Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Proteomic studies of putative molecular signatures for biological effects by Korean Red Ginseng

  • Lee, Yong Yook (The Korean Ginseng Research Institute, Korea Ginseng Corporation) ;
  • Seo, Hwi Won (The Korean Ginseng Research Institute, Korea Ginseng Corporation) ;
  • Kyung, Jong-Su (The Korean Ginseng Research Institute, Korea Ginseng Corporation) ;
  • Hyun, Sun Hee (The Korean Ginseng Research Institute, Korea Ginseng Corporation) ;
  • Han, Byung Cheol (The Korean Ginseng Research Institute, Korea Ginseng Corporation) ;
  • Park, Songhee (The Korean Ginseng Research Institute, Korea Ginseng Corporation) ;
  • So, Seung Ho (The Korean Ginseng Research Institute, Korea Ginseng Corporation) ;
  • Lee, Seung Ho (The Korean Ginseng Research Institute, Korea Ginseng Corporation) ;
  • Yi, Eugene C. (Department of Molecular Medicine and Biopharmaceutical Sciences, School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National University)
  • Received : 2018.08.08
  • Accepted : 2019.05.02
  • Published : 2019.10.15
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Abstract

Background: Korean Red Ginseng (KRG) has been widely used as an herbal medicine to normalize and strengthen body functions. Although many researchers have focused on the biological effects of KRG, more studies on the action mechanism of red ginseng are still needed. Previously, we investigated the proteomic changes of the rat spleen while searching for molecular signatures and the action mechanism of KRG. The proteomic analysis revealed that differentially expressed proteins (DEPs) were involved in the increased immune response and phagocytosis. The aim of this study was to evaluate the biological activities of KRG, especially the immune-enhancing response of KRG. Methods: Rats were divided into 4 groups: 0 (control group), 500, 1000, and 2000 mg/kg administration of KRG powder for 6 weeks, respectively. Isobaric tags for relative and absolute quantitation was performed with Q-Exactive LC-MS/MS to compare associated proteins between the groups. The putative DEPs were identified by a current UniProt rat protein database search and by the Gene Ontology annotations. Results: The DEPs appear to increase the innate and acquired immunity as well as immune cell movement. These results suggest that KRG can stimulate immune responses. This analysis refined our targets of interest to include the potential functions of KRG. Furthermore, we validated the potential molecular targets of the functions, representatively LCN2, CRAMP, and HLA-DQB1, by Western blotting. Conclusion: These results may provide molecular signature candidates to elucidate the mechanisms of the immune response by KRG. Here, we demonstrate a strategy of tissue proteomics for the discovery of the molecular function of KRG.

Keywords

References

  1. Yang H, Son GW, Park HR, Lee SE, Park YS. Effect of Korean Red Ginseng treatment on the gene expression profile of diabetic rat retina. J Ginseng Res 2016;40:1-8. https://doi.org/10.1016/j.jgr.2015.03.003
  2. Kim SJ, Shin JY, Ko SK. Changes in the contents of prosapogenin in Red ginseng (Panax ginseng) depending on the extracting conditions. J Ginseng Res 2016;40:86-9. https://doi.org/10.1016/j.jgr.2015.04.008
  3. Xie YY, Luo D, Cheng YJ, Ma JF, Wang YM, Liang QL. Steaming-induced chemical transformations and holistic quality assessment of red ginseng derived from Panax ginseng by means of HPLC-ESI-MS/MS(n)-based multicomponent quantification fingerprint. J Agric Food Chem 2012;60:8213-24. https://doi.org/10.1021/jf301116x
  4. Provino R. The role of adaptogens in stress management. Australian Journal of Medical Herbalism 2010;22:41.
  5. Suh SO, Kim J, Cho MY. Prospective study for Korean red ginseng extract as an immune modulator following a curative gastric resection in patients with advanced gastric cancer. J Ginseng Res 2004;28:104-10. https://doi.org/10.5142/JGR.2004.28.2.104
  6. Kim JY, Park JY, Kang HJ, Kim OY, Lee JH. Beneficial effects of Korean red ginseng on lymphocyte DNA damage, antioxidant enzyme activity, and LDL oxidation in healthy participants: a randomized, double-blind, placebocontrolled trial. Nutr J 2012;11:1. https://doi.org/10.1186/1475-2891-11-1
  7. Lee ST, Chu K, Sim JY, Heo JH, Kim M. Panax ginseng enhances cognitive performance in Alzheimer disease. Alzheimer Dis Assoc Disord 2008;22:222-6. https://doi.org/10.1097/WAD.0b013e31816c92e6
  8. Shin KS, Lee JJ, Kim YI, Yu JY, Park ES, Im JH. Effect of Korean red ginseng extract on blood circulation in healthy volunteers: a randomized, doubleblind, placebo-controlled trial. J Ginseng Res 2007;31:109-16. https://doi.org/10.5142/JGR.2007.31.2.109
  9. Kennedy D, Reay J, Scholey A. Effects of 8 weeks administration of Korean Panax ginseng extract on the mood and cognitive performance of healthy individuals. J Ginseng Res 2007;31:34. https://doi.org/10.5142/JGR.2007.31.1.034
  10. Choi R, Wong AS, Jia W, Chang IM, Wong RN, Fan TP. Ginseng: a panacea linking East Asia and North America? Science 2015;350:S54-6.
  11. Kang S, Min H. Ginseng, the 'immunity boost': the effects of panax ginseng on immune system. J Ginseng Res 2012;36:354-68. https://doi.org/10.5142/jgr.2012.36.4.354
  12. Lee BJ, Heo H, Oh SC, Lew JH. Comparison study of Korean and Chinese ginsengs on the regulation of lymphocyte proliferation and cytokine production. J Ginseng Res 2008;32:250-6. https://doi.org/10.5142/JGR.2008.32.3.250
  13. Hart A. Predictive medicine for rookies: consumer watchdogs, reviews, & genetics testing firms online. iUniverse; 2005.
  14. Leung EL, Cao ZW, Jiang ZH, Zhou H, Liu L. Network-based drug discovery by integrating systems biology and computational technologies. Brief Bioinform 2013;14:491-505. https://doi.org/10.1093/bib/bbs043
  15. Wang X, Xu X, Tao W, Li Y, Wang Y, Yang L. A systems biology approach to uncovering pharmacological synergy in herbal medicines with applications to cardiovascular disease. Evid Based Complement Alternat Med 2012;2012:519031.
  16. Ru J, Li P, Wang J, Zhou W, Li B, Huang C. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 2014;6:13. https://doi.org/10.1186/1758-2946-6-13
  17. Wang Y, Xu A, Zheng. A systems biology approach to diagnosis and treatments. Science 2014;346:S13-5. https://doi.org/10.1126/science.346.6205.13
  18. Leung EL, Wong VK, Jiang ZH, Li T, Liu L. Integrated network-based medicine: the role of traditional Chinese medicine in developing a new generation of medicine. Science 2014;346:S16-8.
  19. Cha MY, Kwon YW, Ahn HS, Jeong H, Lee YY, Moon M. Protein-induced pluripotent stem cells ameliorate cognitive dysfunction and reduce abeta deposition in a mouse model of Alzheimer's disease. Stem Cells Transl Med 2017;6:293-305. https://doi.org/10.5966/sctm.2016-0081
  20. Stein DR, Hu X, McCorrister SJ, Westmacott GR, Plummer FA, Ball TB. High pH reversed-phase chromatography as a superior fractionation scheme compared to off-gel isoelectric focusing for complex proteome analysis. Proteomics 2013;13:2956-66. https://doi.org/10.1002/pmic.201300079
  21. Keller A, Nesvizhskii AI, Kolker E, Aebersold R. Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal Chem 2002;74:5383-92. https://doi.org/10.1021/ac025747h
  22. Kim YS, Woo JY, Han CK, Chang IM. Safety analysis of panax ginseng in randomized clinical trials: a systematic review. Medicines (Basel) 2015;2:106-26. https://doi.org/10.3390/medicines2020106
  23. Jin YR, Yu JY, Lee JJ, You SH, Chung JH, Noh JY, Im JH, Han XH, Kim TJ, Shin KS, et al. Antithrombotic and antiplatelet activities of Korean red ginseng extract. Basic Clin Pharmacol Toxicol 2007;100:170-5. https://doi.org/10.1111/j.1742-7843.2006.00033.x
  24. Sultan S, Ahmad S, Pascucci M, Ramadori G. Changes of LCNe2 gene expression in different organs in a rat model of tissue damage. Zeitschrift fur Gastroenterologie 2012;50:P2_34.
  25. Nairz M, Ferring-Appel D, Casarrubea D, Sonnweber T, Viatte L, Schroll A. Iron regulatory proteins mediate host resistance to Salmonella infection. Cell Host Microbe 2015;18:254-61. https://doi.org/10.1016/j.chom.2015.06.017
  26. Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet 2005;365:63-78. https://doi.org/10.1016/S0140-6736(04)17667-8
  27. Zanetti M, Gennaro R, Romeo D. Cathelicidins: a novel protein family with a common proregion and a variable C-terminal antimicrobial domain. FEBS Lett 1995;374:1-5. https://doi.org/10.1016/0014-5793(95)01050-O
  28. Larrick JW, Hirata M, Balint RF, Lee J, Zhong J, Wright SC. Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun 1995;63:1291-7. https://doi.org/10.1128/IAI.63.4.1291-1297.1995
  29. Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol 2004;75:39-48. https://doi.org/10.1189/jlb.0403147
  30. Bu HF, Wang X, Zhu YQ, Williams RY, Hsueh W, Zheng X, Rozenfeld RA, Zuo XL, Tan XD. Lysozyme-modified probiotic components protect rats against polymicrobial sepsis: role of macrophages and cathelicidin-related innate immunity. J Immunol 2006;177:8767-76. https://doi.org/10.4049/jimmunol.177.12.8767
  31. Janeway CA, Travers P, Walport M, Shlomchik M. Immunobiology: the immune system in health and disease. 5th ed. New York: Garland Science; 2001.
  32. Tonnelle C, DeMars R, Long EO. DO beta: a new beta chain gene in HLA-D with a distinct regulation of expression. EMBO J 1985;4:2839-47. https://doi.org/10.1002/j.1460-2075.1985.tb04012.x
  33. Dai S, Murphy GA, Crawford F, Mack DG, Falta MT, Marrack P. Crystal structure of HLA-DP2 and implications for chronic beryllium disease. Proc Natl Acad Sci U S A 2010;107:7425-30. https://doi.org/10.1073/pnas.1001772107
  34. Easterfield AJ, Bradley JA, Bolton EM. Complementary DNA sequences encoding the rat MHC class II RT1-Bu and RT1-Du alpha and beta chains. Immunogenetics 2003;55:344-50. https://doi.org/10.1007/s00251-003-0584-7
  35. Montecino-Rodriguez E, Berent-Maoz B, Dorshkind K. Causes, consequences, and reversal of immune system aging. J Clin Invest 2013;123:958-65. https://doi.org/10.1172/JCI64096
  36. Goya RG, Console G, Herenu C, Brown O, Rimoldi OJ. Thymus and aging: potential of gene therapy for restoration of endocrine thymic function in thymus-deficient animal models. Gerontology 2002;48:325-8. https://doi.org/10.1159/000065258
  37. Gruver AL, Hudson LL, Sempowski GD. Immunosenescence of ageing. J Pathol 2007;211:144-56. https://doi.org/10.1002/path.2104
  38. Spurr NK, Leppert M. Report of the committee on the genetic constitution of chromosome 2. Cytogenet Cell Genet 1990;55:86-91. https://doi.org/10.1159/000132998
  39. Tajrishi MM, Tuteja R, Tuteja N. Nucleolin: the most abundant multifunctional phosphoprotein of nucleolus. Commun Integr Biol 2011;4:267-75. https://doi.org/10.4161/cib.4.3.14884
  40. Quiros PM, Espanol Y, Acin-Perez R, Rodriguez F, Barcena C, Watanabe K. ATPdependent Lon protease controls tumor bioenergetics by reprogramming mitochondrial activity. Cell Rep 2014;8:542-56. https://doi.org/10.1016/j.celrep.2014.06.018
  41. Tsai PL, Zhao C, Turner E, Schlieker C. The Lamin B receptor is essential for cholesterol synthesis and perturbed by disease-causing mutations. Elife 2016;5:e16011. https://doi.org/10.7554/eLife.16011
  42. Alberts AW, Strauss AW, Hennessy S, Vagelos PR. Regulation of synthesis of hepatic fatty acid synthetase: binding of fatty acid synthetase antibodies to polysomes. Proc Natl Acad Sci U S A 1975;72:3956-60. https://doi.org/10.1073/pnas.72.10.3956
  43. Carroll RG, Zaslona Z, Galvan-Pena S, Koppe EL, Sevin DC, Angiari S. An unexpected link between fatty acid synthase and cholesterol synthesis in proinflammatory macrophage activation. J Biol Chem 2018;293:5509-21. https://doi.org/10.1074/jbc.RA118.001921
  44. Baron A, Migita T, Tang D, Loda M. Fatty acid synthase: a metabolic oncogene in prostate cancer? J Cell Biochem 2004;91:47-53. https://doi.org/10.1002/jcb.10708
  45. Hunt DA, Lane HM, Zygmont ME, Dervan PA, Hennigar RA. MRNA stability and overexpression of fatty acid synthase in human breast cancer cell lines. Anticancer Res 2007;27:27-34.
  46. Gansler TS, Hardman 3rd W, Hunt DA, Schaffel S, Hennigar RA. Increased expression of fatty acid synthase (OA-519) in ovarian neoplasms predicts shorter survival. Hum Pathol 1997;28:686-92. https://doi.org/10.1016/S0046-8177(97)90177-5
  47. Lee F, Yokota T, Otsuka T, Gemmell L, Larson N, Luh J, Arai K, Rennick D. Isolation of cDNA for a human granulocyte-macrophage colony-stimulating factor by functional expression in mammalian cells. Proc Natl Acad Sci U S A 1985;82:4360-4. https://doi.org/10.1073/pnas.82.13.4360
  48. Lemmon HR. Modulatory effects of North American ginseng extracts on human innate and adaptive immune responses. Electronic Thesis and Dissertation Repository 2012;399.

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