Rhamnan sulfate (RS) is a polysaccharide with a rhamnose backbone isolated from Monostroma nitidum. Like heparin, it exerts anticoagulant activity in the presence of antithrombin. Endothelial cells facilitate the crosstalk between blood coagulation and vascular inflammation. In this study, we compared the effect of RS with that of heparin on blood coagulation and vascular endothelial cells in the presence or absence of inflammatory factors, using human umbilical vein endothelial cells. We found that RS significantly enhances inhibition of thrombin and factor Xa in the presence of antithrombin as well as heparin, and that RS inhibits tissue factor expression and von Willebrand factor release from the endothelial cells treated with or without lipopolysaccharide, tumor necrosis factor-α, or thrombin. Heparin did not show any effects on endothelial cell inflammation. Our findings suggest that RS, like heparin, is an antithrombin-dependent anticoagulant and, unlike heparin, is a potent anti-inflammatory agent acting on vascular endothelial cells.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Activated partial thromboplastin time
Human umbilical vein endothelial cells
Tumor necrosis factor
Von Willebrand factor
Zang L, Shimada Y, Tanaka T, Nishimura N (2015) Rhamnan sulphate from Monostroma nitidum attenuates hepatic steatosis by suppressing lipogenesis in a diet-induced obesity zebrafish model. J Funct Foods 17:364–370. https://doi.org/10.1016/j.jff.2015.05.041
Harada N, Maeda M (1998) Chemical structure of antithrombin-active Rhamnan sulfate from Monostrom nitidum. Biosci Biotechnol Biochem 62:1647–1652. https://doi.org/10.1271/bbb.62.1647
Lee JB, Koizumi S, Hayashi K, Hayashi T (2010) Structure of rhamnan sulfate from the green alga Monostroma nitidum and its anti-herpetic effect. Carbohydr Polym 81:572–577. https://doi.org/10.1016/j.carbpol.2010.03.014
Tako M, Yamashiro Y, Teruya T, Uechi S (2017) Structure-function relationship of rhamnan sulfate isolated from commercially cultured edible green seaweed, Monostroma nitidum. Am J Appl Chem 5:38–44. https://doi.org/10.11648/j.ajac.20170502.13
Li H, Mao W, Hou Y, Gao Y, Qi X, Zhao C, Chen Y, Chen Y, Li N, Wang C (2012) Preparation, structure and anticoagulant activity of a low molecular weight fraction produced by mild acid hydrolysis of sulfated rhamnan from Monostroma latissimum. Bioresour Technol 114:414–418. https://doi.org/10.1016/j.biortech.2012.03.025
Yamashiro Y, Nakamura M, Yogi T, Teruya T, Konishi T, Uechi S, Tako M (2017) Anticoagulant activity of rhamnan sulfate isolated from commercially cultured Monostroma nitidum. Int J Biomed Mater Res 5:37–43. https://doi.org/10.11648/j.ijbmr.20170503.12
Lee JB, Hayashi K, Hayashi T, Sankawa U, Maeda M (1999) Antiviral activities against HSV-1, HCMV, and HIV-1 of rhamnan sulfate from Monostroma latissimum. Planta Med 65:439–441. https://doi.org/10.1055/s-2006-960804
Lee JB, Hayashi K, Maeda M, Hayashi T (2004) Antiherpetic activities of sulfated polysaccharides from green algae. Planta Med 70:813–817. https://doi.org/10.1055/s-2004-827228
Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM (1998) Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 91:3527–3561
Sadler JE (1998) Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem 67:395–424. https://doi.org/10.1146/annurev.biochem.67.1.395
Noone DG, Riedl M, Licht C (2018) The role of von Willebrand factor in thrombotic microangiopathy. Pediatr Nephrol 33:1297–1307. https://doi.org/10.1007/s00467-017-3744-y
Björk I, Lindahl U (1982) Mechanism of the anticoagulant action of heparin. Mol Cell Biochem 48:161–182. https://doi.org/10.1007/BF00421226
Chuang YJ, Swanson R, Raja SM, Olson ST (2001) Heparin enhances the specificity of antithrombin for thrombin and factor Xa independent of the reactive center loop sequence. Evidence for an exosite determinant of factor Xa specificity in heparin-activated antithrombin. J Biol Chem 276:14961–14971. https://doi.org/10.1074/jbc.M011550200
Li N, Liu X, He X, Wang S, Cao S, Xia Z, Xian H, Qin L, Mao W (2017) Structure and anticoagulant property of a sulfated polysaccharide isolated from the green seaweed Monostroma angicava. Carbohydr Polym 159:195–206. https://doi.org/10.1016/j.carbpol.2016.12.013
Liu X, Du P, Liu X, Cao S, Qin L, He M, He X, Mao W (2018) Anticoagulant properties of a green algal rhamnan-type sulfated polysaccharide and its low-molecular-weight fragments prepared by mild acid degradation. Mar Drugs. https://doi.org/10.3390/md16110445
Liu X, Wang S, Cao S, He X, Qin L, He M, Yang Y, Hao J, Mao W (2018) Structural characteristics and anticoagulant property in vitro and in vivo of a seaweed sulfated rhamnan. Mar Drugs. https://doi.org/10.3390/md16070243
Nemerson Y (1988) Tissue factor and hemostasis. Blood 71:1–8
Wada H, Wakita Y, Shiku H (1995) Tissue factor expression in endothelial cells in health and disease. Blood Coagul Fibrinolysis 6(1):S26–S31
Esmon CT (2003) Inflammation and thrombosis. J Thromb Haemost 1:1343–1348
Schneppenheim R, Budde U (2011) von Willebrand factor: the complex molecular genetics of a multidomain and multifunctional protein. J Thromb Haemost 9(Suppl 1):209–215. https://doi.org/10.1111/j.1538-7836.2011.04324.x
Yau JW, Teoh H, Verma S (2015) Endothelial cell control of thrombosis. BMC Cardiovasc Disord 15:130. https://doi.org/10.1186/s12872-015-0124-z
Kolarova H, Ambruzova B, Svihalkova Sindlerova L, Klinke A, Kubala L (2014) Modulation of endothelial glycocalyx structure under inflammatory conditions. Mediators Inflamm 2014:694312. https://doi.org/10.1155/2014/694312
Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, Oude Egbrink MG (2007) The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch 454:345–359. https://doi.org/10.1007/s00424-007-0212-8
van den Berg BM, Vink H, Spaan JA (2003) The endothelial glycocalyx protects against myocardial edema. Circ Res 92:592–594. https://doi.org/10.1161/01.Res.0000065917.53950.75
Morita T, Kato H, Iwanaga S, Takada K, Kimura T (1977) New fluorogenic substrates for alpha-thrombin, factor Xa, kallikreins, and urokinase. J Biochem 82:1495–1498
Okamoto T, Akita N, Nagai M, Hayashi T, Suzuki K (2014) 6-Methylsulfinylhexyl isothiocyanate modulates endothelial cell function and suppresses leukocyte adhesion. J Nat Med 68:144–153. https://doi.org/10.1007/s11418-013-0784-x
This work was supported in part by a Grant-in-Aid for challenging Exploratory Research (Grant number 18659280), a Grant-in-Aid for Scientific Research (B) (Grant number 21309292), and a Grant-in-Aid for Scientific Research (C) (Grant numbers 25460396 and 16K08633) from the Japan Society for the Promotion of Science.
Conflict of interest
This study was performed as a collaborative investigation funded by the Konan Chemical Manufacturing Co. Ltd. The corresponding author had full access to all data in the study and had final responsibility for the decision to submit for publication.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Okamoto, T., Akita, N., Terasawa, M. et al. Rhamnan sulfate extracted from Monostroma nitidum attenuates blood coagulation and inflammation of vascular endothelial cells. J Nat Med 73, 614–619 (2019). https://doi.org/10.1007/s11418-019-01289-5
- Monostroma nitidum
- Rhamnan sulfate
- Vascular endothelium