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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2019

Open Access 01-12-2019 | Cytokines | Research article

Immuno-enhancement effects of Platycodon grandiflorum extracts in splenocytes and a cyclophosphamide-induced immunosuppressed rat model

Authors: Eun-Mi Noh, Jeong-Mi Kim, Hak Yong Lee, Hyun-Kyung Song, Sang Ok Joung, Hye Jeong Yang, Min Jung Kim, Kang Sung Kim, Young-Rae Lee

Published in: BMC Complementary Medicine and Therapies | Issue 1/2019

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Abstract

Background

Platycodon grandiflorum is a flowering plant that is used in traditional medicine for treating pulmonary and respiratory disorders. It exerts various pharmacological effects, including immunomodulatory and anti-cancer activities. The purpose of this study was to confirm the in vitro and in vivo immune-enhancing effects of P. grandiflorum extract (PGE) on splenocytes isolated from cyclophosphamide (CP)-induced immunosuppressed rats.

Methods

For in vitro analysis, splenocytes were treated with PGE at various doses along with CP. Cell viability was measured by a WST-1 assay, and NK cell activity and cytotoxic T lymphocyte (CTL) activity was also examined. In addition, immunoglobulin A (IgA), IgG, and cytokine levels were measured. For in vivo analysis, Sprague Dawley rats were treated with various doses of PGE along with CP. Complete blood count (CBC) was performed, and plasma levels of IgA, IgG, TNF-α, IFN-γ, IL-2, and IL-12 were quantified. Additionally, tissue damage was assessed through histological analyses of the thymus and spleen.

Results

PGE treatment enhanced cell viability and natural killer cell and cytotoxic T lymphocyte activity, and increased the production of CP-induced inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA) in splenocytes. In addition, in CP-treated rats, PGE treatment induced the recovery of white blood cell, neutrophil, and lymphocyte counts, along with mid-range absolute counts, and increased the serum levels of inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA). Moreover, PGE attenuated CP-induced spleen and thymic damage.

Conclusions

Our results confirmed that PGE exerts an immune-enhancing effect both in vitro and in vivo, suggesting that PGE may have applications as a component of immunostimulatory agents or as an ingredient in functional foods.
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Literature
1.
Li W, Liu Y, Wang Z, Han Y, Tian YH, Zhang GS, Sun YS, Wang YP. Platycodin D isolated from the aerial parts of Platycodon grandiflorum protects alcohol-induced liver injury in mice. Food Funct. 2015;6(5):1418–27.PubMedCrossRef
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.PubMedCrossRef
3.
Han LK, Zheng YN, Xu BJ, Okuda H, Kimura Y. Saponins from platycodi radix ameliorate high fat diet-induced obesity in mice. J Nutr. 2002;132(8):2241–5.PubMedCrossRef
4.
Chun J, Joo EJ, Kang M, Kim YS. Platycodin D induces anoikis and caspase-mediated apoptosis via p38 MAPK in AGS human gastric cancer cells. J Cell Biochem. 2013;114(2):456–70.PubMedCrossRef
5.
Wang C, Schuller Levis GB, Lee EB, Levis WR, Lee DW, Kim BS, Park SY, Park E. Platycodin D and D3 isolated from the root of Platycodon grandiflorum modulate the production of nitric oxide and secretion of TNF-alpha in activated RAW 264.7 cells. Int Immunopharmacol. 2004;4(8):1039–49.PubMedCrossRef
6.
Xie Y, Sun HX, Li D. Platycodin D improves the immunogenicity of Newcastle disease virus-based recombinant avian influenza vaccine in mice. Chem Biodivers. 2010;7(3):677–89.PubMedCrossRef
7.
Han EH, Park JH, Kim JY, Chung YC, Jeong HG. Inhibitory mechanism of saponins derived from roots of Platycodon grandiflorum on anaphylactic reaction and IgE-mediated allergic response in mast cells. Food Chem Toxicol. 2009;47(6):1069–75.PubMedCrossRef
8.
9.
10.
11.
Raj S, Gothandam KM. Immunomodulatory activity of methanolic extract of Amorphophallus commutatus var. wayanadensis under normal and cyclophosphamide induced immunosuppressive conditions in mice models. Food Chem Toxicol. 2015;81:151–9.PubMedCrossRef
12.
Shin JS, Chung SH, Lee WS, Lee JY, Kim JL, Lee KT. Immunostimulatory effects of cordycepin-enriched WIB-801CE from Cordyceps militaris in splenocytes and cyclophosphamide-induced immunosuppressed mice. Phytother Res. 2018;32(1):132–9.PubMedCrossRef
13.
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(10):4211–7.PubMedCrossRef
14.
Tripathi DN, Jena GB. Intervention of astaxanthin against cyclophosphamide-induced oxidative stress and DNA damage: a study in mice. Chem Biol Interact. 2009;180(3):398–406.PubMedCrossRef
15.
16.
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.PubMedCrossRef
17.
Haddad PS, Azar GA, Groom S, Boivin M. Natural health products, modulation of immune function and prevention of chronic diseases. Evid Based Complement Alternat Med. 2005;2(4):513–20.PubMedPubMedCentralCrossRef
18.
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.PubMedPubMedCentral
19.
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(3):417–28.PubMedCrossRef
20.
Lee HY, Park YM, Lee YH, Kang YG, Lee HM, Park DS, Yang HJ, Kim MJ, Lee YR. Immunostimulatory effect of Zanthoxylum schinifolium-based complex oil prepared by supercritical fluid extraction in Splenocytes and cyclophosphamide-induced immunosuppressed rats. Evid Based Complement Alternat Med. 2018;2018:8107326.PubMedPubMedCentral
21.
Medzhitov R, Janeway CA Jr. Innate immunity: impact on the adaptive immune response. Curr Opin Immunol. 1997;9(1):4–9.PubMedCrossRef
22.
Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol. 2003;3(9):745–56.PubMedCrossRef
23.
Boyman O, Sprent J. The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol. 2012;12(3):180–90.PubMedCrossRef
24.
Lin PL, Plessner HL, Voitenok NN, Flynn JL. Tumor necrosis factor and tuberculosis. J Invest Dermatol Symp Proc. 2007;12(1):22–5.CrossRef
25.
Fang Q, Wang JF, Zha XQ, Cui SH, Cao L, Luo JP. Immunomodulatory activity on macrophage of a purified polysaccharide extracted from Laminaria japonica. Carbohydr Polym. 2015;134:66–73.PubMedCrossRef
26.
Lee J, Choi JW, Sohng JK, Pandey RP, Park YI. The immunostimulating activity of quercetin 3-O-xyloside in murine macrophages via activation of the ASK1/MAPK/NF-kappaB signaling pathway. Int Immunopharmacol. 2016;31:88–97.PubMedCrossRef
27.
Kim EH, Gwak JY, Chung MJ. Immunomodulatory activity of Platycodon grandiflorum, Codonopsis lanceolata, and Adenophora triphylla extracts in macrophage cells. Korean Soc Food Nutr. 2018;47(11):1069–75.CrossRef
28.
29.
Wang H, Wang M, Chen J, Tang Y, Dou J, Yu J, Xi T, Zhou C. A polysaccharide from Strongylocentrotus nudus eggs protects against myelosuppression and immunosuppression in cyclophosphamide-treated mice. Int Immunopharmacol. 2011;11(11):1946–53.PubMedCrossRef
30.
Diwanay S, Chitre D, Patwardhan B. Immunoprotection by botanical drugs in cancer chemotherapy. J Ethnopharmacol. 2004;90(1):49–55.PubMedCrossRef
31.
Huang GC, Wu LS, Chen LG, Yang LL, Wang CC. Immuno-enhancement effects of Huang qi Liu Yi Tang in a murine model of cyclophosphamide-induced leucopenia. J Ethnopharmacol. 2007;109(2):229–35.PubMedCrossRef
32.
Hu TJ, Shuai XH, Chen JR, Wei YY, Zheng RL. Protective effect of a Potentilla anserine polysaccharide on oxidative damages in mice. Int J Biol Macromol. 2009;45(3):279–83.PubMedCrossRef
33.
Li WJ, Li L, Zhen WY, Wang LF, Pan M, Lv JQ, Wang F, Yao YF, Nie SP, Xie MY. Ganoderma atrum polysaccharide ameliorates ROS generation and apoptosis in spleen and thymus of immunosuppressed mice. Food Chem Toxicol. 2017;99:199–208.PubMedCrossRef
34.
Klimp AH, de Vries EG, Scherphof GL, Daemen T. A potential role of macrophage activation in the treatment of cancer. Crit Rev Oncol Hematol. 2002;44(2):143–61.PubMedCrossRef
35.
Zeng G, Ju Y, Shen H, Zhou N, Huang L. Immunopontentiating activities of the purified polysaccharide from evening primrose in H22 tumor-bearing mice. Int J Biol Macromol. 2013;52:280–5.PubMedCrossRef
36.
Lacy P, Stow JL. Cytokine release from innate immune cells: association with diverse membrane trafficking pathways. Blood. 2011;118(1):9–18.PubMedCrossRef
37.
Van der Meide PH, Schellekens H. Cytokines and the immune response. Biotherapy. 1996;8(3–4):243–9.PubMedCrossRef
38.
Zhou X, Luo L, Dressel W, Shadier G, Krumbiegel D, Schmidtke P, Zepp F, Meyer CU. Cordycepin is an immunoregulatory active ingredient of Cordyceps sinensis. Am J Chin Med. 2008;36(5):967–80.PubMedCrossRef
39.
Osugi Y, Hara J, Tagawa S, Takai K, Hosoi G, Matsuda Y, Ohta H, Fujisaki H, Kobayashi M, Sakata N, et al. Cytokine production regulating Th1 and Th2 cytokines in hemophagocytic lymphohistiocytosis. Blood. 1997;89(11):4100–3.PubMedCrossRef
40.
41.
42.
Decker T, Muller M, Stockinger S. The yin and yang of type I interferon activity in bacterial infection. Nat Rev Immunol. 2005;5(9):675–87.PubMedCrossRef
43.
Giai C, Gonzalez C, Ledo C, Garofalo A, Di Genaro MS, Sordelli DO, Gomez MI. Shedding of tumor necrosis factor receptor 1 induced by protein a decreases tumor necrosis factor alpha availability and inflammation during systemic Staphylococcus aureus infection. Infect Immun. 2013;81(11):4200–7.PubMedPubMedCentralCrossRef
44.
Connor TJ, Brewer C, Kelly JP, Harkin A. Acute stress suppresses pro-inflammatory cytokines TNF-alpha and IL-1 beta independent of a catecholamine-driven increase in IL-10 production. J Neuroimmunol. 2005;159(1–2):119–28.PubMedCrossRef
45.
Kaiko GE, Horvat JC, Beagley KW, Hansbro PM. Immunological decision-making: how does the immune system decide to mount a helper T-cell response? Immunology. 2008;123(3):326–38.PubMedPubMedCentralCrossRef
46.
Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol. 2004;75(2):163–89.PubMedCrossRef
47.
Zhang P, Tey SK, Koyama M, Kuns RD, Olver SD, Lineburg KE, Lor M, Teal BE, Raffelt NC, Raju J, et al. Induced regulatory T cells promote tolerance when stabilized by rapamycin and IL-2 in vivo. J Immunol. 2013;191(10):5291–303.PubMedCrossRef
48.
Dorman SE, Holland SM. Interferon-gamma and interleukin-12 pathway defects and human disease. Cytokine Growth Factor Rev. 2000;11(4):321–33.PubMedCrossRef
49.
Watford WT, Moriguchi M, Morinobu A, O'Shea JJ. The biology of IL-12: coordinating innate and adaptive immune responses. Cytokine Growth Factor Rev. 2003;14(5):361–8.PubMedCrossRef
50.
Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM. Development of TH1 CD4+ T cells through IL-12 produced by listeria-induced macrophages. Science. 1993;260(5107):547–9.PubMedCrossRef
51.
52.
Kos FJ, Engleman EG. Immune regulation: a critical link between NK cells and CTLs. Immunol Today. 1996;17(4):174–6.PubMedCrossRef
53.
Elemans M, Thiebaut R, Kaur A, Asquith B. Quantification of the relative importance of CTL, B cell, NK cell, and target cell limitation in the control of primary SIV-infection. PLoS Comput Biol. 2011;7(3):e1001103.PubMedPubMedCentralCrossRef
54.
Gandhi GR, Neta M, Sathiyabama RG, Quintans JSS, de Oliveira ESAM, Araujo AAS, Narain N, Junior LJQ, Gurgel RQ. Flavonoids as Th1/Th2 cytokines immunomodulators: a systematic review of studies on animal models. Phytomedicine. 2018;44:74–84.PubMedCrossRef
55.
56.
Davis L, Kuttan G. Effect of Withania somnifera on cytokine production in normal and cyclophosphamide treated mice. Immunopharmacol Immunotoxicol. 1999;21(4):695–703.PubMedCrossRef
Metadata
Title
Immuno-enhancement effects of Platycodon grandiflorum extracts in splenocytes and a cyclophosphamide-induced immunosuppressed rat model
Authors
Eun-Mi Noh
Jeong-Mi Kim
Hak Yong Lee
Hyun-Kyung Song
Sang Ok Joung
Hye Jeong Yang
Min Jung Kim
Kang Sung Kim
Young-Rae Lee
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Cytokines
Published in
BMC Complementary Medicine and Therapies / Issue 1/2019
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-019-2724-0

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