1. Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia; Lomonosov Moscow State University, Moscow, Russia 2. Lomonosov Moscow State University, Moscow, Russia 3. Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia 4. Belarusian State University, Minsk, Belarus 5. Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia; Smorodintsev Research Institute of Influenza, Saint Petersburg, Russia
Fucoidan, an anionic polysaccharide from brown algae, demonstrates anticoagulant, antioxidant, anti-inflammatory, antitumor, and antiviral activities. It can form polyelectrolyte complexes with various proteins, including the therapeutically important protein lactoferrin. The aim of this study was to investigate the physicochemical and functional properties of a fucoidan-lactoferrin complex formed by mixing their solutions at physiological pH. The complex, detected using atomic force microscopy, had a negative charge and a hydrodynamic diameter of 382 nm. Interaction with lactoferrin changed the IR spectrum of fucoidan in the absorption band in the range of 1220–1260 cm–1, corresponding to vibrations of the sulfate group. It increased the total antioxidant activity of biopolymers in the Fenton reaction and reduced the anticoagulant activity of fucoidan, assessed by determining the activated partial thromboplastin time. Fucoidan reduced luciferase activity in a luciferin-luciferase model system, and complex formation with lactoferrin attenuated the inhibitory capacity of fucoidan. These results demonstrate the possibility of targeted influence on the functional activity of biopolymers during complex formation and prospects for using fucoidan and lactoferrin as a complex in the development of new drugs and drug delivery systems.
Mosievich D.V., Balabushevich N.G., Mishin P.I., Le-Deygen I.M., Filatova L.Y., Panasenko O.M., Murina M.A., Vakhrusheva T.V., Barinov N.A., Pobeguts O.V., Galyamina M.A., Gorudko I.V., Grigorieva D.V., Pashkevich K.F., Sokolov A.V., Mikhalchik E.V. (2025) Functional activity features of lactoferrin-fucoidan complexes in model systems in vitro. Biomeditsinskaya Khimiya, 71(5), 333-341.
Mosievich D.V. et al. Functional activity features of lactoferrin-fucoidan complexes in model systems in vitro // Biomeditsinskaya Khimiya. - 2025. - V. 71. -N 5. - P. 333-341.
Mosievich D.V. et al., "Functional activity features of lactoferrin-fucoidan complexes in model systems in vitro." Biomeditsinskaya Khimiya 71.5 (2025): 333-341.
Mosievich, D. V., Balabushevich, N. G., Mishin, P. I., Le-Deygen, I. M., Filatova, L. Y., Panasenko, O. M., Murina, M. A., Vakhrusheva, T. V., Barinov, N. A., Pobeguts, O. V., Galyamina, M. A., Gorudko, I. V., Grigorieva, D. V., Pashkevich, K. F., Sokolov, A. V., Mikhalchik, E. V. (2025). Functional activity features of lactoferrin-fucoidan complexes in model systems in vitro. Biomeditsinskaya Khimiya, 71(5), 333-341.
References
Tolstoguzov V. (2002) Thermodynamic aspects of biopolymer functionality in biological systems, foods, and beverages. Crit. Rev. Biotechnol., 22(2), 89–174. CrossRef Scholar google search
Gruškienė R., Galinskaitė A., Kavleiskaja T., Vepštaitė-Monstavičė I., Servienė E., Sereikaitė J. (2024) Application of fucoidan for the encapsulation of yeast K2 toxin. Carbohydrate Polymer Technologies Applications, 7, 100521. CrossRef Scholar google search
Balabushevich N.G., Maltseva L.N., Filatova L.Y., Mosievich D.V., Mishin P.I., Bogomiakova M.E., Lebedeva O.S., Murina M.A., Klinov D.V., Obraztsova E.A., Kharaeva Z.F., Firova R.K., Grigorieva D.V., Gorudko I.V., Panasenko O.M., Mikhalchik E.V. (2024) Influence of natural polysaccharides on the morphology and properties of hybrid vaterite microcrystals. Heliyon, 10(13), e33801. CrossRef Scholar google search
Zayed A., Al-Saedi D.A., Mensah E.O., Kanwugu O.N., Adadi P., Ulber R. (2023) Fucoidan's molecular targets: a comprehensive review of its unique and multiple targets accounting for promising bioactivities supported by in silico studies. Marine Drugs, 22(1), 29. CrossRef Scholar google search
Burova T.V., Grinberg N.V., Dubovik A.S., Plashina I.G., Usov A.I., Grinberg V.Y. (2022) β-Lactoglobulin-fucoidan nanocomplexes: energetics of formation, stability, and oligomeric structure of the bound protein. Food Hydrocolloids, 129, 107666. CrossRef Scholar google search
Haggag Y.A., Abd Elrahman A.A., Ulber R., Zayed A. (2023) Fucoidan in pharmaceutical formulations: a comprehensive review for smart drug delivery systems. Marine Drugs, 21(2), 112. CrossRef Scholar google search
Mensah E.O., Kanwugu O.N., Panda P.K., Parise Adadi P. (2023) Marine fucoidans: structural, extraction, biological activities and their applications in the food industry. Food Hydrocolloids, 142, 108784. CrossRef Scholar google search
Imbs T.I., Ermakova S.P. (2021) Can fucoidans of brown algae be considered as antioxidants? Russian Journal of Marine Biology, 47(3), 157–161. CrossRef Scholar google search
Ermilov F., Zhurishkina E., Vlasova E., Skorik Y., Kulminsaya A., Lapina I. (2025) Effect of polyphenolic impurities on antibacterial and antioxidant activities of fucoidans from Barents Sea Fucus vesiculosus. J. Appl. Phycol., 37(4), 2869–2883. CrossRef Scholar google search
Liu N., Feng G., Zhang X., Hu Q., Sun S., Sun J., Sun Y., Wang R., Zhang Y., Wang P., Li Y. (2021) The functional role of lactoferrin in intestine mucosal immune system and inflammatory bowel disease. Front. Nutr., 8, 759507. CrossRef Scholar google search
Xi X., Wei Z., Xu Y., Xue C. (2023) Clove essential oil Pickering emulsions stabilized with lactoferrin/fucoidan complexes: stability and rheological properties. Polymers, 15(8), 1820. CrossRef Scholar google search
Meng Q., Jiang H., Tu J., He Y., Zhou Z., Wang R., Jin W., Han J., Liu W. (2024) Effect of pH, protein/polysaccharide ratio and preparation method on the stability of lactoferrinpolysaccharide complexes. Food Chem., 456, 140056. CrossRef Scholar google search
Klinov D., Dwir B., Kapon E., Borovok N., Molotsky T., Kotlyar A. (2007) High-resolution atomic force microscopy of duplex and triplex DNA molecules. Nanotechnology, 18(22), 225102. CrossRef Scholar google search
Re R., Pellegrini N., Proteggente A., Pannala A., Yang M., Rice-Evans C. (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med., 26(9–10), 1231–1237. CrossRef Scholar google search
Smirnoff N., Cumbes Q.J. (1989) Hydroxyl radical scavenging activity of compatible solutes. Phytochemistry, 28(4), 1057–1060. CrossRef Scholar google search
Miyamoto A., Nakano S., Nagai K., Kishikawa N., Ohyama K., Aoyama T., Matsumoto Y., Kuroda N. (2017) Development of an evaluation method for hydroxyl radical scavenging activities using sequential injection analysis with chemiluminescence detection. Anal. Sci., 33(6), 697–701. CrossRef Scholar google search
Nagy I., Floyd R.A. (1984) Hydroxyl free radical reactions with amino acids and proteins studied by electron spin resonance spectroscopy and spin-trapping. Biochim. Biophys. Acta, 790(3), 238–250. CrossRef Scholar google search
Kordjazi M., Etemadian Y., Shabanpour B., Pourashouri P. (2019) Chemical composition antioxidant and antimicrobial activities of fucoidan extracted from two species of brown seaweeds (Sargassum ilicifolium and S. angustifolium) around Qeshm Island. Iranian Journal of Fisheries Sciences, 18(3), 457–475. CrossRef Scholar google search
Tissot B., Gonnet F., Iborra A., Berthou C., Thielens N., Arlaud G.J., Daniel R. (2005) Mass spectrometry analysis of the oligomeric C1q protein reveals the B chain as the target of trypsin cleavage and interaction with fucoidan. Biochemistry, 44(7), 2602–2609. CrossRef Scholar google search
Mavlonov G., Lee J., Shin L., Yi T., Abdurakhmonov I. (2011) Low molecular fucoidan and its macromolecular complex with bee venom melittin. Adv. Biosci. Biotechnol., 2(4), 298–303. CrossRef Scholar google search
Lomakina G.Y., Bezrukikh A.E., Ugarova N.N. (2012) Effect of gelatin on properties of Luciola mingrelica firefly luciferase. Moscow Univ. Chem. Bull., 67, 8–12. CrossRef Scholar google search
Leach F.R. (2008) A view on the active site of firefly luciferase. Nat. Prod. Commun., 3(9), 1437–1448. CrossRef Scholar google search
Tissot B., Montdargent B., Chevolot L., Varenne A., Descroix S., Gareil P., Daniel R. (2003) Interaction of fucoidan with the proteins of the complement classical pathway. Biochim. Biophys. Acta, 1651(1–2), 5–16. CrossRef Scholar google search
Ushakova N.A., Morozevich G.E., Ustyuzhanina N.E., Bilan M.I., Usov A.I., Nifantiev N.E., Preobrazhenskaya M.E. (2008) Anticoagulant activity of fucoidans from brown algae. Biomeditsinskaya Khimiya, 54(5), 597–606. Scholar google search
Wang J., Hu S., Nie S., Yu Q., Xie M. (2016) Reviews on mechanisms of in vitro antioxidant activity of polysaccharides. Oxid. Med. Cell. Longev., 2016, 5692852. CrossRef Scholar google search
Zheng L., Zhao M., Xiao C., Zhao Q., Su G. (2016) Practical problems when using ABTS assay to assess the radical-scavenging activity of peptides: importance of controlling reaction pH and time. Food Chem., 192, 288–294. CrossRef Scholar google search
Ogasawara Y., Imase M., Oda H., Wakabayashi H., Ishii K. (2014) Lactoferrin directly scavenges hydroxyl radicals and undergoes oxidative self-degradation: a possible role in protection against oxidative DNA damage. Int. J. Mol. Sci., 15(1), 1003–1013. CrossRef Scholar google search
Renaldi K., Simadibrata M., Syam A.F., Rani A.A., Krisnuhoni E. (2011) Influence of fucoidan in mucus thickness of gastric mucosa in patients with chronic gastritis. The Indonesian Journal of Gastroenterology, Hepatology, and Digestive Endoscopy, 12(2), 79–84. CrossRef Scholar google search