Phytotea “ATINE” enhances the immunomodulatory effect of adaptogenic factors of the Truskavets’ Spa in patients after radical treatment of oncological pathology
DOI:
https://doi.org/10.12775/JEHS.2025.80.60626Keywords
Phytotea “ATINE”, Truskavets’ Spa, oncological patients, immunityAbstract
Background. The beneficial effect of balneofactors of the Truskavets’ Spa on the immune status of patients with various chronic diseases is well known. On the other hand, a similar immunomodulatory effect is exerted by various medicinal plants. Based on this, we set ourselves the goal of clarifying the possibility of enhancing the immunotropic effect of balneofactors by combining them with medicinal plants.
Material and methods. The subjects of the study were 52 patients aged 44÷75 years (36 women aged 59.3±9.3 years and 16 men aged 60.0±8.3 years), who came for rehabilitation at the Truskavets' Spa after radical treatment of oncopathology. The state of cellular, humoral and phagocytic links of immunity was assessed using routine methods, and two equal groups were formed on this basis. Members of the control group received standard balneotherapy for two weeks, while the main group additionally consumed the newly created herbal tea “ATINE”.
Results. Supplementing standard balneotherapy with phytotea “ATINE” significantly modulated its immunotropic effects. First, “ATINE” neutralized the balneotherapy-induced decrease in IgG levels, reversed the tendency to decrease neutrophils content into an increasing trend, initiated an increase in CIC and T-killer levels, as well as enhanced the activating effect of balneotherapy on the level of natural killer cells. Secondly, “ATINE” leveled the balneotherapy-induced increase in the absolute content of B-lymphocytes and IgA in the blood, initiated a decrease in the absolute content of pan-lymphocytes and T-helpers, and deepened the balneotherapy-induced decrease in the relative content of T-helpers and IgM. However, the additional use of “ATINE” did not affect the balneotherapy-induced increase in the bactericidal ability of blood neutrophils and its factors (activity, intensity and completeness of phagocytosis of the Staph. aureus strain), the absolute content of natural killers and the relative content of B-lymphocytes, the reaction of blast transformation of T-lymphocytes to PHA, as well as the entropy of the immunocytogram.
Conclusion. Phytotea “ATINE” enhances the immunomodulatory effect of adaptogenic factors of the Truskavets’ spa in patients after radical treatment of oncological pathology. Based on the analysis of the research document on "ATINE" herbal tea used in patients after radical oncological treatment at the Truskavets Spa, the following conclusions supported by mathematical analysis can be drawn. 1. "ATINE" herbal tea significantly increases NK and T-killer cell levels. Mathematical confirmation: NK cell level increase: standard balneotherapy effect was +0.51±0.09 (p<0.05), while with additional "ATINE" it increased to +0.97±0.10 (p<0.05); "ATINE" effect alone: +0.46±0.10; T-killer level increase: standard balneotherapy +0.05±0.56 (non-significant), with "ATINE" +1.36±0.46 (p<0.05); "ATINE" effect alone on T-killers: +1.31±0.51; Discriminant analysis confirmed these effects with r*=0.654; Wilks' Λ=0.547; χ²(12)=60; p<10⁻⁶. 2. "ATINE" modulates immune response by decreasing T-helper and IgM levels. Mathematical confirmation: T-helper level decrease: standard balneotherapy -0.54±0.28 (non-significant), with "ATINE" -1.16±0.23 (p<0.05); "ATINE" effect alone on T-helpers: -0.62±0.26; IgM level decrease: standard balneotherapy -1.47±0.28 (p<0.05), with "ATINE" -2.59±0.44 (p<0.05); "ATINE" effect alone on IgM: -1.12±0.36; Regression analysis showed strong correlation between T-killer and T-helper level changes: R=0.909; R²=0.826; p<10⁻⁶. 3. "ATINE" increases circulating immune complexes (CIC) without affecting neutrophil bactericidal capacity. Mathematical confirmation: CIC level change: standard balneotherapy -0.12±0.30 (non-significant), with "ATINE" +0.77±0.34 (p<0.05); "ATINE" effect alone on CIC: +0.89±0.32; No difference in neutrophil bactericidal capacity (BCCN): standard balneotherapy +1.10±0.58, with "ATINE" +1.06±0.35 (p<0.05); t-value for effect comparison: 0.00 (complete absence of difference); Mahalanobis distances between groups confirm significant differences between baseline and both therapies (p<10⁻⁶), as well as between standard balneotherapy and therapy with "ATINE" (p=0.075).
References
1.Alyeksyeyev, О. І., Popovych, I. L., Panasyuk, Y. M., Barylyak, L. G., Saranca, S. N., & Shumakov, M. F. (1996). Adaptogens and Radiation [in Ukrainian]. Kyїv: Naukova dumka.
2.Andric, S. A., Kostic, T. S., Stojilkovic, S. S., & Kovacevic, R. Z. (2000). Inhibition of rat testicular androgenesis by a polychlorinated biphenyl mixture aroclor 1248. Biology of Reproduction, 62(6), 1882-1888. https://doi.org/10.1095/biolreprod62.6.1882
3.Asea, A., Kaur, P., Panossian, A., & Wikman, K. G. (2013). Evaluation of molecular chaperons Hsp72 and neuropeptide Y as characteristic markers of adaptogenic activity of plant extracts. Phytomedicine, 20(14), 1323-1329. https://doi.org/10.1016/j.phymed.2013.07.001
4.Avilla, M. N., Malecki, K. M. C., Hahn, M. E., Wilson, R. H., & Bradfield, C. A. (2020). The Ah Receptor: Adaptive metabolism, ligand diversity, and the xenokine model. Chemical Research in Toxicology, 33(4), 860-879. https://doi.org/10.1021/acs.chemrestox.0c00072
5.Bungsu, I., Kifli, N., Ahmad, S. R., Ghani, H., & Cunningham, A. C. (2021). Herbal plants: The role of AhR in mediating immunomodulation. Frontiers in Immunology, 12, 697663. https://doi.org/10.3389/fimmu.2021.697663
6.Busbee, P. B., Rouse, M., Nagarkatti, M., & Nagarkatti, P. S. (2013). Use of natural AhR ligands as potential therapeutic modalities against inflammatory disorders. Nutrition Reviews, 71(6), 353-369. https://doi.org/10.1111/nure.12024
7.Chebanenko, O. I., Flyunt, I. S., Popovych, I. L., Balanovskyi, V. P., & Lakhin, P. V. (1997). Water Naftussya and Water-salt Exchange [in Ukrainian]. Kyїv: Naukova dumka. 141.
8.Chebanenko, O. I., Popovych, I. L., Bulba, A. Y., Ruzhylo, S. V., & Perchenko, V. P. (1997). Choleretic effect of Naftussya water [in Ukrainian]. Kyїv: Komp'yuterpress. 103.
9.Chen, W. C., Chang, L. H., Huang, S. S., Huang, Y. J., Chih, C. L., Kuo, H. C., Lee, Y. H., & Lee, I. H. (2019). Aryl hydrocarbon receptor modulates stroke-induced astrogliosis and neurogenesis in the adult mouse brain. Journal of Neuroinflammation, 16, 187. https://doi.org/10.1186/s12974-019-1572-7
10.Chen, Y., Xu, L., Xie, H. Q. H., Xu, T., Fu, H., Zhang, S., Ho, K., & Zhao, B. (2017). Identification of differentially expressed genes response to TCDD in rat brain after long-term low-dose exposure. Journal of Environmental Sciences, 62, 92-99. https://doi.org/10.1016/j.jes.2017.08.012
11.Congues, F., Wang, P., Lee, J., Lin, D., Shahid, A., Xie, J., & Huang, Y. (2024). Targeting aryl hydrocarbon receptor to prevent cancer in barrier organs. Biochemical Pharmacology, 116156. https://doi.org/10.1016/j.bcp.2024.116156
12.Dardymov, I. V. (1976). Ginseng, Eleutherococcus (To the mechanism of physiological action) [in Russian]. Moskva: Nauka. 189.
13.Datsko, O. R., Bubnyak, A. B., & Ivassivka, S. V. (2008). The organic part in mineral water Naftussya. Development of knowledges about its composition and origination [in Ukrainian]. Medical Hydrology and Rehabilitation, 6(1), 168-174.
14.Denison, M. S., Pandini, A., Nagy, S. R., Baldwin, E. P., & Bonati, L. (2002). Ligand binding and activation of the Ah receptor. Chemico-Biological Interactions, 141(1-2), 3-24. https://doi.org/10.1016/s0009-2797(02)00063-7
15.Denison, M. S., Soshilov, A. A., He, G., DeGroot, D. E., & Zhao, B. (2011). Exactly the same but different: Promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon (dioxin) receptor. Toxicological Sciences, 124, 1-22. https://doi.org/10.1093/toxsci/kfr218
16.Eckers, A., Jakob, S., Heiss, C., Haarmann-Stemmann, T., Goy, C., Brinkmann, V., Cortese-Krott, M. M., Sansone, R., Esser, C., Ale-Agha, N., Altschmied, J., Ventura, N., & Haendeler, J. (2016). The aryl hydrocarbon receptor promotes aging phenotypes across species. Scientific Reports, 6, 19618. https://doi.org/10.1038/srep19618
17.Elson, D. J., & Kolluri, S. K. (2023). Tumor-suppressive functions of the aryl hydrocarbon receptor (AhR) and AhR as a therapeutic target in cancer. Biology, 12(4), 526. https://doi.org/10.3390/biology12040526
18.Esmaealzadeh, N., Iranpanah, A., Sarris, J., & Rahimi, R. (2022). A literature review of the studies concerning selected plant-derived adaptogens and their general function in body with a focus on animal studies. Phytomedicine, 105, 154354. https://doi.org/10.1016/j.phymed.2022.154354
19.Esser, C., & Rannug, A. (2015). The aryl hydrocarbon receptor in barrier organ physiology, immunology, and toxicology. Pharmacological Reviews, 67(2), 259-279. https://doi.org/10.1124/pr.114.009001
20.Fihura, O. A., Ruzhylo, S. V., Korda, M. M., Klishch, I. M., Żukow, X., & Popovych, I. L. (2023). The influence of the Ukrainian phytocomposition "Balm Truskavets'" on parameters of neuro-endocrine-immune complex and biophotonics in humans with maladaptation. Journal of Education, Health and Sport, 13(1), 326-337. http://dx.doi.org/10.12775/JEHS.2023.13.01.048
21.Fihura, O. A. (2023). Аmelioration by phytoadaptogene of effects of balneofactors of Truskavets' Spa on patients with post-radiation encephalopathy. Journal of Education, Health and Sport, 19(1), 36-58. http://dx.doi.org/10.12775/JEHS.2023.19.01.005
22.Fihura, O. A., Ruzhylo, S. V., & Popovych, I. L. (2022). Ukrainian adaptogenic phytocomposition "Balm Truskavets'" modulate EEG, HRV and biophotonics (GDV) parameters. Journal of Marine Medicine, 2(95), 99-108.
23.Fihura, O. A., Ruzhylo, S. V., & Zakalyak, N. R. (2022). Phytoadaptogen reverses the adverse effects of Naftussya bioactive water on dynamic muscle performance in healthy rats. Quality in Sport, 8(2), 45-55.
24.Flyunt, I. S., Chebanenko, L. O., Chebanenko, O. I., Kyjenko, V. M., & Fil', V. M. (2002). Experimental Balneophytotherapy [in Ukrainian]. Kyїv: UNESCO-SOCIO. 196.
25.Flyunt, I. S., Chebanenko, O. I., Hrinchenko, B. V., Barylyak, L. G., & Popovych, I. L. (2002). Balneophytoradiodefensology. Influence of therapeutic factors of Truskavets' spa on the state of adaptation and protection systems of the victims of the Chernobyl disaster [in Ukrainian]. Kyїv: Computerpress. 112.
26.Gerontakos, S. E., Casteleijn, D., Shikov, A. N., & Wardle, J. (2020). A critical review to identify the domains used to measure the effect and outcome of adaptogenic herbal medicines. Yale Journal of Biology and Medicine, 93(2), 327-346.
27.Giani T. S., Faber, S. C., Motta, S., Denison, M. S., & Bonati, L. (2019). Modeling the binding of diverse ligands within the Ah receptor ligand binding domain. Scientific Reports, 9(1), 10693. https://doi.org/10.1038/s41598-019-47138-z
28.Gozhenko, A. I., Zukow, W., Polovynko, I. S., Zajats, L. M., Yanchij, R. I., Portnichenko, V. I., & Popovych, I. L. (2019). Individual immune responses to chronic stress and their neuro-endocrine accompaniment. Radom, Torun: RSW UMK. 200.
29.Gozhenko, А. І., Korda, M. M., Popadynets, O. O., & Popovych, I. L. (2021). Entropy, harmony, synchronization and their neuro-endocrine-immune correlates [in Ukrainian]. Odesa: Feniks. 232.
30.Gumega, M. D., Levytskyi, A. B., & Popovych, I. L. (2011). Balneogastroenterology [in Ukrainian]. Kyїv: UNESCO-SOCIO. 243.
31.Hrinchenko, B. V., Ruzhylo, S. V., Flyunt, I. S., Alyeksyeyev, A. I., & Huchko, B. Y. (1999). The effect of complex balneotherapy at the Truskavets' resort with the use of phytoadaptogen on psychophysiological functions and physical performance [in Ukrainian]. Medical Hydrology and Rehabilitation, 2(1), 31-35.
32.Hrinchenko, B. V. (1998). A comparative study of the effect of balneotherapy with the use of Krymskyi and Bittner balms on physical performance and central hemodynamics [in Ukrainian]. Ukrainian Balneological Journal, 1(4), 36-38.
33.Hu, Q., He, G., Zhao, J., Soshilov, A., Denison, M. S., Zhang, A., Yin, H., Fraccalvieri, D., Bonati, L., Xie, Q., & Zhao, B. (2013). Ginsenosides are novel naturally-occurring aryl hydrocarbon receptor ligands. PLOS ONE, 8(6), e66258. https://doi.org/10.1371/journal.pone.0066258
34.Hyun, S. H., Ahn, H. Y., Kim, H. J., Kim, S. W., So, S. H., In, G., Kim, S. K., & Han, C. K. (2021). Immuno-enhancement effects of Korean Red Ginseng in healthy adults: A randomized, double-blind, placebo-controlled trial. Journal of Ginseng Research, 45(1), 191-198. https://doi.org/10.1016/j.jgr.2020.08.003
35.Ivassivka, S. V. (1997). Biologically active substances of Naftussya water, their genesis and mechanisms of physiological action [in Ukrainian]. Kyїv: Naukova dumka. 110.
36.Ivassivka, S. V., Kovbasnyuk, M. M., Bilas, V. R., & Khodak, O. L. (2004). The effect of balneotherapy on the growth of Plis lymphosarcoma [in Ukrainian]. Medical Hydrology and Rehabilitation, 2(2), 52-57.
37.Ivassivka, S. V., Kovbasnyuk, M. M., Bilas, V. R., & Khodak, O. L. (2005). Effect of Naftussya water on experimental tumors in rats [in Ukrainian]. Medical Hydrology and Rehabilitation, 3(2), 60-67.
38.Ivassivka, S. V., & Kovbasnyuk, M. M. (2011). The role of xenobiotic properties of Naftusya water in the activation of phagocytes and natural killers, the regulation of their interaction in normal and pathological conditions [in Ukrainian]. Medical Hydrology and Rehabilitation, 9(1), 16-36.
39.Jin, W., Ma, R., Zhai, L., Wang, Y., Liu, Y., Dai, Z., Liang, X., Zhang, Y., & Gao, Y. (2020). Ginsenoside Rd attenuates ACTH-induced corticosterone secretion by blocking the MC2R-cAMP/PKA/CREB pathway in Y1 mouse adrenocortical cells. Life Sciences, 245, 117337. https://doi.org/10.1016/j.lfs.2020.117337
40.Keshavarzi, M., Khoshnoud, M. J., Ghaffarian Bahraman, A., & Mohammadi-Bardbori, A. (2020). An endogenous ligand of aryl hydrocarbon receptor 6-formylindolo[3,2-b] carbazole (FICZ) is a signaling molecule in neurogenesis of adult hippocampal neurons. Journal of Molecular Neuroscience, 70, 806-817. https://doi.org/10.1007/s12031-020-01490-2
41.Khodak, O. L., Bilas, V. R., & Nazarenko, N. K. (2006). Variants of immunotropic and clinical effects of balneotherapy at the Truskavets' Spa in people after radical treatment of oncopathology [in Ukrainian]. Medical Hydrology and Rehabilitation, 4(3), 9-32.
42.Khodak, O. L., & Bilas, V. R. (2008). The effect of Naftussya mineral water on the body's nonspecific resistance to neoplastic processes [in Ukrainian]. Medical Hydrology and Rehabilitation, 6(1), 79-84.
43.Kimura, E., & Tohyama, C. (2017). Embryonic and postnatal expression of aryl hydrocarbon receptor mRNA in mouse brain. Frontiers in Neuroanatomy, 11, 4. https://doi.org/10.3389/fnana.2017.00004
44.Klecka, W. R. (1989). Discriminant analysis [trans. from English in Russian] (Seventh Printing, 1986). In Factor, discriminant and cluster analysis (pp. 78-138). Moskwa: Finansy i Statistika.
45.Korda, M. M., Fihura, O. A., Melnyk, O. I., Klishch, I. M., Yanchij, R. I., Zukow, W., Ruzhylo, S. V., Popovych, D. V., & Popovych, I. L. (2024). Ukrainian phytocomposition "Balm Truskavets'", metabolism, physical working capacity and neuro-endocrine-immune complex. Lviv: Svit. http://dx.doi.org/10.5281/zenodo.14640273
46.Kostyuk, P. G., Popovych, I. L., & Іvassivka, S. V. (Eds.). (2006). Chornobyl', adaptive and defensive systems, rehabilitation [in Ukrainian]. Kyїv: Computerpress. 348.
47.Kou, Z., & Dai, W. (2021). Aryl hydrocarbon receptor: Its roles in physiology. Biochemical Pharmacology, 185, 114428. https://doi.org/10.1016/j.bcp.2021.114428
48.Kozyavkina, O. V., Kozyavkina, N. V., Gozhenko, O. A., Gozhenko, A. I., Barylyak, L. G., & Popovych, I. L. (2015). Bioactive water Naftussya and neuroendocrine-immune complex [in Ukrainian]. Kyїv: UNESCO-SOCIO. 349.
49.Kumar, P., Banik, S. P., Goel, A., Chakraborty, S., Bagchi, M., & Bagchi, D. (2023). Chemical, microbial and safety profiling of a standardized Withania somnifera (Ashwagandha) extract and Withaferin A, a potent novel phytotherapeutic of the millennium. Functional Foods in Health and Disease, 13(2), 36-51. https://doi.org/10.31989/ffhd.v13i2.1020
50.Lapovets, L., & Lutsyk, B. (2004). Handbook of laboratory immunology [in Ukrainian]. Lviv. 173.
51.Li, L. A., & Wang, P. W. (2005). PCB126 induces differential changes in androgen, cortisol, and aldosterone biosynthesis in human adrenocortical H295R cells. Toxicological Sciences, 85(1), 530-540. https://doi.org/10.1093/toxsci/kfi130
52.Lu, S., Wu, D., Sun, G., Geng, F., Shen, Y., Tan, J., Sun, X., & Ding, S. (2019). Gastroprotective effects of Kangfuxin against water-immersion and restraint stress-induced gastric ulcer in rats: Roles of antioxidation, anti-inflammation, and pro-survival. Pharmaceutical Biology, 57(1), 770-777. https://doi.org/10.1080/13880209.2019.1679814
53.Lupandin, A. V. (1989). On the role of catecholaminergic synapses in the mechanism of adaptation formation with the participation of polyphenolic adaptogens [in Russian]. Fiziologicheskii Zhurnal SSSR, 75(8), 1082-1088.
54.Lyubitelev, A., & Studitsky, V. (2023). Inhibition of cancer development by natural plant polyphenols: Molecular mechanisms. International Journal of Molecular Sciences, 24(13), 10663. https://doi.org/10.3390/ijms241310663
55.Meerson, F. Z. (1991). Protective effects of adaptation and some prospects for the development of adaptive medicine [in Russian]. Uspekhi Fiziologicheskikh Nauk, 22(2), 52-89.
56.Moreno-Nieves, U. Y., Mundy, D. C., Shin, J. H., Tam, K., & Sunwoo, J. B. (2018). The aryl hydrocarbon receptor modulates the function of human CD56bright NK cells. European Journal of Immunology, 48, 771-776. https://doi.org/10.1002/eji.201747289
57.Murray, I. A., & Perdew, G. H. (2020). How Ah receptor ligand specificity became important in understanding its physiological function. International Journal of Molecular Sciences, 21(24), 9614. https://doi.org/10.3390/ijms21249614
58.Nebert, D. W., & Bausserman, L. L. (1970). Genetic differences in the extent of aryl hydrocarbon hydroxylase induction in mouse fetal cell cultures. Journal of Biological Chemistry, 245(23), 6373-6382.
59.Oh, C. S., Kim, H. J., Jeong, H. W., Park, J. H., & Park, W. (2023). Immunomodulatory effects of Korean Red Ginseng (Panax ginseng) and its active ingredients. Hantopic, 5(2), 1. https://doi.org/10.23146/HAN.2023.4.01
60.Ojo, E. S., & Tischkau, S. A. (2021). The role of AhR in the hallmarks of brain aging: Friend and foe. Cells, 10(10), 2729. https://doi.org/10.3390/cells10102729
61.Panasyuk, Y. M., Levkut, L. H., Popovych, I. L., Alekseyev, O. I., Kovbasnyuk, M. M., & Balanovskyi, V. P. (1994). Experimental study of adaptogenic properties of "Crimean" balm [in Ukrainian]. Fiziologichnyi Zhurnal, 40(3-4), 25-30.
62.Panasyuk, Y. M., Levkut, L. G., Popovych, I. L., Shumakov, M. F., Sychova, A. O., Alekseyev, O. I., & Bakova, M. M. (1996). Adaptogenic agent [in Ukrainian]. Ukraine Patent No. 10271. Bull № 4.
63.Panossian, A. (2023). Challenges in phytotherapy research. Frontiers in Pharmacology, 14, 1199516. https://doi.org/10.3389/fphar.2023.1199516
64.Panossian, A., & Efferth, T. (2022). Network pharmacology of adaptogens in the assessment of their pleiotropic therapeutic activity. Pharmaceuticals, 15(9), 1051. https://doi.org/10.3390/ph15091051
65.Panossian, A., Seo, E. J., & Efferth, T. (2018). Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology. Phytomedicine, 50, 257-284. https://doi.org/10.1016/j.phymed.2018.09.204
66.Panossian, A., Seo, E. J., & Efferth, T. (2019). Effects of anti-inflammatory and adaptogenic herbal extracts on gene expression of eicosanoids signaling pathways in isolated brain cells. Phytomedicine, 60, 152881. https://doi.org/10.1016/j.phymed.2019.152881
67.Panossian, A., & Wikman, G. (2010). Effects of adaptogens on the central nervous system and the molecular mechanisms associated with their stress-protective activity. Pharmaceuticals, 3(1), 188-224. https://doi.org/10.3390/ph3010188
68.Panossian, A. G., Efferth, T., Shikov, A. N., Pozharitskaya, O. N., Kuchta, K., Mukherjee, P. K., Banerjee, S., Heinrich, M., Wu, W., Guo, D. A., & Wagner, H. (2021). Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress- and aging-related diseases. Medicinal Research Reviews, 41(1), 630-703. https://doi.org/10.1002/med.21743
69.Phelan, D., Winter, G. M., Rogers, W. J., Lam, J. C., & Denison, M. S. (1988). Activation of the Ah receptor signal transduction pathway by bilirubin and biliverdin. Archives of Biochemistry and Biophysics, 357(1), 155-163. https://doi.org/10.1006/abbi.1998.0814
70.Poland, A., Glover, E., & Kende, A. S. (1976). Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase. Journal of Biological Chemistry, 251(16), 4936-4946.
71.Popadynets, O., Gozhenko, A., Badyuk, N., Popovych, I., Skaliy, A., Hagner-Derengowska, M., Napierata, M., Muszkieta, R., Sokołowski, D., Zukow, W., & Rybałko, L. (2020). Interpersonal differences caused by adaptogen changes in entropies of EEG, HRV, immunocytogram, and leukocytogram. Journal of Physical Education and Sport, 20(Suppl. 2), 982-999. https://doi.org/10.7752/jpes.2020.s2139
72.Popovych, A. I. (2018). Features of the immunotropic effects of partial components of the balneotherapeutic complex of spa Truskavets'. Journal of Education, Health and Sport, 8(12), 919-935. http://dx.doi.org/10.5281/zenodo.2546368
73.Popovych, A. I. (2019). Features of the neurotropic effects of partial components of the balneotherapeutic complex of spa Truskavets'. Journal of Education, Health and Sport, 9(1), 396-409. http://dx.doi.org/10.5281/zenodo.2596710
74.Popovych, I. L. (2011). Stresslimiting adaptogene mechanism of biological and curative activity of water Naftussya [in Ukrainian]. Kyїv: Computerpress. 300.
75.Popovych, I. L., Flyunt, I. S., Alyeksyeyev, O. I., Barylyak, L. G., & Bilas, V. R. (2003). Sanogenetic bases of rehabilitation on spa Truskavets' urological patients from Chornobylian contingent [in Ukrainian]. Kyїv: Computerpress. 192.
76.Popovych, I. L., Gozhenko, A. I., Korda, M. M., Klishch, I. M., Popovych, D. V., & Zukow, W. (Eds.). (2022). Mineral waters, metabolism, neuro-endocrine-immune complex. Odesa: Feniks. 252.
77.Popovych, I. L., Ivassivka, S. V., & Flyunt, I. S. (2000). Bioactive water Naftussya and the stomach [in Ukrainian]. Kyїv: Computerpress. 234.
78.Popovych, I. L., Kozyavkina, O. V., Kozyavkina, N. V., Korolyshyn, T. A., Lukovych, Y. S., & Barylyak, L. G. (2014). Correlation between indices of the heart rate variability and parameters of ongoing EEG in patients suffering from chronic renal pathology. Neurophysiology, 46(2), 139-148. https://doi.org/10.1007/s11062-014-9420-y
79.Popovych, I. L., Kulchynskyi, A. B., Gozhenko, A. I., Zukow, W., Kovbasnyuk, M. M., & Korolyshyn, T. A. (2018). Interrelations between changes in parameters of HRV, EEG and phagocytosis at patients with chronic pyelonephritis and cholecystitis. Journal of Education, Health and Sport, 8(2), 135-156. http://dx.doi.org/10.5281/zenodo.1179635
80.Popovych, I., Ruzhylo, S., Ivassivka, S., & Aksentiychuk, B. (Eds.). (2005). Balneocardioangiology. The impact of balneotherapy in the spa Truskavets' on the cardiovascular system and physical performance [in Ukrainian]. Kyїv: Computerpress. 239.
81.Potapovich, A. I., Lulli, D., Fidanza, P., Kostyuk, V. A., De Luca, C., Pastore, S., & Korkina, L. G. (2011). Plant polyphenols differentially modulate inflammatory responses of human keratinocytes by interfering with activation of transcription factors NFκB and AhR and EGFR–ERK pathway. Toxicology and Applied Pharmacology, 255(2), 138-149. https://doi.org/10.1016/j.taap.2011.06.007
82.Quintana, F. J., & Sherr, D. H. (2013). Aryl hydrocarbon receptor control of adaptive immunity. Pharmacological Reviews, 65(4), 1148-1161. https://doi.org/10.1124/pr.113.007823
83.Rejano-Gordillo, C., Marín-Díaz, B., Ordiales-Talavero, A., Merino, J., González-Rico, F., & Fernandez-Salguero, P. (2022). From nucleus to organs: Insights of aryl hydrocarbon receptor molecular mechanisms. International Journal of Molecular Sciences, 23(23), 14919. https://doi.org/10.3390/ijms232314919
84.Ruzhylo, S. V., Popovych, A. I., Zakalyak, N. R., Chopyk, R. V., Fihura, O. A., Bilas, V. R., Badiuk, N. S., Gozhenko, A. I., Popovych, I. L., & Zukow, W. (2021). Bioactive water Naftussya and ozokerite have the same neuro-endocrine-immune effects in male rats caused by aryl hydrocarbons. PharmacologyOnLine, 3, 213-226.
85.Saha, N., & Samuel, M. (2024). Dietary xenobiotics and their role in immunomodulation. Food Science and Biotechnology, 1-13. https://doi.org/10.1007/s10068-024-01454-x
86.Sergeeva, I., Kiseleva, T., Pomozova, V., Shkrabtak, N., Frolova, N., & Vereshchagin, A. (2021). Experimental studies of the effect of schisandra chinensis extract on the state of adaptive capabilities of rats under chronic and general exposure to cold. International Journal of Environmental Research and Public Health, 18(22), 11780. https://doi.org/10.3390/ijerph182211780
87.Shin, J. H., Moreno-Nieves, U. Y., Zhang, L. H., Chen, C., Dixon, A. L., Linde, M. H., Mace, E. M., & Sunwoo, J. B. (2021). AHR regulates NK cell migration via ASB2-mediated ubiquitination of Filamin A. Frontiers in Immunology, 12, 624284. https://doi.org/10.3389/fimmu.2021.624284
88.Struk, Z. D., Melnyk, O. I., Zukow, W., & Popovych, I. L. (2019). The diversity of immune reactions to balneotherapy and their accompaniments. Journal of Education, Health and Sport, 9(11), 349-373. http://dx.doi.org/10.5281/zenodo.3533871
89.Sun, X. B., Matsumoto, T., & Yamada, H. (1992). Anti-ulcer activity and mode of action of the polysaccharide fraction from the leaves of Panax ginseng. Planta Medica, 58(5), 432-435. https://doi.org/10.1055/s-2006-961504
90.Szaefer, H., Licznerska, B., & Baer-Dubowska, W. (2024). The aryl hydrocarbon receptor and its crosstalk: A chemopreventive target of naturally occurring and modified phytochemicals. Molecules, 29(18), 4283. https://doi.org/10.3390/molecules29184283
91.Tang, J. S., Cait, A., Li, Y., Abolins-Thompson, H., Gell, K., Herst, P. M., Vissers, M., & Gasser, O. (2021). Practical approach to explore the effects of polyphenols on aryl hydrocarbon receptor regulated immune function. Journal of Agricultural and Food Chemistry, 69(31), 8625-8633. https://doi.org/10.1021/acs.jafc.1c01845
92.Tekin, İ. Ö., & Marotta, F. (2018). Polyphenols and immune system. In R. R. Watson, V. R. Preedy, & S. Zibadi (Eds.), Polyphenols: Prevention and treatment of human disease (pp. 263-276). Academic Press. https://doi.org/10.1016/B978-0-12-813008-7.00021-X
93.Todorova, V., Ivanov, K., & Ivanova, S. (2021). Comparison between the biological active compounds in plants with adaptogenic properties (Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus and Panax ginseng). Plants, 11(1), 64. https://doi.org/10.3390/plants11010064
94.Trego, M. L., Hoh, E., Kellar, N. M., Meszaros, S., Robbins, M. N., Dodder, N. G., Whitehead, A., & Lewison, R. L. (2018). Comprehensive screening links halogenated organic compounds with testosterone levels in male Delphinus delphis from the Southern California Bight. Environmental Science & Technology, 52(5), 3101-3109. https://doi.org/10.1021/acs.est.7b04652
95.Tserkovnyuk, A. V., & Ruzhylo, S. V. (2001a). Aerobic training optimization of the effect of balneotherapy at the Truskavets' resort on physical performance and its support systems [in Ukrainian]. Ukrainian Balneological Journal, 2, 39-45.
96.Tserkovnyuk, A. V., & Ruzhylo, S. V. (2001b). The influence of aerobic training against the background of balneotherapy at the Truskavets' resort on physical performance and its hemodynamic and metabolic support [in Ukrainian]. Ukrainian Balneological Journal, 1, 55-64.
97.Wang, X., Hawkins, B. T., & Miller, D. S. (2011). Aryl hydrocarbon receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier. FASEB Journal, 25, 644-652. https://doi.org/10.1096/fj.10-169227
98.Wang, Y., Ye, X., Ma, Z., Liang, Q., Lu, B., Tan, H., Xiao, C., Zhang, B., & Gao, Y. (2008). Induction of cytochrome P450 1A1 expression by ginsenoside Rg1 and Rb1 in HepG2 cells. European Journal of Pharmacology, 601(1-3), 73-78. https://doi.org/10.1016/j.ejphar.2008.10.057
99.Winkelmann, T., Thayer, J. F., Pohlak, S. T., Nees, F., Grimm, O., & Flor, H. (2017). Structural brain correlates of heart rate variability in healthy young adult population. Brain Structure and Function, 222(2), 1061-1068. https://doi.org/10.1007/s00429-016-1185-1
100.Xue, Z., Li, D., Yu, W., Zhang, Q., Hou, X., He, Y., & Kou, X. (2017). Mechanisms and therapeutic prospects of polyphenols as modulators of the aryl hydrocarbon receptor. Food & Function, 8(4), 1414-1437. https://doi.org/10.1039/c6fo01810f
101.Yang, X., Liu, H., Ye, T., Lei, X., Jiang, K., Zhou, Y., Xiao, X., Xie, K., Wang, G., & Duan, C. (2020). AhR activation attenuates calcium oxalate nephrocalcinosis by diminishing M1 macrophage polarization and promoting M2 macrophage polarization. Theranostics, 10(26), 12011-12025. https://doi.org/10.7150/thno.51144
102.Ye, L., Zhao, B., Hu, G., Chu, Y., & Ge, R. S. (2011). Inhibition of human and rat testicular steroidogenic enzyme activities by bisphenol A. Toxicology Letters, 207(2), 137-142. https://doi.org/10.1016/j.toxlet.2011.09.001
103.Zhang, M., Ma, L., Luo, J., Ren, T., Liu, S., Pan, L., Liang, J., Wang, Z., Jiang, K., Xiao, X., & Zheng, F. (2024). Low-medium polarity ginsenosides from wild ginseng improves immunity by activating the AhR/MAPK pathway through tryptophan metabolism driven by gut microbiota. Journal of Agricultural and Food Chemistry, 72(47), 26142-26154. https://doi.org/10.1021/acs.jafc.4c04830
104.Zhou, L. (2016). AHR function in lymphocytes: Emerging concepts. Trends in Immunology, 37(1), 17-31. https://doi.org/10.1016/j.it.2015.11.007
105.Zukow, W., Fihura, O. A., Żukow, X., Muszkieta, R., Hagner-Derengowska, M., Smoleńska, O., Michalska, A., Melnyk, O. I., Ruzhylo, S. V., Zakalyak, N. R., Kondratska, H. D., Voloshyn, O. R., & Popovych, I. L. (2024). Prevention of adverse effects of balneofactors at Truskavets' Spa on gastroenterologic patients through phytoadaptogens and therapeutic physical education: Mechanisms of rehabilitation. Journal of Physical Education and Sport, 24(4), 791-810. https://doi.org/10.7752/jpes.2024.04093
106.Zukow, W., Fihura, O. A., Korda, M. M., Klishch, I. M., Ruzhylo, S. V., Melnyk, O. I., Yanchij, R. I., & Popovych, I. L. (2024). Modulating effects of Ukrainian phytocomposition "Balm Truskavets'" on post stress changes in neuroendocrine-immune complex, metabolome, electrocardiogram, and gastric mucosa at rats. Journal of Education, Health and Sport, 64, 55171. https://dx.doi.org/10.12775/JEHS.2024.64.55171
107.Zukow, W., Fil, V. M., Kovalchuk, H. Y., Voloshyn, O. R., Kopko, I. Y., Lupak, O. M., Ivasivka, A. S., Musiyenko, O. V., Bilas, V. R., & Popovych, I. L. (2022). The role of innate muscular endurance and resistance to hypoxia in reactions to acute stress of immunity in rats. Journal of Physical Education and Sport, 22(7), 1608-1617. https://doi.org/10.7752/jpes.2022.07202
108.Zukow, W., Flyunt, I-S. S., Ponomarenko, R. B., Rybak, N. Y., Fil', V. M., Kovalchuk, H. Y., Sarancha, S. M., & Nahurna, Y. V. (2020). Polyvariant change of step-test under the influence of natural adaptogens and their accompaniments. Pedagogy and Psychology of Sport, 6(2), 74-84. https://doi.org/10.12775/PPS.2020.06.02.008
109.Zukow, W., Flyunt, I-S. S., Ruzhylo, S. V., Kovalchuk, H. Y., Nahurna, Y. V., Popovych, D. V., & Sarancha, S. M. (2021). Forecasting of multivariant changes in step test under the influence of natural adaptogens. Pedagogy and Psychology of Sport, 7(1), 85-93. https://doi.org/10.12775/PPS.2021.07.01.007
110.Zukow, W., Gozhenko, O. A., Zavidnyuk, Y. V., Korda, M. M., Mysula, I. R., Klishch, I. M., Zhulkevych, I. V., Popovych, I. L., Muszkieta, R., Napierata, M., Hagner-Derengowska, M., & Skaliy, A. (2020). Role of organic carbon and nitrogen of mineral waters in their neuro-endocrine effects at female rats. International Journal of Applied Exercise Physiology, 9(4), 20-25.
111.Zukow, W., Muszkieta, R., Hagner-Derengowska, M., Smoleńska, O., Żukow, X., Fil, V. M., Kovalchuk, H. Y., Voloshyn, O. R., Kopko, I. Y., Lupak, O. M., Ivasivka, A. S., Musiyenko, O. V., Ruzhylo, S. V., Kindrat, V., & Popovych, I. L. (2022a). Role of organic substances of Naftussya bioactive water in its effects on dynamic and static fitness in rats. Journal of Physical Education and Sport, 22(11), 2733-2742. https://doi.org/10.7752/jpes.2022.11347
112.Zukow, W., Muszkieta, R., Hagner-Derengowska, M., Smoleńska, O., Żukow, X., Melnyk, O. I., Popovych, D. V., Tserkoniuk, R. G., Hryhorenko, A. M., Yanchij, R. I., Kindrat, V., & Popovych, I. L. (2022b). Effects of rehabilitation at the Truskavets' spa on physical working capacity and its neural, metabolic, and hemato-immune accompaniments. Journal of Physical Education and Sport, 22(11), 2708-2722. https://doi.org/10.7752/jpes.2022.11344
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Copyright (c) 2025 Igor Bombushkar, Mykhaylo Korda, Anatoliy Gozhenko, Ivan Savytskyi, Oleksandr Chebanenko, Nataliya Badiuk, Walery Zukow, Anatoliy Anchev, Viktor Duzhar, Dariya Popovych, Igor Popovych

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