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2',4'-二羟基查耳酮和2',4'-二羟基二氢查耳酮对凝血酶诱导的血小板抑制作用是通过抑制活性氧生成和血栓素合酶a活性介导的:来自……的多酚类次生代谢产物的构效关系

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 .

作者信息

Fock Ekaterina, Pronin Nikita, Rukoyatkina Natalia, Whaley Anastasiia, Gambaryan Stepan, Whaley Andrei

机构信息

Laboratory of Cellular Mechanisms of Blood Homeostasis, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint Petersburg, Russia.

Department of Pharmacognosy, Saint Petersburg State Chemical and Pharmaceutical University, Saint Petersburg, Russia.

出版信息

Nat Prod Res. 2025 Jun;39(12):3382-3390. doi: 10.1080/14786419.2024.2334882. Epub 2024 Apr 3.

Abstract

In this study, we expanded our previous work by testing compounds 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 and 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.

摘要

在本研究中,我们扩展了之前的工作,通过测试化合物在低浓度(30µM)下抑制血小板活化的能力,具体方式为抑制活性氧(ROS)生成、血栓素合酶(TxS)活性以及激活环核苷酸途径。我们还研究了其中一些化合物是否能增强P2Y12 ADP受体抑制剂的作用,并讨论了所测试化合物可能的构效关系。我们发现,在此浓度下,只有化合物 和 显著抑制凝血酶诱导的血小板活化,同时伴有ROS生成和血栓素合酶活性的抑制。相应地,这些化合物显著增强了坎格雷洛对凝血酶诱导的血小板活化的抑制作用。在其他一些情况下,ROS生成和血栓素合酶活性的抑制与血小板抑制并无关联,这表明这些化合物可能影响血小板中某些尚未明确的激活途径,从而抵消它们的抑制作用。

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