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Euchrestaflavanone A can attenuate thrombosis through inhibition of collagen-induced platelet activation

  • Shin, Jung-Hae (Department of Biomedical Laboratory Science, Catholic Kwandong University) ;
  • Kwon, Hyuk-Woo (Department of Biomedical Laboratory Science, Far East University)
  • Received : 2020.09.22
  • Accepted : 2020.10.19
  • Published : 2020.12.31

Abstract

Euchrestaflavanone A (EFA) is a flavonoid found in the root bark of Cudrania tricuspidata. C. tricuspidata extract, widely used throughout Asia in traditional medicine, has been investigated phytochemically and biologically and is known to have anti-obesity, anti-inflammatory, and anti-tumor effects. It has been reported that C. tricuspidata extract also possesses anti-platelet effects; however, the mechanism of its anti-platelet and anti-thrombotic activities is yet to be elucidated. In this study, we investigated the effects of EFA on the modulation of platelet function using collagen-induced human platelets. Our results showed that EFA markedly inhibited platelet aggregation. Furthermore, it downregulated glycoprotein IIb/IIIa (αIIb/β3)-mediated signaling events, including platelet adhesion, granule secretion, thromboxane A2 production, and clot retraction, but upregulated the cyclic adenosine monophosphate-dependent pathway. Taken together, EFA possesses strong anti-platelet and anti-thrombotic properties and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

Keywords

References

  1. Chen H, Kahn ML (2003) Reciprocal signaling by integrin and nonintegrin receptors during collagen activation of platelets. Mol Cell Biol 23: 4764-4777 https://doi.org/10.1128/MCB.23.14.4764-4777.2003
  2. Farndale RW (2006) Collagen-induced platelet activation. Blood Cell Mol Dis 36: 162-165 https://doi.org/10.1016/j.bcmd.2005.12.016
  3. Phillips DR, Nannizzi-Alaimo L, Prasad KS (2001) Beta3 tyrosine phosphorylation in alphaIIbbeta3 (platelet membrane GP IIb-IIIa) outside-in integrin signaling. Thromb Haemost 86: 246-258 https://doi.org/10.1055/s-0037-1616222
  4. Andrews RK, Berndt MC (2004) Platelet physiology and thrombosis. Thromb Res 114: 447-453 https://doi.org/10.1016/j.thromres.2004.07.020
  5. Jackson SP (2011) Arterial thrombosis-insidious, unpredictable and deadly. Nat Med 17: 1423-1436 https://doi.org/10.1038/nm.2515
  6. Kim DC, Yoon CS, Quang TH, Ko W, Kim JS, Oh H, Kim YC (2016) Prenylated flavonoids from Cudrania tricuspidata suppress lipopolysaccharide-induced neuroinflammatory activities in BV2 microglial cells. Int J Mol Sci 17:255 https://doi.org/10.3390/ijms17020255
  7. Xin LT, Yue SJ, Fan YC, Wu JS, Yan D, Guan HS, Wang CY (2017) Cudrania tricuspidata: an updated review on ethnomedicine, phytochemistry and pharmacology. RSC advances 7: 31807-31832 https://doi.org/10.1039/C7RA04322H
  8. Shin JH, Ha JY, Kwon HW (2020) Inhibitory Actions of Steppogenin on Platelet Activity Through Regulation of Glycoprotein IIb/IIIa and Ca2+ Mobilization. Korean J Pharmacogn 51: 100-106 https://doi.org/10.22889/KJP.2020.51.2.100
  9. Shin JH (2020) Inhibitory Effects of Isoderrone on Platelet Aggregation through Regulation of Cyclic Nucleotides. J Korean Soc Food Sci Nutr 49: 796-802 https://doi.org/10.3746/jkfn.2020.49.8.796
  10. Shin JH, Kwon HW, Lee DH (2019) Ginsenoside F4 inhibits platelet aggregation and thrombus formation by dephosphorylation of IP3RI and VASP. J Appl Biol Chem 62: 93-100 https://doi.org/10.3839/jabc.2019.014
  11. Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260: 3440-3450 https://doi.org/10.1016/S0021-9258(19)83641-4
  12. VargaSzabo D, Braun A, Nieswandt B (2009) Calcium signaling in platelets. J Thromb Haemost 7: 1057-1066 https://doi.org/10.1111/j.1538-7836.2009.03455.x
  13. Quinton TM, Dean WL (1992) Cyclic AMP-dependent phosphorylation of the inositol-1,4,5-trisphosphate receptor inhibits Ca2+ release from platelet membranes. Biochem Bioph Res Co 184: 893-899 https://doi.org/10.1016/0006-291X(92)90675-B
  14. Cavallini L, Coassin M, Borean A, Alexandre A (1996) Prostacyclin and sodium nitroprusside inhibit the activity of the platelet inositol 1,4,5-trisphosphate receptor and promote its phosphorylation. J Biol Chem 271: 5545-5551 https://doi.org/10.1074/jbc.271.10.5545
  15. Patrono C (1994) Aspirin as an antiplatelet drug. N Engl J Med 330: 1287-1294 https://doi.org/10.1056/NEJM199405053301808
  16. Kramer RM, Roberts EF, Um SL, Borsch-Haubold AG, Watson SP, Fisher MJ, Jakubowski JA (1996) p38 mitogen-activated protein kinase phosphorylates cytosolic phospholipase A2 (cPLA2) in thrombin-stimulated platelets. evidence that proline-directed phosphorylation is not required for mobilization of arachidonic acid by cPLA2. J Biol Chem 271: 27723-27729 https://doi.org/10.1074/jbc.271.44.27723
  17. McNicol A, Shibou TS (1998) Translocation and phosphorylation of cytosolic phospholipase A2 in activated platelets. Thromb Res 92: 19-26 https://doi.org/10.1016/S0049-3848(98)00097-8
  18. Kwon HW (2018) Inhibitory Effects of PD98059, SB203580, and SP600125 on α-and δ-granule Release and Intracellular Ca2+ Levels in Human Platelets. Biomed Sci Lett 24: 253-262 https://doi.org/10.15616/BSL.2018.24.3.253
  19. Shin JH, Kwon HW, Rhee MH, Park HJ (2019) Inhibitory effects of thromboxane A2 generation by ginsenoside Ro due to attenuation of cytosolic phospholipase A2 phosphorylation and arachidonic acid release. J Ginseng Res 43: 236-241 https://doi.org/10.1016/j.jgr.2017.12.007
  20. Laurent V, Loisel TP, Harbeck B, Wehman A, Grobe L, Jockusch BM, Carlier MF (1999) Role of proteins of the Ena/VASP family in actin-based motility of Listeria monocytogenes. yJ Cell Biol 144: 1245-1258 https://doi.org/10.1083/jcb.144.6.1245
  21. Sudo T, Ito H, Kimura Y (2003) Phosphorylation of the vasodilator-stimulated phosphoprotein (VASP) by the anti-platelet drug, cilostazol, in platelets. Platelets 14: 381-390 https://doi.org/10.1080/09537100310001598819
  22. Woulfe DS (2010) Akt signaling in platelets and thrombosis. Expert review of hematology 3: 81-91 https://doi.org/10.1586/ehm.09.75
  23. Schwarz UR, Walter U, Eigenthaler M (2001) Taming platelets with cyclic nucleotides. Biochem Pharmacol 62: 1153-1161 https://doi.org/10.1016/S0006-2952(01)00760-2
  24. Smolenski A (2012) Novel roles of cAMP/cGMP-dependent signaling in platelets J Thromb Haemost 10: 167-176 https://doi.org/10.1111/j.1538-7836.2011.04576.x

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