Protective аction of ginseng root extract on myofibril apoptosis and immune response in rats after exhausting physical exercise. Part II. Effect of ginseng root extract on immunity and regulation of energy metabolism

Abstract

The quest for new bioactive compounds with an immune-oriented focus, as well as the study of the mechanisms of immunotropic action of the plant adaptogens used to restore and strengthen the immune system in athletes after intense physical exertion is a priority area of the research in sports medicine.

The aim of the study was to investigate the effect intragastric administration of ginseng root extract (GRE) (ginsenosides) on immunity and regulation of energy metabolism in rats after exhausting physical exercise (EPE).

Material and methods. The study was conducted on 5 groups of male Wistar rats with an initial body weight of ≈250 g. Animals of the control (the 1st) and experimental groups were placed on a treadmill for 20 min 3 times a week for 2 weeks, after the training was completed, an EPE test was performed (except for the control). 30 min before the training and EPE, rats of groups 3–5 were intragastrically administered GRE in physiological solution at doses of 2.7, 13.5 and 27.0 mg per 1 kg of body weight in terms of ginsenosides, respectively; animals of groups 1 and 2 – physiological solution. Animals were withdrawn from the experiment within 30 min after the cessation of EPE. Expression of CD45R, CD3, CD4, CD8a, CD161 receptors on rat peripheral blood lymphocytes was determined by direct immunofluorescence staining of whole blood cells using a panel of monoclonal antibodies on an FC-500 flow cytometer. A basic commercial kit was used to determine the levels of cytokines: interferon γ (IFN-γ), interleukin 1β (IL-1β), IL-4, IL-6, IL-10, IL-17A and tumor necrosis factor α (TNF-α), hormones leptin and ghrelin. Measurements were performed on a Luminex 200 multiplex analyzer using xMAP (multianalyte profiling) technology and Luminex xPONENT Version 3.1 software.

Results. EPE in rats caused changes in the composition of lymphocyte subpopulations, manifested in an increase in the relative content of CD8+ cytotoxic lymphocytes in the peripheral blood with a decrease in the immunoregulatory index (СD4+/CD8+). Increased plasma levels of pro-inflammatory cytokines (IL-17A and TNF-α) found in group 2 rats after EPE indicate the presence of inflammatory processes in damaged organs and tissues, including skeletal muscles. Intragastric administration of ginseng root extract to rats had a dose-dependent protective effect, as evidenced by normalization of the composition of lymphocyte subpopulations, a decrease in the levels of pro-inflammatory cytokines, an increase in the activity of Treg (regulatory T-lymphocytes) and Th2 (T-helpers type 2) with an increase in the production of IL-10 and IL-4, positive modulation of the IL-10/IL-17A ratio and restoration of the overall cytokine profile to control values. Ginseng root extract also has a positive effect on energy metabolism, in which regulation leptin and ghrelin participate. Administration of the maximum dose of ginseng root extract (27 mg/kg body weight) to rats induced activation of innate immunity, as evidenced by an increase in the relative content of NK and NKT cells in the peripheral blood.

Conclusion. The obtained results confirm the regulatory and normalizing effect of ginseng root extract (ginsenosides) on the immune status and energy metabolism of Wistar rats after EPE, which indicates the prospect of its use in stressful situations caused by physical overexertion in humans.

Keywords: ginseng root extract; exhausting physical exercise; cellular immunity; cytokines; leptin; ghrelin

Funding. The research was carried out using subsidy for the implementation of a state assignment within the framework of the Fundamental Scientific Research Program (Topic No. FGMF-2025-0001).

Conflict of interest. The authors declare no conflict of interest.

Contribution. Study concept and design – Aksenov I.V., Krasutskiy A.G.; Tutelyan V.A., Nikityuk D.B.; data collection and statistical processing – Trushina E.N., Rieger N.A., Timonin A.N., Mustafina O.K.; writing the text – Trushina E.N., Rieger N.A.; editing – Tutelyan V.A., Nikityuk D.B.; approval of the final version of the article, responsibility for the integrity of all parts of the article – all authors.

For citation: Trushina E.N., Rieger N.A., Mustafina O.K., Timonin A.N., Aksenov I.V., Krasutsky A.G., Tutelyan V.A., Nikityuk D.B. Protective аction of ginseng root extract on myofibril apoptosis and immune response in rats after exhausting physical exercise. Part II. Effect of ginseng root extract on immunity and regulation of energy metabolism. Voprosy pitaniia [Problems of Nutrition]. 2025; 94 (2): 61–72. DOI: https://doi.org/10.33029/0042-8833-2025-94-2-61-72 (in Russian)

References

1. Bay M.L., Pedersen B.K. Muscle-organ crosstalk: focus on immunometabolism. Front Physiol. 2020; 11: 567881. DOI: https://doi.org/10.3389/fphys.2020.567881

2. Padilha C.S., Von Ah Morano A.E., Krüger K., Rosa-Neto J.C., Lira F.S. The growing field of immunometabolism and exercise: key findings in the last 5 years. J Cell Physiol. 2022; 237 (11): 4001–20. DOI: https://doi.org/10.1002/jcp.30866

3. Suzuki K. Recent progress in applicability of exercise immunology and inflammation research to sports nutrition. Nutrients. 2021; 13: 4299. DOI: https://doi.org/10.3390/nu13124299

4. Wahl P., Mathes S., Bloch W., Zimmer P. Acute impact of recovery on the restoration of cellular immunological homeostasis. Int J Sports Med. 2020; 41: 12–20. DOI: https://doi.org/10.1055/a-1015-0453

5. Kozlov V.A., Kudaeva О.Т. The review contains literature data concerning the influence of physical activity on innate and acquired immunity. Possible reasons and mechanisms of exercise stress influence on immunity are discussed. Meditsinskaya immunologiya [Medical Immunology]. 2002; 4 (3): 427–38. (in Russian)

6. Pal’tsyn A.A. Myokines. Pathologicheskaya fiziologiya i experimental’naya terapiya [Pathological Physiology and Experimental Therapy]. 2020; 64 (1); 135–41. DOI: https://doi.org/10.25557/0031-2991-2020-01-135-141 (in Russian)

7. Picó C., Palou M., Pomar C.A., Rodríguez A.M., Palou A. Leptin as a key regulator of the adipose organ. Rev Endocr Metab Disord. 2021; 23: 13–30. DOI: https://doi.org/10.1007/s11154-021-09687-5

8. Romantsova T.I., Volkova G.E. Leptin and ghrelin: antagonism and interaction in the regulation of energy metabolism. Ozhirenie i metabolism [Obesity and Metabolism]. 2005; 2 (2): 2–8. DOI: https://doi.org/10.14341/2071-8713-4924 (in Russian)

9. Gajewska A., Strzelecki D., Gawlik-Kotelnicka O. Ghrelin as a biomarker of «immunometabolic depression» and its connection with dysbiosis. Nutrients. 2023; 15 (18): 3960. DOI: https://doi.org/10.3390/nu15183960

10. Todorova V., Ivanov K., Delattre C., Nalbantova V., Karcheva-Bahchevanska D., Ivanova S. Plant adaptogens – history and future perspectives. Nutrients. 2021; 13 (8): 2861. DOI: https://doi.org/10.3390/nu13082861

11. Yu S.E., Mwesige B., Yi Y.S., Yoo B.C. Ginsenosides: the need to move forward from bench to clinical trials. J Ginseng Res. 2019; 43 (3): 361– 7. DOI: https://doi.org/10.1016/j.jgr.2018.09.001

12. He Y., Hu Z., Li A., Zhu Z., Yang N., Ying Z. et al. Recent advances in biotransformation of saponins. Molecules. 2019; 24 (13): 2365. DOI: https://doi.org/10.3390/molecules2413236

13. He B., Chen D., Zhang X., Yang R., Yang Y., Chen P., et al. Oxidative stress and ginsenosides: an update on the molecular mechanisms. Oxid Med Cell Longev. 2022; 2022): 9299574. DOI: https://doi.org/10.1155/2022/9299574

14. Kim J.N., Kim D.H., Jo S., Cho M.J., Cho Y.R., Lee Y.J., et al. Immunomodulatory functional foods and their molecular mechanisms. Exp Mol Med. 2022; 54 (1): 1–11. DOI: https://doi.org/10.1038/s12276-022-00724-0

15. He L.X., Ren J.W, Liu R., Chen Q.H., Zhao J., Wu X., et al. Ginseng (Panax ginseng Meyer) oligopeptides regulate innate and adaptive immune responses in mice via increased macrophage phagocytosis capacity, NK cell activity and Th cells secretion. Food Funct. 2017; 8 (10): 3523–32. DOI: https://doi.org/10.1039/c7fo00957g

16. Um Y., Eo H.J., Kim H.J., Kim K., Jeon K.S., Jeong J.B. Wild simulated ginseng activates mouse macrophage, RAW264.7 cells through TRL2/4-dependent activation of MAPK, NF-κB and PI3K/AKT pathways. J Ethnopharmacol. 2020; 263: 113218. DOI: https://doi.org/10.1016/j.jep.2020.113218

17. Lim T.G., Jang Mi, Cho C.W., Hong H.D., Kim K.T., Lee S.Y., et al. White ginseng extract induces immunomodulatory effects via the MKK4-JNK pathway. Food Sci Biotechnol. 2016; 25: 1737–44. DOI: https://doi.org/10.1007/s10068-016-0265-6

18. Trushina E.N., Mustafina O.K., Aksenov I.V., Krasutsky A.G., Tutelyan V.A., Nikityuk D.B. Protective action of ginseng root extract on myofibril apoptosis and immune response in rats after exhausting physical exercise. Part I. Effect of ginseng root extract on myofibril apoptosis in rats’ gastrocnemius muscle. Voprosy pitaniia [Problems of Nutrition]. 2025; 94 (1): 111–7. DOI: https://doi.org/10.33029/0042-8833-2025-94-1-111-117 (in Russian)

19. Trushina E.N., Mustafina O.K., Aksenov I.V., Krasutsky A.G., Nikityuk D.B., Tutelyan V.A. Bioactive compounds anthocyanins as a factor in the nutritional recovery of the body’s adaptive potential after intense physical activity in the experiment: assessment of immunological and hematological indicators of adaptation. Voprosy pitaniia [Problems of Nutrition]. 2023; 92 (1): 6–15. DOI: https://doi.org/10.33029/0042-8833-2023-92-1-6-15 (in Russian)

20. Malsagova K.A., Astrelina T.A., Balakin E.I., Kobzeva I.V., Adoeva E.Ya., Yurku K.A. et al. Influence of Sports Training in Foothills on the Professional Athlete’s Immunity. Sports (Basel). 2023; 11 (2):30. DOI: https://doi.org/10.3390/sports11020030

21. Schlagheck M.L., Walzik D., Joisten N., Koliamitra C., Hardt L., Metcalfe A.J., et al. Cellular immune response to acute exercise: comparison of endurance and resistance exercise. Eur J Haematol. 2020; 105 (1): 75–84. DOI: https://doi.org/10.1111/ejh.13412

22. Yang W., Hu P. Skeletal muscle regeneration is modulated by inflammation. J Orthop Translat. 2018; 7 (13): 25–32. DOI: https://doi.org/10.1016/j.jot.2018.01.002

23. Guo Y.T., Peng Y.C., Yen H.Y., Wu J.C., Hou W.H. Effects of probiotic supplementation on immune and inflammatory markers in athletes: a meta-analysis of randomized clinical trials. Medicina (Kaunas). 2022; 58 (9): 1188. DOI: https://doi.org/10.3390/medicina58091188

24. Shek P.N., Sabiston B.H., Buguet A., Radomski M.W. Strenuous exercise and immunological changes: a multiple-time-point analysis of leukocyte subsets, CD4/CD8 ratio, immunoglobulin production and NK cell response. Int J Sports Med. 1995; 16 (7): 466–74. DOI: https://doi.org/10.1055/s-2007-973039

25. Simpson R.J., Boßlau T.K., Weyh C.W., Niemiro G.M., Batatinha H., Smith K.A., et al. Exercise and adrenergic regulation of immunity. Brain Behav Immun. 2021; 97: 303–18. DOI: https://doi.org/10.1016/j.bbi.2021.07.010

26. Graff R.M., Kunz H.E., Agha N.H., Baker F.L., Laughlin M., Bigley A.B., et al. Agha/β 2-Adrenergic receptor signaling mediates the preferential mobilization of differentiated subsets of CD8+ T-cells, NK-cells and non-classical monocytes in response to acute exercise in humans. Brain Behav Immun. 2018; 74: 143–53. DOI: https://doi.org/10.1016/j.bbi.2018.08.017

27. Kurowski M., Seys S., Bonini M., Del Giacco S., Delgado L., Diamant Z., et al. Physical exercise, immune response, and susceptibility to infections-current knowledge and growing research areas. Allergy. 2022; 77 (9): 2653–64. DOI: https://doi.org/10.1111/all.15328

28. Rooney B.V., Bigley A.B., LaVoy E.C., Laughlin M., Pedlar C., Simpson R.J. Lymphocytes and monocytes egress peripheral blood within minutes after cessation of steady state exercise: a detailed temporal analysis of leukocyte extravasation. Physiol Behav. 2018; 194: 260–7. DOI: https://doi.org/10.1016/j.physbeh.2018.06.008

29. Llavero F., Alejo L.B., Fiuza-Luces C., López Soto A., Valenzuela P.L., Castillo-García A., et al. Exercise training effects on natural killer cells: a preliminary proteomics and systems biology approach. Exerc Immunol Rev. 2021; 27: 125–41. PMID: 33965896.

30. Pal A., Schneider J., Schlüter K., Steindorf K., Wiskemann J., Rosenberger F., et al. Different endurance exercises modulate NK cell cytotoxic and inhibiting receptors. Eur J Appl Physiol. 2021; 121 (12): 3379–87. DOI: https://doi.org/10.1007/s00421-021-04735-z

31. Akinfieva O.V., Bubnova L.N., Bessmel’tsev S.S NKT cells: characteristic features and functional significance in the immune response regulation. Onkogematologiya [Oncohemotology]. 2010; (4): 39–47. (in Russian)

32. Suzuki K., Hayashida H. Effect of exercise intensity on cell-mediated immunity. Sports (Basel). 2021; 9 (1): 8. DOI: https://doi.org/10.3390/sports9010008

33. Anderson K.C., Zieff G., Paterson C., Stoner L., Weltman A., Allen J.D. The effect of acute exercise on pre-prandial ghrelin levels in healthy adults: a systematic review and meta-analysis. Peptides. 2021; 145: 170625. DOI: https://doi.org/10.1016/j.peptides.2021.170625

34. Tacad D.K.M., Tovar A.P., Richardson C.E., Horn W.F., Krishnan G.P., Keim N.L., et al. Satiety associated with calorie restriction and time-restricted feeding: peripheral hormones. Adv Nutr. 2022; 13 (3): 792–820. DOI: https://doi.org/10.1093/advances/nmac014

35. da Silva Pereira J.A., da Silva F.C., de Moraes-Vieira P. The impact of ghrelin in metabolic diseases: an immune perspective. J Diabetes Res. 2017; 2017: 4527980. DOI: https://doi.org/10.1155/2017/4527980

36. Lim W.C., Shin E.J., Lim T.G., Choi J.W., Song N.E., Hong H.D., et al. Ginsenoside Rf enhances exercise endurance by stimulating myoblast differentiation and mitochondrial biogenesis in C2C12 myotubes and ICR mice. Foods. 2022; 11 (12): 1709. DOI: https://doi.org/10.3390/foods11121709

37. Lee S.Y., Jeong J.J., Eun S.H., Kim D.H. Anti-inflammatory effects of ginsenoside Rg1 and its metabolites ginsenoside Rh1 and 20(S)-protopanaxatriol in mice with TNBS-induced colitis. Eur J Pharmacol. 2015; 762: 333–43. DOI: https://doi.org/10.1016/j.ejphar.2015.06.011

38. Jung J.H., Kang T.K., Oh J.H., Jeong J.U., Ko K.P., Kim S.T. The effect of Korean red ginseng on symptoms and inflammation in patients with allergic rhinitis. Ear Nose Throat J. 2020; 100: S712–9. DOI: https://doi.org/10.1177/0145561320907172

39. Liu T., Wang D., Zhou X., Song J., Yang Z., Shi C., et al. Study on the mechanism of American ginseng extract for treating type 2 diabetes mellitus based on metabolomics. Front Pharmacol. 2022; 2 (13): 960050. DOI: https://doi.org/10.3389/fphar.2022.960050

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

SCImago Journal & Country Rank
Scopus CiteScore
CHIEF EDITOR
CHIEF EDITOR
Viktor A. Tutelyan
Full Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Scientific Director of the Federal Research Centre of Nutrition, Biotechnology and Food Safety (Moscow, Russia)

Journals of «GEOTAR-Media»