Browse > Article
http://dx.doi.org/10.5483/BMBRep.2012.45.7.065

Anticoagulant activities of oleanolic acid via inhibition of tissue factor expressions  

Lee, Won-Hwa (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)
Yang, Eun-Ju (BK21 Research Team for Developing Functional Health Food Materials, Kyungpook National University)
Ku, Sae-Kwang (Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University)
Song, Kyung-Sik (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)
Bae, Jong-Sup (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)
Publication Information
BMB Reports / v.45, no.7, 2012 , pp. 390-395 More about this Journal
Abstract
Oleanolic acid (OA), a triterpenoid known for its anti-inflammatory and anti-cancer properties, is commonly present in several medicinal plants but its anticoagulant activities have not been studied. Here, the anticoagulant properties of OA were determined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrin polymerization as well as cell-based thrombin and activated factor X (FXa) generation activities. Data showed OA prolonged aPTT and PT significantly and inhibited thrombin catalyzed fibrin polymerization. In addition, OA inhibited the activities of thrombin and FXa and inhibited the generation of thrombin or FXa in human endothelial cells. OA also inhibited TNF-${\alpha}$-induced tissue factor expression on human endothelial cells. In accordance with these anticoagulant activities, OA showed an anticoagulant effect in vivo. These results indicate that OA possesses antithrombotic activities and suggest that daily consumption of a herb containing OA may be preventing thrombosis in pathological states.
Keywords
aPTT; Coagulation cascade; Oleanolic acid; PT; Thrombin;
Citations & Related Records

Times Cited By Web Of Science : 0  (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Kaiser, L. and Sparks, H. V. Jr. (1987) Endothelial cells. Not just a cellophane wrapper. Arch. Intern. Med. 147, 569-573.   DOI   ScienceOn
2 Davie, E. W. (1995) Biochemical and molecular aspects of the coagulation cascade. Thromb. Haemost. 74, 1-6.
3 Chong, A. Y., Blann, A. D. and Lip, G. Y. (2003) Assessment of endothelial damage and dysfunction: observations in relation to heart failure. QJM 96, 253-267.   DOI   ScienceOn
4 Davie, E. W., Fujikawa, K. and Kisiel, W. (1991) The coagulation cascade: initiation, maintenance, and regulation. Biochemistry 30, 10363-10370.   DOI   ScienceOn
5 Monroe, D. M., Hoffman, M. and Roberts, H. R. (2002) Platelets and thrombin generation. Arterioscler. Thromb. Vasc. Biol. 22, 1381-1389.   DOI   ScienceOn
6 Quinn, C., Hill, J. and Hassouna, H. (2000) A guide for diagnosis of patients with arterial and venous thrombosis. Clin. Lab. Sci. 13, 229-238.
7 Della Valle, P., Crippa, L., Garlando, A. M., Pattarini, E., Safa, O., Vigano D'Angelo, S. and D'Angelo, A. (1999) Interference of lupus anticoagulants in prothrombin time assays: implications for selection of adequate methods to optimize the management of thrombosis in the antiphospholipid- antibody syndrome. Haematologica 84, 1065-1074.
8 Furie, B. and Furie, B. C. (2005) Thrombus formation in vivo. J. Clin. Invest. 115, 3355-3362.   DOI   ScienceOn
9 Li, S. S. (2002) Mistletoe lectins: telomerase inhibitors in alternative cancer therapy. Drug. Discov. Today 7, 896-897.   DOI   ScienceOn
10 Ghosh, S., Ezban, M., Persson, E., Pendurthi, U., Hedner, U. and Rao, L. V. (2007) Activity and regulation of factor VIIa analogs with increased potency at the endothelial cell surface. J. Thromb. Haemost. 5, 336-346.   DOI   ScienceOn
11 Fischer, K. G. (2007) Essentials of anticoagulation in hemodialysis. Hemodial. Int. 11, 178-189.   DOI   ScienceOn
12 Cho, S. O., Ban, J. Y., Kim, J. Y., Jeong, H. Y., Lee, I. S., Song, K. S., Bae, K. and Seong, Y. H. (2009) Aralia cordata protects against amyloid beta protein (25-35)-induced neurotoxicity in cultured neurons and has antidementia activities in mice. J. Pharmacol. Sci. 111, 22-32.   DOI   ScienceOn
13 Nowak, P., Zbikowska, H. M., Ponczek, M., Kolodziejczyk, J. and Wachowicz, B. (2007) Different vulnerability of fibrinogen subunits to oxidative/nitrative modifications induced by peroxynitrite: functional consequences. Thromb. Res. 121, 163-174.   DOI   ScienceOn
14 Bae, J. S. and Rezaie, A. R. (2008) Protease activated receptor 1 (PAR-1) activation by thrombin is protective in human pulmonary artery endothelial cells if endothelial protein C receptor is occupied by its natural ligand. Thromb. Haemost. 100, 101-109.
15 Dejana, E., Callioni, A., Quintana, A. and de Gaetano, G. (1979) Bleeding time in laboratory animals. II - A comparison of different assay conditions in rats. Thromb. Res. 15, 191-197.   DOI   ScienceOn
16 Yoon, T. J., Yoo, Y. C., Kang, T. B., Song, S. K., Lee, K. B., zHer, E., Song, K. S. and Kim, J. B. (2003) Antitumor activity of the Korean mistletoe lectin is attributed to activation of macrophages and NK cells. Arch. Pharm. Res. 26, 861- 867.   DOI   ScienceOn
17 Kim, B. K., Choi, M. J., Park, K. Y. and Cho, E. J. (2010) Protective effects of Korean mistletoe lectin on radical-induced oxidative stress. Biol. Pharm. Bull. 33, 1152-1158.   DOI   ScienceOn
18 Yoon, T. J., Yoo, Y. C., Kang, T. B., Shimazaki, K., Song, S. K., Lee, K. H., Kim, S. H., Park, C. H., Azuma, I. and Kim, J. B. (1999) Lectins isolated from Korean mistletoe (Viscum album coloratum) induce apoptosis in tumor cells. Cancer Lett. 136, 33-40.   DOI   ScienceOn
19 Yoon, T. J., Yoo, Y. C., Kang, T. B., Her, E., Kim, S. H., Kim, K., Azuma, I. and Kim, J. B. (2001) Cellular and humoral adjuvant activity of lectins isolated from Korean mistletoe (Viscum album colaratum). Int. Immunopharmacol. 1, 881-889.   DOI   ScienceOn
20 Bae, J. S. (2011) Antithrombotic and profibrinolytic activities of phloroglucinol. Food Chem. Toxicol. 49, 1572-1577.   DOI   ScienceOn
21 Liu, J. (2005) Oleanolic acid and ursolic acid: research perspectives. J. Ethnopharmacol. 100, 92-94.   DOI   ScienceOn
22 Dzubak, P., Hajduch, M., Vydra, D., Hustova, A., Kvasnica, M., Biedermann, D., Markova, L., Urban, M. and Sarek, J. (2006) Pharmacological activities of natural triterpenoids and their therapeutic implications. Nat. Prod. Rep. 23, 394-411.   DOI   ScienceOn
23 Rao, L. V., Rapaport, S. I. and Lorenzi, M. (1988) Enhancement by human umbilical vein endothelial cells of factor Xa-catalyzed activation of factor VII. Blood 71, 791-796.
24 Sugo, T., Nakamikawa, C., Tanabe, S. and Matsuda, M. (1995) 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, 244-250.   DOI