{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T06:37:33Z","timestamp":1774852653459,"version":"3.50.1"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T00:00:00Z","timestamp":1456272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T00:00:00Z","timestamp":1456272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of this study was to discover small-molecule anticoagulants from <jats:italic>Scolopendra subspinipes mutilans<\/jats:italic> (SSM). A new acylated polyamine (<jats:bold>1<\/jats:bold>) and a new sulfated quinoline alkaloid (<jats:bold>2<\/jats:bold>) were isolated from SSM. Treatment with the new alkaloids <jats:bold>1<\/jats:bold>, <jats:bold>2<\/jats:bold>, and indole acetic acid <jats:bold>4<\/jats:bold> prolonged the activated partial thromboplastin time and prothrombin time and inhibited the activity and production of thrombin and activated factor X. Furthermore, compounds <jats:bold>1<\/jats:bold>, <jats:bold>2<\/jats:bold>, and <jats:bold>4<\/jats:bold> inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these potential <jats:italic>in vitro<\/jats:italic> antiplatelet activities, compounds <jats:bold>1<\/jats:bold>, <jats:bold>2<\/jats:bold>, and <jats:bold>4<\/jats:bold> showed enhanced antithrombotic effects in an <jats:italic>in vivo<\/jats:italic> pulmonary embolism and arterial thrombosis model. Compounds <jats:bold>1<\/jats:bold>, <jats:bold>2<\/jats:bold>, and <jats:bold>4<\/jats:bold> also elicited anticoagulant effects in mice. Collectively, this study may serve as the groundwork for commercializing SSM or compounds <jats:bold>1<\/jats:bold>, <jats:bold>2<\/jats:bold>, and <jats:bold>4<\/jats:bold> as functional food components for the prevention and treatment of pathogenic conditions and serve as new scaffolds for the development of anticoagulants.<\/jats:p>","DOI":"10.1038\/srep21956","type":"journal-article","created":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T11:14:29Z","timestamp":1456312469000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Antithrombotic and antiplatelet activities of small-molecule alkaloids from Scolopendra subspinipes mutilans"],"prefix":"10.1038","volume":"6","author":[{"given":"Wonhwa","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JungIn","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roshan","family":"Kulkarni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi-Ae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Sam","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MinKyun","family":"Na","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong-Sup","family":"Bae","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,2,24]]},"reference":[{"key":"BFsrep21956_CR1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.4103\/1947-2714.110430","volume":"5","author":"A Fares","year":"2013","unstructured":"Fares, A. Winter cardiovascular diseases phenomenon. N. Am. J. Med. Sci. 5, 266\u2013279 (2013).","journal-title":"N. Am. J. Med. Sci."},{"key":"BFsrep21956_CR2","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1056\/NEJMra071014","volume":"357","author":"G Davi","year":"2007","unstructured":"Davi, G. & Patrono, C. Platelet activation and atherothrombosis. N. Engl. J. Med. 357, 2482\u20132494 (2007).","journal-title":"N. Engl. J. Med."},{"key":"BFsrep21956_CR3","first-page":"131\/131","volume":"10","author":"MD Cai","year":"2013","unstructured":"Cai, M. D. et al. Scolopendra subspinipes mutilans attenuates neuroinflammation in symptomatic hSOD1G93A mice. J. Neuroinflammation. 10, 131\/131\u2013131\/139, 139 pp (2013).","journal-title":"J. Neuroinflammation."},{"key":"BFsrep21956_CR4","first-page":"39","volume":"7","author":"W Ma","year":"2015","unstructured":"Ma, W., Zhang, D., Zheng, L., Zhan, Y. & Zhang, Y. Potential roles of Centipede Scolopendra extracts as a strategy against EGFR-dependent cancers. Am. J. Transl. Res. 7, 39\u201352 (2015).","journal-title":"Am. J. Transl. Res."},{"key":"BFsrep21956_CR5","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s10989-013-9387-3","volume":"20","author":"Y Kong","year":"2014","unstructured":"Kong, Y. et al. Antithrombotic Peptides from Scolopendra subspinipes mutilans Hydrolysates. In.t J. Pept. Res. Ther. 20, 245\u2013252 (2014).","journal-title":"In.t J. Pept. Res. Ther."},{"key":"BFsrep21956_CR6","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.jep.2012.10.048","volume":"145","author":"Y Kong","year":"2013","unstructured":"Kong, Y., Huang, S. L., Shao, Y., Li, S. & Wei, J. F. Purification and characterization of a novel antithrombotic peptide from Scolopendra subspinipes mutilans. J. Ethnopharmacol. 145, 182\u2013186 (2013).","journal-title":"J. Ethnopharmacol."},{"key":"BFsrep21956_CR7","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s10989-013-9353-0","volume":"19","author":"Y Kong","year":"2013","unstructured":"Kong, Y. et al. A Novel Factor Xa-Inhibiting Peptide from Centipedes Venom. Int. J. Pept. Res. Ther. 19, 303\u2013311 (2013).","journal-title":"Int. J. Pept. Res. Ther."},{"key":"BFsrep21956_CR8","doi-asserted-by":"crossref","first-page":"6197","DOI":"10.1021\/pr300881d","volume":"11","author":"ZC Liu","year":"2012","unstructured":"Liu, Z. C. et al. Venomic and transcriptomic analysis of centipede Scolopendra subspinipes dehaani. J. Proteome. Res. 11, 6197\u20136212 (2012).","journal-title":"J. Proteome. Res."},{"key":"BFsrep21956_CR9","doi-asserted-by":"crossref","first-page":"17534","DOI":"10.1073\/pnas.1306285110","volume":"110","author":"S Yang","year":"2013","unstructured":"Yang, S. et al. Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models. Proc. Natl. Acad. Sci. USA 110, 17534\u201317539 (2013).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFsrep21956_CR10","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1021\/np960188t","volume":"59","author":"SS Moon","year":"1996","unstructured":"Moon, S. S. et al. Jineol, a cytotoxic alkaloid from the centipede Scolopendra subspinipes. J. Nat. Prod. 59, 777\u2013779 (1996).","journal-title":"J. Nat. Prod."},{"key":"BFsrep21956_CR11","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1080\/10286020.2013.768235","volume":"15","author":"YD Fu","year":"2013","unstructured":"Fu, Y. D., Li, Z. L., Pu, S. B. & Qian, S. H. Two new compounds from Scolopendra multidens Newport. J. Asian. Nat. Prod. Res. 15, 363\u2013367 (2013).","journal-title":"J. Asian. Nat. Prod. Res."},{"key":"BFsrep21956_CR12","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1248\/bpb.29.735","volume":"29","author":"MA Yoon","year":"2006","unstructured":"Yoon, M. A. et al. Antioxidant effects of quinoline alkaloids and 2,4-di-tert-butylphenol isolated from Scolopendra subspinipes. Biol. Pharm. Bull. 29, 735\u2013739 (2006).","journal-title":"Biol. Pharm. Bull."},{"key":"BFsrep21956_CR13","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1248\/cpb.49.930","volume":"49","author":"N Noda","year":"2001","unstructured":"Noda, N., Yashiki, Y., Nakatani, T., Miyahara, K. & Du, X. M. A novel quinoline alkaloid possessing a 7-benzyl group from the centipede, Scolopendra subspinipes. Chem. Pharm. Bull. 49, 930\u2013931 (2001).","journal-title":"Chem. Pharm. Bull."},{"key":"BFsrep21956_CR14","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.3390\/md9071210","volume":"9","author":"C Abed","year":"2011","unstructured":"Abed, C. et al. A new hydroxylated nonaprenylhydroquinone from the Mediterranean marine sponge Sarcotragus spinosulus. Mar. Drugs. 9, 1210\u20131219 (2011).","journal-title":"Mar. Drugs."},{"key":"BFsrep21956_CR15","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1021\/np50123a018","volume":"58","author":"S Derosa","year":"1995","unstructured":"Derosa, S., Crispino, A., Degiulio, A., Iodice, C. & Milone, A. Sulfated polyprenylhydroquinones from the sponge ircinia-spinosula. J. Nat. Prod. 58, 1450\u20131454 (1995).","journal-title":"J. Nat. Prod."},{"key":"BFsrep21956_CR16","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1007\/BF00979674","volume":"19","author":"KD McCormick","year":"1993","unstructured":"McCormick, K. D. & Meinwald, J. Neurotoxic acylpolyamines from spider venoms. J. Chem. Ecol. 19, 2411\u20132451 (1993).","journal-title":"J. Chem. Ecol."},{"key":"BFsrep21956_CR17","doi-asserted-by":"crossref","first-page":"14283","DOI":"10.1073\/pnas.0806840105","volume":"105","author":"FC Schroeder","year":"2008","unstructured":"Schroeder, F. C. et al. NMR-spectroscopic screening of spider venom reveals sulfated nucleosides as major components for the brown recluse and related species. Proc. Natl. Acad. Sci. 105, 14283\u201314287 (2008).","journal-title":"Proc. Natl. Acad. Sci"},{"key":"BFsrep21956_CR18","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1021\/np960188t","volume":"59","author":"S-S Moon","year":"1996","unstructured":"Moon, S.-S. et al. Jineol, a Cytotoxic Alkaloid from the Centipede Scolopendra subspinipes. J. Nat. Prod. 59, 777\u2013779 (1996).","journal-title":"J. Nat. Prod."},{"key":"BFsrep21956_CR19","first-page":"501","volume":"37","author":"JF Siuda","year":"1974","unstructured":"Siuda, J. F. Chemical defense mechanisms of marine organisms. Identification of 8-hydroxy-4-quinolone from the ink of the giant octopus, Octopus dofleini martini. Lloydia 37, 501\u2013503 (1974).","journal-title":"Lloydia"},{"key":"BFsrep21956_CR20","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1007\/BF01989428","volume":"49","author":"A Evidente","year":"1993","unstructured":"Evidente, A., Iacobellis, N. S. & Sisto, A. Isolation of indole-3-acetic acid methyl ester, a metabolite of indole-3-acetic acid from Pseudomonas amygdali. Experientia 49, 182\u2013183 (1993).","journal-title":"Experientia"},{"key":"BFsrep21956_CR21","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1080\/10286020.2013.768235","volume":"15","author":"Y-D Fu","year":"2013","unstructured":"Fu, Y.-D., Li, Z.-L., Pu, S.-B. & Qian, S.-H. Two new compounds from Scolopendra multidens Newport. J. Asian Nat. Prod. Res. 15, 363\u2013367 (2013).","journal-title":"J. Asian Nat. Prod. Res."},{"key":"BFsrep21956_CR22","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1248\/bpb.29.735","volume":"29","author":"M-A Yoon","year":"2006","unstructured":"Yoon, M.-A. et al. Antioxidant effects of quinoline alkaloids and 2,4-Di-tert-butylphenol isolated from Scolopendra subspinipes. Biol. Pharm. Bull. 29, 735\u2013739 (2006).","journal-title":"Biol. Pharm. Bull."},{"key":"BFsrep21956_CR23","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1248\/cpb.49.930","volume":"49","author":"N Noda","year":"2001","unstructured":"Noda, N., Yashiki, Y., Nakatani, T., Miyahara, K. & Du, X.-M. A novel quinoline alkaloid possessing a 7-benzyl group from the centipede, Scolopendra subspinipes. Chem. Pharm. Bull. 49, 930\u2013931 (2001).","journal-title":"Chem. Pharm. Bull."},{"key":"BFsrep21956_CR24","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/jat.727","volume":"21","author":"KH Diehl","year":"2001","unstructured":"Diehl, K. H. et al. A good practice guide to the administration of substances and removal of blood, including routes and volumes. J Appl Toxicol 21, 15\u201323 (2001).","journal-title":"J Appl Toxicol"},{"key":"BFsrep21956_CR25","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1161\/ATVBAHA.107.157479","volume":"28","author":"Y Izuhara","year":"2008","unstructured":"Izuhara, Y. et al. Inhibition of plasminogen activator inhibitor-1: its mechanism and effectiveness on coagulation and fibrosis. Arterioscler. Thromb. Vasc. Biol. 28, 672\u2013677 (2008).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"BFsrep21956_CR26","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1365-2141.2009.07819.x","volume":"147","author":"AH Wei","year":"2009","unstructured":"Wei, A. H., Schoenwaelder, S. M., Andrews, R. K. & Jackson, S. P. New insights into the haemostatic function of platelets. Br. J. Haematol. 147, 415\u2013430 (2009).","journal-title":"Br. J. Haematol."},{"key":"BFsrep21956_CR27","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1182\/blood.V95.3.894.003k15_894_902","volume":"95","author":"A Elzagallaai","year":"2000","unstructured":"Elzagallaai, A., Rose, S. D. & Trifaro, J. M. Platelet secretion induced by phorbol esters stimulation is mediated through phosphorylation of MARCKS: a MARCKS-derived peptide blocks MARCKS phosphorylation and serotonin release without affecting pleckstrin phosphorylation. Blood 95, 894\u2013902 (2000).","journal-title":"Blood"},{"key":"BFsrep21956_CR28","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1093\/jb\/117.2.244","volume":"117","author":"T Sugo","year":"1995","unstructured":"Sugo, T., Nakamikawa, C., Tanabe, S. & Matsuda, M. Activation of prothrombin by factor Xa bound to the membrane surface of human umbilical vein endothelial cells: its catalytic efficiency is similar to that of prothrombinase complex on platelets. J. Biochem. 117, 244\u2013250 (1995).","journal-title":"J. Biochem."},{"key":"BFsrep21956_CR29","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1182\/blood.V71.3.791.791","volume":"71","author":"LV Rao","year":"1988","unstructured":"Rao, L. V., Rapaport, S. I. & Lorenzi, M. Enhancement by human umbilical vein endothelial cells of factor Xa-catalyzed activation of factor VII. Blood 71, 791\u2013796 (1988).","journal-title":"Blood"},{"key":"BFsrep21956_CR30","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/j.1538-7836.2007.02308.x","volume":"5","author":"S Ghosh","year":"2007","unstructured":"Ghosh, S. et al. Activity and regulation of factor VIIa analogs with increased potency at the endothelial cell surface. J. Thromb. Haemost. 5, 336\u2013346 (2007).","journal-title":"J. Thromb. Haemost."},{"key":"BFsrep21956_CR31","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1183\/09031936.95.08081352","volume":"8","author":"F Philip-Joet","year":"1995","unstructured":"Philip-Joet, F. et al. Fibrinolytic and inflammatory processes in pleural effusions. Eur. Respir. J. 8, 1352\u20131356 (1995).","journal-title":"Eur. Respir. J."},{"key":"BFsrep21956_CR32","doi-asserted-by":"crossref","first-page":"5797","DOI":"10.1016\/S0021-9258(18)60636-2","volume":"263","author":"RR Schleef","year":"1988","unstructured":"Schleef, R. R., Bevilacqua, M. P., Sawdey, M., Gimbrone, M. A., Jr. & Loskutoff, D. J. Cytokine activation of vascular endothelium. Effects on tissue-type plasminogen activator and type 1 plasminogen activator inhibitor. J. Biol. Chem. 263, 5797\u20135803 (1988).","journal-title":"J. Biol. Chem."},{"key":"BFsrep21956_CR33","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1124\/jpet.103.054346","volume":"307","author":"E Hamaguchi","year":"2003","unstructured":"Hamaguchi, E., Takamura, T., Shimizu, A. & Nagai, Y. Tumor necrosis factor-alpha and troglitazone regulate plasminogen activator inhibitor type 1 production through extracellular signal-regulated kinase- and nuclear factor-kappaB-dependent pathways in cultured human umbilical vein endothelial cells. J. Pharmacol. Exp. Ther. 307, 987\u2013994 (2003).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"BFsrep21956_CR34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1055\/s-0038-1642645","volume":"74","author":"EW Davie","year":"1995","unstructured":"Davie, E. W. Biochemical and molecular aspects of the coagulation cascade. Thromb. Haemost. 74, 1\u20136 (1995).","journal-title":"Thromb. Haemost."},{"key":"BFsrep21956_CR35","doi-asserted-by":"crossref","first-page":"10363","DOI":"10.1021\/bi00107a001","volume":"30","author":"EW Davie","year":"1991","unstructured":"Davie, E. W., Fujikawa, K. & Kisiel, W. The coagulation cascade: initiation, maintenance, and regulation. Biochemistry 30, 10363\u201310370 (1991).","journal-title":"Biochemistry"},{"key":"BFsrep21956_CR36","first-page":"229","volume":"13","author":"C Quinn","year":"2000","unstructured":"Quinn, C., Hill, J. & Hassouna, H. A guide for diagnosis of patients with arterial and venous thrombosis. Clin. Lab. Sci. 13, 229\u2013238 (2000).","journal-title":"Clin. Lab. Sci"},{"key":"BFsrep21956_CR37","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0021-9150(00)00454-8","volume":"152","author":"S Lopez","year":"2000","unstructured":"Lopez, S., Peiretti, F., Bonardo, B., Juhan-Vague, I. & Nalbone, G. Effect of atorvastatin and fluvastatin on the expression of plasminogen activator inhibitor type-1 in cultured human endothelial cells. Atherosclerosis 152, 359\u2013366 (2000).","journal-title":"Atherosclerosis"},{"key":"BFsrep21956_CR38","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1097\/00000542-199910000-00031","volume":"91","author":"GJ Despotis","year":"1999","unstructured":"Despotis, G. J., Gravlee, G., Filos, K. & Levy, J. Anticoagulation monitoring during cardiac surgery: a review of current and emerging techniques. Anesthesiology 91, 1122\u20131151 (1999).","journal-title":"Anesthesiology"},{"key":"BFsrep21956_CR39","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1161\/STR.0b013e318284056a","volume":"44","author":"EC Jauch","year":"2013","unstructured":"Jauch, E. C. et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association\/American Stroke Association. Stroke 44, 870\u2013947 (2013).","journal-title":"Stroke"},{"key":"BFsrep21956_CR40","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/j.1365-2141.2005.05753.x","volume":"131","author":"CT Esmon","year":"2005","unstructured":"Esmon, C. T. The interactions between inflammation and coagulation. Br. J. Haematol. 131, 417\u2013430 (2005).","journal-title":"Br. J. Haematol."},{"key":"BFsrep21956_CR41","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1189\/jlb.0607373","volume":"83","author":"M Schouten","year":"2008","unstructured":"Schouten, M., Wiersinga, W. J., Levi, M. & van der Poll, T. Inflammation, endothelium, and coagulation in sepsis. J. Leukoc. Biol. 83, 536\u2013545 (2008).","journal-title":"J. Leukoc. Biol."},{"key":"BFsrep21956_CR42","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1001\/jama.2014.65","volume":"311","author":"PS Wells","year":"2014","unstructured":"Wells, P. S., Forgie, M. A. & Rodger, M. A. Treatment of venous thromboembolism. JAMA 311, 717\u2013728 (2014).","journal-title":"JAMA"},{"key":"BFsrep21956_CR43","doi-asserted-by":"crossref","first-page":"258\u2009S","DOI":"10.1378\/chest.108.4_Supplement.258S","volume":"108","author":"J Hirsh","year":"1995","unstructured":"Hirsh, J. et al. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 108, 258\u2009S\u2013275\u2009S (1995).","journal-title":"Chest"},{"key":"BFsrep21956_CR44","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/glycob\/cwf077","volume":"12","author":"MS Pereira","year":"2002","unstructured":"Pereira, M. S., Melo, F. R. & Mourao, P. A. Is there a correlation between structure and anticoagulant action of sulfated galactans and sulfated fucans? Glycobiology 12, 573\u2013580 (2002).","journal-title":"Glycobiology"},{"key":"BFsrep21956_CR45","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1164\/rccm.201311-2033OC","volume":"189","author":"JS Bae","year":"2014","unstructured":"Bae, J. S. et al. Transforming Growth Factor beta-induced Protein Promotes Severe Vascular Inflammatory Responses. Am. J. Respir. Crit Care Med. 189, 779\u2013786 (2014).","journal-title":"Am. J. Respir. Crit Care Med."},{"key":"BFsrep21956_CR46","doi-asserted-by":"crossref","first-page":"336","DOI":"10.5483\/BMBRep.2014.47.6.198","volume":"47","author":"SK Ku","year":"2014","unstructured":"Ku, S. K., Han, M. S., Lee, M. Y., Lee, Y. M. & Bae, J. S. Inhibitory effects of oroxylin A on endothelial protein C receptor shedding in vitro and in vivo . BMB Rep. 47, 336\u2013341 (2014).","journal-title":"BMB Rep"},{"key":"BFsrep21956_CR47","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1007\/s12272-014-0403-8","volume":"37","author":"SK Ku","year":"2014","unstructured":"Ku, S. K. & Bae, J. S. Antithrombotic activities of sulforaphane via inhibiting platelet aggregation and FIIa\/FXa. Arch. Pharm. Res. 37, 1454\u20131463 (2014).","journal-title":"Arch. Pharm. Res."},{"key":"BFsrep21956_CR48","doi-asserted-by":"crossref","first-page":"376","DOI":"10.5483\/BMBRep.2014.47.7.195","volume":"47","author":"SK Ku","year":"2014","unstructured":"Ku, S. K. & Bae, J. S. Antiplatelet and antithrombotic activities of purpurogallin in vitro and in vivo . BMB Rep. 47, 376\u2013381 (2014).","journal-title":"BMB Rep"},{"key":"BFsrep21956_CR49","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1002\/jcb.24163","volume":"113","author":"TH Kim","year":"2012","unstructured":"Kim, T. H., Ku, S. K. & Bae, J. S. Antithrombotic and profibrinolytic activities of eckol and dieckol. J. Cell. Biochem. 113, 2877\u20132883 (2012).","journal-title":"J. Cell. Biochem."},{"key":"BFsrep21956_CR50","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0049-3848(79)90064-1","volume":"15","author":"E Dejana","year":"1979","unstructured":"Dejana, E., Callioni, A., Quintana, A. & de Gaetano, G. Bleeding time in laboratory animals. II\u2014A comparison of different assay conditions in rats. Thromb. Res. 15, 191\u2013197 (1979).","journal-title":"Thromb. Res."},{"key":"BFsrep21956_CR51","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.thromres.2007.03.017","volume":"121","author":"P Nowak","year":"2007","unstructured":"Nowak, P., Zbikowska, H. M., Ponczek, M., Kolodziejczyk, J. & Wachowicz, B. Different vulnerability of fibrinogen subunits to oxidative\/nitrative modifications induced by peroxynitrite: functional consequences. Thromb. Res. 121, 163\u2013174 (2007).","journal-title":"Thromb. Res."},{"key":"BFsrep21956_CR52","doi-asserted-by":"crossref","first-page":"140","DOI":"10.5483\/BMBRep.2011.44.2.140","volume":"44","author":"SY Kim","year":"2011","unstructured":"Kim, S. Y. et al. PKC inhibitors RO 31-8220 and Go 6983 enhance epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation. BMB Rep. 44, 140\u2013145 (2011).","journal-title":"BMB Rep"},{"key":"BFsrep21956_CR53","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s12272-014-0410-9","volume":"38","author":"W Lee","year":"2015","unstructured":"Lee, W., Ku, S. K. & Bae, J. S. Antiplatelet, anticoagulant, and profibrinolytic activities of baicalin. Arch. Pharm. Res. 38, 893\u2013903 (2015).","journal-title":"Arch. Pharm. Res."},{"key":"BFsrep21956_CR54","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.jacc.2004.02.059","volume":"44","author":"S Goto","year":"2004","unstructured":"Goto, S., Tamura, N. & Ishida, H. Ability of anti-glycoprotein IIb\/IIIa agents to dissolve platelet thrombi formed on a collagen surface under blood flow conditions. J. Am. Coll. Cardiol. 44, 316\u2013323 (2004).","journal-title":"J. Am. Coll. Cardiol."},{"key":"BFsrep21956_CR55","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1055\/s-2007-967173","volume":"73","author":"CC Wu","year":"2007","unstructured":"Wu, C. C., Wu, C. I., Wang, W. Y. & Wu, Y. C. Low concentrations of resveratrol potentiate the antiplatelet effect of prostaglandins. Planta Med. 73, 439\u2013443 (2007).","journal-title":"Planta Med."},{"key":"BFsrep21956_CR56","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1016\/S0021-9258(19)83641-4","volume":"260","author":"G Grynkiewicz","year":"1985","unstructured":"Grynkiewicz, G., Poenie, M. & Tsien, R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem. 260, 3440\u20133450 (1985).","journal-title":"J. Biol. Chem."},{"key":"BFsrep21956_CR57","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1016\/j.fct.2011.04.003","volume":"49","author":"JS Bae","year":"2011","unstructured":"Bae, J. S. Antithrombotic and profibrinolytic activities of phloroglucinol. Food Chem. Toxicol. 49, 1572\u20131577 (2011).","journal-title":"Food Chem. Toxicol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep21956.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep21956","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep21956.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T04:00:15Z","timestamp":1672891215000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep21956"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,24]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,2,29]]}},"alternative-id":["BFsrep21956"],"URL":"https:\/\/doi.org\/10.1038\/srep21956","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,24]]},"assertion":[{"value":"1 October 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 February 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21956"}}