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http://dx.doi.org/10.5483/BMBRep.2012.45.4.221

Anticoagulant activities of curcumin and its derivative  

Kim, Dong-Chan (Laboratory of Microvascular Circulation Research, NEUORNEX Inc.)
Ku, Sae-Kwang (Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University)
Bae, Jong-Sup (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)
Publication Information
BMB Reports / v.45, no.4, 2012 , pp. 221-226 More about this Journal
Abstract
Curcumin, a polyphenol responsible for the yellow color of the curry spice turmeric, possesses antiinflammatory, antiproliferative and antiangiogenic activities. However, anticoagulant activities of curcumin have not been studied. Here, the anticoagulant properties of curcumin and its derivative (bisdemethoxycurcumin, BDMC) were determined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT) as well as cell-based thrombin and activated factor X (FXa) generation activities. Data showed that curcumin and BDMC prolonged aPTT and PT significantly and inhibited thrombin and FXa activities. They inhibited the generation of thrombin or FXa. In accordance with these anticoagulant activities, curcumin and BDMC showed anticoagulant effect in vivo. Surprisingly, these anticoagulant effects of curcumin were better than those of BDMC indicating that methoxy group in curcumin positively regulated anticoagulant function of curcumin. Therefore, these results suggest that curcumin and BDMC possess antithrombotic activities and daily consumption of the curry spice turmeric might help maintain anticoagulant status.
Keywords
aPTT; Curcumin; HUVECs; PT;
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1 Zeitlin, P. (2004) Can curcumin cure cystic fibrosis? N. Engl. J. Med. 351, 606-608.   DOI   ScienceOn
2 Ahsan, H., Parveen, N., Khan, N. U. and Hadi, S. M. (1999) Pro-oxidant, anti-oxidant and cleavage activities on DNA of curcumin and its derivatives demethoxycurcumin and bisdemethoxycurcumin. Chem. Biol. Interact. 121, 161-175.   DOI   ScienceOn
3 Davie, E. W. (1995) Biochemical and molecular aspects of the coagulation cascade. Thromb. Haemost. 74, 1-6.
4 Davie, E. W., Fujikawa, K. and Kisiel, W. (1991) The coagulation cascade: initiation, maintenance, and regulation. Biochemistry 30, 10363-10370.   DOI   ScienceOn
5 Hoffman, M. M. and Monroe, D. M. (2005) Rethinking the coagulation cascade. Curr. Hematol. Rep. 4, 391-396.
6 Hoffmann, J. N., Vollmar, B., Romisch, J., Inthorn, D., Schildberg, F. W. and Menger, M. D. (2002) Antithrombin effects on endotoxin-induced microcirculatory disorders are mediated mainly by its interaction with microvascular endothelium. Crit. Care. Med. 30, 218-225.   DOI   ScienceOn
7 Monroe, D. M., Hoffman, M. and Roberts, H. R. (2002) Platelets and thrombin generation. Arterioscler. Thromb. Vasc. Biol. 22, 1381-1389.   DOI   ScienceOn
8 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.
9 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.
10 Furie, B. and Furie, B. C. (2005) Thrombus formation in vivo. J. Clin. Invest. 115, 3355-3362.   DOI   ScienceOn
11 Jurenka, J. S. (2009) Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern. Med. Rev. 14, 141-153.
12 Bengmark, S., Mesa, M. D. and Gil, A. (2009) Plant-derived health: the effects of turmeric and curcuminoids. Nutr. Hosp. 24, 273-281.
13 Joshi, J., Ghaisas, S., Vaidya, A., Vaidya, R., Kamat, D. V., Bhagwat, A. N. and Bhide, S. (2003) Early human safety study of turmeric oil (Curcuma longa oil) administered orally in healthy volunteers. J. Assoc. Physicians. India. 51, 1055-1060.
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 Yoshizumi, M., Fujita, Y., Izawa, Y., Suzaki, Y., Kyaw, M., Ali, N., Tsuchiya, K., Kagami, S., Yano, S., Sone, S. and Tamaki, T. (2004) Ebselen inhibits tumor necrosis factor-alpha-induced c-Jun N-terminal kinase activation and adhesion molecule expression in endothelial cells. Exp. Cell. Res. 292, 1-10.   DOI   ScienceOn
17 Kaiser, L. and Sparks, H. V. Jr. (1987) Endothelial cells. Not just a cellophane wrapper. Arch. Intern. Med. 147, 569-573.   DOI   ScienceOn
18 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
19 Surapisitchat, J., Hoefen, R. J., Pi, X., Yoshizumi, M., Yan, C. and Berk, B. C. (2001) Fluid shear stress inhibits TNF-alpha activation of JNK but not ERK1/2 or p38 in human umbilical vein endothelial cells: Inhibitory crosstalk among MAPK family members. Proc. Natl. Acad. Sci. U.S.A. 98, 6476-6481.   DOI   ScienceOn
20 Berk, B. C., Abe, J. I., Min, W., Surapisitchat, J. and Yan, C. (2001) Endothelial atheroprotective and anti-inflammatory mechanisms. Ann. N. Y. Acad. Sci. 947, 93-109; discussion 109-111.
21 Anand, P., Thomas, S. G., Kunnumakkara, A. B., Sundaram, C., Harikumar, K. B., Sung, B., Tharakan, S. T., Misra, K., Priyadarsini, I. K., Rajasekharan, K. N. and Aggarwal, B. B. (2008) Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem. Pharmacol. 76, 1590-1611.   DOI   ScienceOn
22 Somparn, P., Phisalaphong, C., Nakornchai, S., Unchern, S. and Morales, N. P. (2007) Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives. Biol. Pharm. Bull. 30, 74-78.   DOI   ScienceOn
23 Sandur, S. K., Pandey, M. K., Sung, B., Ahn, K. S., Murakami, A., Sethi, G., Limtrakul, P., Badmaev, V. and Aggarwal, B. B. (2007) Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis. 28, 1765-1773.   DOI   ScienceOn
24 Fischer, K. G. (2007) Essentials of anticoagulation in hemodialysis. Hemodial. Int. 11, 178-189.   DOI   ScienceOn
25 Guo, L. Y., Cai, X. F., Lee, J. J., Kang, S. S., Shin, E. M., Zhou, H. Y., Jung, J. W. and Kim, Y. S. (2008) Comparison of suppressive effects of demethoxycurcumin and bisdemethoxycurcumin on expressions of inflammatory mediators in vitro and in vivo. Arch. Pharm. Res. 31, 490-496.   DOI   ScienceOn
26 Sreejayan, N. and Rao, M. N. (1996) Free radical scavenging activity of curcuminoids. Arzneimittelforschung 46, 169-171.
27 Thapliyal, R., Deshpande, S. S. and Maru, G. B. (2001) Effects of turmeric on the activities of benzo(a)pyrene-induced cytochrome P-450 isozymes. J. Environ. Pathol. Toxicol. Oncol. 20, 59-63.
28 Syu, W. J., Shen, C. C., Don, M. J., Ou, J. C., Lee, G. H. and Sun, C. M. (1998) Cytotoxicity of curcuminoids and some novel compounds from Curcuma zedoaria. J. Nat. Prod. 61, 1531-1534.   DOI   ScienceOn
29 Li, Y. B., Gao, J. L., Lee, S. M., Zhang, Q. W., Hoi, P. M. and Wang, Y. T. (2011) Bisdemethoxycurcumin protects endothelial cells against t-BHP-induced cell damage by regulating the phosphorylation level of ERK1/2 and Akt. Int. J. Mol. Med. 27, 205-211.
30 Liu, Y. L., Yang, H. P., Gong, L., Tang, C. L. and Wang, H. J. (2011) Hypomethylation effects of curcumin, demethoxycurcumin and bisdemethoxycurcumin on WIF-1 promoter in non-small cell lung cancer cell lines. Mol. Med. Report. 4, 675-679.
31 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   ScienceOn
32 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.
33 Shankar, R., de la Motte, C. A., Poptic, E. J. and DiCorleto, P. E. (1994) Thrombin receptor-activating peptides differentially stimulate platelet-derived growth factor production, monocytic cell adhesion, and E-selectin expression in human umbilical vein endothelial cells. J. Biol. Chem. 269, 13936-13941.
34 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
35 Ammon, H. P. and Wahl, M. A. (1991) Pharmacology of Curcuma longa. Planta. Med. 57, 1-7.   DOI   ScienceOn
36 Bao, W., Li, K., Rong, S., Yao, P., Hao, L., Ying, C., Zhang, X., Nussler, A. and Liu, L. (2010) Curcumin alleviates ethanol-induced hepatocytes oxidative damage involving heme oxygenase-1 induction. J. Ethnopharmacol. 128, 549-553.   DOI   ScienceOn
37 Bachmeier, B., Nerlich, A. G., Iancu, C. M., Cilli, M., Schleicher, E., Vene, R., Dell'Eva, R., Jochum, M., Albini, A. and Pfeffer, U. (2007) The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice. Cell. Physiol. Biochem. 19, 137-152.   DOI   ScienceOn
38 Aggarwal, B. B., Sundaram, C., Malani, N. and Ichikawa, H. (2007) Curcumin: the Indian solid gold. Adv. Exp. Med. Biol. 595, 1-75.   DOI
39 Inoue, K., Nomura, C., Ito, S., Nagatsu, A., Hino, T. and Oka, H. (2008) Purification of curcumin, demethoxycurcumin, and bisdemethoxycurcumin by high-speed countercurrent chromatography. J. Agric. Food. Chem. 56, 9328-9336.   DOI   ScienceOn
40 Greenwald, P., Milner, J. A., Anderson, D. E. and McDonald, S. S. (2002) Micronutrients in cancer chemoprevention. Cancer. Metastasis. Rev. 21, 217-230.   DOI   ScienceOn
41 Lim, G. P., Chu, T., Yang, F., Beech, W., Frautschy, S. A. and Cole, G. M. (2001) The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J. Neurosci. 21, 8370-8377.