Journal of Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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Inhibitory effects of scoparone through regulation of PI3K/Akt and MAPK on collagen-induced human platelets

  • Lee, Dong-Ha (Department of Biomedical Laboratory Science, Namseoul University)
  • Received : 2020.03.04
  • Accepted : 2020.03.23
  • Published : 2020.06.30
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Abstract

When blood vessels are damaged, a fast hemostatic response should occur to minimize blood loss and maintain normal circulation. Platelet activation and aggregation are essential in this process. However, excessive platelet aggregation or abnormal platelet aggregation may be the cause of cardiovascular diseases such as thrombosis, stroke, and atherosclerosis. Therefore, finding a substance capable of regulating platelet activation and suppressing agglutination reaction is important for the prevention and treatment of cardiovascular diseases. 6,7-Dimethoxy-2H-chromen-2-one (Scoparone), found primarily in the roots of Artemisia or Scopolia plants, has been reported to have a pharmacological effect on immunosuppression and vasodilation, but studies of platelet aggregation and its mechanisms are still insufficient. This study confirmed the effect of scoparone on collagen-induced human platelet aggregation, TXA2 production, and major regulation of intracellular granule secretion (ATP and serotonin release). In addition, the effect of scoparone on the phosphorylation of the phosphoproteins PI3K/Akt and mitogen-activated protein kinases (MAPK) involved in signal transduction in platelet aggregation was studied. As a result, scoparone significantly inhibited the phosphorylation of PI3K/Akt and MAPK, which significantly inhibited platelet aggregation through TXA2 production and intracellular granule secretion (ATP and serotonin release). Therefore, we suggest that scoparone is an antiplatelet substance that regulates the phosphorylation of phosphoproteins such as PI3K/Akt and MAPK and is of value as a preventive and therapeutic agent for platelet-derived cardiovascular disease.

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References

  1. Jackson SP (2011) Arterial thrombosis--insidious, unpredictable and deadly. Nat Med 17: 1423-1436 https://doi.org/10.1038/nm.2515
  2. Schwartz SM, Heimark RL, Majesky MW (1990) Developmental mechanisms underlying pathology of arteries. Physiol Rev 70: 1177-1209 https://doi.org/10.1152/physrev.1990.70.4.1177
  3. Payrastre B, Missy K, Trumel C, Bodin S, Plantavid M, Chap H (2000) The integrin alpha IIb/beta 3 in human platelet signal transduction. Biochem Pharmacol 60(8): 1069-1074 https://doi.org/10.1016/S0006-2952(00)00417-2
  4. Morello F, Perino A, Hirsch E (2009) Phosphoinositide 3-kinase signalling in the vascular system. Cardiovasc Res 82(2): 261-271 https://doi.org/10.1093/cvr/cvn325
  5. Jennings LK (2009) Role of platelets in atherothrombosis. Am J Cardiol 103: 4A-10A https://doi.org/10.1016/j.amjcard.2008.11.017
  6. Sabatine MS, Jang IK (2000) The use of glycoprotein IIb/IIIa inhibitors in patients with coronary artery disease. Am J Med 109(3): 224-237 https://doi.org/10.1016/S0002-9343(00)00474-5
  7. Cattanco M, Tenconi PM, Lecchi A, Mannucci PM (1991) In vitro effects of picotamide on human platelet aggregation, the release reaction and thromboxane B2 production. Thromb Res 62: 717-724 https://doi.org/10.1016/0049-3848(91)90375-7
  8. Su CY, Shiao MS, Wang CT (1999) Differential effects of ganodermic acid S on the thromboxane A2-signaling pathways in human platelets. Biochem Pharmacol 58: 587-595 https://doi.org/10.1016/S0006-2952(99)00136-7
  9. Adam F, Kauskot A, Rosa JP, Bryckaert M (2008) Mitogenactivated protein kinases in hemostasis and thrombosis. J Thromb Haemost 6: 2007-2016 https://doi.org/10.1111/j.1538-7836.2008.03169.x
  10. Bugaud F, Nadal-Wollbold F, Levy-Toledano S, Rosa JP, Bryckaert M (1990) Regulation of c-jun-NH2 terminal kinase and extracellular-signal regulated kinase in human platelets. Blood 94: 3800-3805 https://doi.org/10.1182/blood.v94.11.3800.423k25_3800_3805
  11. Kramer RM, Roberts EF, Strifler BA, Johnstone EM (1995) Thrombin induces activation of p38 MAP kinase in human platelets. J Biol Chem 270: 27395-27398 https://doi.org/10.1074/jbc.270.46.27395
  12. Nadal-Wollbold F, Pawlowski M, Levy-Toledano S, Berrou E, Rosa JP, Bryckaert M (2002) Platelet ERK2 activation by thrombin is dependent on calcium and conventional protein kinases C but not Raf-1 or B-Raf. FEBS Lett 531: 475-482 https://doi.org/10.1016/S0014-5793(02)03587-1
  13. Patrono C (1994) Aspirin as an antiplatelet drug. N Engl J Med 330: 1287-1294 https://doi.org/10.1056/NEJM199405053301808
  14. Flevaris P, Li Z, Zhang G, Zheng Y, Liu J, Du X (2009) Two distinct roles of mitogen-activated protein kinases in platelets and a novel Rac1-MAPK-dependent integrin outside-in retractile signaling pathway. Blood 113: 893-901 https://doi.org/10.1182/blood-2008-05-155978
  15. Kramer RM, Roberts EF, Um SL, Borsch-Haubold AG, Watson SP, Fisher MJ, Jakubowski JA (1996) p38 mitogenactivated protein kinase phosphorylates cytosolic phospholipase A2 (cPLA2) in thrombinstimulated 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
  16. 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
  17. Chuang WY, Kung PH, Kuo CY, Wu CC (2013) Sulforaphane prevents human platelet aggregation through inhibiting the phosphatidylinositol 3-kinase/Akt pathway, Thromb. Haemost 109(6): 1120-1130 https://doi.org/10.1160/TH12-09-0636
  18. Huang HC, Chu SH, Chao PD (1991) Vasorelaxants from Chinese herbs, emodin and scoparone, possess immunosuppressive properties. Eur J Pharmacol 198: 211-213 https://doi.org/10.1016/0014-2999(91)90624-Y
  19. Huang HC, Lee CR, Weng YI, Lee MC, Lee YT (1992) Vasodilator effect of scoparone (6,7-dimethoxycoumarin) from a Chinese herb. Eur J Pharmacol 218: 123-128 https://doi.org/10.1016/0014-2999(92)90155-W
  20. Lu C, Li Y, Hu S, Cai Y, Yang Z, Peng K (2018) Scoparone prevents IL-$1{\beta}$-induced inflammatory response in human osteoarthritis chondrocytes through the PI3K/Akt/NF-${\kappa}B$ pathway. Biomed Pharmacother 106: 1169-1174 https://doi.org/10.1016/j.biopha.2018.07.062
  21. Lee DH (2019) Antiplatelet effects of scoparone through up-regulation of cAMP and cGMP on U46619-induced human platelets. J Appl Biol Chem 62: 425-431 https://doi.org/10.3839/jabc.2019.058
  22. 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
  23. Chang MC, Wang TM, Yeung SY, Jeng PY, Liao CH, Lin CC, Lin BR, Jeng JH (2011) Antiplatelet effect by p-cresol, a uremic and environmental toxicant, is related to inhibition of reactive oxygen species, ERK/p38 signaling and thromboxane A2 production. Atherosclerosis 219(2): 559-565 https://doi.org/10.1016/j.atherosclerosis.2011.09.031
  24. Cipollone F, Patrignani P, Greco A, Panara MR, Padovano R, Cuccurullo F Patrono C, Rebuzzi AG, Liuzzo G, Quaranta G, Maseri A (1997) Differential suppression of thromboxane biosynthesis by indobufen and aspirin in patients with unstable angina. Circulation 96: 1109-1116 https://doi.org/10.1161/01.CIR.96.4.1109
  25. Patrono C (2001) Aspirin: new cardiovascular uses for an old drug. Am J Med 110: 62S-65S https://doi.org/10.1016/S0002-9343(00)00645-8
  26. Irfan M, Jeong D, Saba E, Kwon HW, Shin JH, Jeon BR, Kim S, Kim SD, Lee DH, Nah SY, Rhee MH (2019) Gintonin modulates platelet function and inhibits thrombus formation via impaired glycoprotein VI signaling. Platelets 30(5): 589-598 https://doi.org/10.1080/09537104.2018.1479033
  27. McNicol A, Jackson EC (2003) Inhibition of the MEK/ERK pathway has no effect on agonist-induced aggregation of human platelets. Biochem Pharmacol 65(8): 1243-1250 https://doi.org/10.1016/S0006-2952(03)00069-8

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