BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

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)
  • Received : 2011.08.09
  • Accepted : 2011.10.11
  • Published : 2012.04.30

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

File

Download PDF

Acknowledgement

Supported by : NRF

References

  1. Davie, E. W. (1995) Biochemical and molecular aspects of the coagulation cascade. Thromb. Haemost. 74, 1-6.
  2. Davie, E. W., Fujikawa, K. and Kisiel, W. (1991) The coagulation cascade: initiation, maintenance, and regulation. Biochemistry 30, 10363-10370. https://doi.org/10.1021/bi00107a001
  3. Hoffman, M. M. and Monroe, D. M. (2005) Rethinking the coagulation cascade. Curr. Hematol. Rep. 4, 391-396.
  4. 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. https://doi.org/10.1097/00003246-200201000-00031
  5. Monroe, D. M., Hoffman, M. and Roberts, H. R. (2002) Platelets and thrombin generation. Arterioscler. Thromb. Vasc. Biol. 22, 1381-1389. https://doi.org/10.1161/01.ATV.0000031340.68494.34
  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. https://doi.org/10.1172/JCI26987
  9. 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.
  10. Bengmark, S., Mesa, M. D. and Gil, A. (2009) Plant-derived health: the effects of turmeric and curcuminoids. Nutr. Hosp. 24, 273-281.
  11. 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.
  12. Ammon, H. P. and Wahl, M. A. (1991) Pharmacology of Curcuma longa. Planta. Med. 57, 1-7. https://doi.org/10.1055/s-2006-960004
  13. 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. https://doi.org/10.1016/j.jep.2010.01.029
  14. 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.
  15. 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. https://doi.org/10.1159/000099202
  16. Aggarwal, B. B., Sundaram, C., Malani, N. and Ichikawa, H. (2007) Curcumin: the Indian solid gold. Adv. Exp. Med. Biol. 595, 1-75. https://doi.org/10.1007/978-0-387-46401-5_1
  17. 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. https://doi.org/10.1021/jf801815n
  18. Greenwald, P., Milner, J. A., Anderson, D. E. and McDonald, S. S. (2002) Micronutrients in cancer chemoprevention. Cancer. Metastasis. Rev. 21, 217-230. https://doi.org/10.1023/A:1021202709003
  19. 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.
  20. Zeitlin, P. (2004) Can curcumin cure cystic fibrosis? N. Engl. J. Med. 351, 606-608. https://doi.org/10.1056/NEJMcibr041584
  21. 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. https://doi.org/10.1016/S0009-2797(99)00096-4
  22. Sreejayan, N. and Rao, M. N. (1996) Free radical scavenging activity of curcuminoids. Arzneimittelforschung 46, 169-171.
  23. 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.
  24. 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. https://doi.org/10.1021/np980269k
  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. https://doi.org/10.1007/s12272-001-1183-8
  26. 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.
  27. 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.
  28. 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. https://doi.org/10.1093/jb/117.2.244
  29. 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.
  30. 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. https://doi.org/10.1111/j.1538-7836.2007.02308.x
  31. Kaiser, L. and Sparks, H. V. Jr. (1987) Endothelial cells. Not just a cellophane wrapper. Arch. Intern. Med. 147, 569-573. https://doi.org/10.1001/archinte.1987.00370030173034
  32. 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. https://doi.org/10.1093/qjmed/hcg037
  33. 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. https://doi.org/10.1073/pnas.101134098
  34. 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.
  35. 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. https://doi.org/10.1016/j.yexcr.2003.08.003
  36. 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. https://doi.org/10.1016/j.bcp.2008.08.008
  37. 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. https://doi.org/10.1248/bpb.30.74
  38. 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. https://doi.org/10.1093/carcin/bgm123
  39. Fischer, K. G. (2007) Essentials of anticoagulation in hemodialysis. Hemodial. Int. 11, 178-189. https://doi.org/10.1111/j.1542-4758.2007.00166.x
  40. 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.
  41. 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. https://doi.org/10.1016/0049-3848(79)90064-1

Cited by

  1. Antiplatelet, anticoagulant, and profibrinolytic activities of baicalin vol.38, pp.5, 2015, https://doi.org/10.1007/s12272-014-0410-9
  2. Electrospun polylactide-based materials for curcumin release: Photostability, antimicrobial activity, and anticoagulant effect vol.133, pp.5, 2016, https://doi.org/10.1002/app.42940
  3. Antibacterial non-woven nanofibers of curcumin acrylate oligomers vol.39, pp.6, 2015, https://doi.org/10.1039/C4NJ01936A
  4. Curcumin improves the integrity of blood–spinal cord barrier after compressive spinal cord injury in rats vol.346, pp.1-2, 2014, https://doi.org/10.1016/j.jns.2014.07.056
  5. Effects of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine on Anticoagulation in Mice and the Inhibition of Experimental Thrombosis in Rats vol.64, pp.6, 2014, https://doi.org/10.1097/FJC.0000000000000152
  6. Molecular mechanisms of curcumin and its semisynthetic analogues in prostate cancer prevention and treatment vol.152, 2016, https://doi.org/10.1016/j.lfs.2016.03.036
  7. Antiplatelet activities of hyperosidein vitroandin vivo vol.18, pp.3, 2014, https://doi.org/10.1080/19768354.2014.925970
  8. Chemical constituents and biological research on plants in the genusCurcuma vol.57, pp.7, 2017, https://doi.org/10.1080/10408398.2016.1176554
  9. Hybridization of polyvinylpyrrolidone to a binary composite of curcumin/α-glucosyl stevia improves both oral absorption and photochemical stability of curcumin vol.213, 2016, https://doi.org/10.1016/j.foodchem.2016.07.025
  10. Anti-inflammation performance of curcumin-loaded mesoporous calcium silicate cement vol.116, pp.9, 2017, https://doi.org/10.1016/j.jfma.2017.06.005
  11. Molecular Analysis of Curcumin-induced Polarization of Murine RAW264.7 Macrophages vol.63, pp.6, 2014, https://doi.org/10.1097/FJC.0000000000000079
  12. Probable Interaction Between an Oral Vitamin K Antagonist and Turmeric (Curcuma longa) vol.69, pp.6, 2014, https://doi.org/10.2515/therapie/2014062
  13. Anti-coagulant activity of plants: mini review vol.44, pp.3, 2017, https://doi.org/10.1007/s11239-017-1546-5
  14. Zingiberaceae extracts for pain: a systematic review and meta-analysis vol.14, pp.1, 2015, https://doi.org/10.1186/s12937-015-0038-8
  15. Antiplatelet, anticoagulant, and profibrinolytic activities of withaferin A vol.60, pp.3, 2014, https://doi.org/10.1016/j.vph.2014.01.009
  16. Factor Xa inhibits HMGB1-induced septic responses in human umbilical vein endothelial cells and in mice vol.112, pp.4, 2014, https://doi.org/10.1160/TH14-03-0233
  17. Antiplatelet, anticoagulant, and profibrinolytic activities of cudratricusxanthone A vol.37, pp.8, 2014, https://doi.org/10.1007/s12272-013-0290-4
  18. Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer’s disease vol.115, pp.03, 2016, https://doi.org/10.1017/S0007114515004687
  19. Curcumin may impair iron status when fed to mice for six months vol.2, 2014, https://doi.org/10.1016/j.redox.2014.01.018
  20. A novel multifunctional biomedical material based on polyacrylonitrile: Preparation and characterization vol.62, 2016, https://doi.org/10.1016/j.msec.2016.02.026
  21. Curcumin inhibits hypoxia-induced proliferation and invasion of MG-63 osteosarcoma cells via downregulating Notch1 vol.15, pp.4, 2017, https://doi.org/10.3892/mmr.2017.6159
  22. Curcumin inhibits hypoxia inducible factor-1α-induced epithelial-mesenchymal transition in HepG2 hepatocellular carcinoma cells vol.10, pp.5, 2014, https://doi.org/10.3892/mmr.2014.2551
  23. Preparation of hemocompatible cellulosic paper based on P(DMAPS)-functionalized surface vol.116, 2014, https://doi.org/10.1016/j.colsurfb.2014.01.048
  24. Intravenous curcumin efficacy on healing and scar formation in rabbit ear wounds under nonischemic, ischemic, and ischemia-reperfusion conditions vol.22, pp.6, 2014, https://doi.org/10.1111/wrr.12231
  25. Use of complementary and alternative medicine by patients with end-stage renal disease on haemodialysis in Trinidad: A descriptive study vol.17, pp.1, 2017, https://doi.org/10.1186/s12906-017-1755-7
  26. Curcumin-loaded poly(l-lactide-co-D,l-lactide) electrospun fibers: Preparation and antioxidant, anticoagulant, and antibacterial properties vol.29, pp.6, 2014, https://doi.org/10.1177/0883911514553508
  27. Anticoagulant activities of piperlonguminine in vitro and in vivo vol.46, pp.10, 2013, https://doi.org/10.5483/BMBRep.2013.46.10.028
  28. Effects of curcumin on growth of human cervical cancer xenograft in nude mice and underlying mechanism vol.38, pp.1, 2017, https://doi.org/10.1590/1678-457x.02817
  29. Curcumin-loaded self-nanomicellizing solid dispersion system: part II: in vivo safety and efficacy assessment against behavior deficit in Alzheimer disease vol.8, pp.5, 2018, https://doi.org/10.1007/s13346-018-0570-0
  30. Use of Curcumin, a Natural Polyphenol for Targeting Molecular Pathways in Treating Age-Related Neurodegenerative Diseases vol.19, pp.6, 2018, https://doi.org/10.3390/ijms19061637
  31. Curcumin in turmeric: Basic and clinical evidence for a potential role in analgesia vol.43, pp.4, 2018, https://doi.org/10.1111/jcpt.12703
  32. Which supplements can I recommend to my osteoarthritis patients? vol.57, pp.suppl_4, 2018, https://doi.org/10.1093/rheumatology/key005
  33. Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases vol.23, pp.4, 2018, https://doi.org/10.3390/molecules23040835
  34. An anticoagulant peptide from beta-casein: identification, structure and molecular mechanism vol.10, pp.2, 2019, https://doi.org/10.1039/C8FO02235F
  35. Curcumin-Loaded Starch Micro/Nano Particles for Biomedical Application: The Effects of Preparation Parameters on Release Profile pp.00389056, 2019, https://doi.org/10.1002/star.201800305