Russian Journal of BiotherapyRussian Journal of BiotherapyРоссийский биотерапевтический журнал1726-97841726-9792Publishing House ABV Press119910.17650/1726-9784-2019-19-2-13-21REVIEWSОБЗОРЫ ЛИТЕРАТУРЫPHYTOADAPTOGENS IN THE TUMOURS BIOTHERAPY AND GERIATRICS (PART 1)ФИТОАДАПТОГЕНЫ В БИОТЕРАПИИ ОПУХОЛЕЙ И ГЕРИАТРИИ (ЧАСТЬ 1)https://orcid.org/0000-0002-6365-2888BocharovaO. A.БочароваО. А.
Russian Federation

24 Kashirskoye Shosse, Moscow 115478

Ольга Алексеевна Бочарова

115478 Москва, Каширское шоссе, 24

imufarm@rambler.ruhttps://orcid.org/0000-0003-4893-1472KarpovaR. V.КарповаР. В.
Russian Federation

24 Kashirskoye Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0003-2342-9881BocharovE. V.БочаровЕ. В.
Russian Federation

24 Kashirskoye Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

VershinskayaA. A.ВершинскаяА. А.
Russian Federation

24 Kashirskoye Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

BaryshnikovaM. A.БарышниковаМ. А.
Russian Federation

24 Kashirskoye Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

KazeevI. V.КазеевИ. В.
Russian Federation

24 Kashirskoye Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-5071-3581KucheryanuV. G.КучерянуВ. Г.
Russian Federation

8 Baltiyskaya St., Moscow 125315

125315 Москва, ул. Балтийская, 8

https://orcid.org/0000-0002-0132-167XKiselevskiyM. V.КиселевскийМ. В.
Russian Federation

24 Kashirskoye Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian FederationФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииInstitute of General Pathology and PathophysiologyФГБНУ «Научно-исследовательский институт общей патологии и патофизиологии»1806202019213211706202017062020https://bioterapevt.abvpress.ru/jour/article/view/1199

The review reflects the history of phytoadaptogens studies (ginseng, eleutherococcus, etc.), which are considered to be geroprotectors by Eastern medicine for centures. They have a complex of protective effects on the body, as well as increasing its antitumor resistance. The first part of the review describes the antistress, immuno- and hormone-modulating, cognitive and neuroprotective properties of adapto gens. Together with the synchronizing effects on biorthms adaptogens are essential for preventive oncology.

В обзоре отражена история исследований фитоадаптогенов (женьшень, элеутерококк и др.), которые восточная медицина издавна считает геропротекторами. Обладая комплексным защитным действием на организм, они повышают и его проти воопухолевую резистентность. В 1-й части обзора описаны антистрессорные, иммуно- и гормономодулирующие, когнитив ные и нейропротекторные свойства адаптогенов. Вместе с тем при синхронизирующем воздействии на биоритмы адапто гены имеют существенное значение для профилактической онкологии.

adaptogenspreventive oncologygeroprotectorsimmunomodulatorsneuroprotectorsадаптогеныпрофилактическая онкологиягеропротекторыиммуномодуляторынейропротекторы1. Бочарова О.А., Барышников А.Ю., Давыдов М.И. Фитоадаптогены в онкологии и геронтологии. М.: МИА, 2008. 224 с. [Bocharova O.A., Baryshnikov A.Yu., Davydov M.I. Phytoadaptogens in oncology and gerontology. Moscow: Medical News Agency, 2008. 224 p. (In Russ.)].Бочарова О.А., Барышников А.Ю., Давыдов М.И. Фитоадаптогены в онкологии и геронтологии. М.: МИА, 2008. 224 с. [Bocharova O.A., Baryshnikov A.Yu., Davydov M.I. Phytoadaptogens in oncology and gerontology. Moscow: Medical News Agency, 2008. 224 p. (In Russ.)].2. Модянова Е.А., Бочарова О.А., Маленков А.Г. Профилактическое действие контактинов-кейлонов на спонтанный канцерогенез у линейных мышей. Экспериментальная онкология 1983;5(3):39–42. [Modyanova E.A., Bocharova O.A., Malenkov A.G. The kontaktins-chalones preventive action on spontaneous carcinogenesis in mice inbred strains. Eksperimental’naya onkologiya = Experimental Oncology 1983;5(3):39–42. (In Russ.)].Модянова Е.А., Бочарова О.А., Маленков А.Г. Профилактическое действие контактинов-кейлонов на спонтанный канцерогенез у линейных мышей. Экспериментальная онкология 1983;5(3):39–42. [Modyanova E.A., Bocharova O.A., Malenkov A.G. The kontaktins-chalones preventive action on spontaneous carcinogenesis in mice inbred strains. Eksperimental’naya onkologiya = Experimental Oncology 1983;5(3):39–42. (In Russ.)].3. Shikov A.N., Pozharitskaya O.N., Makarov V.G. et al. Medicinal plants of the Russian Pharmacopoeia: their history and applications. J Ethnopharmacol 2014;154(3):481–536. DOI: 10.1016/j.jep.2014.04.007.Shikov A.N., Pozharitskaya O.N., Makarov V.G. et al. Medicinal plants of the Russian Pharmacopoeia: their history and applications. J Ethnopharmacol 2014;154(3):481–536. DOI: 10.1016/j.jep.2014.04.007.4. Арушанян Э.Б., Бейер Э.В. Растительные адаптогены. Ставрополь: СтГМАМ, 2009. 232 с. [Arushanyan E.B., Beyer E.V. Plant adaptogens. Stavropol’: StSMAM, 2009. 232 р. (In Russ.)].Арушанян Э.Б., Бейер Э.В. Растительные адаптогены. Ставрополь: СтГМАМ, 2009. 232 с. [Arushanyan E.B., Beyer E.V. Plant adaptogens. Stavropol’: StSMAM, 2009. 232 р. (In Russ.)].5. Ota T., Fujikawa-yamamoto K., Zong Z.P. et al. Plant-glycoside modulation of cell surface related to control of differentiation in cultured B16 melanoma cells. Cancer Res 1987;47(14):3863–7.Ota T., Fujikawa-yamamoto K., Zong Z.P. et al. Plant-glycoside modulation of cell surface related to control of differentiation in cultured B16 melanoma cells. Cancer Res 1987;47(14):3863–7.6. Zeng X.L., Tu Z.G. Induction of differentiation by ginsenoside Rh2 in hepatocarcinoma cell SMMC-7721. Ai Zheng 2004;23(8):879–84.Zeng X.L., Tu Z.G. Induction of differentiation by ginsenoside Rh2 in hepatocarcinoma cell SMMC-7721. Ai Zheng 2004;23(8):879–84.7. Dai C.Y., Liu P.F., Liao P.R. et al. Optimization of flavonoids extraction process in Panax notoginseng stem leaf and a study of antioxidant activity and its effects on mouse melanoma B16 cells. Molecules 2018;23(9):2219. DOI: 10.3390/molecules23092219.Dai C.Y., Liu P.F., Liao P.R. et al. Optimization of flavonoids extraction process in Panax notoginseng stem leaf and a study of antioxidant activity and its effects on mouse melanoma B16 cells. Molecules 2018;23(9):2219. DOI: 10.3390/molecules23092219.8. Lee B., Sur B., Park J. et al. Ginsenoside Rg3 alleviates lipopolysaccharideinduced learning and memory impairments by anti-inflammatory activity in rats. Biomol Ther 2013;21(5):381–90. DOI: 10.4062/biomolther.2013.053.Lee B., Sur B., Park J. et al. Ginsenoside Rg3 alleviates lipopolysaccharideinduced learning and memory impairments by anti-inflammatory activity in rats. Biomol Ther 2013;21(5):381–90. DOI: 10.4062/biomolther.2013.053.9. Fang F., Chen X., Huang T. et al. Multifaced neuroprotective effects of Ginsenoside Rg1 in an Alzheimer mouse model. Biochim Biophys Acta 2012;1822(2):286–92. DOI: 10.1016/j.bbadis.2011.10.004.Fang F., Chen X., Huang T. et al. Multifaced neuroprotective effects of Ginsenoside Rg1 in an Alzheimer mouse model. Biochim Biophys Acta 2012;1822(2):286–92. DOI: 10.1016/j.bbadis.2011.10.004.10. Oliynyk S., Oh S. Actoprotective effect of ginseng: improving mental and physical performance. J Ginseng Res 2013;37(2):144–66. DOI: 10.5142/jgr.2013.37.144.Oliynyk S., Oh S. Actoprotective effect of ginseng: improving mental and physical performance. J Ginseng Res 2013;37(2):144–66. DOI: 10.5142/jgr.2013.37.144.11. Amsterdam J.D., Panossian A.G. Rhodiola rosea L. as a putative botanical antidepressant. Phytomedicine 2016;23(7):770–83. DOI: 10.1016/j.phymed.2016.02.009.Amsterdam J.D., Panossian A.G. Rhodiola rosea L. as a putative botanical antidepressant. Phytomedicine 2016;23(7):770–83. DOI: 10.1016/j.phymed.2016.02.009.12. Lee T.K., O’Brien K.F., Wang W.D. et al. Radioprotective effect of American ginseng on human lymphocytes at 90 minutes postirradiation: a study of 40 cases. J Altern Complement Med 2010;16(5):561–7. DOI: 10.1089/acm.2009.0590.Lee T.K., O’Brien K.F., Wang W.D. et al. Radioprotective effect of American ginseng on human lymphocytes at 90 minutes postirradiation: a study of 40 cases. J Altern Complement Med 2010;16(5):561–7. DOI: 10.1089/acm.2009.0590.13. Alekseeva S.N., Antipina U.D., Arzhakova L.I. et al. New applications of adaptogens to reduce radiation side effects. Wiad Lek 2015;68(4):487–9.Alekseeva S.N., Antipina U.D., Arzhakova L.I. et al. New applications of adaptogens to reduce radiation side effects. Wiad Lek 2015;68(4):487–9.14. Hwang S.H., Shin E.J., Shin T.J. et al. Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, attenuates Alzheimer’s disease-related neuropathies: involvement of nonamyloidogenic processing. J Alzheimers Dis 2012;31(1):207–23. DOI: 10.3233/JAD-2012-120439.Hwang S.H., Shin E.J., Shin T.J. et al. Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, attenuates Alzheimer’s disease-related neuropathies: involvement of nonamyloidogenic processing. J Alzheimers Dis 2012;31(1):207–23. DOI: 10.3233/JAD-2012-120439.15. Ghaeminia M., Rajkumar R., Koh H.L. et al. Ginsenoside Rg1 modulates medial prefrontal cortical firing and suppresses the hippocampo-medial prefrontal cortical long-term potentiation. J Ginseng Res 2018;42(3):298–303. DOI: 10.1016/j.jgr.2017.03.010.Ghaeminia M., Rajkumar R., Koh H.L. et al. Ginsenoside Rg1 modulates medial prefrontal cortical firing and suppresses the hippocampo-medial prefrontal cortical long-term potentiation. J Ginseng Res 2018;42(3):298–303. DOI: 10.1016/j.jgr.2017.03.010.16. Song X.Y., Hu J.F., Chu S.F. et al. Ginsenoside Rg1 attenuates okadaic acid induced spatial memory impairment by the GSK3β/tau signaling pathway and the Aβ formation prevention in rats. Eur J Pharmacol 2013;710(1–3):29–38. DOI: 10.1016/j.ejphar.2013.03.051.Song X.Y., Hu J.F., Chu S.F. et al. Ginsenoside Rg1 attenuates okadaic acid induced spatial memory impairment by the GSK3β/tau signaling pathway and the Aβ formation prevention in rats. Eur J Pharmacol 2013;710(1–3):29–38. DOI: 10.1016/j.ejphar.2013.03.051.17. Zhang X., Li X., Xiong P. et al. Effects of Panax notoginseng saponins on liver graft rejection in rats and the mechanisms. Nan Fang Yi Ke Da Xue Xue Bao 2019;39(4):394–400. DOI: 10.12122/j.issn.1673-4254.2019.04.03.Zhang X., Li X., Xiong P. et al. Effects of Panax notoginseng saponins on liver graft rejection in rats and the mechanisms. Nan Fang Yi Ke Da Xue Xue Bao 2019;39(4):394–400. DOI: 10.12122/j.issn.1673-4254.2019.04.03.18. Choudhry Q.N., Kim J.H., Cho H.T. et al. Ameliorative effect of black ginseng extract against oxidative stress-induced cellular damages in mouse hepatocytes. J Ginseng Res 2019;43(2):179–85. DOI: 10.1016/j.jgr.2017.10.003.Choudhry Q.N., Kim J.H., Cho H.T. et al. Ameliorative effect of black ginseng extract against oxidative stress-induced cellular damages in mouse hepatocytes. J Ginseng Res 2019;43(2):179–85. DOI: 10.1016/j.jgr.2017.10.003.19. Radad K., Moldzio R., Rausch W.D. Ginsenosides and their CNS targets. CNS Neurosci Ther 2011;17(6):761–8. DOI: 10.1111/j.1755-5949.2010.00208.x.Radad K., Moldzio R., Rausch W.D. Ginsenosides and their CNS targets. CNS Neurosci Ther 2011;17(6):761–8. DOI: 10.1111/j.1755-5949.2010.00208.x.20. Tan X., Gu J., Zhao B. et al. Ginseng improves cognitive deficit via the RAGE/ NF-κB pathway in advanced glycation end product-induced rats. J Ginseng Res 2015;39(2):116–24. DOI: 10.1016/j.jgr.2014.09.002.Tan X., Gu J., Zhao B. et al. Ginseng improves cognitive deficit via the RAGE/ NF-κB pathway in advanced glycation end product-induced rats. J Ginseng Res 2015;39(2):116–24. DOI: 10.1016/j.jgr.2014.09.002.21. Kim S., Kim M.S., Park K. et al. Hippocampus-dependent cognitive enhancement induced by systemic gintonin administration. J Ginseng Res 2016;40(1):55–61. DOI: 10.1016/j.jgr.2015.05.001.Kim S., Kim M.S., Park K. et al. Hippocampus-dependent cognitive enhancement induced by systemic gintonin administration. J Ginseng Res 2016;40(1):55–61. DOI: 10.1016/j.jgr.2015.05.001.22. Zhang X., Shi M., Bjørås M. et al. Ginsenoside Rd promotes glutamate clearance by up-regulating glial glutamate transporter GLT-1 via PI3K/ AKT and ERK1/2 pathways. Front Pharmacol 2013;4:152. DOI: 10.3389/fphar.2013.00152.Zhang X., Shi M., Bjørås M. et al. Ginsenoside Rd promotes glutamate clearance by up-regulating glial glutamate transporter GLT-1 via PI3K/ AKT and ERK1/2 pathways. Front Pharmacol 2013;4:152. DOI: 10.3389/fphar.2013.00152.23. Chu S., Gu J., Feng L. et al. Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses. Int Immunopharmacol 2014;19(2):317–26. DOI: 10.1016/j.intimp.2014.01.018.Chu S., Gu J., Feng L. et al. Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses. Int Immunopharmacol 2014;19(2):317–26. DOI: 10.1016/j.intimp.2014.01.018.24. Shin B.K., Kwon S.W., Park J.H. Chemical diversity of ginseng saponins from Panax ginseng. J Ginseng Res 2015;39(4):287–98. DOI: 10.1016/j.jgr.2014.12.005.Shin B.K., Kwon S.W., Park J.H. Chemical diversity of ginseng saponins from Panax ginseng. J Ginseng Res 2015;39(4):287–98. DOI: 10.1016/j.jgr.2014.12.005.25. Wang G.L., Wang Y.P., Zheng J.Y. et al. Monoaminergic and aminoacidergic receptors are involved in the antidepressant-like effect of ginsenoside Rb1 in mouse hippocampus (CA3) and prefrontal cortex. Brain Res 2018;1699:44–53. DOI: 10.1016/j.brainres.2018.05.035.Wang G.L., Wang Y.P., Zheng J.Y. et al. Monoaminergic and aminoacidergic receptors are involved in the antidepressant-like effect of ginsenoside Rb1 in mouse hippocampus (CA3) and prefrontal cortex. Brain Res 2018;1699:44–53. DOI: 10.1016/j.brainres.2018.05.035.26. Panossian A., Nikoyan N., Okanyan N. et al. Comparative study of Rhodiola preparations on behavioral despair of rats. Phytomedicine 2008;15(1–2):84–91. DOI: 10.1016/j.phymed.2007.10.003Panossian A., Nikoyan N., Okanyan N. et al. Comparative study of Rhodiola preparations on behavioral despair of rats. Phytomedicine 2008;15(1–2):84–91. DOI: 10.1016/j.phymed.2007.10.00327. Lu G.H., Zhou Q.K., Sun S.Q. et al. Differentiation of Asian ginseng, American ginseng and Notoginseng by Fourier transform infrared spectroscopy combined with two-dimensional correlation infrared spectroscopy. J Mol Str 2008;883(3):91–8. DOI: 10.1016/j.molstruc.2007.12.008.Lu G.H., Zhou Q.K., Sun S.Q. et al. Differentiation of Asian ginseng, American ginseng and Notoginseng by Fourier transform infrared spectroscopy combined with two-dimensional correlation infrared spectroscopy. J Mol Str 2008;883(3):91–8. DOI: 10.1016/j.molstruc.2007.12.008.28. Zhu J.D., Wang J.J., Zhang X.H. et al. Panax ginseng extract attenuates neuronal injury and cognitive deficits in rats with vascular dementia induced by chronic cerebral hypoperfusion. Neural Regen Res 2018;13(4):664–72. DOI: 10.4103/1673-5374.230292.Zhu J.D., Wang J.J., Zhang X.H. et al. Panax ginseng extract attenuates neuronal injury and cognitive deficits in rats with vascular dementia induced by chronic cerebral hypoperfusion. Neural Regen Res 2018;13(4):664–72. DOI: 10.4103/1673-5374.230292.29. Szczuka D., Nowak A., Zakłos-Szyda M. et al. American Ginseng (Panax quinquefolium L.) as a Source of Bioactive Phytochemicals with Pro-Health Properties. Nutrients 2019;11(5):1041–60. DOI: 10.3390/nu11051041.Szczuka D., Nowak A., Zakłos-Szyda M. et al. American Ginseng (Panax quinquefolium L.) as a Source of Bioactive Phytochemicals with Pro-Health Properties. Nutrients 2019;11(5):1041–60. DOI: 10.3390/nu11051041.30. Zhang X., Wang Y., Ma C. et al. Ginsenoside Rd and ginsenoside Re offer neuroprotection in a novel model of Parkinson’s disease. Am J Neurodegener Dis 2016;5(1):52–61.Zhang X., Wang Y., Ma C. et al. Ginsenoside Rd and ginsenoside Re offer neuroprotection in a novel model of Parkinson’s disease. Am J Neurodegener Dis 2016;5(1):52–61.31. Wang G.L., He Z.M., Zhu H.Y. et al. Involvement of serotonergic, noradrenergic and dopaminergic systems in the antidepressant-like effect of ginsenoside Rb1, a major active ingredient of Panax ginseng C.A. Meyer. J Ethnopharmacol 2017;204:118–24. DOI: 10.1016/j.jep.2017.04.009.Wang G.L., He Z.M., Zhu H.Y. et al. Involvement of serotonergic, noradrenergic and dopaminergic systems in the antidepressant-like effect of ginsenoside Rb1, a major active ingredient of Panax ginseng C.A. Meyer. J Ethnopharmacol 2017;204:118–24. DOI: 10.1016/j.jep.2017.04.009.32. Jang A.Y., Song E.J., Shin S.H. et al. Potentiation of natural killer (NK) cell activity by methanol extract of cultured cambial meristematic cells of wild ginseng and its mechanism. Life Sci 2015;135:138–46. DOI: 10.1016/j.lfs.2015.06.018.Jang A.Y., Song E.J., Shin S.H. et al. Potentiation of natural killer (NK) cell activity by methanol extract of cultured cambial meristematic cells of wild ginseng and its mechanism. Life Sci 2015;135:138–46. DOI: 10.1016/j.lfs.2015.06.018.33. Li B., Zhang N., Feng Q. et al. The core structure characterization and of ginseng neutral polysaccharide with the immuneenhancing activity. Int J Biol Macromol 2019;123:713–22. DOI: 10.1016/j.ijbiomac.2018.11.140.Li B., Zhang N., Feng Q. et al. The core structure characterization and of ginseng neutral polysaccharide with the immuneenhancing activity. Int J Biol Macromol 2019;123:713–22. DOI: 10.1016/j.ijbiomac.2018.11.140.34. Kaur P., Robin., Makanjuola V.O. et al. Immunopotentiating significance of conventionally used plant adaptogens as modulators in biochemical and molecular signalling pathways in cell mediated processes. Biomed Pharmacother 2017;95:1815–29. DOI: 10.1016/j.biopha.2017.09.081.Kaur P., Robin., Makanjuola V.O. et al. Immunopotentiating significance of conventionally used plant adaptogens as modulators in biochemical and molecular signalling pathways in cell mediated processes. Biomed Pharmacother 2017;95:1815–29. DOI: 10.1016/j.biopha.2017.09.081.35. Akhter K.F., Mumin M.A., Lui E.M.K., Charpentier P.A. Fabrication of fluorescent labeled ginseng polysaccharide nanoparticles for bioimaging and their immunomodulatory activity on macrophage cell lines. Int J Biol Macromol 2018;109:254–62. DOI: 10.1016/j.ijbiomac.2017.12.050.Akhter K.F., Mumin M.A., Lui E.M.K., Charpentier P.A. Fabrication of fluorescent labeled ginseng polysaccharide nanoparticles for bioimaging and their immunomodulatory activity on macrophage cell lines. Int J Biol Macromol 2018;109:254–62. DOI: 10.1016/j.ijbiomac.2017.12.050.36. Lee J.H., Han Y. Ginsenoside Rg1 helps mice resist to disseminated condidiasis by Thl type differentiation of CD4+ T cell. Int Immunopharmacol 2006;6(9):1424–30. DOI: 10.1016/j.intimp.2006.04.009.Lee J.H., Han Y. Ginsenoside Rg1 helps mice resist to disseminated condidiasis by Thl type differentiation of CD4+ T cell. Int Immunopharmacol 2006;6(9):1424–30. DOI: 10.1016/j.intimp.2006.04.009.37. Lee B.H., Lee Y.H., Lee S.M. et al. Identification of ginsenoside interaction sites in 5-MT3A receptors. Neuropharmacology 2007;52(4):1139–50. DOI: 10.1016/j.neuropharm.2006.12.001.Lee B.H., Lee Y.H., Lee S.M. et al. Identification of ginsenoside interaction sites in 5-MT3A receptors. Neuropharmacology 2007;52(4):1139–50. DOI: 10.1016/j.neuropharm.2006.12.001.38. Yamazaki Т., Shimosava S., Sasaki H. (+)-Syringaresinol-di-O-beta-D-glucoside, a phenolic compound from Acanthopanax senticosus harmus, suppressed proinflamatory mediators in SW982 human synovial sarcoma cells by inhibiting activating protein-1 and/or nuclear factor-kappa B activities. Toxicol In Vitro 2007;2(8):1530–37. DOI: 10.1016/j.tiv.2007.04.016.Yamazaki Т., Shimosava S., Sasaki H. (+)-Syringaresinol-di-O-beta-D-glucoside, a phenolic compound from Acanthopanax senticosus harmus, suppressed proinflamatory mediators in SW982 human synovial sarcoma cells by inhibiting activating protein-1 and/or nuclear factor-kappa B activities. Toxicol In Vitro 2007;2(8):1530–37. DOI: 10.1016/j.tiv.2007.04.016.39. Choi K., Kim M., Ryu J. Ginsenosides compound К and Rh2 inhibit tumor necrosis factor-alpha-induced activation of the NF-kappa В and JNK path-ways in human astroglial cells. Neurosci Lett 2007;421(1):37–41. DOI: 10.1016/j.neulet.2007.05.017.Choi K., Kim M., Ryu J. Ginsenosides compound К and Rh2 inhibit tumor necrosis factor-alpha-induced activation of the NF-kappa В and JNK path-ways in human astroglial cells. Neurosci Lett 2007;421(1):37–41. DOI: 10.1016/j.neulet.2007.05.017.40. Kang K.S., Yokozawa Т., Yamode N. et al. ESR study on the structure and hydroxyl radical-scavenging activity relationships of ginsenosides isolated from Panax ginseng C.A. Meyer. Biol Pharm Bull 2007;30(5):917–21. DOI: 10.1248/bpb.30.917.Kang K.S., Yokozawa Т., Yamode N. et al. ESR study on the structure and hydroxyl radical-scavenging activity relationships of ginsenosides isolated from Panax ginseng C.A. Meyer. Biol Pharm Bull 2007;30(5):917–21. DOI: 10.1248/bpb.30.917.41. Song H., Park J., Choi K. et al. Ginsenoside Rf inhibits cyclooxygenase-2 induction via peroxisome proliferator-activated receptor gamma in A549 cells. J Ginseng Res 2019;43(2):319–25. DOI: 10.1016/j.jgr.2018.11.007.Song H., Park J., Choi K. et al. Ginsenoside Rf inhibits cyclooxygenase-2 induction via peroxisome proliferator-activated receptor gamma in A549 cells. J Ginseng Res 2019;43(2):319–25. DOI: 10.1016/j.jgr.2018.11.007.42. Park W., Lim W., Cho Y. et al. Inhibitory effects of ginsenoside-Rb1 on activation of the 12-o-tetradecanoylphorbal 13-ace-tate-induced cyclooxygenase-2 promoter. Planta Med 2006;72(3):272–5. DOI: 10.1055/s-2005-873172.Park W., Lim W., Cho Y. et al. Inhibitory effects of ginsenoside-Rb1 on activation of the 12-o-tetradecanoylphorbal 13-ace-tate-induced cyclooxygenase-2 promoter. Planta Med 2006;72(3):272–5. DOI: 10.1055/s-2005-873172.43. Lee S.K., Wong C.K., Poon P.M. et al. In vitro immunomodulatory activities of a newly concocted traditional Chinese medicine formula: VI-28. Phytother Res 2006;20(10):883–8. DOI: 10.1002/ptr.1955.Lee S.K., Wong C.K., Poon P.M. et al. In vitro immunomodulatory activities of a newly concocted traditional Chinese medicine formula: VI-28. Phytother Res 2006;20(10):883–8. DOI: 10.1002/ptr.1955.44. Yu J.L., Dou D.Q., Chen X.H. et al. Protopanaxatriol-type ginsenosides differentially modulate type 1 and type 2 cytokines production from murine splenocytes. Planta Med 2005;71(3):202–7. DOI: 10.1055/s-2005-837817.Yu J.L., Dou D.Q., Chen X.H. et al. Protopanaxatriol-type ginsenosides differentially modulate type 1 and type 2 cytokines production from murine splenocytes. Planta Med 2005;71(3):202–7. DOI: 10.1055/s-2005-837817.45. García A., de Sanctis J.B. An overview of adjuvant formulations and delivery systems. APMIS 2014;122(4):257–67. DOI: 10.1111/apm.12143.García A., de Sanctis J.B. An overview of adjuvant formulations and delivery systems. APMIS 2014;122(4):257–67. DOI: 10.1111/apm.12143.46. Sun B., Yu S., Zhao D. Polysaccharides as vaccine adjuvants. Vaccine 2018;36(35):5226–34. DOI: 10.1016/j.vaccine.2018.07.040.Sun B., Yu S., Zhao D. Polysaccharides as vaccine adjuvants. Vaccine 2018;36(35):5226–34. DOI: 10.1016/j.vaccine.2018.07.040.47. Park J.S., Hwang S.Y., Lee W.S. et al. The therapeutic effect of tissue cultured root of wild Panax ginseng C.A. Mayer on spermatogenetic disorder. Arch Pharm Res 2006;29(9):800–7. DOI: 10.1007/bf02974082.Park J.S., Hwang S.Y., Lee W.S. et al. The therapeutic effect of tissue cultured root of wild Panax ginseng C.A. Mayer on spermatogenetic disorder. Arch Pharm Res 2006;29(9):800–7. DOI: 10.1007/bf02974082.48. Kim S.K., GyuKo I., Park H.J. et al. Effects of Panax ginseng on the nerve growth factor expression in testosterone induced benign prostatic hyperplasia. Saudi J Biol Sci 2018;25(1):66–70. DOI: 10.1016/j.sjbs.2016.07.005.Kim S.K., GyuKo I., Park H.J. et al. Effects of Panax ginseng on the nerve growth factor expression in testosterone induced benign prostatic hyperplasia. Saudi J Biol Sci 2018;25(1):66–70. DOI: 10.1016/j.sjbs.2016.07.005.49. Tsai S.C., Chiao Y.C., Lu C.C. Stimulation of the secretion of luteinizing hormone by ginsenosideRbl in male rats. Chin J Physiol 2003;46(1):1–7.Tsai S.C., Chiao Y.C., Lu C.C. Stimulation of the secretion of luteinizing hormone by ginsenosideRbl in male rats. Chin J Physiol 2003;46(1):1–7.50. Xie X., Eberding A., Madera C. et al. Rh2 synergistically enhances paclitaxel or mitoxantrone in prostate cancer models. J Urol 2006;175(5):1926–31. DOI: 10.1016/S0022-5347(05)00891-8.Xie X., Eberding A., Madera C. et al. Rh2 synergistically enhances paclitaxel or mitoxantrone in prostate cancer models. J Urol 2006;175(5):1926–31. DOI: 10.1016/S0022-5347(05)00891-8.51. Panossian A. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Ann N Y Acad Sci 2017;1401(1):49–64. DOI: 10.1111/nyas.13399.Panossian A. Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals. Ann N Y Acad Sci 2017;1401(1):49–64. DOI: 10.1111/nyas.13399.52. Гольдберг Е.Д., Разина Т.Г., Зуева Е.П. и др. Растения в комплексной терапии опухолей. М.: Издательство РАМН, 2008. 432 с. [Goldberg E.D., Razina T.G., Zueva E.P. et al. Plants in complex therapy of tumors. Мoscow: RAMS Publishing House, 2008. 432 р. (In Russ.)].Гольдберг Е.Д., Разина Т.Г., Зуева Е.П. и др. Растения в комплексной терапии опухолей. М.: Издательство РАМН, 2008. 432 с. [Goldberg E.D., Razina T.G., Zueva E.P. et al. Plants in complex therapy of tumors. Мoscow: RAMS Publishing House, 2008. 432 р. (In Russ.)].