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Immunomodulatory Properties of Sea Cucumber Triterpene Glycosides

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Book cover Marine and Freshwater Toxins

Part of the book series: Toxinology ((TOXI))

Abstract

Sea cucumbers (or holothurians) belonging to the class Holothuroidea (Echinodermata) are marine invertebrate habitually found in the benthic areas and deep seas across the world. Many holothurians are known to be toxic. Triterpene glycosides are the main poison compounds of the sea cucumbers and play a role in the defense of holothuroids as a toxin. The triterpene glycosides are composed of a carbohydrate chain and triterpene aglycone and are widely distributed in sea cucumbers. Most aglycones have 18(20)-lactones and belong to the holostane type. Carbohydrate chains of sea cucumber glycosides have from two to six monosaccharide residues including xylose, quinovose, glucose and 3-O-methylglucose and sometimes 3-O-methylxylose, 3-О-methylquinovose, 3-О-methylglucuronic acid and 6-О-acetylglucose. They may contain one, two or three sulfate groups. At the micromolar concentrations sea cucumber glycosides show hemolytic, cytotoxic, antifungal and other biological activities caused by membranotropic action. Some sea cucumber glycosides show an immunostimulatory effect at sub-toxic nanomolar concentrations. Incubation of immune cells with the glycosides induces their activation resulting in an increase of immune cell adhesion on an extracellular matrix, enhancement of cell spreading and motility, increase of macrophage lysosomal activity, ROS formation and phagocytic activity. Injection of sub-toxic doses of some glycosides induces an increase in the number of antibody-producing plaque-forming cells in mouse spleens, an increase in the number, size and acidity of lysosomes of peritoneal macrophages, an increase of phagocytic index. It was shown that glycosides moderately induce production of some cytokines, restore the level of some CD-markers of lymphocytes, increase bactericidal activity of leucocytes and induce a significant increase in mouse resistance to lethal doses of some pathogenic microorganisms and radiation. A novel nanoparticulate antigen delivery system, tubular immunostimulating complex, consisting of cholesterol, triterpene glycoside cucumarioside A2-2, and glycolipid monogalactosyldiacylglycerol from marine macrophytes was developed. This complex influences cytokine mechanisms of immunological regulation and its adjuvant effect varied depending on its composition. Proteomic methods have demonstrated that the mechanism of immunomodulatory action of some sea cucumber glycosides on immune cells includes regulation of the expression of certain proteins involved in formation of the immune response. These glycosides regulate the expression of proteins associated with lysosome maturation, activation and merging, phagocytosis, cytoskeletal reorganization, cell adhesion, motility and proliferation of immune cells. It was found that the most likely membrane targets of cucumarioside A2-2 can be purinergic receptors of P2X family. These findings suggest that this glycoside can act as an allosteric regulator which able to withdraw purine receptor inactivation by extracellular ATP and provide a recovery of Ca2+ conductivity of macrophage membrane.

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References

  • Agafonova IG, Aminin DL, Avilov SA, Stonik VA. Influence of cucumariosides upon intracellular [Ca2+]i and lysosomal activity of macrophages. J Agric Food Chem. 2003;51:6982–6.

    Article  CAS  PubMed  Google Scholar 

  • Aminin DL, Osipov AN, Korepanova EA, Anisimov MM. Effect of holotoxin A1 on microviscosity of model and biological membranes. Biophyzika. 1989;34:318–19.

    CAS  Google Scholar 

  • Aminin DL, Agafonova IG, Berdyshev EV, Isachenko EG, Avilov SA, Stonik VA. Immunomodulatory properties of cucumariosides from the edible Far-Eastern holothurian Cucumaria japonica. J Med Food. 2001;4(3):127–35.

    Article  CAS  PubMed  Google Scholar 

  • Aminin DL, Pinegin BV, Pichugina LV, Zaporozhets TS, Agafonova IG, Boguslavsky VM, Silchenko AS, Avilov SA, Stonik VA. Immunomodulatory properties of cumaside. Int Immunopharm. 2006;6(7):1070–82.

    Article  CAS  Google Scholar 

  • Aminin DL, Agafonova IG, Kalinin VI, Silchenko AS, Avilov SA, Stonik VA, Woodward C, Collin P. Immunomodulatory properties of frondoside A, a major triterpene glycoside from the North Atlantic commercially harvested sea cucumber Cucumaria frondosa. J Med Food. 2008a;11(3):443–53.

    Article  CAS  PubMed  Google Scholar 

  • Aminin DL, Shevchenko VP, Nagaev IY, Gladkikh RV, Kapustina II, Likhatskaya GN, Avilov SA, Stonik VA. The use of tritium-labeled triterpene glycosides from the Holothurian Cucumaria japonica in pharmacokinetic studies. Dokl Biol Sci. 2008b;422:345–7.

    Article  CAS  PubMed  Google Scholar 

  • Aminin DL, Koy C, Dmitrenok PS, Müller-Hilke B, Koczan D, Arbogast B, Silchenko AS, Kalinin VI, Avilov SA, Stonik VA, Collin PD, Thiersen HJ, Deinzer ML, Glocker MO. Immunomodulatory effects of Holothurian triterpene glycosides on mammalian splenocytes determined by mass spectrometric proteome analysis. J Proteomics. 2009;72(5):886–906.

    Article  CAS  PubMed  Google Scholar 

  • Aminin DL, Silchenko AS, Avilov SA, Stepanov VG, Kalinin VI. Immunomodulatory action of monosulfated triterpene glycosides from the sea cucumber Cucumaria okhotensis Levin et Stepanov: stimulation of activity of mouse peritoneal macrophages. Nat Prod Commun. 2010a;5(12):1877–80.

    CAS  PubMed  Google Scholar 

  • Aminin DL, Chaykina EL, Agafonova IG, Avilov SA, Kalinin VI, Stonik VA. Antitumor activity of the immunomodulatory leads Cumaside. Int Immunopharmacol. 2010b;10:648–54.

    Article  CAS  PubMed  Google Scholar 

  • Aminin DL, Gorpenchenko TY, Bulgakov VP, Andryjashchenko PV, Avilov SA, Kalinin VI. Triterpene glycoside cucumarioside A2-2 from sea cucumber stimulates mouse immune cell adhesion, spreading and motility. J Med Food. 2011a;14(6):594–600.

    Article  CAS  PubMed  Google Scholar 

  • Aminin DL, Zaporozhets TS, Adryjashchenko PV, Avilov SA, Kalinin VI, Stonik VA. Radioprotective properties of Cumaside, a complex of triterpene glycosides from the sea cucumber Cucumaria japonica and cholesterol. Nat Prod Commun. 2011b;6(5):587–92.

    CAS  PubMed  Google Scholar 

  • Aminin DL, Pislyagin EA, Menchinskaya ES, Astashev ME, Sokolov PA, Yurchenko EA, Stonik VA. New anticancer and immunomodulatory compounds from sea cucumbers. Proceedings of the “2nd International workshop on marine bioresources of Vietnam”; 2013 June 5–6; Hanoi, Vietnam; 2013.

    Google Scholar 

  • Astashev ME, Pislyagin EA, Sokolov RA, Yurchenko EA, Aminin DL. Influence of cucumarioside A2-2 on dynamics of Ca2+ transport in immune cells. In: Zinchenko VP, Berezhnov AV, editors. Proceedings of International Conference “Receptors and intracellular signaling”; 2013 May 27–30; Puschino, Russia;2013.

    Google Scholar 

  • Bakus GJ. Defensive mechanisms and ecology of some tropical holothurians. Mar Biol. 1968;2:23–32.

    Article  Google Scholar 

  • Batrakov SG, Gurshovitch ES, Drozhzhyna NS. Triterpene glycosides with antifungal activity isolated from sea cucumber Cucumaria japonica. Antibiotik. 1980;6:408–11.

    Google Scholar 

  • Beirne L, Fitzmier K, Miller M. “Holothuroidea” (On-line). Biological diversity 2001. Accessed 2005 Jan 28; http://www.earlham.edu/~beirnlu/seacucumber.htm

  • Belousov MV, Novozheeva TP, Ahmedzhanov RR, Novitskaya LN, Yusubov MC, Aminin DL, Avilov SA, Stonik VA. Influence of preparation Cumaside on functional conditions of internal organs of rats. Bull Sib Med. 2008a;2:20–2.

    Google Scholar 

  • Belousov MV, Novozheeva TP, Ahmedzhanov RR, Novitskaya LN, Yusubov MC, Aminin DL, Avilov SA, Stonik VA. Influence of preparation Cumaside on functional conditions of internal organs of rats. (Pathomorphological investigation). Bull Sib Med. 2008b;3:9–12.

    Google Scholar 

  • Belousov MV, Novozheeva TP, Ahmedzhanov RR, Novitskaya LN, Yusubov MC, Aminin DL, Avilov SA, Stonik VA. Toxicological investigation of preparation Cumaside. Exp Klin Pharm. 2010;73(2):22–4.

    CAS  Google Scholar 

  • Bordbar S, Anwar F, Saari N. High-value components and bioactives from sea cucumbers for functional foods-a review. Mar Drugs. 2011;9:1761–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brusca RC, Brusca GJ. Invertebrates. 2nd ed. Sunderland: Sinauer Associates; 2003. p. 936.

    Google Scholar 

  • Cheeke PR. Actual and potential applications of Yucca schidigera and Quillaja saponaria saponins in human and animal nutrition. Proc Am Soc Animal Sci. 1999; 1:1–10.

    Google Scholar 

  • Descotes J, editor. Human toxicology. Amsterdam: Elsevier; 1996.

    Google Scholar 

  • Dyck SV, Gerbaux P, Flammang P. Qualitative and quantitative saponin contents in five sea cucumbers from the Indian Ocean. Mar Drugs. 2010;8:173–89.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dyck SV, Caulier G, Todesco M, Gerbaux P, Fournier I, Wisztorski M, Flammang P. The triterpene glycosides of Holothuria forskali: usefulness and efficiency as a chemical defense mechanism against predatory fish. J Exp Biol. 2011;214:1347–56.

    Article  PubMed  Google Scholar 

  • Fell SD. Wilderness: Sea cucumber irritation. In: Davis CP, editor. 2012; http://www.emedicinehealth.com/wilderness_sea_cucumber_irritation

  • Flammang P, Ribesse J, Jangoux M. Biomechanics of adhesion in sea cucumber Cuvierian tubules (Echinodermata, Holothuroidea). Integr Comp Biol. 2002;42(6):1107–15.

    Article  PubMed  Google Scholar 

  • Francis G, Kerem Z, Makkar HPS, Becker K. The biological action of saponins in animal systems: a review. Br J Nutr. 2002;88:587–605.

    Article  CAS  PubMed  Google Scholar 

  • Frey DG. The use of sea cucumber in poisoning fishes. Copeia. 1951;2:175–6.

    Article  Google Scholar 

  • Gorshkov BA, Gorshkova IA, Stonik VA, Elyakov GB. Effect of marine glycosides on adenosinetriphospatase activity. Toxicon. 1982;20(3):655–8.

    Article  CAS  PubMed  Google Scholar 

  • Gorshkova IA, Kalinovsky AI, Ilyin SG, Gorshkov BA, Stonik VA. Physicochemical characteristics of interaction of toxic triterpene glycosides from holothurians with rat brain Na+-K+-ATPase. Toxicon. 1989a;27(8):937–45.

    Article  CAS  PubMed  Google Scholar 

  • Gorshkova IA, Gorshkov BA, Stonik VA. Inhibition of rat brain Na+-K+-ATPase by triterpene glycosides from holothurians. Toxicon. 1989b;27(8):927–36.

    Article  CAS  PubMed  Google Scholar 

  • Gorshkova IA, Kalinin VI, Gorshkov BA, Stonik VA. Two different modes of inhibition of the rat brain Na+-K+-ATPase by triterpene glycosides, psolusosides A and B, from the holothurian Psolus fabricii. Comp Biochem Physiol. 1999;122(1):C101–8.

    Google Scholar 

  • Gorshkova IA, Ilyin SG, Stonik VA. Physicochemical characteristics of interaction of saponins from holothurians (sea cucumber) with cell membranes. In: Oleszek W, Marston A, editors. Saponin in food, feedstuffs and medicinal plants. Springer Netherlands; 2000.

    Google Scholar 

  • Grishin YI, Besednova NN, Stonik VA, Kovalevskaya AM, Avilov SA. Regulation of hemopoiesis and immunogenesis by holothurian triterpene glycosides. Radiobiologija. 1990;30:556.

    Google Scholar 

  • Grishin YI, Kovalevskaya AM, Stonik VA, Avilov SA, Vlaznev VP, Slugin VS. Immunostimulators for animal breeding, KM and KM-2. Nov Zverovod. 1991;2:19–23.

    Google Scholar 

  • Grishin YI, Kovalevskaya AM, Stonik VA, Avilov SA, Vlaznev VP, Slugin VS. Means for prophylaxis and cure of Aleutian illness of minks. Patent of Russian Federation No. 2036654. 1995.

    Google Scholar 

  • Holliman J. Toxic seafood ingestions. 2012; http://open.umich.edu/sites/default/files/2012-gemc-resident-holliman-toxic_seafoods_ifem-oer-edited.pdf

  • Ishida H, Hirota Y, Nakazava H. Effect of sub-skinning concentration of saponin on intracellular Ca2+ and plasma membrane fluidity in cultured cardiac cells. Biochim Biophys Acta. 1993;1145:58–62.

    Article  CAS  PubMed  Google Scholar 

  • Kalinin VI, Aminin DL, Avilov SA, Silchenko AS, Stonik VA. In: Atta-ur-Rahman, editor. Studies in natural product chemistry (bioactive natural products). Amsterdam: Elsevier; 2008.

    Google Scholar 

  • Kim SK, Himaya SW. Triterpene glycosides from sea cucumbers and their biological activities. Adv Food Nutr Res. 2012;65:297–319.

    Article  PubMed  Google Scholar 

  • Kostetsky EY, Sanina NM, Mazeika AN, Tsybulsky AV, Vorobieva NS, Shnyrov VL. Tubular immunostimulating complex based on cucumarioside A2-2 and monogalactosyldiacylglycerol from marine macrophytes. J Nanobiotechnol. 2011;9(35):1–9.

    Google Scholar 

  • Kropp RK. Responses of five holothurian species to attacks by a predatory gastropod, Tonna perdix. Pac Sci. 1982;36(4):445–52.

    Google Scholar 

  • Lasley BJ, Nigrelli RF. The effects of crude holothurin on leucocyte phagocytosis. Toxicon. 1970;8:301–6.

    Article  CAS  PubMed  Google Scholar 

  • Maier MS, Roccatagliata AJ, Kurriss A, Chludil H, Seldes AM. Two new cytotoxic and virucidal trisulfated glycosides from the Antharctic sea cucumber Staurocucumis liouvillei. J Nat Prod. 2001;64:732–6.

    Article  CAS  PubMed  Google Scholar 

  • Nigrelli RF. The Effects of holothurin on fish and mice with sarcoma 180. Zoologica (New York). 1952;37:89–90.

    CAS  Google Scholar 

  • Nigrelli RF, Jakowska S. Effects of holothurin, a steroid saponin from the Bahamian sea cucumber (Actinopyga agassiri) on various biological system. Ann N Y Acad Sci. 1960;90:884–92.

    Article  CAS  PubMed  Google Scholar 

  • Osbourn A, Goss RJ, Field RA. The saponins – polar isoprenoids with important and diverse biological activities. Nat Prod Rep. 2011;28:1261–8.

    Article  CAS  PubMed  Google Scholar 

  • Pislyagin EA, Gladkikh RV, Kapustina II, Kim NY, Shevchenko VP, Nagaev IY, Avilov SA, Aminin DL. Interaction of holothurian triterpene glycoside with biomembranes of mouse immune cells. Int Immunopharmacol. 2012;14:1–8.

    Article  CAS  PubMed  Google Scholar 

  • Pislyagin EA, Dmitrenok PS, Gorpenchenko TY, Avilov SA, Silchenko AS, Aminin DL. Determination of cucumarioside A2-2 in mouse spleen by radiospectroscopy, MALDI-MS and MALDI-IMS. Eur J Pharm Sci. 2013;49:461–7.

    Article  CAS  PubMed  Google Scholar 

  • Podolak I, Galanty A, Sobolewska D. Saponins as cytotoxic agents: a review. Phytochem Rev. 2010;9:425–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Polycarpova SI, Volkova ON, Sedov AM, Stonik VA, Likhoded VG. Cytogenetic study of cucumarioside mutagenicity. Genetika. 1990;26:1682–4.

    Google Scholar 

  • Popov AM, Rovin YG, Anisimov MM, Likhatskaya GN, Strigina LI. Influence of triterpene glycosides on stability of bilayer lipid membranes included different sterols. Biophisika. 1982;26(5):827–31.

    Google Scholar 

  • Poverenniy AM. Probable causes of high radiosensitivity of hematopoiesis. Radiobiologia. 1990;30(4):538.

    Google Scholar 

  • Rajput ZI, Hu S, Xiao C, Arijo AG. Adjuvant effects of saponins on animal immune responses. J Zhejiang Univ Sci B. 2007;8(3):153–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodriguez J, Castro R, Riguera R. Holothurinosides: new antitumor non sulphated triterpene glycosides from the sea cucumber Holothuria forskali. Tetrahedron. 1991;47:4753–62.

    Article  CAS  Google Scholar 

  • Rubtsov BV, Ruzhitsky AO, Klebanov GI, Sedov AM, Vladimirov YuA. Influence of some triterpene glycosides of marine invertebrates on permeability of biological and artificial membranes. Izvestya AN SSSR, Ser Biol. 1980;3:402–7.

    Google Scholar 

  • Sanina NM, Kostetsky EY, Shnyrov VL, Tsybulsky AV, Novikova OD, Portniagina OY, Vorobieva NS, Mazeika AN, Bogdanov MV. The influence of monogalactosyldiacylglycerols from different marine macrophytes on immunogenicity and conformation of protein antigen of tubular immunostimulating complex. Biochimie. 2012;94:1048–56.

    Article  CAS  PubMed  Google Scholar 

  • Sedov AM, Elkina SI, Sergeev VV, Kalina NG, Sakandelidze OG, Batrakov SG, Girshovich ES. Ability of holothurian triterpene glycosides to stimulate antibacterial resistance in the model disease of mouse salmonellosis. J Microbiol Epidemiol Immunobiol. 1984a;5:55–8.

    Google Scholar 

  • Sedov AM, Shepeleva IB, Zakharova NS, Sakandelidze OG, Sergeev VV, Moshiashvili IY. Influence of cucumarioside (triterpene glycoside) from holothurian Cucumaria japonica upon development of mouse immune response to corpuscular vaccine application. J Microbiol Epidemiol Immunobiol. 1984b;9:100–4.

    Google Scholar 

  • Sedov AM, Apollonin AV, Sevastyanova EK, Alekseeva IA, Batrakov SG, Batrakov SG, Sakandelidze OG, Likhoded VG, Stonik VA, Avilov SA, Kupera VV. Holothurian triterpene glycoside stimulation of non-specific antibacterial resistance of mice to opportunistic gram-negative microorganisms. Antibiotiki Chimiother. 1990;35:23–6.

    CAS  Google Scholar 

  • Shimada S. Antifungal steroid glycoside from sea cucumbers. Science. 1969;163:1462–5.

    Article  CAS  PubMed  Google Scholar 

  • Silchenko AS, Kalinovsky AI, Avilov SA, Andryjaschenko PV, Dmitrenok PS, Menchinskaya ES, Aminin DL, Kalinin VI. Structure of cucumarioside I2 from the sea cucumber Eupentacta fraudatrix (Djakonov et Baranova) and cytotoxic and immunostimulatory activities of this saponin and relative compounds. Nat Prod Res 2013; 27(19):1776–83.

    Google Scholar 

  • Slugin VS. Aleutian illness of minks and methods of its elimination [PhD thesis]. Moscow; 1982, p. 343.

    Google Scholar 

  • Stonik VA, Aminin DL, Boguslavski VM, Avilov SA, Agafonova IG, Silchenko AS, Ponomarenko P, Prokofieva NG, Chaikina EL. Immunomostimulatory means Cumaside and pharmaceutical composition on its base. Patent of the Russian Federation No. 2271820. 2005.

    Google Scholar 

  • Sun H, Yang Z, Ye Y. Structure and biological activity of protopanaxatriol-type saponins from the roots of Panax notoginseng. Int Immunopharmacol. 2006;6:14–25.

    Article  CAS  PubMed  Google Scholar 

  • Turischev SN, Bolshakova GB, Sakandelidze OG. Influence of complexes of holothurian triterpene glycosides on liver regeneration. Izv Akad Nauk SSSR, Ser Biol. 1991;2:306–10.

    Google Scholar 

  • Williamson JA, Burnett JW, Fenner PJ, Rifkin JF, editors. Venomous and poisonous marine animals: a medical and biological handbook. Sydney: Surf Life Saving Queensland; 1996.

    Google Scholar 

  • Yamanouchi T. On the poisonous substance contained in holothurians. Publ Seto Marine Biol Lab. 1955;4:183–203.

    CAS  Google Scholar 

  • Zaki MA. Effects of the crude toxin of sea cucumbers holothuria atra on some hematological and biochemical parameters in rats. Egypt J Nat Toxins. 2005;2:71–86.

    Google Scholar 

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Acknowledgements

This work was supported by the Grant of RFBR No. 14-04-01822-а.

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Authors and Affiliations

  1. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Prospect 100 let Vladivostoky, 159, 690022, Vladivostok, Russia

    Dmitry Aminin

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  1. Dmitry Aminin
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Correspondence to Dmitry Aminin .

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Editors and Affiliations

  1. Dept of Anatomy, Natl Univ of Singapore, Singapore, Singapore

    P. Gopalakrishnakone

  2. Universidade Estadual Paulista, Botucatu, São Paulo, Brazil

    Vidal Haddad Jr.

  3. Department of Life Sciences, University of Trieste, Trieste, Italy

    Aurelia Tubaro

  4. College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea (Republic of)

    Euikyung Kim

  5. College of Medicine, University of Florida, Gainesville, Florida, USA

    William R. Kem

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Aminin, D. (2016). Immunomodulatory Properties of Sea Cucumber Triterpene Glycosides. In: Gopalakrishnakone, P., Haddad Jr., V., Tubaro, A., Kim, E., Kem, W. (eds) Marine and Freshwater Toxins. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6419-4_3

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