On the anticoagulant and antiaggregatory properties of a glucosamine sulfate molecule
https://doi.org/10.14412/1996-7012-2019-3-135-141
Abstract
Glucosamine is part of the human metabolome required for the biosynthesis of polymer glycosaminoglycans in connective tissue. In addition, the glucosamine molecule itself has anti-inflammatory and regenerative properties. This paper presents the results of a systematic analysis of fundamental and clinical studies, which indicate the anticoagulant and antiaggregatory effects of a highly purified pharmaceutical substance of microcrystalline glucosamine sulfate (mGS). The main molecular mechanisms of its antithrombotic effects are most probably the mGS molecular mimicry of heparan sulfate activity, the activation of CD44 receptor, and the inactivation of the NF-KB signaling pathways in platelets. A quantitative chemoreactome study has shown that the antithrombotic effects of mGS in the human reactome are due to the inhibition of: ’) proper platelet aggregation; 2) platelet adhesion and activation receptors; 3) endogenous synthesis of thromboxanes; 4) coagulation by reducing the activity of coagulation factors.
About the Authors
I. Yu. Torshin
Institute of Pharmacoinformatics, Federal Research Center «Informatics and Management, Russian Academy of Sciences
Russian Federation
Russian Federation
44, Vavilov St., Build. 2, Moscow 119333.
A. M. Lila
V.A. Nasonova Research Institute of Rheumatology; Department of Rheumatology, Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
Russian Federation
Russian Federation
34A, Kashirskoe Shosse, Moscow 115522; 2/1, Barrikadnaya St., Build. 1, Moscow 125993.
O. A. Gromova
Institute of Pharmacoinformatics, Federal Research Center «Informatics and Management, Russian Academy of Sciences
Russian Federation
Russian Federation
Olga Alekseevna Gromova.
44, Vavilov St., Build. 2, Moscow 119333.
A. V. Naumov
Russian Gerontology Research and Clinical Center, N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation
16, First Leonov St., Moscow 129226.
Russian Federation
16, First Leonov St., Moscow 129226.
A. N. Gromov
Institute of Pharmacoinformatics, Federal Research Center «Informatics and Management, Russian Academy of Sciences
Russian Federation
Russian Federation
44, Vavilov St., Build. 2, Moscow 119333.
References
1. Gromova OA, Torshin IYu, Lila AM, Gromov AN. Molecular mechanisms of action of glucosamine sulfate in the treatment of degenerative-dystrophic diseases of the joints and spine: results of proteomic analysis. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, neuropsychiatry, psychosomatics. 2018; 10(2): 38—44. (In Russ.). doi: 10.14412/2074-2711-2018-2-38-44.
2. Lila AM, Gromova OA, Torshin IYu, et al. Molecular effects of chondroguard in osteoarthritis and herniated discs. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, neuropsychiatry, psychosomatics. 2017;9(3):88—97. (In Russ.). doi:10.14412/2074-2711-2017-3-88-97.
3. Yokotani K, Nakanishi T, Chiba T, et al. Glucosamine and chondroitin sulfate do not enhance anticoagulation activity of warfarin in mice in vivo. Shokuhin Shokuhin Eiseigaku Zasshi. 2014;55(4):183-7. doi:10.3358/shokueishi.55.183
4. Bertram J, Ragatz BH, Baldwin W, Iatrides PG. The effects of glucosamine on platelet aggregation. Thromb Res. 1981 Aug 1; 23(3):301-7. doi: 10.1016/0049-3848(81)90019-0.
5. Legrand Y, Caen JP, Robert L. Effect of glucosamine on platelet-collagen reaction. Proc Soc Exp Biol Med. 1968 Mar;127(3): 941-3. doi: 10.3181/00379727-127-32840.
6. Reginster J-YL, Arden NK, Haugen IK, et al. Guidelines for the conduct of pharmacological clinical trials in hand osteoarthritis: Consensus of a Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum. 2018 Aug;48(1):1-8. doi: 10.1016/j.semarthrit.
7. Pocobelli G, Kristal AR, Patterson RE, et al. Total mortality risk in relation to use of less-common dietary supplements. Am J Clin Nutr. 2010 Jun;91(6):1791-800. doi: 10.3945/ajcn.2009.28639. Epub 2010 Apr 21.
8. Katoh A, Kai H, Harada H, et al. Oral Administration of Glucosamine Improves Vascular Endothelial Function by Modulating Intracellular Redox State. Int Heart J. 2017 Dec 12;58(6):926-932. doi: 10.1536/ihj.16-534. Epub 2017 Nov 17.
9. Kinlough-Rathbone RL, Packham MA, Mustard JF. Effect of amino sugars on platelet aggregation and on fibrinogen binding. Thromb Haemost. 1984 Aug 31;52(1): 75-80.
10. Tandon NN, Ordinas A, Jamieson GA. Effects of N-acetylglucosamine and platelet inhibitors on the synergistic interaction of platelets and aggregating agents in the presence of wheat germ agglutinin. Biochim Biophys Acta. 1982 Nov 24;719(2):388-95. doi:10.1016/0304-4165(82)90114-3
11. Lu-Suguro JF, Hua J, Sakamoto K, Nagaoka I. Inhibitory action of glucosamine on platelet activation in guinea pigs. Inflamm Res. 2005 Dec;54(12):493-9. doi: 10.1007/s00011-005-1384-3.
12. Hua J, Suguro S, Iwabuchi K, et al. Glucosamine, a naturally occurring amino monosaccharide, suppresses the АДФ-mediated platelet activation in humans. Inflamm Res. 2004 Dec;53(12):680-8. doi: 10.1007/s00011-004-1312-y.
13. Lin PC, Jones SO, McGlasson DL. Effects of glucosamine and Celadrin on platelet function. Clin Lab Sci. 2010 Wnter;23(1):32-6.
14. Lima MA, Viskov C, Herman F, et al. Ultra-low-molecular-weight heparins: precise structural features impacting specific anticoagulant activities. Thromb Haemost. 2013 Mar; 109(3):471-8. doi: 10.1160/TH12-11-0795. Epub 2013 Jan 17.
15. McCarty MF. Glucosamine may retard atherogenesis by promoting endothelial production of heparan sulfate proteoglycans. Med Hypotheses. 1997 Mar;48(3):245-51.
16. Edavettal SC, Lee KA, Negishi M, et al. Crystal structure and mutational analysis of heparan sulfate 3-O-sulfotransferase isoform 1. J Biol Chem. 2004 Jun 11;279(24):25789-97. doi: 10.1074/jbc.M401089200. Epub 2004 Apr 1.
17. Walenga JM, Petitou M, Samama M, et al. Importance of a 3-O-sulfate group in a heparin pentasaccharide for antithrombotic activity. Thromb Res. 1988 Dec 15;52(6):553-63. doi:10.1016/0049-3848(88)90128-4.
18. Meuleman DG, Hobbelen PM, Van Dinther TG, et al. Antifactor Xa activity and antithrombotic activity in rats of structural analogues of the minimum antithrombin III binding sequence: discovery of compounds with a longer duration of action than of the natural pentasaccharide. Semin Thromb Hemost. 1991;17 Suppl 1:112-7.
19. Monaco C, Paleolog E. Nuclear factor kB: a potential therapeutic target in atherosclerosis and thrombosis. Cardiovasc Res. 2004 Mar 1;61(4):671-82. doi: 10.1016/j.cardiores.2003.11.038.
20. Malaver E, Romaniuk MA, D'Atri LP, et al. NF-kB inhibitors impair platelet activation responses. J Thromb Haemost. 2009; 7:1333-43. doi: 10.1111/j.1538-7836.2009.03492.x. Epub 2009 Jun 3.
21. Liu G, Liu G, Alzoubi K, et al. CD44 sensitivity of platelet activation, membrane scrambling and adhesion under high arterial shear rates. Thromb Haemost. 2016 Jan;115(1): 99-108. doi: 10.1160/TH14-10-0847. Epub 2015 Sep 10.
22. Torshin IYu, Gromova OA, Lila AM, et al. The results of postgenomic analysis of a glucosamine sulfate molecule indicate the prospects of treatment for comorbidities. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2018;12(4):129—136. (In Russ.). doi: 10.14412/1996-7012-2018-4-129-136.
23. Torshin IYu, Gromova OA, Naumov AV, et al. Chemical transcriptome analysis of glucosamine sulfate molecule in the context of post-genomic pharmacology. RMJ. 2019;1(1): 2-9. (In Russ.).
24. Kravchenko VV, Pan Z, Han J, et al. Platelet-activating factor induces NF-kappa B activation through a G protein-coupled pathway. J Biol Chem. 1995 Jun 23;270(25): 14928-34. doi: 10.1074/jbc.270.25.14928.
25. Mao G, Jin J, Kunapuli SP, Rao AK. Nuclear factor-kB regulates expression of platelet phospholipase C-beta2 (PLCB2). Thromb Haemost. 2016 Oct 28;116(5):931-940. doi: 10.1160/TH15-09-0749. Epub 2016 Jul 28.
26. Grundler K, Rotter R, Tilley S, et al. The proteasome regulates collagen-induced platelet aggregation via nuclear-factor-kappa-B (NFkB) activation. Thromb Res. 2016 Dec;148:15-22. doi: 10.1016/j.thromres.2016.10.009. Epub 2016 Oct 13.
27. Rivadeneyra L, Carestia A, Etulain J, et al. Regulation of platelet responses triggered by Toll-like receptor 2 and 4 ligands is another non-genomic role of nuclear factor-kB. Thromb Res. 2014 Feb;133(2):235-43. doi: 10.1016/j.thromres.2013.11.028. Epub 2013 Dec 1.
28. Song D, Ye X, Xu H, Liu SF. Activation of endothelial intrinsic NF-kB pathway impairs protein C anticoagulation mechanism and promotes coagulation in endotoxemic mice. Blood. 2009 Sep 17;114(12):2521-9. doi: 10.1182/blood-2009-02-205914. Epub 2009 Jul 20.
29. Torshin I.Y. The study of the solvability of the genome annotation problem on sets of elementary motifs. Pattern Recognition and Image Analysis. 2011;21(4):652-62.
30. Torshin IY, Rudakov KV. On the applica¬tion of the combinatorial theory of solvability to the analysis of chemographs. Part 1: fundamentals of modern chemical bonding theory and the concept of the chemograph. Pattern Recognition and Image Analysis. 2014; 24(1): 11-23.
31. Torshin IY, Rudakov KV. On the applica¬tion of the combinatorial theory of solvability to the analysis of chemographs. Part 2: local completeness of invariants of chemographs in view of the combinatorial theory of solvability. Pattern Recognition and Image Analysis. 2014;24(2):196-208.
32. Torshin IYu, Rudakov KV. On the theoretical basis of the metric analysis of poorly formalized problems of recognition and classification. Pattern Recognition and Image Analysis. 2015;25(4):577-87. doi: 10.1134/S1054661815040252
33. Torshin IY, Rudakov KV. On metric spaces arising during formalization of problems of recognition and classification. Part 1: properties of compactness. Pattern Recognition and Image Analysis. 2016;26(2):274-84. doi: 10.1134/S1054661816020255
34. Torshin IYu, Rudakov KV. On metric spaces arising during formalization of problems of recognition and classification. Part 2: density properties. Pattern Recognition and Image Analysis. 2016;26(3):483-96. doi: 10.1134/S1054661816030202
Review
For citations:
Torshin IY, Lila AM, Gromova OA, Naumov AV, Gromov AN. On the anticoagulant and antiaggregatory properties of a glucosamine sulfate molecule. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2019;13(3):135-141. (In Russ.) https://doi.org/10.14412/1996-7012-2019-3-135-141
Views:
787
Email this article 