title: Flavonolignans inhibit ADP induced blood platelets activation and aggregation in whole blood.
abstract: Flavonolignans are a group of active chemical compounds presented in the silymarin - a standardized extract obtained from fruits and seeds of Milk thistle (Silybum marianum L. Gaernt.). Since the 70s of the last century, flavonolignans have been regarded to the official medicine as a substances having hepatoprotective properties. However many researches performed in recent years have demonstrated that flavonolignans posses many other healthy properties including modulation of variety cell-signaling pathways. The aim of our study was to examine the effects of three major flavonolignans (silybin, silychristin and silydianin) on ADP-induced blood platelet activation using the flow cytometry analysis as well as determine the mechanism of this interaction by bioinformatic ligand docking method. We observed that all tested flavonolignans in dose-dependent manner inhibit formation of blood platelet aggregates and microparticles as well as decrease expression of P-selectin and activation of integrin αIIbβ3. Our computer-generated models confirm the flow cytometry analysis. We observed that all tested flavonolignans have conformations which are able to bind to the extracellular domain of P2Y12 receptor and probably block interaction with ADP. Our studies may help in the development of a new potential anti-platelet agent, which might be an alternative to the current using drugs.
authors.affiliation: Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland. Electronic address: mbijak@biol.uni.lodz.pl.
authors.forename: Michal
authors.initials: M
authors.lastname: Bijak
authors.affiliation: Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Szelenberger
authors.affiliation: Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Saluk
authors.affiliation: Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Nowak
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D044947:Flavonolignans / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D010974:Platelet Aggregation / Q000187:drug effects*; D011487:Protein Conformation; D058925:Receptors, Purinergic P2Y12 / Q000737:chemistry / Q000378:metabolism
chemical_list: D044947:Flavonolignans; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate
keywords: Blood platelets; Flavonolignans; Silymarin