Effect of individual substances isolated from Silene jeniseensis Willd on the state of the main links of immunity at experimental immune deficiency

Introduction. The search, development and introduction of new drugs with an immunotropic effect are one of the priority tasks of modern immunopharmacology. Numerous studies have proven the immunotropic activity of individual substances isolated from medicinal plants (flavonoids, polysaccharides, ecdysteroids, terpenoids, etc.). In the present study, it is of interest to determine the immunomodulatory effect of individual substances isolated from Silene jeniseensis Willd.
The aim of the study. Determination of the immunomodulatory activity of individual substances isolated from Silene jeniseensis: flavonoid isoorientin-2”-O-rhamnoside, polysaccharide arabino-3.6-galactan and ecdysteroid 20-hydroxyecdysone under conditions of cyclophosphamide induced experimental immunosuppression.
Methods. Experiments were carried out on F1 (CBAxC57Bl/6) mice. Immunodeficiency was modeled by intraperitoneal administration of cyclophosphamide to control group animals in the dose 250 mg/kg once. Experimental groups of mice received the test substances intragastrically once a day for 14 days against the background of immunosuppression in the following doses: isoorientin-2”-O-rhamnoside – 10 mg/ kg, arabino-3.6-galactan – 3 mg/kg, 20-hydroxyecdysone – 3 mg/kg. The effect of substances on cellular immunity was determined in a delayed hypersensitivity reaction, humoral immunity was determined in an antibody formation reaction by local hemolysis according to A.J. Cunningham. The phagocytic activity of peritoneal macrophages was studied in relation to colloidal ink particles.
Results. With the introduction of isoorientin-2”-O-rhamnoside, arabino-3.6-galactan and 20-hydroxyecdysone in experimental animals, there was an increase in the index of delayed-type hypersensitivity reaction by 1.3–1.4 times, the absolute and relative number of antibody-forming cells by 1.4–1.7 times, phagocytic index by 1.2–1.5 times compared with the data in the control group, which indicates the leveling of the suppressive effect of cyclophosphamide on cell-mediated immune response, antibody genesis and phagocytosis of macrophages.
Conclusion. Isoorientin-2”-O-rhamnoside and arabino-3.6-galactan have the most pronounced immunomodulatory effect. The obtained data allow us to consider the studied substances as promising plant immunomodulators.

1. Ismailov IZ, Zurdinov AZ, Sabirova TS. Development and application of immunomodulators at the present stage: Problems and prospects. Nauchnyy zhurnal. 2017; 1(14): 83-87. (In Russ.).

2. Dutova SV, Karpova MR. Prospects for the study of immunotropic phytopreparations. Vestnik Khakasskogo gosudarstvennogo universiteta im. N.F. Katanova. 2016; 18: 117-121. (In Russ.).

3. Dhama K, Saminathan M, Jacob SS. Effect of immunomodulation and immunomodulatory agents on health with some bioactive principles, modes of action and potent biomedical applications. Int J Pharmacol. 2015; 11(4): 253-290.

4. Rama Bhat P. A review on immunomodulatory effects of plant extracts. Virol Immunol J. 2018; 2(6): 000167.

5. Wainwright CL, Teixeira MM, Adelson DL, Buenz EJ, David B, Glaser KB, et al. Future directions for the discovery of natural product-derived immunomodulating drugs: An IUPHAR positional review. Pharmacol Res. 2022; 177: 106076. doi: 10.1016/j.phrs.2022.106076

6. Novikova IA. Modern aspects of the clinical use of immunomodulators. Mezhdunarodnye obzory: klinicheskaya praktika i zdorov’e. 2016; 1(19): 59-67. (In Russ.).

7. Sambukova TV, Ovchinnikov BV, Ganapol’skij VP, Yatmanov AN, Shabanov PD. Prospects for the use of phytopreparations in modern pharmacology. Reviews on Clinical Pharmacology and Drug Therapy. 2017; 15(2): 56-63. (In Russ.). doi: 10.17816/RCF15256-63

8. David B, Wolfender J-L, Dias DA. The pharmaceutical industry and natural products: Historical status and new trends. Phytochem Rev. 2015; 14(2): 299-315. doi: 10.1007/s11101-014-9367-z

9. Tusupbekova GA, Rakhmetova AM, Moldakaryzova AZh, Alshynbekova GK, Tuleukhanov ST, Ashimkhanova GS, et al. The main properties of immunomodulating phytopreparations and the effectiveness of their use. Vestnik KazNMU. 2019; 1: 487-490. (In Russ.).

10. Jantan I, Ahmadand W, Bukhari S-N-A. Plant-derived immunomodulators: An insight on their preclinical evaluation and clinical trials. Front Plant Sci. 2015; 6: 665. doi: 10.3389/fpls.2015.00655

11. Kuznetsova LV. Influence of flavonoids on the indices of cellular immunity in children and adolescents who are ill with influenza and acute respiratory viral infections before and after treatment. Laboratory diagnostics. Eastern Europe. 2017; 6(3): 429-436. (In Russ.).

12. Ivanova EV, Voronkova IP, Bondarenko AI, Tarenkova IV. Immunotropic effect of medicinal plants with different trace element composition. Russian Journal of Immunology. 2021; 24(2): 331-336. (In Russ.). doi: 10.46235/1028-7221-994-IEO

13. Behl T, Kumar K, Brisc C, Rus M, Nistor-Cseppento DC, Bustea C, et al. Exploring the multifocal role of phytochemicals as immunomodulators. Biomed Pharmacother. 2021; 133: 110959. doi: 10.1016/j.biopha.2020.110959

14. Khobrakova VB, Khalzanova AV, Olennikov DN, Pavlova SI, Abiduyeva LR. Immunomodulatory activity of Silene jeniseensis Willd dry extract in experimental immunodeficiency. Pathological physiology and experimental therapy. 2020; 64(1): 113-117. (In Russ.). doi: 10.25557/0031-2991.2020.01.113-117

15. Olennikov DN, Kashchenko NI. New C,O-glycosylflavones from the genus Silene. Chem Nat Compd. 2020; 56(6): 1026-1034. doi: 10.1007/s10600-020-03220-x

16. Olennikov DN, Kashchenko NI. Phytoecdysteroids of Silene jenisseensis. Chem Nat Compd. 2017; 53(6): 1199-1201. doi: 10.1007/s10600-017-2239-1

17. Olennikov DN, Nazarova AV, Rokhin AV, Tankhaeva LM, Kornopol’tseva TA. Lamiaceae carbohydrates. VII. Glucoarabinogalactan from Panzerina lanata. Chem Nat Compd. 2009; 45(6): 864-866. doi: 10.1007/s10600-010-9486-8

18. Mironov AN. Guidelines for conducting preclinical trials of medicines, part 1. Moscow: Grif i K, 2012. (In Russ.).

19. Cunningham АJ. A method of increased sensitivity for detecting single antibody forming cells. Nature. 1965; 207(5001): 1106-1107. doi: 10.1038/2071106a0

20. Sergiyenko VI, Bondareva IB. Mathematical statistics in clinical research. Moscow: GEOTAR-Media, 2006. (In Russ.).

21. Ganeshpurkar A, Saluja AK. Protective effect of rutin on humoral and cell mediated immunity in rat model. Chem Biol Interact. 2017; 273: 154-159. doi: 10.1016/j.cbi.2017.06.006

22. Ganeshpurkar A, Saluja AK. Protective effect of catechin on humoral and cell mediated immunity in rat model. Int Immunopharmacol. 2018; 54: 261-266. doi: 10.1016/j.intimp.2017.11.022

23. Awad E, Awaad AS, Esteban MA. Effects of dihydroquercetin obtained from deodar (Cedrus deodara) on immune status of gilthead seabream (Sparus aurata L.). Fish Shellfish Immunol. 2015; 43(1): 43-50. doi: 10.1016/j.fsi.2014.12.009

24. Abd-Alla HI, Moharram FA, Gaara AH, El-Safty MM. Phytoconstituents of Jatropha curcas L. leaves and their immunomodulatory activity on humoral and cell-mediated immune response in chicks. Z Naturforsch C J Biosci. 2009; 64(7-8): 495-501. doi: 10.1515/znc-2009-7-805

25. Khobrakova VB, Budayeva YeR, Olennikov DN, Zilfikarov IN. Immunomodulatory activity of Gentiana algida Pall extract. Pharmaceutical Chemistry Journal. 2017; 51(5): 40-43. (In Russ.). doi: 10.30906/0023-1134-2017-51-5-40-43

26. Hosseinzade A, Sadeghi O, Naghdipour Biregani A, Soukhtehzari S, Brandt GS, Esmaillzadeh A. Immunomodulatory effects of flavonoids: Possible induction of t CD4+ regulatory cells through suppression of mTOR pathway signaling activity. Front Immunol. 2019; 10: 51. doi: 10.3389/fimmu.2019.00051

27. Bobayev ID, Alimova MT, Putiyeva ZhM, Kosnazarov ST, Ramazanov NSh. Experimental study of the immunostimulating effect of phytoecdysteroids Silene viridiflora L. Theoretical and applied ecology. 2012; 1: 55-57. (In Russ.).

28. Shakhmurova GA, Batyrbekov AA, Egamova FR, Khushbaktova ZA, Syrov VN. Experimental evaluation of the immunotropic action of total ecdysteroid-containing preparations from Silene brahuica and Ajuga turkestanica. Immunologia. 2013; 34(1): 24-26. (In Russ.).

29. Bajguz A, Bąkała I, Talarek M. Chapter 5 – Ecdysteroids in plants and their pharmacological effects in vertebrates and humans. Stud Nat Prod Chem. 2015; 45: 121-145. doi: 10.1016/B978-0-444-63473-3.00005-8

30. Khobrakova VB, Olennikov DN. Immunomodulatory properties of plant glucans in experimental immunosuppression. Acta biomedica scientifica. 2012; 6(88): 103-104. (In Russ.).

31. Budayeva YeR, Khobrakova VB. Influence of fractions obtained from the aerial part of Gentiana algida Pall. On the state of the cellular and humoral links of the immune response. Acta biomedica scientifica. 2015; 2: 70-72. (In Russ.).

32. Yu J, Cong L, Wang C, Li H, Zhang C, Guan X, et al. Immunomodulatory effect of Schisandra polysaccharides in cyclophosphamideinduced immunocompromised mice. Exp Ther Med. 2018; 15(6): 4755-4762. doi: 10.3892/etm.2018.6073

33. Li M, Yan YX, Yu QT, Deng Y, Wu DT, Wang Y, et al. Comparison of immunomodulatory effects of fresh garlic and black garlic polysaccharides on RAW 264.7 macrophages. J Food Sci. 2017; 82(3): 765-771. doi: 10.1111/1750-3841.13589

34. Ueno M, Cho K, Hirata N, Yamashita K, Yamaguchi K, Kim D, Oda T. Macrophage-stimulating activities of newly isolated complex polysaccharides from Parachlorella kessleri strain KNKA001. Int J Biol Macromol. 2017; 104(Pt A): 400-406. doi: 10.1016/j.ijbiomac.2017.06.014

35. Yin M, Zhang Y, Li H. Advances in research on immunoregulation of macrophages by plant polysaccharides. Front Immunol. 2019; 10: 145. doi: 10.3389/fimmu.2019.00145