Food Science and Biotechnology

, Volume 28, Issue 6, pp 1819–1828 | Cite as

Red ginseng extract regulates differentiation of monocytes to macrophage and inflammatory signalings in human monocytes

  • Bobin Kang
  • Chae Young Kim
  • Jisu Hwang
  • Sojung Sun
  • Hyunwon Yang
  • Hyung Joo Suh
  • Hyeon-Son ChoiEmail author


This study was aimed to investigate the effect of red ginseng extract (RGE) on monocyte to macrophage differentiation and inflammatory signalings in THP-1 human monocytes. In HPLC analysis, RGE contained saponin level of 516 μg/mg (extract) with 14 ginsenosides. RGE effectively suppressed the monocyte-to-macrophage differentiation induced by phorbol 12-myristate 13-acetated (PMA) by inhibiting the THP-1 cell adhesion. This result is evidenced by the down-regulation of cluster of differentiation molecule β (CD11β) and CD36. RGE significantly reduced translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (78%), while cytosolic NF-κB was increased (53%), compared with LPS group. In addition, RGE significantly increased the protein abundance of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its target protein, hemoxygenase-1 (HO-1), but, Kelch-like ECH-associated protein 1 (KEAP1), a negative regulator of Nrf2, was greatly decreased by RGE. Furthermore, RGE effectively mediated the regulation of Nrf2 level in nucleus and cytoplasm of THP-1.


Human monocyte (THP-1) Red ginseng extract (RGE) Monocyte-to-macrophage differentiation Inflammatory signaling 



This study was supported by a research grant from Seoul Women’s University (2019).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

10068_2019_611_MOESM1_ESM.docx (72 kb)
Supplementary material 1 (DOCX 71 kb)


  1. Ahmed T, Raza SH, Maryam A, Setzer WN, Braidy N, Nabavi SF, De Oliveira MR, Nabavi SM. Ginsenoside Rb1 as a neuroprotective agent: a review. Brain Res. Bull. 125: 30–43(2016)CrossRefGoogle Scholar
  2. Baek KS, YI YS, Son YJ, Yoo S, Sung NY, Kim Y, Hong S, Aravinthan A, Kim JH, Cho JY. In vitro and in vivo anti-inflammatory activities of Korean Red Ginseng-derived components. J. Ginseng Res. 40: 437–444 (2016)CrossRefGoogle Scholar
  3. Bak MJ, Truong VL, Ko SY, Nguyen XN, Jun M, Hong SG, Lee JW, Jeong WS. Induction of Nrf2/ARE-mediated cytoprotective genes by red ginseng oil through ASK1-MKK4/7-JNK and p38 MAPK signaling pathways in HepG2 cells. J. Ginseng Res. 40: 423–430 (2016)CrossRefGoogle Scholar
  4. Belcher JD, Mahaseth H, Welch TE, Otterbein LE, Hebbel RP, Vercellotti GM. Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice. J. Clin. Invest. 116: 808–816 (2006)CrossRefGoogle Scholar
  5. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 9: 7204–7218 (2017)PubMedPubMedCentralGoogle Scholar
  6. Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 32: 593–604(2010)CrossRefGoogle Scholar
  7. Han K, Shin IC, Choi KJ, Yun YP, Hong JT, Oh KW. Korea red ginseng water extract increases nitric oxide concentrations in exhaled breath. Nitric oxide 12: 159–162 (2005)CrossRefGoogle Scholar
  8. Hong M, Lee YH, Kim MS, Suk KT, Bang CS, Yoon JH, Baik GH, Kim DJ, Kim MJ. Anti-inflammatory and antifatigue effect of Korean Red Ginseng in patients with nonalcoholic fatty liver disease. J. Ginseng Res. 40: 203–210 (2016)CrossRefGoogle Scholar
  9. Kang B, Kim JH, Kim CY, Hong J, Choi HS. Dibenzoylmethane, a component of licorice, suppresses monocyte-to-macrophage differentiation and inflammatory responses in human monocytes and mouse macrophages. Biol. Pharm. Bull. 41: 1228–1236 (2018)CrossRefGoogle Scholar
  10. Kang OJ, Kim JS. Comparison of ginsenoside contents in different parts of Korean Ginseng (Panax ginseng C.A. Meyer). Prev. Nutr. Food Sci. 21: 389–392 (2016)CrossRefGoogle Scholar
  11. Keum YS, Park KK, Lee JM, Chun KS, Park JH, Lee SK, Kwon H, Surh YJ. Antioxidant and anti-tumor promoting activities of the methanol extract of heat-processed ginseng. Cancer Lett. 150: 41–48 (2000)CrossRefGoogle Scholar
  12. Kim WY, Kim JM, Han SB, Lee SK, Kim ND, Park MK, Kim CK, Park JH. Steaming of ginseng at high temperature enhances biological activity. J. Nat. Prod. 63: 1702–1704 (2000)CrossRefGoogle Scholar
  13. Kobayashi EH, Suzuki T, Funayama R, Nagashima T, Hayashi M, Sekine H, Tanaka N, Moriguchi T, Motohashi H, Nakayama K. Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat. Commun. 7: 11624 (2016)CrossRefGoogle Scholar
  14. León B, Ardav NC. Monocyte migration to inflamed skin and lymph nodes is differentially controlled by L-selectin and PSGL-1. Blood 111: 3126–3130 (2008)CrossRefGoogle Scholar
  15. Lee JM, Hwang KT, Jun WJ, Park CS, Lee MY. Antiinflammatory effect of lactic acid bacteria: inhibition of cyclooxygenase-2 by suppressing nuclear factor-kappaB in Raw264. 7 macrophage cells. J. Microbiol. Biotechnol. 18: 1683–1688 (2008)PubMedGoogle Scholar
  16. Li J, Ichikawa T, Jin Y, Hofseth LJ, Nagakatti P, Nagakatti M, Windust A, Cui T. An essential role of Nrf2 in American ginseng-mediated anti-oxidative actions in cardiomyocytes. J. Ethnopharmacol. 130: 222–230 (2010)CrossRefGoogle Scholar
  17. Loboda A, Damulewicz M, Pyza E, Jozkowicz A, Dulak J. Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism. Cell. Mol. Life Sci. 73: 3221–3247 (2016)CrossRefGoogle Scholar
  18. Ning C, Gao X, Wang C, Kong Y, Liu Z, Sun H, Sun P, Huo X, Ma X, Meng Q, Liu K. Ginsenoside Rg1 protects against acetaminophen-induced liver injury via activating Nrf2 signaling pathway in vivo and in vitro. Regul. Toxicol. Pharmacol. 98: 58–68(2018)CrossRefGoogle Scholar
  19. Panichi V, Scatena A, Migliori M, Marchetti V, Paoletti S, Beati S. Biomarkers of chronic inflammatory state in uremia and cardiovascular disease. Int. J. Inflam. 2012: 360147 (2012)CrossRefGoogle Scholar
  20. Park, E, Jung H, Yang H, Yoo M, Kim C, Kim K. Optimized THP-1 differentiation is required for the detection of responses to weak stimuli. Inflamm. Res. 56: 45–50 (2007)CrossRefGoogle Scholar
  21. Saba E, Lee YY, Kim MK, Kim SH, Rhee MH. A comparative study on immune-stimulatory and antioxidant activities of various types of ginseng extracts in murine and rodent models. J. Ginseng Res. 148: 37–43 (2018)CrossRefGoogle Scholar
  22. ScheinmanRI, Cogswell PC, Lofquist AK, Baldwin AS. Role of transcriptional activation of IκBα in mediation of immunosuppression by glucocorticoids. Science 270: 283–286(1995)CrossRefGoogle Scholar
  23. Shi Y, Miao W, Teng J, Zhang L. Ginsenoside Rb1 protects the brain from damage induced by epileptic seizure via Nrf2/ARE signaling. Cell. Physiol. Biochem. 45: 212–225 (2018)CrossRefGoogle Scholar
  24. Sun Z, Chin YE, Zhang DD. Acetylation of Nrf2 by p300/CBP augments promoter-specific DNA binding of Nrf2 during the antioxidant response. Mol. Cell. Biol. 29: 2658–2672 (2009)CrossRefGoogle Scholar
  25. Sung NY, Jung PM, Yoon M, Kim JS, Choi JI, Jeong HG, Lee JW, Kim JH. Anti-inflammatory effect of sweetfish-derived protein and its enzymatic hydrolysate on LPS-induced RAW264. 7 cells via inhibition of NF-κB transcription. Fish. Sci. 78: 381–390 (2012)CrossRefGoogle Scholar
  26. Tafani M, Sansone L, Limana F, Arcangeli T, De Santis E, Polese M, Fini M, Russo MA. The interplay of reactive oxygen species, hypoxia, inflammation, and sirtuins in cancer initiation and progression. Oxid. Med. Cell. Longev. 2016: 3907147 (2016)CrossRefGoogle Scholar
  27. Wang L, Li X, Song YM, Wang B, Zhang FR, Yang R, Wang HQ, Zhang GJ. Ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to γ-radiation by targeting the nuclear factor-κB pathway. Mol. Med. Rep. 12: 609–614 (2015)CrossRefGoogle Scholar
  28. Wardyn JD, Ponsford AH, Sanderson CM. Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways. Biochem. Soc. Trans. 43: 621–626 (2015)CrossRefGoogle Scholar
  29. Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature 496: 445 (2013)CrossRefGoogle Scholar
  30. Yang J, Zhang L, Yu C, Yang XF, Wang H. Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases. Biomark. Res. 2: 1 (2014)CrossRefGoogle Scholar
  31. Yang WS, Yi, YS, Kim D, Kim MH, Park JG, Kim E, Lee SY, Yoon K, Kim JH, Park J. Nuclear factor kappa-B-and activator protein-1-mediated immunostimulatory activity of compound K in monocytes and macrophages. J. Ginseng Res. 41: 298–306 (2017)CrossRefGoogle Scholar
  32. Yayeh T, Jung KH, Jeong HY, Park JH, Song YB, Kwak YS, Kang HS, Cho JY, Oh JW, Kim SK. Korean red ginseng saponin fraction downregulates proinflammatory mediators in LPS stimulated RAW264. 7 cells and protects mice against endotoxic shock. J. Ginseng Res. 36: 263–269 (2012)CrossRefGoogle Scholar
  33. Zhong Y, Liu T, Lai W, Tan Y, Tian D, Guo Z. Heme oxygenase-1-mediated reactive oxygen species reduction is involved in the inhibitory effect of curcumin on lipopolysaccharide-induced monocyte chemoattractant protein-1 production in RAW264. 7 macrophages. Mol. Med. Rep. 7: 242–246 (2013)CrossRefGoogle Scholar

Copyright information

© The Korean Society of Food Science and Technology 2019

Authors and Affiliations

  • Bobin Kang
    • 1
  • Chae Young Kim
    • 1
  • Jisu Hwang
    • 1
  • Sojung Sun
    • 2
  • Hyunwon Yang
    • 2
  • Hyung Joo Suh
    • 1
  • Hyeon-Son Choi
    • 3
    Email author
  1. 1.Department of Public Health SciencesKorea UniversitySeoulRepublic of Korea
  2. 2.Department of Bioenvironmental Technology, College of Natural ScienceSeoul Women’s UniversitySeoulRepublic of Korea
  3. 3.Department of Food Science and Technology, College of Natural ScienceSeoul Women’s UniversitySeoulRepublic of Korea

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