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Журнал микробиологии, эпидемиологии и иммунобиологии. 2019; : 56-64

Активность препаратов, содержащих эхинохром А, в отношении вируса простого герпеса 2-го типа in vitro и in vivo

Крылова Н. В., Ленёва И. А., Федореев С. А., Эбралидзе Л. К., Мищенко Н. П., Васильева Е. А., Фалынскова И. Н., Иунихина О. В., Лавров В. Ф., Свитич О. А.

https://doi.org/10.36233/0372-9311-2019-6-56-64

Аннотация

Целью работы было изучение активности эхинохрома А – нафтохиноидного пигмента из морских ежей и его композиции с антиоксидантами в отношении вируса простого герпеса 2-го типа (ВПГ-2) in vitro и in vivo.

Материалы и методы. Штамм ВПГ-2 (G ATCC VR-734) выращивали на культуре клеток Vero. Цитотоксическую и анти-ВПГ-2 активность препаратов оценивали in vitro по жизнеспособности клеток и подавлению цитопатогенного действия вируса с помощью МТТ-анализа. Эффективность препаратов у мышей с генитальным герпесом оценивали, учитывая изменения их массы тела, средней продолжительности жизни и показателей вирусной нагрузки.

Результаты и обсуждение. Композиция антиоксидантов: эхинохрома А, аскорбиновой кислоты и α-токоферола (5 : 5 :1) – демонстрировала более высокую противовирусную активность, чем один эхинохром А. Пероральное введение мышам композиции антиоксидантов предотвращало гибель 90% инфицированных ВПГ-2 животных и достоверно снижало вагинальную вирусную нагрузку. Противовирусная активность эхинохрома А и композиции антиоксидантов, вероятно, обусловлена как вирусингибирующей активностью препаратов, так и их антиоксидантными свойствами.

Заключение. Результаты исследования позволяют рассматривать эхинохром А и композицию антиоксидантов на его основе как перспективные лекарственные средства, обладающие противовирусными свойствами.

Список литературы

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15. Santana S., Sastre I., Recuero M., Bullido M.J., Aldudo J. Oxidative stress enhances neurodegeneration markers induced by herpes simplex virus type1 infection in human neuroblastoma cells. PLoS One. 2013; 8(10): e75842. Doi: https://doi.org/0.1371/journal.pone.0075842

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17. Boominathan S.P., Sarangan G., Srikakulapu S., Rajesh S., Duraipandian C., Srikanth P. Antiviral activity of bioassay guided fractionation of Plumbago Zeylanica roots against Herpes simplex virus type 2. WJPPS. 2014; 3(12): 1003-17.

18. Roa-Linares V.C., Miranda-Brand Y., Tangarife-Castaño V., Ochoa R., García P.A., Castro M.Á., et al. Anti-Herpetic, Anti-Dengue and Antineoplastic Activities of Simple and Heterocycle-Fused Derivatives of Terpenyl-1,4-Naphthoquinone and 1,4-Anthraquinone. Molecules. 2019; 24(7). Doi: https://doi.org/10.3390/molecules24071279

Journal of microbiology, epidemiology and immunobiology. 2019; : 56-64

Activity of compounds containing echinochrome A against herpes simplex virus type 2 in vitro and in vivo

Krylova N. V., Leneva I. A., Fedoreev S. A., Ebralidze L. K., Mishchenko N. P., Vasileva E. V., Falynskova I. N., Iunikhina O. V., Lavrov V. F., Svitich O. A.

https://doi.org/10.36233/0372-9311-2019-6-56-64

Abstract

The aim of the work was to study the activity of echinochrome A, a naphthoquinoid pigment from sea urchins, and its antioxidant composition against herpes simplex virus type 2 (HSV-2) in vitro and in vivo.

Materials and methods. Strain HSV-2 (G ATCC VR-734) was grown in Vero cells. The cytotoxic and anti-HSV-2 activity of the compounds was assessed in vitro by the cell viability and by cytopathic effect inhibition of virus using MTT test. The efficacy of compounds in mice model of vaginitis caused by HSV-2 was determined by the average lifetime, body weight and viral load changes.

Results and discussion. The antioxidant composition (echinochrome A, ascorbic acid and α-tocopherol (5:5:1)), showed a higher antiviral efficacy than echinochrome A alone. Oral administration of the antioxidant composition protected 90% of the infected mice against death and reduced vaginal viral loads. The antiviral activity of echinochrome A and the antioxidant composition is probably due to the virus-inhibiting activity of the compounds and their antioxidant properties.

Conclusion. The results obtained allow considering the tested compounds as promising agents with antiviral properties.

References

1. WHO. Report on global sexually transmitted infection surveillance, 2018. Geneva; 2018.

2. Looker K.J., Magaret A.S., Turner K.M.E., Vickerman P., Gottlieb S.L., Newman L.M. Global Estimates of Prevalent and Incident Herpes Simplex Virus Type 2 Infections in 2012. PLoS One. 2015; 10(1): e114989. Doi: https://doi.org/10.1371/journal.pone.0114989

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5. Elyakov G.B., Maximov O.B., Mischenko N.P., Koltsova E.A., Fedoreev S.A., Glebko L.I., et al. Composition Comprising di-and Trisodium Salts of Echinochrome for Treating Ocular Conditions. European Patent № 1121929; 2004.

6. Elyakov G.B., Maximov O.B., Mischenko N.P., Koltsova E.A., Fedoreev S.A., Glebko L.I., et al. Drug preparation “Histochrome” for treating acute myocardial infarction and ischemic heart diseases. European Patent № 1121930; 2007.

7. Stonik V.A., Gusev E.I., Martynov M.Yu., Guseva M.R., Shchukin I.A., Agafonova I.G., et al. New medications for treatment of hemorrhagic stroke. High-resolution MRI in evaluation of histochrome in experimental hemorrhagic stroke. Dokl. Boil. Sci. 2005; 405: 421-3.

8. Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods. 1983; 65(1-2): 55-63. Doi: https://doi.org/10.1016/0022-1759(83)90303-4

9. Weislow O.S., Kiser R., Fine D.L., Bader J., Shoemaker R.H., Boyd M.R. New soluble-formazan assay for HIV-1 cytopathic effects: Application to high-flux screening of synthetic and natural products for AIDS-antiviral activity. J. Natl. Cancer Inst. 1989; 81(8): 577-86. Doi: https://doi.org/10.1093/jnci/81.8.577

10. Deryagina V.P., Ryzhova N.I., Il'nitskii A.P., Travkin A.G., Treshchalina E.M., Andronova N.V. Deistvie prirodnogo antioksidanta ekhinokhroma na rost podkozhno perevitoi adenokartsinomy Erlikha. Rossiiskii onkologicheskii zhurnal. 2003; (5): 32-6.

11. Kern E.R., Richards J.T., Glasgow L.A., Overall J.C. Jr, de Miranda P. Optimal treatment of herpes simplex virus encephalitis in mice with oral acyclovir. Am. J. Med. 1982; 73(1A): 125-31. Doi: https://doi.org/10.1016/0002-9343(82)90077-8

12. Prichard M.N., Kern E.R., Hartline C.B., Lanier E.R., Quenelle D.C. CMX001 Potentiates the Efficacy of Acyclovir in Herpes Simplex Virus Infections. Antimicrob. Agents Chemother. 2011; 55(10): 4728-34. Doi: https://doi.org/10.1128/AAC.00545-11

13. Reed L.J., Muench H. A simple method of estimating fifty percent’s endpoints. Am. J. Hyg. 1938; 27: 493-7.

14. Cymerys J., Chodkowski M., Słońska A., Krzyżowska M., Bańbura M.W. Disturbances of mitochondrial dynamics in cultured neurons infected with human herpesvirus type 1 and type 2. J. Neurovirol. 2019; June 3. Doi: https://doi.org/10.1007/s13365-019-00762-x

15. Santana S., Sastre I., Recuero M., Bullido M.J., Aldudo J. Oxidative stress enhances neurodegeneration markers induced by herpes simplex virus type1 infection in human neuroblastoma cells. PLoS One. 2013; 8(10): e75842. Doi: https://doi.org/0.1371/journal.pone.0075842

16. Fedoreyev S.A., Krylova N.V., Mishchenko N.P., Vasileva E.A., Pislyagin E.A., Iunikhina O.V., et al. Antiviral and antioxidant properties of echinochrome A. Mar. Drugs. 2018; 16(12). Doi: https://doi.org/10.3390/md16120509

17. Boominathan S.P., Sarangan G., Srikakulapu S., Rajesh S., Duraipandian C., Srikanth P. Antiviral activity of bioassay guided fractionation of Plumbago Zeylanica roots against Herpes simplex virus type 2. WJPPS. 2014; 3(12): 1003-17.

18. Roa-Linares V.C., Miranda-Brand Y., Tangarife-Castaño V., Ochoa R., García P.A., Castro M.Á., et al. Anti-Herpetic, Anti-Dengue and Antineoplastic Activities of Simple and Heterocycle-Fused Derivatives of Terpenyl-1,4-Naphthoquinone and 1,4-Anthraquinone. Molecules. 2019; 24(7). Doi: https://doi.org/10.3390/molecules24071279