DOI QR코드

DOI QR Code

Immunostimulatory Effect of Fermented Red Ginseng in the Mouse Model

  • Received : 2014.01.27
  • Accepted : 2014.03.14
  • Published : 2014.03.31

Abstract

In this study, Woongjin fermented red ginseng extract (WFRG) was evaluated for its potential ability to act as an adjuvant for the immune response of mice. For the in vitro study, macrophages were treated with serial concentrations ($1{\mu}g/mL$, $10{\mu}g/mL$, and $100{\mu}g/mL$) of WFRG. For in vivo studies, mice were administered different concentrations (10 mg/kg/day, 100 mg/kg/day, and 200 mg/kg/day) of WFRG orally for 21 days. In vitro, the production of nitric oxide and TNF-${\alpha}$ by RAW 264.7 cells increased in a dose-dependent manner. In vivo, WFRG enhanced the proliferation of splenocytes induced by two mitogens (i.e., concanavalin A and lipopolysaccharide [LPS]) and increased LPS-induced production of TNF-${\alpha}$ and IL-6, but not IL-$1{\beta}$. In conclusion, WFRG has the potential to modulate immune function and should be further investigated as an immunostimulatory agent.

References

  1. Im SA, Kim GW, Lee CK. 2003. Immunomodulatory activity of Salicornia herbacea L. components. Nat Prod Sci 9: 273-277.
  2. Maeda R, Ida T, Ihara H, Sakamoto T. 2012. Immunostimulatory activity of polysaccharides isolated from Caulerpa lentillifera on macrophage cells. Biosci Biotechnol Biochem 76:501-505. https://doi.org/10.1271/bbb.110813
  3. Kenarova B, Neychev H, Hadjiivanova C, Petkov VD. 1990. Immunomodulating activity of ginsenoside $Rg_1$ from Panax ginseng. Jpn J Pharmacol 54: 447-454. https://doi.org/10.1254/jjp.54.447
  4. Kwon JY, Hong SH, Park SD, Ahn SG, Yoon JH, Kwon BM, Kim SA. 2012. 2'-Benzoyloxycinnamaldehyde inhibits nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells via regulation of AP-1 pathway. Eur J Pharmacol 696: 179-186. https://doi.org/10.1016/j.ejphar.2012.09.027
  5. Lee KJ, Lee SY, Ji GE. 2013. Diabetes-ameliorating effects of fermented red ginseng and causal effects on hormonal interactions: testing the hypothesis by multiple group path analysis. J Med Food 16: 383-395. https://doi.org/10.1089/jmf.2012.2583
  6. Di Rosa M, Malaguarnera G, De Gregorio C, Palumbo M, Nunnari G, Malaguarnera L. 2012. Immuno-modulatory effects of vitamin D3 in human monocyte and macrophages. Cell Immunol 280: 36-43. https://doi.org/10.1016/j.cellimm.2012.10.009
  7. Kwon OK, Ahn KS, Park JW, Jang HY, Joung H, Lee HK, Oh SR. 2012. Ethanol extract of Elaeocarpus petiolatus inhibits lipopolysaccharide-induced inflammation in macrophage cells. Inflammation 35: 535-544. https://doi.org/10.1007/s10753-011-9343-3
  8. Won DP, Lee JS, Kwon DS, Lee KE, Shin WC, Hong EK. 2011. Immunostimulating activity by polysaccharides isolated from fruiting body of Inonotus obliquus. Mol Cells 31: 165-173. https://doi.org/10.1007/s10059-011-0022-x
  9. Qureshi AA, Guan XQ, Reis JC, Papasian CJ, Jabre S, Morrison DC, Qureshi N. 2012. Inhibition of nitric oxide and inflammatory cytokines in LPS-stimulated murine macrophages by resveratrol, a potent proteasome inhibitor. Lipids Health Dis 11: 76. https://doi.org/10.1186/1476-511X-11-76
  10. Dhib-Jalbut S, Sumandeep S, Valenzuela R, Ito K, Patel P, Rametta M. 2013. Immune response during interferon beta-1b treatment in patients with multiple sclerosis who experienced relapses and those who were relapse-free in the START study. J Neuroimmunol 254: 131-140. https://doi.org/10.1016/j.jneuroim.2012.08.012
  11. Hoge J, Yan I, Janner N, Schumacher V, Chalaris A, Steinmetz OM, Engel DR, Scheller J, Rose-John S, Mittrucker HW. 2013. IL-6 controls the innate immune response against listeria monocytogenes via classical IL-6 signaling. J Immunol 190: 703-711. https://doi.org/10.4049/jimmunol.1201044
  12. Jiao L, Wan D, Zhang X, Li B, Zhao H, Liu S. 2012. Characterization and immunostimulating effects on murine peritoneal macrophages of oligosaccharide isolated from Panax ginseng C.A. Meyer. J Ethnopharmacol 144: 490-496. https://doi.org/10.1016/j.jep.2012.09.004
  13. Wu HW, Yun KM, Han DW, Xu RL, Zhao YC. 2012. Effects of glycine on phagocytosis and secretion by Kupffer cells in vitro. World J Gastroenterol 18: 2576-2581. https://doi.org/10.3748/wjg.v18.i20.2576
  14. Wei X, Chen J, Su F, Su X, Hu T, Hu S. 2012. Stereospecificity of ginsenoside Rg3 in promotion of the immune response to ovalbumin in mice. Int Immunol 24: 465-471. https://doi.org/10.1093/intimm/dxs043
  15. Wang CZ, Du GJ, Zhang Z, Wen XD, Calway T, Zhen Z, Musch MW, Bissonnette M, Chang EB, Yuan CS. 2012. Ginsenoside compound K, not Rb1, possesses potential chemopreventive activities in human colorectal cancer. Int J Oncol 40: 1970-1976.
  16. Wu L, Jin Y, Yin C, Bai L. 2012. Co-transformation of Panax major ginsenosides Rb1 and Rg1 to minor ginsenosides C-K and F1 by Cladosporium cladosporioides. J Ind Microbiol Biotechnol 39: 521-527. https://doi.org/10.1007/s10295-011-1058-9
  17. Kim MC, Lee GH, Kim SJ, Chung WS, Kim SS, Ko SG, Um JY. 2012. Immune-enhancing effect of Danggwibohyeoltang, an extract from Astragali Radix and Angelicae gigantis Radix, in vitro and in vivo. Immunopharmacol Immunotoxicol 34: 66-73. https://doi.org/10.3109/08923973.2011.576254
  18. Cavalcanti YV, Brelaz MC, Neves JK, Ferraz JC, Pereira VR. 2012. Role of TNF-alpha, IFN-gamma, and IL-10 in the development of pulmonary tuberculosis. Pulm Med 2012:745483.
  19. Goyal N, Shukla G. 2013. Probiotic Lactobacillus rhamnosus GG modulates the mucosal immune response in Giardia intestinalis-infected BALB/c mice. Dig Dis Sci 58: 1218-1225. https://doi.org/10.1007/s10620-012-2503-y
  20. Rodrigues AA, Clemente TM, Dos Santos MA, Machado FC, Gomes RG, Moreira HH, Cruz MC, Brígido PC, Dos Santos PC, Martins FA, Bahia D, Maricato JT, Janini LM, Reboredo EH, Mortara RA, da Silva CV. 2012. A recombinant protein based on Trypanosoma cruzi P21 enhances phagocytosis. PLoS One 7: e51384. https://doi.org/10.1371/journal.pone.0051384
  21. Adolph S, Fuhrmann H, Schumann J. 2012. Unsaturated fatty acids promote the phagocytosis of P. aeruginosa and R. equi by RAW264.7 macrophages. Curr Microbiol 65: 649-655. https://doi.org/10.1007/s00284-012-0207-3
  22. Wang L, An DS, Kim SG, Jin FX, Kim SC, Lee ST, Im WT. 2012. Ramlibacter ginsenosidimutans sp. nov., with ginsenoside-converting activity. J Microbiol Biotechnol 22: 311-315. https://doi.org/10.4014/jmb.1106.06041
  23. Kim YJ, Kwon HC, Ko H, Park JH, Kim HY, Yoo JH, Yang HO. 2008. Anti-tumor activity of the ginsenoside Rk1 in human hepatocellular carcinoma cells through inhibition of telomerase activity and induction of apoptosis. Biol Pharm Bull 31: 826-830. https://doi.org/10.1248/bpb.31.826
  24. Jin H, Seo JH, Uhm YK, Jung CY, Lee SK, Yim SV. 2012. Pharmacokinetic comparison of ginsenoside metabolite IH-901 from fermented and non-fermented ginseng in healthy Korean volunteers. J Ethnopharmacol 139: 664-667. https://doi.org/10.1016/j.jep.2011.11.052
  25. Niu T, Smith DL, Yang Z, Gao S, Yin T, Jiang ZH, You M, Gibbs RA, Petrosino JF, Hu M. 2013. Bioactivity and bioavailability of ginsenosides are dependent on the glycosidase activities of the A/J mouse intestinal microbiome defined by pyrosequencing. Pharm Res 30: 836-846. https://doi.org/10.1007/s11095-012-0925-z
  26. Hou JG, Xue JJ, Sun MQ, Wang CY, Liu L, Zhang DL, Lee MR, Gu LJ, Wang CL, Wang YB, Zheng Y, Li W, Sung CK. 2012. Highly selective microbial transformation of major ginsenoside Rb1 to gypenoside LXXV by Esteya vermicola CNU120806. J Appl Microbiol 113: 807-814. https://doi.org/10.1111/j.1365-2672.2012.05400.x
  27. Cho E, Cho SH. 2013. Effects of Korean red ginseng extract on the prevention of atopic dermatitis and its mechanism on early lesions in a murine model. J Ethnopharmacol 145: 294-302. https://doi.org/10.1016/j.jep.2012.11.006
  28. Park HM, Kim SJ, Mun AR, Go HK, Kim GB, Kim SZ, Jang SI, Lee SJ, Kim JS, Kang HS. 2012. Korean red ginseng and its primary ginsenosides inhibit ethanol-induced oxidative injury by suppression of the MAPK pathway in TIB-73 cells. J Ethnopharmacol 141: 1071-1076. https://doi.org/10.1016/j.jep.2012.03.038
  29. Fu BD, Bi WY, He CL, Zhu W, Shen HQ, Yi PF, Wang L, Wang DC, Wei XB. 2012. Sulfated derivatives of 20(S)-ginsenoside Rh2 and their inhibitory effects on LPS-induced inflammatory cytokines and mediators. Fitoterapia 84: 303-307.
  30. Kim CT, Kim BS, Kim MJ, Park BH, Kwon S, Maeng HY, Kwak J, Chun J, Cho YJ, Kim N, Kim CJ, Maeng JS. 2012. Draft genome sequencing of Bacillus sp. strain M2-6, isolated from the roots of Korean ginseng, Panax ginseng C.A. Meyer, after high-hydrostatic-pressure processing. J Bacteriol 194:7003-7004. https://doi.org/10.1128/JB.01939-12
  31. Shehzad O, Kim HP, Kim YS. 2013. State-of-the-art separation of ginsenosides from Korean white and red ginseng by countercurrent chromatography. Anal Bioanal Chem 405:4523-4530. https://doi.org/10.1007/s00216-012-6609-z

Cited by

  1. Effects of bamboo salt and its component, hydrogen sulfide, on enhancing immunity vol.14, pp.2, 2016, https://doi.org/10.3892/mmr.2016.5407
  2. Pectin lyase-modified red ginseng extract exhibits potent anti-glycation effects in vitro and in vivo vol.21, pp.2, 2017, https://doi.org/10.20463/jenb.2017.0011
  3. GS-E3D, a new pectin lyase-modified red ginseng extract, inhibited diabetes-related renal dysfunction in streptozotocin-induced diabetic rats vol.17, pp.1, 2017, https://doi.org/10.1186/s12906-017-1925-7
  4. Immunostimulatory Effect of Enzyme-Modified Hizikia fusiformein a Mouse Model In Vitro and Ex Vivo vol.19, pp.1, 2017, https://doi.org/10.1007/s10126-017-9727-y