Thrombin-induced platelet inhibition by 2′,4′-dihydroxychalcone and 2′,4′-dihydroxydihydrochalcone is mediated by inhibition of ROS production and Thromboxane synthase a activity: structure-activity relationship of polyphenol secondary metabolites from Empetrum nigrum

Abstract

In this study, we expanded our previous work by testing compounds 1–12 for their ability to inhibit platelet activation at low (30 µM) concentration by inhibition of ROS production, thromboxane synthase (TxS) activity, and activation of cyclic nucleotide pathways. We also investigated whether some of these compounds could potentiate the effects of P2Y12 ADP receptor inhibitor action and discussed possible structure-activity relationships of the tested compounds. We showed that at this concentration only compounds 7 and 12 significantly inhibited thrombin-induced platelet activation which was accompanied by inhibition of ROS production and thromboxane synthase activity. Correspondingly, these compounds significantly potentiated the inhibitory effect of cangrelor on thrombin-induced platelet activation. In some other cases, inhibition of ROS production and thromboxane synthase activity did not correlate with platelet inhibition, indicating that these compounds could affect some, still unidentified, activatory pathways in platelets that counteract their inhibitory effects.