Browse > Article
http://dx.doi.org/10.22889/KJP.2021.52.1.26

Anti-thrombus Effects of Isoscopoletin by Regulating Cyclic Nucleotides on U46619-induced Platelets  

Lee, Dong-Ha (Department of Biomedical Laboratory Science, Molecular Diagnostics Research Institute, Namseoul University)
Publication Information
Korean Journal of Pharmacognosy / v.52, no.1, 2021 , pp. 26-33 More about this Journal
Abstract
During blood vessel damage, an essential step in the hemostatic process is platelet activation. However, it is important to properly control platelet activation, as various cardiovascular diseases, such as stroke, atherosclerosis, and myocardial infarction, are also caused by excessive platelet activation. Found primarily in the roots of plants of the genus Artemisia or Scopolia, isoscopoletin has been studied to demonstrate its potential pharmacological effects against Alzheimer's disease and anticancer, but the mechanisms and roles involved in thrombus formation and platelet aggregation are insufficient. This study investigated the effect of isoscopoletin on U46619-induced human platelet activation. As a result, isoscopoletin significantly increased the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) dose-dependently. In addition, isoscopoletin significantly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphprotein (VASP), which are known substrates for cAMP-dependent kinases and cGMP-dependent kinases. Phosphorylated IP3R by isoscopoletin inhibited Ca2+ mobilization from the dense tubular system Ca2+ channels to cytosol, and phosphorylated VASP was involved in the inhibition of fibrinogen binding through αIIb/β3 inactivation in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clotting production. Therefore, this study suggests that isoscopoletin has a potent antiplatelet effect and may be helpful for platelet-related thrombotic diseases.
Keywords
Cyclic nucleotide; Inositol 1; 4; 5-triphosphate receptor; Intracellular $Ca^{2+}$; Isoscopoletin; Vasodilator-stimulated phosphoprotein;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Cattanco, M., Tenconi, P. M., Lecchi, A. and Mannucci, P. M. (1991) In vitro effects of picotamide on human platelet aggregation, the release re- action and thromboxane B2 production. Thromb. Res. 62: 717-724.   DOI
2 Su, C. Y., Shiao, M. S. and Wang, C. T. (1999) Differential effects of ganodermic acid S on the thromboxane A2-signaling pathways in human platelets. Biochem. Pharmacol. 58: 587-595.   DOI
3 Quinton, T. M. and Dean, W. L. (1992) Cyclic AMP-dependent phosphorylation of the inositol-1,4,5-trisphosphate receptor inhibits Ca2+ release from platelet membranes. Biochemical and Biochem. Biophys. Res. Commun. 184: 893-899.   DOI
4 Menshikov, M. Y. U., Ivanova, K., Schaefer, M., Drummer, C. and Gerzer, R. (1993) Influence of the cGMP analog 8-PCPT-cGMP on agonist-induced increases in cytosolic ionized Ca2+ and on aggregation of human platelets. Eur. J. Pharmacol. 245: 281-284.   DOI
5 Cavallini, L., Coassin, M., Borean, A. and 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.   DOI
6 Choi, B. R., Kim, H. K. and Park, J. K. (2017) Penile erection induced by scoparone from Artemisia capillaris through the nitric oxide-cyclic guanosine monophosphate signaling pathway. World. J. Mens. Health. 35: 196-204.   DOI
7 Wen, L., Feil, S., Wolters, M., Thunemann, M., Regler, F., Schmidt, K., Friebe, A., Olbrich, M., Langer, H., Gawaz, M., de Wit, C. and Feil, R. (2018) A shear-dependent NO-cGMPcGKI cascade in platelets acts as an auto-regulatory brake of thrombosis. Nat. Commun. 16: 4301.
8 Gao, J., Tao, J., Liang, W., Zhao, M., Du, X., Cui, S., Duan, H., Kan, B., Su, X. and Jiang, Z. (2015) Identification and characterization of phosphodiesterases that specifically degrade 3'3'-cyclic GMP-AMP. Cell. Res. 25: 539-550.   DOI
9 Haslam, R. J., Dickinson, N. T. and Jang, E. K. (1999) Cyclic nucleotides and phos- phodiesterases in platelets. Thromb. Haemost. 82: 412-423.   DOI
10 Schwarz, U. R., Walter, U. and Eigenthaler, M. (2001) Taming platelets with cyclic nucleotides. Biochem. Pharmacol. 62: 1153-1161.   DOI
11 Laurent, V., Loisel, T. P., Harbeck, B., Wehman, A., Grobe, L., Jockusch, B. M., Frank, J. W., Gertler, B. and Carlier, M. F. (1999) Role of proteins of the Ena/VASP family in actin-based motility of Listeria monocytogenes. J. Cell. Biol. 144: 1245-1258.   DOI
12 Shin, J. H., Kwon, H. W. and Lee, D. H. (2019) Ginsenoside F4 inhibits platelet aggregation and thrombus formation by dephosphorylation of IP3RI and VASP. J. Appl. Biol. Chem. 62: 93-100.   DOI
13 Sudo, T., Ito, H. and Kimura, Y. (2003) Phosphorylation of the vasodilator-stimulated phosphoprotein (VASP) by the antiplatelet drug, cilostazol, in platelets. Platelets 14: 381-390.   DOI
14 Ali, M. Y., Jannat, S., Jung, H. A., Choi, R. J., Roy, A. and Choi, J. S. (2016) Anti-Alzheimer's disease potential of coumarins from Angelica decursiva and Artemisia capillaris and structure-activity analysis. Asian. Pac. J. Trop. Med. 9: 103-111.   DOI
15 Dong, J., Yuan, J., Wang, J. L., Ji, R. F., Quan, Q. H., Guo, X. Y., Gao, J. and Liu, Y. G. (2017) Study on screening antitumor active fractions and chemical components in active fractions from root of Anaycclus pyrethrum. Zhongguo. Zhong. Yao. Za. Zhi. 42: 3932-3937.
16 Grynkiewicz, G., Poenie, M. and Tsien, R. Y. (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem. 260: 3440-3450.   DOI
17 Nishikawa, M., Tanaka, T. and Hidaka, H. (1980) Ca2+-calmodulin-dependent phosphorylation and platelet secretion. Nature 287: 863-865.   DOI
18 Kuo, J. F., Andersson, R. G., Wise, B. C., Mackerlova, L., Salomonsson, I., Brackett, N. L., Katoh, N., Shoji, M. and Wrenn, R. W. (1980) Calcium-dependent protein kinase: widespread occurrence in various tissues and phyla of the animal kingdom and comparison of effects of phospholipid, calmodulin, and trifluoperazine. Proc. Natl. Acad. Sci. 77: 7039-7043.   DOI
19 Lee, D. H. (2020) Inhibitory effects of scoparone through regulation of PI3K/Akt and MAPK on collagen-induced human platelets. J. Appl. Biol. Chem. 63: 131-136.   DOI
20 Wangorsch, G., Butt, E., Mark, R., Hubertus, K., Geiger, J., Dandekar, T. and Dittrich, M. (2011) Time-resolved in silico modeling of finetuned cAMP signaling in platelets: feedback loops, titrated phospho-rylations and pharmacological modulation, BMC Syst. Biol. 5: 178.   DOI
21 Napenas, J., Oost, F. C., DeGroot, A., Loven, B., Hong, C. H., Brennan, M. T., Lockhart, P. B. and van Diermen, D. E. (2013) Review of postoperative bleeding risk in dental patients on antiplatelet therapy. Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. 115: 491-499.   DOI
22 Payrastre, B., Missy, K., Trumel, C., Bodin, S., Plantavid, M. and Chap, H. (2000) The integrin alpha IIb/beta 3 in human platelet signal transduction. Biochem. Pharmacol. 60: 1069-1074.   DOI
23 Topol, E. J., Byzova, T. V. and Plow, E. F. (1999) Platelet GPIIb-IIIa blockers. The Lancet 353: 227-231.   DOI
24 Jackson, S. P. (2011) Arterial thrombosis?insidious, unpredictable and deadly. Nat. Med. 17: 1423-1436.   DOI
25 Schwartz, S. M., Heimark, R. L. and Majesky, M. W. (1990) Developmental mechanisms underlying pathology of arteries. Physiol. Rev. 70: 1177-1209.   DOI
26 Furuichi, T. and Mikoshiba, K. (1995) Inositol 1, 4, 5-trisphosphate receptor-mediated Ca2+ signaling in the brain. J. Neurochem. 64: 953-960.   DOI
27 Ohkubo, S., Nakahata, N. and Ohizumi, Y. (1996) Thromboxane A2-mediated shape change: independent of Gq-phospholipase C-Ca2+ pathway in rabbit platelets. Br. J. Pharmacol. 117: 1095-1104.   DOI
28 Saitoh, M., Naka, M. and Hidaka, H. (1986) The modulatory role of myosin light chain phosphorylation in human platelet activation. Biochem. Biophys. Res. Commun. 140: 280-287.   DOI