compared to the effects of other metabolites of quercetin. Dietary intervention studies investigating the effects of single consumption of plant-based foods as dietary sources of polyphenols have shown that consumption of chokeberry juice beneficially influenced platelet activation status by reducing the percentage of P - selectin - positive platelets under basal conditions, as well as reducing he percentage and density of P - selectin after ex vivo agonistic action of adenosine diphosphate and arachidonic acid..