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Immune-enhancing effect of hydrolyzed and fermented Platycodon grandiflorum extract in cyclophosphamide-induced immunosuppressed BALB/c mice

  • Hyun Sook Lee (Department of Food Science and Nutrition, Dongseo University) ;
  • So Mi Kim (Regional Strategic Industry Innovation Center, Hallym University) ;
  • Jae In Jung (Regional Strategic Industry Innovation Center, Hallym University) ;
  • Jihoon Lim (R&D Center, World Food Services Co. Ltd.) ;
  • Moonjea Woo (R&D Center, World Food Services Co. Ltd.) ;
  • Eun Ji Kim (Regional Strategic Industry Innovation Center, Hallym University)
  • Received : 2022.05.24
  • Accepted : 2022.08.16
  • Published : 2023.04.01

Abstract

BACKGROUND/OBJECTIVES: The immunomodulatory effect of Platycodon grandiflorum (PG) has been reported, but studies on its mechanism are still lacking. This study was undertaken to confirm whether the hydrolyzed and fermented PG extract (HFPGE) obtained by adding hydrolysis and fermentation to the extraction process has an immune-enhancing effect in the in vivo system. MATERIALS/METHODS: Five-week-old BALB/c mice were divided into 4 groups: normal control group (NOR), control group (CON), 150 mg/kg body weight (BW)/day HFPGE-treated group (T150), and 300 mg/kg BW/day HFPGE-treated group (T300). The mice were administered HFPGE for 4 weeks and intraperitoneally injected with cyclophosphamide (CPA, 80 mg/kg BW/day) on day 6, 7, and 8, respectively, to induce immunosuppression. The levels of immunoglobulins (Igs) and cytokines were measured in the serum. In splenocytes, proliferation and cytokine levels were measured. RESULTS: Serum IgA, IgG, and IgM levels were observed to decrease after CPA treatment, which was recovered by HFPGE administration. The levels of serum interleukin (IL)-12, tumor necrosis factor (TNF)-α, IL-8, and transforming growth factor (TGF)-β were also decreased after exposure to CPA but increased after HFPGE administration. Decreased splenocyte proliferation was seen in CPA-treated mice, but was observed to increase in the T150 and T300 groups as compared to the NOR group. Compared to the CON group, splenocyte proliferation stimulated with concanavalin A (ConA) or lipopolysaccharide (LPS) in the HFPGE-treated groups was significantly increased. The cytokines secreted by ConA-stimulated splenocytes (IL-2, IL-12, interferon-γ, TNF-α) were increased in the T150 and T300 groups, and cytokines secreted by LPS-stimulated splenocytes (IL-4, IL-8, TGF-β) were also increased by HFPGE administration. CONCLUSION: These results suggest that HFPGE stimulates the immunity in immunosuppressed conditions, thereby enhancing the immune response. Therefore, it is expected that HFPGE has the potential to be used as functional food and medicine for immune recovery in various immunocompromised situations.

Keywords

Acknowledgement

This research was supported by an R&D grant from the Gangneung Science & Industry Promotion Agency of Korea in 2020-2021.

References

  1. Park HY, Shin JH, Boo HO, Gorinstein S, Ahn YG. Discrimination of Platycodon grandiflorum and Codonopsis lanceolata using gas chromatography-mass spectrometry-based metabolomics approach. Talanta 2019;192:486-91. https://doi.org/10.1016/j.talanta.2018.09.051
  2. Zhang L, Wang Y, Yang D, Zhang C, Zhang N, Li M, Liu Y. Platycodon grandiflorus - an ethnopharmacological, phytochemical and pharmacological review. J Ethnopharmacol 2015;164:147-61. https://doi.org/10.1016/j.jep.2015.01.052
  3. Nyakudya E, Jeong JH, Lee NK, Jeong YS. Platycosides from the roots of Platycodon grandiflorum and their health benefits. Prev Nutr Food Sci 2014;19:59-68. https://doi.org/10.3746/pnf.2014.19.2.059
  4. Ji MY, Bo A, Yang M, Xu JF, Jiang LL, Zhou BC, Li MH. The pharmacological effects and health benefits of Platycodon grandiflorus - a medicine food homology species. Foods 2020;9:E142.
  5. Li W, Tian YH, Liu Y, Wang Z, Tang S, Zhang J, Wang YP. Platycodin D exerts anti-tumor efficacy in H22 tumor-bearing mice via improving immune function and inducing apoptosis. J Toxicol Sci 2016;41:417-28. https://doi.org/10.2131/jts.41.417
  6. Huang YH, Jung DW, Lee OH, Kang IJ. Fermented Platycodon grandiflorum extract inhibits lipid accumulation in 3T3-L1 adipocytes and high-fat diet-induced obese mice. J Med Food 2016;19:1004-14. https://doi.org/10.1089/jmf.2016.3805
  7. Jung JI, Lee HS, Kim SM, Kim S, Lim J, Woo M, Kim EJ. Immunostimulatory activity of hydrolyzed and fermented Platycodon grandiflorum extract occurs via the MAPK and NF-κB signaling pathway in RAW 264.7 cells. Nutr Res Pract 2022;16:e39.
  8. Parkin J, Cohen B. An overview of the immune system. Lancet 2001;357:1777-89. https://doi.org/10.1016/S0140-6736(00)04904-7
  9. Wang K, Conlon M, Ren W, Chen BB, Baczek T. Natural products as targeted modulators of the immune system. J Immunol Res 2018;2018:7862782.
  10. Sakthivel KM, Guruvayoorappan C. Acacia ferruginea inhibits cyclophosphamide-induced immunosuppression and urotoxicity by modulating cytokines in mice. J Immunotoxicol 2015;12:154-63. https://doi.org/10.3109/1547691X.2014.914988
  11. Pass GJ, Carrie D, Boylan M, Lorimore S, Wright E, Houston B, Henderson CJ, Wolf CR. Role of hepatic cytochrome p450s in the pharmacokinetics and toxicity of cyclophosphamide: studies with the hepatic cytochrome p450 reductase null mouse. Cancer Res 2005;65:4211-7. https://doi.org/10.1158/0008-5472.CAN-04-4103
  12. Tripathi DN, Jena GB. Intervention of astaxanthin against cyclophosphamide-induced oxidative stress and DNA damage: a study in mice. Chem Biol Interact 2009;180:398-406. https://doi.org/10.1016/j.cbi.2009.03.017
  13. Noh EM, Kim JM, Lee HY, Song HK, Joung SO, Yang HJ, Kim MJ, Kim KS, Lee YR. Immuno-enhancement effects of Platycodon grandiflorum extracts in splenocytes and a cyclophosphamide-induced immunosuppressed rat model. BMC Complement Altern Med 2019;19:322.
  14. Zhou Y, Chen X, Yi R, Li G, Sun P, Qian Y, Zhao X. Immunomodulatory effect of tremella polysaccharides against cyclophosphamide-induced immunosuppression in mice. Molecules 2018;23:E239.
  15. Yu Q, Nie SP, Wang JQ, Liu XZ, Yin PF, Huang DF, Li WJ, Gong DM, Xie MY. Chemoprotective effects of Ganoderma atrum polysaccharide in cyclophosphamide-induced mice. Int J Biol Macromol 2014;64:395-401. https://doi.org/10.1016/j.ijbiomac.2013.12.029
  16. Lee S, Han EH, Lim MK, Lee SH, Yu HJ, Lim YH, Kang S. Fermented Platycodon grandiflorum extracts relieve airway inflammation and cough reflex sensitivity in vivo. J Med Food 2020;23:1060-9. https://doi.org/10.1089/jmf.2019.4595
  17. Wu Y, Zhu CP, Zhang Y, Li Y, Sun JR. Immunomodulatory and antioxidant effects of pomegranate peel polysaccharides on immunosuppressed mice. Int J Biol Macromol 2019;137:504-11. https://doi.org/10.1016/j.ijbiomac.2019.06.139
  18. Mallery DL, McEwan WA, Bidgood SR, Towers GJ, Johnson CM, James LC. Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21). Proc Natl Acad Sci U S A 2010;107:19985-90. https://doi.org/10.1073/pnas.1014074107
  19. Woof JM, Kerr MA. The function of immunoglobulin A in immunity. J Pathol 2006;208:270-82. https://doi.org/10.1002/path.1877
  20. Racine R, McLaughlin M, Jones DD, Wittmer ST, MacNamara KC, Woodland DL, Winslow GM. IgM production by bone marrow plasmablasts contributes to long-term protection against intracellular bacterial infection. J Immunol 2011;186:1011-21. https://doi.org/10.4049/jimmunol.1002836
  21. Wang J, Tong X, Li P, Cao H, Su W. Immuno-enhancement effects of Shenqi Fuzheng Injection on cyclophosphamide-induced immunosuppression in BALB/c mice. J Ethnopharmacol 2012;139:788-95. https://doi.org/10.1016/j.jep.2011.12.019
  22. Lee I, Kwon DH, Lee SH, Lee SD, Kim DW, Lee JH, Hyun SK, Kang KH, Kim CM, Kim BW, et al. Immunomodulation effect of Ulmus macrocarpa Hance water extract on BALB/c mice. J Life Sci 2014;24:1151-6. https://doi.org/10.5352/JLS.2014.24.10.1151
  23. Ryu HS. Effects of water extract from Platycodon grandiflorum on mouse immune cell activation ex vivo by oral administration. Korean J Food Nutr 2014;27:99-104. https://doi.org/10.9799/ksfan.2014.27.1.099
  24. Ader JL, Rostaing L. Cyclosporin nephrotoxicity: pathophysiology and comparison with FK-506. Curr Opin Nephrol Hypertens 1998;7:539-45. https://doi.org/10.1097/00041552-199809000-00009
  25. Artym J, Zimecki M, Kruzel ML. Effect of lactoferrin on the methotrexate-induced suppression of the cellular and humoral immune response in mice. Anticancer Res 2004;24:3831-6.
  26. Kim HS, Chung KT, Lee IH, Choi WB, Lee JH, Hyun SK, Kim BW, Hwang HJ. Effect of Alpina officinarum ethanol extract on immunoregulatory activities in the mice. J Life Sci 2014;24:61-6. https://doi.org/10.5352/JLS.2014.24.1.61
  27. Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med 2004;351:2715-29. https://doi.org/10.1056/NEJMra033540
  28. Bronte V, Pittet MJ. The spleen in local and systemic regulation of immunity. Immunity 2013;39:806-18. https://doi.org/10.1016/j.immuni.2013.10.010
  29. Weissman IL, Anderson DJ, Gage F. Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol 2001;17:387-403. https://doi.org/10.1146/annurev.cellbio.17.1.387
  30. Massberg S, Schaerli P, Knezevic-Maramica I, Kollnberger M, Tubo N, Moseman EA, Huff IV, Junt T, Wagers AJ, Mazo IB, et al. Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues. Cell 2007;131:994-1008. https://doi.org/10.1016/j.cell.2007.09.047
  31. Lee EB, Lee SH, Park YG, Choi JH, Lee HK, Jang HH, Hwang GA, Choe JS, Park SY, Choi AJ, et al. Platycodon grandiflorum extract ameliorates cyclophosphamide-induced immunosuppression in mice. J East Asian Soc Diet Life 2019;29:303-9. https://doi.org/10.17495/easdl.2019.8.29.4.303
  32. Jung CW, Kim SJ, Anh NH, Lee EG, Kim TH, Kwon SW, et al. The clinical effects of Platycodon grandiflorum: a systematic review. Korean J Pharmacogn 2021;52:1-12.