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http://dx.doi.org/10.3839/jabc.2022.060

Inhibition of collagen-induced platelet aggregation by Sanggenon N via the Ca2+ signaling pathway  

Hyuk-Woo Kwon (Department of Biomedical Laboratory Science and Microbiological Resource Research Institute, Far East University)
Publication Information
Journal of Applied Biological Chemistry / v.65, no.4, 2022 , pp. 463-469 More about this Journal
Abstract
Cudrania tricuspidata (C. tricuspidata), a medicinal plant widely employed throughout Asia in ethnomedicine, has various bioactive properties, including antidiabetic, antiobesity, antitumor, and anti-inflammatory activities. In addition, the C. tricuspidata root extract reportedly inhibits platelet aggregation. Therefore, we focused on the active substances present in the C. tricuspidata extract. Sanggenon N (SN) is a flavonoid found in the root bark of C. tricuspidata. In the present study, we examined the inhibitory effects of SN on platelet aggregation, phosphoproteins, thromboxane A2 generation, and integrin αIIbβ3 activity. SN inhibited collagen-induced human platelet aggregation in a dose-dependent manner without cytotoxicity. Furthermore, SN suppressed Ca2+ mobilization and influx through associated signaling molecules, such as inositol 1, 4, 5-triphosphate receptor I (Ser1756), and extracellular signal-regulated kinase. In addition, SN inhibited thromboxane A2 generation and associated signaling molecules, including cytosolic phospholipase A2 and mitogen-activated protein kinase p38. Finally, SN could inhibit integrin (αIIb/β3) activity by regulating vasodilator-stimulated phosphoprotein and Akt. Collectively, SN possesses potent antiplatelet effects and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.
Keywords
$Ca^{2+}$ influx; $Ca^{2+}$ mobilization; Cudrania tricuspidata; Sanggenon N;
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