nbsprotВестник войск РХБ защитыJournal of NBC Protection Corps2587-57283034-279127 Научный центр10.35825/2587-5728-2019-3-1-23-39xohphsnbsprot-227Research ArticleБиологическая безопасность и защита от биологических угрозBiological Security and Protection against Biological ThreatsТоксические свойства тритерпеновых гликозидов голотурийToxic properties of holothurian’s triterpene glycosidesАмининД. Л.AmininD. L.

Аминин Дмитрий Львович. Заведующий лабораторией, старший научный сотрудник, д-р биол. наук 

Проспект 100-летия Владивостока, д. 159, г. Владивосток, 690022

Dmitry Lvovich Aminin. Head of the laboratory, Senior Researcher, Doctor of Biological Sciences

Prospect 100-let Vladivostoky, 159, Vladivostok 690022

daminin@piboc.dvo.ruКалининВ. И.KalininV. I.

Калинин Владимир Иванович. Ведущий научный сотрудник Тихоокеанского института биоорганической химии им Г.Б. Елякова ДВО РАН, д-р биол. наук

Проспект 100-летия Владивостока, д. 159, г. Владивосток, 690022

Vladimir Ivanovich Kalinin. Leading Researcher, Doctor of Biological Sciences 

Prospect 100-let Vladivostoky, 159, Vladivostok 690022

Тихоокеанский институт биоорганической химии им Г.Б. Елякова ДВО РАН (ТИБОХ ДВО РАН)РоссияG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of SciencesRussian Federation201910072023312339Copyright © Аминин Д.Л., Калинин В.И., 20232023Аминин Д.Л., Калинин В.И.Aminin D.L., Kalinin V.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nbsprot.ru/jour/article/view/227

Голотурии (или морские огурцы) – распространенные во всех районах мирового океана животные, относящиеся к типу иглокожих. Они продуцируют низкомолекулярные метаболиты – тритерпеновые гликозиды, являющиеся их средством химической защиты от морских хищников. Тритерпеновые гликозиды голотурий высокотоксичны. В экспериментах на различных типах клеток и клеточных линиях они проявляют гемолитическую, иммунотоксическую, цитотоксическую, эмбриотоксическую и нейротоксическую активности в диапазоне концентраций 1×10-4–1×10-6 М. По токсичности для экспериментальных животных при внутривенном или внутрибрюшинном введении некоторые из них сопоставимы с боевыми отравляющими веществами, например, с сернистым ипритом. В основе токсических свойств гликозидов лежит способность к взаимодействию с ∆5-стеринами (главным образом, с холестерином) плазматических мембран и формированию ион-проводящих комплексов. В свою очередь это ведет к изменению ионной проницаемости и избирательности биомембран, нарушению барьерных свойств, ионного гомеостаза и осмолярности клеток, а далее к лизису клеток и их гибели. Содержание тритерпеновых гликозидов в тканях голотурий может достигать значительного количества – до 1 г/кг. Особенно много таких соединений локализовано в кювьеровых трубочках – специальных органах защиты, которые имеются у большинства видов тропических голотурий. Для России тритерпеновые гликозиды голотурий представляют еще не оцененную должным образом биологическую опасность, так как голотурии являются промысловыми животными и широко используются как пищевые продукты, для приготовления лечебных добавок и лекарственных препаратов. Попадание токсичных тритерпеновых гликозидов на кожу и слизистые глаз способно вызвать местные поражения, проникновение в кровоток человека, может привести к лизису эритроцитов крови, подавлению его иммунитета к инфекционным агентам. Контроль качественного и количественного содержания гликозидов в пищевых и лечебных продуктах из голотурий и определение структур этих гликозидов должен быть составной частью мер по повышению биологической безопасности граждан Российской Федерации.

Holothurians (or sea cucumbers) are echinoderms and are found in all areas of the world oceans. These animals produce special low-molecular metabolites - triterpene glycosides, which are a means of chemical protection of holothurians from predators. The content of triterpene glycosides in the tissues of holothurians can reach a significant amount of up to 1 g/kg, and especially many of these compounds are localized in the Cuvierian tubules - special protection organ presents in a number of tropical holothurians. Tritirepene glycosides of holothurians are quite toxic, they exhibit hemolytic, cytotoxic and neurotoxic activity at a concentration range of 1×104–1×106 M. The toxic properties of glycosides are based on the ability of these compounds to interact with ∆5-sterols (mainly cholesterol) of plasma membranes and form ion-conducting complexes. In turn, this leads to a change in the ion permeability and selectivity of biomembranes, disruption of barrier properties, ion homeostasis and osmolarity of cells, and further to cell lysis and death.Contact with holoturias when diving in shallow water, which is fraught with damage to the eyes and mucous membranes by triterpene glycosides, may be of some danger to humans. Excessive consumption of commercial edible holothurians in food, especially without prior heat treatment, as is customary in some South-East Asia countries, can lead to diarrhea and dyspepsia. Triterpene glycosides in the bloodstream can lead to blood lysis and serious consequences up to death.The holothurians are animals commercially harvested in Russia. They are used in food and for the preparation of medicinal supplements and preparations. Excessive consumption of commercial edible holothurians for food, especially without long-term boiling, as is customary in Southeast Asia, can lead to diarrhea and dyspepsia. Triterpene glycosides in the bloodstream can lead to blood lysis and serious consequences up to death. The use of dietary supplements with an uncontrolled glycoside content is fraught with similar consequences, and the presence of immunosuppressants among glycosides that have fallen into such additives and drugs can worsen the condition of patients or sick animals. Control of the qualitative and quantitative content of glycosides in food and medicinal products from holothurians should be an integral part of measures to improve the biological safety of citizens of the Russian Federation.

гемолитическая активностьголотуриииммуномодулирующие свойствамембранотропные свойстванейротоксические свойстватоксические свойстватритерпеновые гликозидыцитотоксическая активностьhemolytic activityholothuriansimmunomodulatory propertiesmembranotropic propertiesneurotoxic propertiescytotoxic activityReferencesSmirnov A.V. System of the class Holothuroidea // Paleontol. J. 2012. V. 46, № 8. P. 793–832.Smirnov A.V. System of the class Holothuroidea // Paleontological Journal. 2012 V. 46, No. 8. P. 793–832.Miller A.K., Kerr A.M., Paulay G., et al. Molecular phylogeny of extant Holothuroidea (Echinodermata) // Mol. Phylogen. Evolut. 2017. V. 111. P. 110–131.Miller A.K., Kerr A.M., Paulay G. et al. Molecular phylogeny of extant Holothuroidea (Echinodermata) // Molecular Phylogenetics Evolution. 2017. V. 111. P. 110–131.Beirne L., Fitzmier K., Miller M. Holothuroidea // Biol. Div. 2001. On-line. March 20, 2017. http://www.earlham.edu/~beirnlu/seacucumber.htmBeirne L., Fitzmier K., Miller M. Holothuroidea //. Biological Diversity. 2001. On-line. March 20, 2017. http://www.earlham.edu/~beirnlu/seacucumber.htmBrusca R.C., Brusca G.J. Invertebrates. 2 ed. Sunderland, Massachusetts: Sinauer Associates Inc., 2003.Brusca R.C., Brusca G.J. Invertebrates (second edition). Sunderland, Massachusetts: Sinauer Associates Inc., 2003. 936 p.Kitagawa I., Kobayashi M., Okamoto Y., et al. Structures of sarasinosides A 1, B1, and C1 – new norlanostane triterpenoid oligoglycosides from the Palanan marine sponge Sateropus sarasinosum // Chem. Pharm. Bull. 1987. V. 35, № 12. P. 5036–5039.Kitagawa I., Kobayashi M., Okamoto Y. et al. Structures of sarasinosides A 1, B1, and C1 – new norlanostane triterpenoid oligoglycosides from the Palanan marine sponge Sateropus sarasinosum // Chem. Pharm. Bull. 1987. V. 35, No. 12. P. 5036–5039.Kobayashi M., Hori М., Каn К., et al. Marine natural products. XXVII. Distribution of lanostane – type triterpene oligoglycosides in 10 kinds of okinawan sea cucumbers // Chem. Pharm. Bull. 1991. V. 39, № 9. P. 2282–2287.Kobayashi M., Hori М., Каn К. et al. Marine natural products. XXVII. Distribution of lanostane – type triterpene oligoglycosides in 10 kinds of okinawan sea cucumbers // Chem. Pharm. Bull. 1991. V. 39, No. 9. P. 2282–2287.Стоник В.А. Морские полярные стероиды // Успехи химии. 2001. T. 70, № 8. C. 763–807.Stonik V.A. Marine polar steroids // The Success of Chemistry 2001. V. 70, No. 8. P. 763–807 (in Russian).Kalinin V.I., Ivanchina N.V., Krasokhin V.B., et al. Glycosides from marine sponges (Porifera, Demospongiae): structures, taxonomical distribution, biological activities and biological roles // Mar. Drugs. 2012. V. 10. P. 1671–1710.Kalinin V.I., Ivanchina N.V., Krasokhin V.B. et al. Glycosides from marine sponges (Porifera, Demospongiae): structures, taxonomical distribution, biological activities and biological roles // Mar. Drugs. 2012. V. 10. P. 1671–1710.Habermehl G., Volkwein G. Aglycones of the toxins from the cuvierian organs of Holothuria forskali and a new nomenclature for the aglycones from Holothurioidea // Toxicon. 1971. V. 9, № 4. P. 319–326.Habermehl G., Volkwein G. Aglycones of the toxins from the cuvierian organs of Holothuria forskali and a new nomenclature for the aglycones from Holothurioidea // Toxicon. 1971. V. 9. No. 4. P. 319–326.Авилов С.А., Калинин В.И., Калиновский А.И., Стоник В.А. Кукумариозид G2 – минорный тритерпеновый гликозид из голотурии Eupentacta fraudatrix // Химия природ. cоед. 1991. № 3. C. 438–439.Avilov S.A., Kalinin V.I., Kalinivsky A.I., Stonik V.A. Cucumarioside G 2 – minor triterpene glycoside from the sea cucumber Eupentacta fraudatrix // Chemistry of Natural Compounds 1991. No. 3. P. 438–439 (in Russian).Авилов С.А., Калиновский А.И., Стоник В.А. Два новых тритерпеновых гликозида из голотурии Duasmodactyla kurilensis // Химия природ. cоед. 1991. № 2. C. 221–226.Avilov S.A., Kalinovsky A.I., Stonik V.A. Two new triterpene glycosides from sea cucumber Duasmodactyla kurilensis // Chemistry of Natural Compounds. 1991. No. 2. P. 221–226 (in Russian).Silchenko A.S., Kalinovsky A.I., Avilov S.A., et al. Fallaxosides B 1 and D3, triterpene glycosides with novel skeleton types of aglycones from the sea cucumber Cucumaria fallax // Tetrahedron. 2017. V. 73. P. 2335–2341.Silchenko A.S., Kalinovsky A.I., Avilov S.A. et al. Fallaxosides B 1 and D3, triterpene glycosides with novel skeleton types of aglycones from the sea cucumber Cucumaria fallax // Tetrahedron. 2017. V. 73. P. 2335–2341.Калинин В.И., Левин В.С., Стоник В.А. Химическая морфология: тритерпеновые гликозиды голотурий (Holothurioidea, Echinodermata). Владивосток: Дальнаука, 1994.Kalinin V.I., Levin V.S., Stonik V.A. Chemical morphology: triterpene glycosides of sea cucumbers (Holothurioidea, Echinodermata). Vladivostok: Dalnauka, 1994. 284 p. (in Russian).Карлина А.Е. Безотходная технология пищевых продуктов и биологически активных добавок из кукумарий дальневосточных морей. Автореф. дис. … канд. техн. наук. Владивосток, 2009.Karlina A.E. Wast free technology of food and food supplements from cucumarias of the Far Eastern seas. Summary of the dissertation for obtaining of the research degree of candidate of technical sciences. Vladivostok, 2009. 24 p. (in Russian).Matsuno T., Sakushika A., Takashi I. Seasonal variations of saponin and its distribution in the body of seacucumber Stichopus japonicus // Bull. Jpn. Soc. Sci. Fisher. 1973. V. 39, № 3. P. 307–310.Matsuno T., Sakushika A., Takashi I. Seasonal variations of saponin and its distribution in the body of seacucumber Stichopus japonicus // Bull. Jpn. Soc. Sci. Fisher. 1973. V. 39, № 3. P. 307–310.Аминин Д.Л., Анисимов М.М. Содержание голотоксинов в тканях голотурии Stichopus japonicus S. в разные сезоны года и их влияние на созревание ооцитов // Журн. эвол. биохим. физиол. 1987. Т. 23, № 4. С. 545–547.Aminin D.L., Anisimov M.M. Contents of holotoxins in tissues of the sea cucumber Stichopus japonicus S. in different year season and their influence on oocytes maturation // Journal of Evol. Biochem. Physiol. 1987. V. 23, No. 4. P. 545–547. (in Russian).Mitu S.A., Bose U., Suwansa-ard S., et al. Evidence for a saponin biosynthesis pathway in the body wall of the commercially significant sea cucumber Holothuria scabra // Marine Drugs. 2017. V. 15, № 11. P. 349.Mitu S.A., Bose U., Suwansa-ard S. et al. Evidence for a saponin biosynthesis pathway in the body wall of the commercially significant sea cucumber Holothuria scabra // Mar. Drugs. 2017. V. 15. 349. P. 1–13.Kalinin V.I., Aminin D.L., Avilov S.A., et al. Triterpene glycosides from sea cucucmbers (Holothurioidae, Echinodermata), biological activities and functions // Studies in Natural Product Chemistry (Bioactive Natural Products) / Ed. Atta-ur-Rahman. Amsterdam: Elsevier Sci. Publ., 2008. V. 35. Chap. 4. P. 135–196.Kalinin V.I., Aminin D.L., Avilov S.A., et al. Triterpene glycosides from sea cucucmbers (Holothurioidae, Echinodermata), biological activities and functions // Studies in Natural Product Chemistry (Bioactive Natural Products) / Ed. Atta-ur-Rahman. Amsterdam: Elsevier Sci. Publ., 2008. V. 35. Chap. 4. P. 135–196.Frey D.G. The use of sea cucumbers in poisoning fishes // Copeia. 1951. P. 175–176.Frey D.G. The use of sea cucumbers in poisoning fishes // Copeia. 1951. P. 175–176.Van Dyck S., Gerbaux P., Flammang P. Qualitative and quantitative saponin contents in five sea cucumbers from the Indian Ocean // Marine Drugs. 2010. V. 8. P. 173–189.Van Dyck S., Gerbaux P., Flammang P. Qualitative and quantitative saponin contents in five sea cucumbers from the Indian Ocean // Mar. Drugs. 2010. V. 8. P. 173–189.Жизнь животных. Т. 2. Беспозвоночные / Под ред. Зенкевича Л.А. М.: Просвещение, 1971. С. 239.Zenkevich L.A. (ed.) Animal life. V. 2. Invertebrates. Moscow: Education, 1971. P. 239. (in Russian).Van Dyck S., Caulier G., Todesco M., et al. The triterpene glycosides of Holothuria forskali: usefulness and efficiency as a chemical defense mechanism against predatory fish // J. Exp. Biol. 2011. V. 214, № 8. P. 1347–1356.Van Dyck S., Caulier G., Todesco M. et al. The triterpene glycosides of Holothuria forskali: Usefulness and efficiency as a chemical defense mechanism against predatory fish // J. Exp. Biol. 2011. V. 214, No. 8. P. 1347–1356.Nigrelli R.F. The effects of holothurin on fish and mice with sarcoma 180 // Zoologica (New York). 1952. V. 37. P. 89–90.Nigrelli R.F. The effects of holothurin on fish and mice with sarcoma 180 // Zoologica (New York). 1952. V. 37. P. 89–90.Yamanouchi T. On the poisonous substance contained in holothurians // Publ. Seto Mar. Biol. Lab. 1955. V. 4, № 2–3. P. 183–203.Yamanouchi T. On the poisonous substance contained in holothurians // Publ. Seto Mar. Biol. Lab. 1955. V. 4, No. 2–3. P. 183–203.Nigrelli R.F., Jakowska S. Effects of holothurin, a steroid saponin from the Bahamian Sea cucumber (Actinopyga agassizi), on various biological systems // Ann. N.Y. Acad. Sci. 1960. V. 90. P. 884–892.Nigrelli R.F., Jakowska S. Effects of holothurin, a steroid saponin from the Bahamian sea cucumber (Actinopyga agassizi), on various biological systems // Ann. N.Y. Acad. Sci. V. 90. P. 884–892.Friess S.L., Standaert F.G., Whitcomb E.R., et al. Some pharmacologic properties of holothurin, an active neurotoxin from the sea cucumber // Pharmacol. Exp. Therap. 1959. V. 126. P. 323–329.Friess S.L., Standaert F.G., Whitcomb E.R. et al. Some pharmacologic properties of holothurin, an active neurotoxin from the sea cucumber // Pharmacol. Exp. Therap. 1959. V. 126. P. 323–329.Поликарпова С.И., Волкова О.Н., Седов A.M. и др. Цитогенетическое изучение мутагенности кукумариозида // Генетика. 1990. Т. 26, № 9. С. 1682–1684.Polikarpova S.I., Volkova O.N., Sedov A.M. et al. Cytogenetic investigation of mutagenesity of cucumarioside // Genetika. 1990. V 26, No. 9. P. 1682–1684 (in Russian).Thron C.D. Hemolysis by holothurin A, digitonin and quiiaia saponin: estimates of the requared cellular lysin uptakes and free lysin concentrations // J. Pharm. Exp. Therap. 1964. V. 145, № 2. P. 194–202.Thron C.D. Hemolysis by holothurin A, digitonin and quiiaia saponin: estimates of the requared cellular lysin uptakes and free lysin concentrations // J. Pharm. Exp. Therap. 1964. V. 145, No. 2. P. 194–202.Jakowska S., Nigrelli R.F., Murray P.M., Veltry A.M. Hemopoetic effect of holothurin, steroid saponin from sea cucumber Actinopyga agassizi on Rana pipiens // Anat. Rec. 1958. V. 132. P. 459.Jakowska S., Nigrelli R.F., Murray P.M., Veltry A.M. Hemopoetic effect of holothurin, steroid saponin from sea cucumber Actinopyga agassizi on Rana pipiens // Anat. Rec. 1958. V. 132. P. 459.Poscidio G.N. The mutagenicity potential of holothurin of some Philippine holothurians // Philipp. J. Sci. 1983. V. 112. P. 1–12.Poscidio G.N. The mutagenicity potential of holothurin of some Philippine holothurians // Philipp. J. Sci. 1983. V. 112. P. 1–12.Kalinin V.I., Volkova O.V., Likhatskaya G.N., et al. Hemolytic activity of triterpene glucosides from the Cucumariidae family holothurians and evolution of this group of toxins // J. Nat. Toxins. 1992. V. 1, № 2. P. 17–30.Kalinin V.I., Volkova O.V., Likhatskaya G.N. et al. Hemolytic activity of triterpene glucosides from the Cucumariidae family holothurians and evolution of this group of toxins // J. Nat. Toxins. 1992. V. 1, No. 2. P. 17–30.Kalinin V.I., Prokofieva N.G., Likhatskaya G.N., et al. Hemolytic activities of triterpene glycosides from the holothurian order Dendrochirotida: Some trends in the evolution of this group of toxins // Toxicon. 1996. V. 34, № 4. P. 475–483.Kalinin V.I., Prokofieva N.G., Likhatskaya G.N. et al. Hemolytic activities of triterpene glycosides from the holothurian order Dendrochirotida: Some trends in the evolution of this group of toxins // Toxicon. 1996. V. 34. No. 4. P. 475–483.Aminin D.L., Pislyagin E.A., Menchinskaya E.S., et al. Immunomodulatory and anticancer activity of sea cucumber triterpene glycosides // Studies in Natural Product Chemistry (Bioactive Natural Products) / Ed. Atta-urRahman. Amsterdam: Elsevier Sci. Publ., 2014. V. 41. Chap. 3. P. 75–94.Aminin D.L., Pislyagin E.A., Menchinskaya E.S. et al. Immunomodulatory and anticancer activity of sea cucumber triterpene glycosides // Studies in Natural Product Chemistry (Bioactive Natural Products) / Ed. Atta-urRahman. Amsterdam: Elsevier Sci. Publ., 2014. V. 41. Chap. 3. P. 75–94.Aminin D.L., Menchinskaya E.S., Pisliagin E.A., et al. Anticancer activity of sea cucumber triterpene glycosides // Marine Drugs. 2015. V. 13. P. 1202–1223.Aminin D.L., Menchinskaya E.S., Pisliagin E.A. et al. Anticancer activity of sea cucumber triterpene glycosides // Marine Drugs. 2015. V. 13. P. 1202–1223.Aminin D.L., Menchinskaya E.S., Pislyagin E.A., et al. Sea cucumber triterpene glycosides as anticancer agents // Studies in Natural Product Chemistry (Bioactive Natural Products) / Ed. Atta-ur-Rahman. Amsterdam: Elsevier Sci. Publ., 2016. V. 49. Chap. 2. P. 55–105.Aminin D.L., Menchinskaya E.S., Pislyagin E.A. et al. Sea cucumber triterpene glycosides as anticancer agents // Studies in Natural Product Chemistry (Bioactive Natural Products) / Ed. Atta-ur-Rahman. Amsterdam: Elsevier Sci. Publ., 2016. V. 49. Chap. 2. P. 55–105.Friess S.L., Duran R.C., Chanley J.D., Mezzetti T. Some structural requirements underlying holothurin A interactions with synaptic chemoreceptors // Biochem. Pharmacol. 1965. V. 14. P. 1237–1247.Friess S.L., Duran R.C., Chanley J.D., Mezzetti T. Some structural requirements underlying holothurin A interactions with synaptic chemoreceptors // Biochem. Pharmacol. 1965. V. 14. P. 1237–1247.Friess S.L., Durant R.C., Chanley J.D., Fash F.J. Role of the sulphate charge center in irreversible interactions of holothurin A with chemoreceptors // Biochem. Pharmacol. 1967. V. 16. P. 1617–1625.Friess S.L., Durant R.C., Chanley J.D., Fash F.J., Role of the sulphate charge center in irreversible interactions of holothurin A with chemoreceptors // Biochem. Pharmacol. 1967. V. 16. P. 1617–1625.Friess S.L., Durant R.C., Chanley J.D. Further studies on biological actions of steroidal saponins produced by poisonous echinoderms // Toxicon. 1968. V. 6. P. 81–84.Friess S.L., Durant R.C., Chanley J.D. Further studies on biological actions of steroidal saponins produced by poisonous echinoderms // Toxicon. 1968. V. 6. P. 81–84.Friess S.L., Chanley J.D., Hudak W.V., Weems H.B. Interaction of the Echinoderm toxin Holothurin A and its desulfated derivative with the cat superior cervical ganglion preparation // Toxicon. 1970. № 8. P. 211–219.Friess S.L., Chanley J.D., Hudak W.V., Weems H.B. Interaction of the Echinoderm toxin Holothurin A and its desulfated derivative with the cat superior cervical ganglion preparation // Toxicon. 1970. No. 8. P. 211–219.De Groof R.C., Narahashi T. The effects of holothurin A on the resting membrane potential and conductance of squid axon // Europ. J. Pharmacol. 1976. V. 36. P. 337–346.De Groof R.C., Narahashi T. The effects of holothurin A on the resting membrane potential and conductance of squid axon // Europ. J. Pharmacol. 1976. V. 36. P. 337–346.Dettbarn W.D., Higman H.B., Bartels E., Podleski T. Effects of marine toxins on electrical activity and K+ efflux of excitable membranes // Biochem. Biophys. Acta. 1965. V. 94. P. 472–478.Dettbarn W.D., Higman H.B., Bartels E., Podleski T. Effects of marine toxins on electrical activity and K+ efflux of excitable membranes // Biochem. Biophys. Acta. 1965. V. 94. P. 472–478.Ruggieri C.D., Nigrelli R.F. Physiologically active substances from Echinoderms // Bioactive compounds from the sea / Eds. Humm, H.J., Lane C.H. N.Y.: Dekker Inc., 1974. P. 183–195.Ruggieri C.D., Nigrelli R.F. Physiologically active substances from Echinoderms // Bioactive compounds from the sea / Eds. Humm, H.J., Lane C.H. N.-Y.: Dekker Inc., 1974. P. 183–195.Kaul P.N., Daffari P. Marine pharmacology: bioactive molecules from the sea // Ann. Rev. Pharmacol. Toxicol. 1986. V. 26. P. 117–142.Kaul P.N., Daffari P. Marine pharmacology: bioactive molecules from the sea // Ann. Rev. Pharmacol. Toxicol. 1986. V. 26. P. 117–142.Verbist J.E. Pharmacological effects of compounds from echinoderms // Echinoderm studies. V. 4 / Eds. Jangoux M., Lawrence J.M. Rotterdam: A.A. Balkema, 1993. P. 111–186.Verbist J.E. Pharmacological effects of compounds from echinoderms // Echinoderm studies. V. 4 / Eds. Jangoux M., Lawrence J.M. Rotterdam: A.A. Balkema, 1993. P. 111–186.Gorshkov B.A., Gorshkova I.A., Stonik V.A., Elyakov G.B. Effect of marine glycosides on adenosine triphospatase activity // Toxicon. 1982. V. 20, № 3. P. 655–658.Gorshkov B.A., Gorshkova I.A., Stonik V.A., Elyakov G.B. Effect of marine glycosides on adenosine triphospatase activity // Toxicon. 1982. V. 20, No. 3. P. 655–658.Gorshkova I.A., Gorshkov B.A., Stonik V.A. Inhibition of rat brain Na+-K+-ATPase by triterpene glycosides from holothurians // Toxicon. 1989. V. 27, № 8. P. 927–936.Gorshkova I.A., Gorshkov B.A., Stonik V.A. Inhibition of rat brain Na+-K+-ATPase by triterpene glycosides from holothurians // Toxicon. 1989. V. 27, No. 8. P. 927–936.Gorshkova I.A., Kalinovsky A.I., Ilyin S.G., et al. Physicochemical characteristics of interaction of toxic triterpene glycosides from holothurians with rat brain Na+- K+-ATPase // Toxicon. 1989. V. 27, № 8. P. 937–945.Gorshkova I.A., Kalinovsky A.I., Ilyin S.G. et al. Physicochemical characteristics of interaction of toxic triterpene glycosides from holothurians with rat brain Na+-K+-ATPase // Toxicon. 1989. V. 27, No. 8. P. 937–945.Gorshkova I.A., Kalinin V.I., Gorshkov B.A., Stonik V.A. 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. V. 122, № 1. P. 101–108.Gorshkova I.A., Kalinin V.I., Gorshkov B.A., Stonik V.A. 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. V. 122, No. 1. P. 101–108.Gorshkova I.A., Ilyin S.G., Stonik V.A. Physicochemical characteristics of interaction of saponins from holothurians (sea cucumber) with cell membranes // Saponin in food, feedstuffs and medicinal plants / Eds. Oleszek W., Marston A. Springer, Dordrecht : Kluwer Academic Publ., 2000. P. 219–225. https://doi.org/10.1007/978-94-015-9339-7.Gorshkova I.A., Ilyin S.G., Stonik V.A. Physicochemical characteristics of interaction of saponins from holothurians (sea cucumber) with cell membranes // Saponin in food, feedstuffs and medicinal plants / Eds.Oleszek W., Marston A. Kluwer Academic Publ., 2000. P. 219–225.Kitagawa I., Kobayashi M., Inamoto T., et al. Marine natural products. XIV. Structures of echinosides A and B, antifungal lanostane-oligosides from the sea cucumber Actinopyga echinites (Jaeger) // Chem. Pharm. Bull. 1985. V. 33, № 12. P. 5214–5224.Kitagawa I., Kobayashi M., Inamoto T. et al. Marine natural products. XIV. Structures of echinosides A and B, antifungal lanostane-oligosides from the sea cucumber Actinopyga echinites (Jaeger) // Chem. Pharm. Bull. 1985. V. 33, No. 12. P. 5214–5224.Рубцов Б.В., Ружницкий А.О., Клебанов Г.И., и др. Влияние некоторых тритерпеновых гликозидов морских беспозвоночных на проницаемость биологических и искусственных мембран // Изв. АН СССР. Сер. Биол. 1980. № 3. C. 436–445.Rubtsov V.B., Ruzhnitsky A.O., Klebanov G.I. et al. Influence of some triterpene glycosides of marine invertebrates on permeability of biological and artificial membranes // Izv. AN SSSR. Ser. Biol. 1980. No. 3. P. 436–445.Kuznetsova T.A., Anisimov M.M., Popov A.M., et al. Comparative study in vitro of physiological activity of triterpene glycosides of marine invertebrates of Echinoderm type // Comp. Biochem. Physiol. 1982. V. 73. P. 41–43.Kuznetsova T.A., Anisimov M.M., Popov A.M. et al. Comparative study in vitro of physiological activity of triterpene glycosides of marine invertebrates of Echinoderm type // Comp. Biochem. Physiol. 1982. V. 73. P. 41–43.Мальцев И.И., Стехова С.И., Шенцова Е.Б. и др. Противомикробная активность гликозидов из голотурий семейства Stichopodidae // Хим.-фарм. журн. 1985. № 1. C. 54–56.Maltsev I.I., Stekhova S.I., Shchentsova E.B., Anisimov M.M., Stonik V.A. Antimicrobial activity of glycosides from sea cucumebrs of the family Stichopodidae // Khim. Pharm. Zhurn. 1985. No. 1. P. 54–56 (in Russian).Olsen R.A. Triterpene glycosides as inhibitors of fungal growth and metabolism. Role of the sterol contents of some fungi // Physiol. Plant. 1973. V. 28. P. 507–515.Olsen R.A. Triterpene glycosides as inhibitors of fungal growth and metabolism. Role of the sterol contents of some fungi // Physiol. Plant. 1973. V. 28. P. 507–515.Olsen R.A. Triterpene glycosides as inhibitors of fungal growth and metabolism. The effect of aescin on fungi with reduced sterol contents // Physiol. Plant. 1973. V. 29 P. 145–149.Olsen R.A. Triterpene glycosides as inhibitors of fungal growth and metabolism. The effect of aescin on fungi with reduced sterol contents // Physiol. Plant. 1973. V. 29. P. 145–149.Попов А.М., Лоенко Ю.Н., Анисимов М.М. Изменение чувствительности опухолевых клеток к действию тритерпеновых гликозидов липосомами // Антибиотики. 1981. T. 26, № 3. C. 127–129.Popov A.M., Loenko Yu.N., Anisimov M.M. The change of sensibility of tumor cells againt the action of triterpene glycosides by liposoms // Antibiotiki. 1981. V. 26, No. 3. P. 127–129 (in Russian).Попов А.М., Калиновская Н.И., Кузнецова Т.А. и др. Роль стеринов в мембранотропной активности тритерпеновых гликозидов // Антибиотики. 1983. № 9. C. 656–659.Popov A.M., Kaliniovska N.I., Kuznetsova T.A. et al. Role of sterols in membranotropic activity of triterpene glycosides // Antibiotiki. 1983. No. 9. P. 656–659 (in Russian).Попов А.М. Изучение мембранотропной активности некоторых тритерпеновых гликозидов. Автореф. дис. ... канд. биол. наук. Владивосток, 1984.Popov A.M. The studies of membranotropic activities of some triterpene glycosides: sCand. Diss. Biol. Sci., Summary. Vladivostok, 1984. 24 p. (in Russian).Лихацкая Г.Н., Яровая Т.П., Руднев В.С. и др. Образование комплекса тритерпенового гликозида голотурина А с холестерином в липосомальных мембранах // Биофизика. 1985. T. 30, № 2. C. 358–359.Likhatska G.N., Jarovaya T.P., Rudnev V.S. et al. Formation of the complex of triterpene glycoside holothurine A with cholesterol in liposomal membranes // Biofizika. 1985. V. 30, No. 2. P. 358–359 (in Russian).Лихацкая Г.Н. Тритерпеновые и стероидные гликозиды и мембраны. Молекулярные механизмы взаимодействия гликозидов с мембранами. Saarbrucken: LAP LAMBERT Academic Publ. GmbH & Co. KG, 2011.Likhatska G.N. Triterpene and steroid glycosides and membranes. Molecilar mechanisms of interaction of glycosides with membranes. Saarbrucken: LAP LAMBERT Academic Publ. KG, 2011. 115 p.Лихацкая Г.Н. Механизмы взаимодействия тритерпеновых и стероидных гликозидов с липидными мембранами. Автореф. дис. канд. физ-мат. наук. Владивосток, 2006.Likhatska G.N. Mekhanisms of interaction of triterpene and steroid glycosides with lipid membranes. Cand. Diss. Phys.- Math. Sci., Summary. Vladivostok, 2006. 23 p. (in Russian).Анисимов М.М. Тритерпеновые гликозиды и структурно-функциональные свойства мембран // Биол. науки. 1987. № 10. С. 49–63.Anisimov M.M. Triterpene glycosides and structural-functional properties of membranes // Biol. Nauki. 1987. No. 10. P. 49–63.Анисимов М.М., Аминин Д.Л., Ровин Ю.Г. и др. Об устойчивости клеток голотурии Stichopus japonicus к действию эндотоксина – стихопозида А // Докл. АН СССР. 1983. T. 270, № 4. C. 991–993.Anisimov M.M., Aminin D.L., Rovin Yu.G. et al. On resistibility of cells of the sea cucumber Stichopus japonicus against action of endotoxin – stichoposide А // Dokl. AN SSSR. 1983. V. 270, No. 4. P. 991–993 (in Russian).Аминин Д.Л., Анисимов М.М., Мокрецова Н.Д. и др. Влияние тритерпеновых и стероидных гликозидов на овоциты, яйца и эмбрионы голотурии Stichopus japonicus и морского ежа Strongylocentrorus nudus // Биол. моря. 1986. № 3. C. 49–52.Aminin D.L., Anisimov M.M., Mokretsova N.D. et al. Influence of triterpene and steroid glycosides on ovocites, eggs and embryous of the sea cucumber Stichopus japonicus and sea urchin trongylocentrorus nudus // Biol. Morya. 1986. No. 3. P. 49–52 (in Russian).Claereboudt E.J.S., Eeckhaut I., Lins L., Deleu M. How different sterols contribute to saponin tolerant plasma membranes in sea cucumbers // Scientific Reports. 2018. V. 8. 10845. P. 1–11.Claereboudt E.J.S., Eeckhaut I., Lins L., Deleu M. How different sterols contribute to saponin tolerant plasma membranes in sea cucumbers // Scientific Reports. 2018. V. 8. 10845. P. 1–11.Aminin D.L. Immunomodulatory properties of sea cucumber triterpene glycosides // Marine and Freshwater Toxins. Toxinology / Eds. Gopalakrishnakone P., Haddad Jr. V., Tubaro A., et al. Springer: Amsterdam. Netherlands, 2016. Chap. 19. P. 381–401.Aminin D.L. Immunomodulatory properties of sea cucumber triterpene glycosides // Marine and Freshwater Toxins. Toxinology / Eds. Gopalakrishnakone P., Haddad Jr. V., Tubaro A. et al. Springer: Amsterdam. Netherlands, 2016. Chap. 19. P. 381–401.Aminin D., Pislyagin E., Astashev M., et al. Glycosides from edible sea cucumbers stimulate macrophages via purinergic receptors // Sci. Rep. 2016. V. 6. 39683. P. 1–11.Aminin D., Pislyagin E., Astashev M. et al. Glycosides from edible sea cucumbers stimulate macrophages via purinergic receptors // Sci. Rep. 2016. V. 6. 39683. P. 1–11.Aminin D.L., Agafonova I.G., Berdyshev E.V., et al. Immunomodulatory properties of cucumariosides from the edible Far-Eastern holothurian Cucumaria japonica // J. Med. Food. 2001. V. 4, № 3. P. 127–135.Aminin D.L., Agafonova I.G., Berdyshev E.V. et al. Immunomodulatory properties of cucumariosides from the edible Far-Eastern holothurian Cucumaria japonica // J. Med. Food. 2001. V. 4, No. 3. P. 127–135.Aminin D.L., Agafonova I.G., Kalinin V.I. et al. Immunomodulatory properties of frondoside A, a major triterpene glycoside from the North Atlantic commercially harvested sea cucumber Cucumaria frondosa // J. Med. Food. 2008. V. 11, № 3. P. 443–453.Aminin D.L., Agafonova I.G., Kalinin V.I. et al. Immunomodulatory properties of frondoside A, a major triterpene glycoside from the North Atlantic commercially harvested sea cucumber Cucumaria frondosa // J. Med. Food. 2008. V. 11, No. 3. P. 443–453.Pislyagin E.A., Gladkikh R.V., Kapustina I.I. et al. Interaction of holothurian triterpene glycoside with biomembranes of mouse immune cells // Int. Immunopharmacol. 2012. V. 14. P. 1–8.Pislyagin E.A., Gladkikh R.V., Kapustina I.I. et al. Interaction of holothurian triterpene glycoside with biomembranes of mouse immune cells // Int. Immunopharmacol. 2012. V. 14. P. 1–8.

The authors declare that there are no conflicts of interest present.