Biologically active substances from marine hydrobionts of the Pacific Ocean as the basis for developing new medicines

Introduction: Since 1970s, a school of thought on management of innate and acquired immunity systems using biologically active substances of the Far East marine origin has been developed by the Immunology Laboratory of Somov Research Institute of Epidemiology and Microbiology of the Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor). Biopolymers, which constitute the structural basis of live marine organisms and sustain numerous vital processes, draw special attention as potential candidates for pharmaceutical forms. The objective of our study was to summarize the results of long-term research on biologically active substances (BAS) from marine aquatic organisms (hydrobionts) of the Pacific Ocean as the basis for developing medicinal preparations for infectious disease prevention and treatment and dietary supplements for food and functional food products. Methods: We have selected and analyzed 46 principal published works of the researchers of the Institute found in electronic databases (Web of Science, PubMed, and eLibrary) using appropriate keywords. Results: We established that over 500 substances from various hydrobionts of the Pacific Ocean including invertebrates, fish, algae, marine bacteria (polycationic and polyanionic polysaccharides of brown and red algae), pectins (colloidal carbohydrates of high molecular weight and complex structure), lipopolysaccharides and polysaccharides from marine proteobacteria, glycoproteins, proteoglycans, glycolipids, low-molecular compounds of marine origin (sulfated polyoxysteroids, peptides, beta-glucans, nucleic acids, amino acid complexes, naphthoquinones and spinochromes of sea urchins) had been studied for their biological properties over the past almost half a century. The studies produced abundant new data on immunomodulatory, antibacterial, antiviral, antitumor, anti-adhesive, anti-endotoxic, pro-apoptotic, hepatoprotective, and hypolipidemic properties of biologically active substances, substantiated feasibility of designing innovative BAS-based medicines, and developed environmentally safe functional food products and dietary supplements. Conclusions: Biologically active substances from marine hydrobionts are a promising source for the development of novel domestic pharmaceuticals.

1. Zaporozhets TS, Gazha AK, Zvyagintseva TN, Malyarenko OS, Besednova NN. Cellular and molecular mechanisms of immunomodulatory action of fucoidan from brown alga Fucus evanescens. Tikhookeanskiy Meditsinskiy Zhurnal. 2018;(4(74)):49–52. (In Russian). doi: 10.17238/PmJ1609-1175.2018.4.49-52

2. Makarenkova ID, Akhmatova NK, Ermakova SP, Besednova NN. Morphofunctional changes of dendritic cells induced by sulfated polysaccharides of brown algae. Biomeditsinskaya Khimiya. 2017;63(1):39–46. (In Russian). doi: 10.18097/PBMC2017630139

3. Gazha AK, Zaporozhets TS, Kuznetsova TA, Besedno va NN, Zvyaguintseva TN. Effect of sulfated polysaccharides from brown algae on apoptosis of human peripheral blood lymphocytes. Byulleten’ Eksperimental’noy Biologii i Meditsiny. 2015;159(5):573–576.

4. Kuznetsova TA, Smolina TP, Makarenkova ID, et al. Immunoadjuvant activity of fucoidans from the brown alga Fucus evanescens. Mar Drugs. 2020;18(3):155. doi: 10.3390/md18030155

5. Kuznetsova TA, Ivanushko LA, Persiyanova EV, et al. Evaluation of adjuvant effects of fucoidane from brown seaweed Fucus evanescens and its structural analogues for the strengthening vaccines effectiveness. Biomeditsinskaya Khimiya. 2017;63(6):553–558. (In Russian). doi: 10.18097/PBMC20176306553

6. Kuznetsova TA, Stepanova LA, Ermakova SP. Increasing the immunogenicity of the inactivated influenza virus A/ California/7/09 (H1N1) using as adjuvant fucoidan from brown alga Fucus evanescens. Zdorov’e. Meditsinskaya Ekologiya. Nauka. 2017;(3(70)):57–59. (In Russian). doi: 10.5281/zenodo.818164

7. Persiyanova EV, Kuznetsova TA, Silchenko AS. Effect of sulfated polysaccharides from marine hydrobionts on humoral immune response to ovalbumin in mice. Byulleten’ Eksperimental’noy Biologii i Meditsiny. 2020;169(2):207–210.

8. Kuznetsova TA, Persiyanova EV, Shutikova AL, Besednova NN, Ermakova SP, Stepanova LA. Adjuvant for Anti-viral Vaccines. Patent RU 2676266 C2 issued on December 27, 2018. (In Russian). Accessed on March 17, 2021. https://yandex.ru/patents/doc/RU2676266C2_20181227

9. Zaporozhets TS, Kryzhanovsky SP, Persianova EV, et al. Efficacy of fucoidan from brown algae of the Okhotsk Sea Fucus evanescens in vaccination against seasonal influenza in the elderly people. Antibiotiki i Khimioterapiya. 2019;64(5-6):32–38. (In Russian). doi: 10.24411/0235-2990-2019-100028

10. Kuznetsova TA, Besednova NN, Mamaev AN, Mo mot AP, Shevchenko NM, Zvyagintseva TN. Anticoagulant activity of fucoidan from brown algae Fucus evanescens of the Okhotsk Sea. Byulleten’ Eksperimental’noy Biologii i Meditsiny. 2003;136(11):532–534. (In Russian).

11. Zaporozhets TS, Kuznetsova ТА, Smolina TP, Shevchenko NM, Zvyagintseva TN, Besednova NN. Immunotropic and anticoagulant properties of fucoidan from brown seaweed Fucus evanescens: perspectives of application in medicine. Zhurnal Mikrobiologii, Epidemiologii i Immunobiologii. 2006;(S3):54–58. (In Russian).

12. Lapikova ES, Drozd NN, Tolstenkov AS, et al. Inhibition of thrombin and factor Xa by Fucus evanescens fucoidan and its modified analogs. Bull Exp Biol Med. 2008;146(3):328–33. doi: 10.1007/s10517-008-0267-3

13. Lapikova ES, Drozd NN, Makarov VA, et al. Influence of intravenous injection of fucoidan from brown seaweed Fucus evanescens by plasma rabbits anticoagulant activity and neutralisation by sulphate protamin of fucoidans antithrombin activity in vitro. Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya. 2012;56(2):42–44. (In Russian).

14. Krylova NV, Ermakova SP, Lavrov VF, et al. The comparative analysis of antiviral activity of native and modified Fucoidans from brown algae Fucus evanescens in vitro and in vivo. Mar Drugs. 2020;18(4):224. doi: 10.3390/md18040224

15. Makarenkova ID, Kryilova NV, Leonova GN, Besednova NN, Zvyagintseva TN, Shevchenko NM. Protective effects of fucoidan derived from brown algae Laminaria japonica under experimental tick-borne encephalitis. Tikhookeanskiy Meditsinskiy Zhurnal. 2009;(3(37)):89–92. (In Russian).

16. Krizshanovsky SP, Kuznetsova TA, Geltser BI, Zaporozhets TS, Ermakova SP, Besednova NN. Fucoidan from brown algae Fucus evanescens: new perspectives in the treatment of atherosclerosis. Rossiyskiy Bioterapevticheskiy Zhurnal. 2017;16(1):82–87. (In Russian). doi: 10.17650/1726-9784-2017-16-1-82-87

17. Ivanushko LA, Besednova NN, Kryzhanovsky SP. [Polysaccharides of brown algae as a means of accompanying basic therapy in patients with ischemic heart disease with dyslipidemia.] Rossiyskiy Immunologicheskiy Zhurnal. 2015;9(2):784–786. (In Russian).

18. Krizshanovsky SP, Geltser BI, Kuznetsova TA, Persiyanova EV, Zaporozhets TS. The effectiveness of combined therapy for dyslipidemia with atorvastatin and biologically active substances from marine hydrobionts. Rossiyskiy ioterapevticheskiy Zhurnal. 2017;16(2):97–102. (In Russian). doi: 10.17650/1726-9784-2017-16-2-97-102

19. Ivanushko LA, Kryzhanovsky SP. Correction cytokine status in patients with coronary heart disease dyslipidemia accompanied sulfated polysaccharide from the brown alga Fucus evanescens. Zdorov’e. Meditsinskaya Ekologiya. Nauka. 2014;(3(57)):27–28. (In Russian).

20. Besednova NN, Kryzhanovskiy SP, Zvyagintseva TN, Persiyanova YeV, Korneeva IA. Polysaccharides of marine algae in the correction of disorders associated with metabolic syndrome. Antibiotiki i Khimioterapiya. 2019;64(3-4):59–70. (In Russian).

21. Filonova NV, Zaporozhets TS, Ermolitskaya SA, et al. Effect of fucoidan from Fucus evanescens on the parameters of cytokine status in patients with chronic hepatitis C. Tsitokiny i Vospalenie. 2011;10(4):105–110. (In Russian).

22. Filonova NV, Zaporozhets TS, Zvyagintseva TN. [Influence of fucoidan from Fucus evanescens on humoral factors of natural resistance in patients with chronic viral hepatitis C.] Zhurnal Infektsionnoy Patologii. 2010;17(3):203. (In Russian).

23. Zaporozhets TS, Maystrovsky KV, Rapovka VG, Ivanushko LA, Smolina TP, Gazha AK. Estimating systemic inflammatory response in patients with obliterating arterial sclerosis of lower limb arteries. Tikhookeanskiy Meditsinskiy Zhurnal. 2012;(1(47)):72–77. (In Russian).

24. Maistrovsky KV, Rapovka VG, Zaporozhets TS. [The Use of Brown Algae Polysaccharides in Complex Treatment of Obliterating Atherosclerosis of Vessels of the Lower Extremities.] Vladivostok: Dalnauka Publ., 2014. (In Russian).

25. Kuznetsova TA, Zaporozhets TS, Besednova NN, et al. Efficiency of a new synbiotic drink in treatment of chronic diseases of gastrointestinal tract and concomitant dysbacteriosis. Antibiotiki i Khimioterapiya. 2013;58(9-10):21–26. (In Russian).

26. Kuznetsova TA, Zaporozhets TS, Besednova NN, et al. Method of Drug-free Therapy of Patients with Chronic Gastrointestinal Diseases. Patent RU 2489157 C1 issued on August 10, 2013. Accessed on March 17, 2021. https://patents.s3.yandex.net/RU2489157C1_20130810.pdf.html

27. Zaporozhets TS, Kuznetsova TA, Kryzhanovsky SP, Ermakova SP, Besednova NN. [Functional Food Products Based on Seaweed Polysaccharides.] Vladivostok: Dalnauka Publ., 2020. (In Russian).

28. Kuznetsova TA, Persiyanova EV, Ivanushko LA. Adjuvant. Patent RU 2736933 issued on November 23, 2020. Accessed on March 18, 2021. https://patents.s3.yandex.net/RU2736933C1_20201123.pdf

29. Gazha AK, Kuznetsova TA, Smolina TP, Kokoulin MS. Biological activity of polysaccharides from sea bacteria. Zdorov’e. Meditsinskaya Ekologiya. Nauka. 2019;(3(79)):23–27. (In Russian). doi: 10.5281/zenodo.3559614

30. Smolina TP, Kuznetsova TA, Ivanushko LA, Gazha AK, Silchenko AS, Besednova NN. Phenotypic changes in subpopulations of human NK and NKT cells induced by sulfated polysaccharides. Antibiotiki i Khimioterapiya. 2019;64(9-10):3–7. (In Russian). doi: 10.24411/0235-2990-2019-10049

31. Smolina TP, Zaporozhets TS, Besednova NN. Modification of levels of adhesion molecules expression of human innate immunity cells by glycopolymers of marine bacteria. Antibiotiki i Khimioterapiya. 2015;60(3-4):37–41. (In Russian).

32. Smolina TP, Zaporozhets TS, Besednova NN. Activation of innate immunity human cells by lipopolisaccharide and extracellular polysaccharid produced by marine bacteria. Antibiotiki i Khimioterapiya. 2017;62(7-8):3–7. (In Russian).

33. Krylova NV, Smolina TP, Berlizova MV, Leonova GN. Immunocorrective and antiviral activity of polysaccharide from marine bacteria against tick-borne encephalitis virus. Antibiotiki i Khimioterapiya. 2019;64(11-12):16–24. (In Russian). doi: 10.1016/0235-2990-2019-64-11-12-16-24

34. Kuznetsova TA, Besednova NN, Zaporozhets TS, Smolina TP, Gazha AK, Ivanushko LA. Comparative study of immunomodulatory activity of peptides, tinrostim and thymalin. Antibiotiki i Khimioterapiya. 2013;58(11-12):8–12. (In Russian).

35. Kuznetsova TA, Kinyaikin MF, Sukhanova GI, Besednova NN. Use of tinrostim for treatment of immune and hemostasis disorders as a part of combined therapy of patients with chronic obstructive pulmonary disease. Pulmonologiya. 2010;(1):106–109. (In Russian). doi: 10.18093/0869-0189-2010-1-106-109

36. Besednova NN, Epshtein LM. [Biologically Active Food Supplement Tinrostim (Guidelines for Practitioners).] Vladivostok: TINRO-Center Publ., 2007. (In Russian).

37. Kryizhanovsky SP, Yatskova MA, Golovacheva VD. Hypolipidemic effects of sea urchin-derived bioactive food additives in monotherapy and in combination with atorvastatin. Tikhookeanskiy Meditsinskiy Zhurnal. 2012;(1(47)):29–31. (In Russian).

38. Dobryakov EYu, Persiyanova EV, Zaporozhets TS, Vitkovskaya DV. Application of biologically active substances from sea urchins as a means of support of treatment and prevention of diseases of the digestive system. Zdorov’e. Meditsinskaya Ekologiya. Nauka. 2017;(3(70)):84–87. (In Russian). doi: 10.5281/zenodo.817781

39. Kivaeva IF, Golovacheva VD, Yatskova MA, Dobryakov EYu, Kryizhanovskiy SP, Lvanushko LA. Integrated chitosan and molluskam based dietary supplement as a maintenance medication for baseline therapy of gastric and duodenal ulcer. Tikhookeanskiy Meditsinskiy Zhurnal. 2009;(3):123–125. (In Russian).

40. Besednova NN, Kovalev NN, Fedyanina LN, Pozdnyakova YuM, Kryzhanovsky SP, Zaporozhets TS. [Deoxyribo nucleic Acid of Pro- and Eukaryotes: Medical Aspects of Application.] Vladivostok: Dalnauka Publ., 2018. (In Russian).

41. Potapova VV, Ivanushko LA, Besednova NN, et al. The influence of BASF from tissue and organs of marine hydrobionts on blood formation at acute radiation sickness. Izvestiya TINRO. 2004;139:418–425. (In Russian).

42. Besednova NN, Ivanushko LA, Zvyagintseva TN, Yelyakova LA. [Immunotropic properties of 1,3;1-6-β-D-glucans.] Antibiotiki i Khimioterapiya. 2000;45(2):37–44. (In Russian).

43. Kuznetsova TA, Besednova NN, Usov VV, Andryukov BG. Biocompatible and biodegradable wound dressings on the basis of seaweed polysaccharides (review of literature). Vestnik Khirurgii im. I.I. Grekova. 2020;179(4):109–115. (In Russian). doi: 10.24884/0042-4625-2020-179-4-109-115

44. Kuznetsova TA, Besednova NN, Kovalev NN, et al. Experimental evaluation of the effectiveness of wound dressings based on biologically active substances from marine hydrobionts. Biologiya Morya. 2016;42(5):387–392. (In Russian).

45. Kuznetsova TA, Besednova NN, Zaporozhets TS, Kovalev NN, Usov VV, Zemlyanoi AB. Biologically active substances from marine hydrobionts with antibacterial activity in composition of new wound dressings. Antibiotiki i Khimioterapiya. 2016;61(3-4):14–18. (In Russian).

46. Kuznetsova TA, Besednova NN, Kovalev NN, et al. Method for preparing gel for wound and burn healing. Patent RU 2545893 issued on February 26, 2015. (In Russian). Accessed on March 17, 2021. https://patents.google.com/patent/RU2545893C1/ru