DOI QR코드

DOI QR Code

Non-saponin fraction of red ginseng inhibits monocyte-to-macrophage differentiation and inflammatory responses in vitro

홍삼 비사포닌 분획의 단핵세포 분화와 염증반응에 대한 억제효과

  • Kang, Bobin (Department of Integrated Biomedical and Life Science, Graduate School, Korea University) ;
  • Kim, Chae Young (Department of Integrated Biomedical and Life Science, Graduate School, Korea University) ;
  • Hwang, Jisu (Department of Integrated Biomedical and Life Science, Graduate School, Korea University) ;
  • Choi, Hyeon-Son (Department of Food Science and Technology, College of Natural Science, Seoul Women's University)
  • 강보빈 (고려대학교 보건과학대 의생명융합과학과) ;
  • 김채영 (고려대학교 보건과학대 의생명융합과학과) ;
  • 황지수 (고려대학교 보건과학대 의생명융합과학과) ;
  • 최현선 (서울여자대학교 식품공학과)
  • Received : 2018.11.11
  • Accepted : 2018.12.27
  • Published : 2019.02.28

Abstract

The aim of this study was to investigate the effects of red ginseng-derived non-saponin fraction (NSF) on inflammatory responses and monocyte-to-macrophage differentiation in RAW264.7 and THP-1. NSF effectively inhibited inflammatory responses by downregulating nitric oxide (NO) production and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). NSF ($2000{\mu}g/mL$) decreased the levels of NO, iNOS, and COX-2 by 33, 83, and 64%, respectively. NSF inhibited the differentiation of monocyte-to-macrophage by decreasing cell adherence along with downregulation of the cluster of differentiation molecule $11{\beta}$ ($CD11{\beta}$) and CD36. In addition, pro-inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin 6, and monocyte chemoattractant protein 1 (MCP-1), were significantly reduced with NSF treatment. The NSF-mediated inhibition of inflammatory responses was due to the regulation of nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). NSF effectively suppressed the translocation of $NF-{\kappa}B$ into the nucleus, while nuclear Nrf2 and its target protein, heme oxygenase-1, levels were significantly increased.

Keywords

Non-saponin fraction of red ginseng;nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$);nuclear factor (erythroid-derived 2)-like 2 (Nrf2);inflammatory responses;monocyte-to-macrophage differentiation

SPGHB5_2019_v51n1_70_f0001.png 이미지

Fig. 1. Effect of NSF on viability of RAW264.7 and THP-1 cells.

SPGHB5_2019_v51n1_70_f0002.png 이미지

Fig. 2. Effect of NSF on inflammatory responses in RAW264.7 cells.

SPGHB5_2019_v51n1_70_f0003.png 이미지

Fig. 3. Effect of NSF on monocyte-to-macrophage differentiation and differentiation factors in THP-1 cells.

SPGHB5_2019_v51n1_70_f0004.png 이미지

Fig. 4. Effect of NSF on inflammatory cytokines in RAW264.7 (A) and THP-1 (B) cells.

SPGHB5_2019_v51n1_70_f0005.png 이미지

Fig. 5. Effect of NSF on NF-κB translocation into nucleus in RAW264.7 cells.

SPGHB5_2019_v51n1_70_f0006.png 이미지

Fig. 6. Effect of NSF on the protein expression level of Nrf2, Keap1, and HO-1, and Nrf2 nuclear translocation in RAW264.7 cells.

Table 1. Total polyphenol contents (TPC), total flavonoid contents (TFC) and radical scavenging activities of NSF

SPGHB5_2019_v51n1_70_t0001.png 이미지

Acknowledgement

Supported by : 고려인삼학회, 서울여자대학교

References

  1. Chang H. Effect of processing methods on the saponin contents of Panax ginseng leaf-tea. J. Food Sci. Nut. 16: 46-53 (2003)
  2. Chang YS, Chang YH, Sung JH. The effect of ginseng and caffeine products on the antioxidative activities of mouse kidney. J. Ginseng Res. 30: 15-21 (2006) https://doi.org/10.5142/JGR.2006.30.1.015
  3. Choi Kt. Botanical characteristics, pharmacological effects and medicinal components of Korean Panax ginseng CA Meyer. Acta Pharmacol. Sin. 29: 1109-18 (2008) https://doi.org/10.1111/j.1745-7254.2008.00869.x
  4. Coussens LM, Werb Z. Inflammation and cancer. Nature 420: 860-867 (2002) https://doi.org/10.1038/nature01322
  5. Deshmane SL, Kremlev S, Amini S, Sawaya BE. Monocyte chemoattractant protein-1 (MCP-1): An overview. J. Interferon Cytokine Res. 29: 313-326 (2009) https://doi.org/10.1089/jir.2008.0027
  6. Doss G, Agoramoorthy G, Chakraborty C. TNF/TNFR: drug target for autoimmune diseases and immune-mediated inflammatory diseases. Front Biosci. (Landmark Ed.). 19: 1028-1040 (2014) https://doi.org/10.2741/4265
  7. Dubinski A, Zdrojewicz Z. The role of interleukin-6 in development and progression of atherosclerosis. Pol. Merkur. Lekarski. 22: 291-294 (2007)
  8. Han BC, Ahn H, Lee J, Jeon E, Seo S, Jang KH, et al. Nonsaponin fractions of Korean Red Ginseng extracts prime activation of NLRP3 inflammasome. J. Ginseng Res. 41: 513-523 (2017) https://doi.org/10.1016/j.jgr.2016.10.001
  9. Hayden JM, Brachova L, Higgins K, Obermiller L, Sevanian A, Khandrika S. Induction of monocyte differentiation and foam cell formation in vitro by 7-ketocholesterol. J. Lipid Res. 43: 26-35 (2002)
  10. Huang J, Zhu M, Tao Y, Wang S, Chen J, Sun W. Therapeutic properties of quercetin on monosodium urate crystal-induced inflammation in rat. J. Pharm. Pahrmacol. 64: 1119-1127 (2012) https://doi.org/10.1111/j.2042-7158.2012.01504.x
  11. Jang A, Sueng YC, Ji JG. The comparative study on physiological activity of White ginseng, Red ginseng and Black ginseng extract. J. of Digital Convergence. 14: 459-471 (2016)
  12. Jeong HJ, Lee SG, Lee EJ, Park WD, Kim JB, Kim HJ. Antioxidant activity and anti-hyperglycemic activity of medicinal herbal extracts according to extraction methods. Korean J. Food Sci. Technol. 42: 571-577 (2010)
  13. Jiang Y, You XY, Fu KL, Yin WL. Effects of extract from Mangifera indica leaf on monosodium urate crystal-induced gouty arthritis in rats. Evid. Based. Complement Alternat. Med. 2012:1-6 (2012)
  14. Kim CY, Kang BB, Suh HJ, Choi HS. Red ginseng-derived saponin fraction suppresses the obesity-induced inflammatory responses via Nrf2-HO-1 pathway in adipocyte-macrophage co-culture system. Biomed. Pharmacother. 108: 1507-1516 (2018) https://doi.org/10.1016/j.biopha.2018.09.169
  15. Kim SI, Lee YH, Kang KS. 10-Acetyl panaxytriol, a new cytotoxic polyacetylene from Panax ginseng. Yakhak Hoeji. 33:118-123 (1989)
  16. Kobayashi EH, Suzuki T, Funayama R, Nagashima T, Hayashi M, Sekine H, et al. Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat. Commun. 7: 1-14 (2016)
  17. Konno C, Hikino H. Isolation and hypoglycemic activity of panaxans M, N, O and P, glycans of Panax ginseng roots. Int. J. Crude Drug Res. 25: 53-56 (1987) https://doi.org/10.3109/13880208709060912
  18. Kristiansen OP, Mandrup-Poulsen T. Interleukin-6 and diabetes: the good, the bad, or the indifferent? Diabetes 54: S114-S124 (2005) https://doi.org/10.2337/diabetes.54.suppl_2.S114
  19. Kuzmich N, Sivak K, Chubarev V, Porozov Y, Savateeva-Lyubimova T, Peri F. TLR4 signaling pathway modulators as potential therapeutics in inflammation and sepsis. Vaccines 5: 1-25 (2017)
  20. Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA. Chronic inflammation and cytokines in the tumor microenvironment. J. Immunol Res. 2014, Article ID 149185:1-19 (2014)
  21. Lee TS, Chau LY. Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat. Med. 8: 240-246 (2002) https://doi.org/10.1038/nm0302-240
  22. Lessner SM, Prado HL, Waller EK, Galis ZS. Atherosclerotic lesions grow through recruitment and proliferation of circulating monocytes in a murine model. Am. J. Pathol.160(6): 2145-55 (2002) https://doi.org/10.1016/S0002-9440(10)61163-7
  23. Libby P. Inflammation and cardiovascular disease mechanisms. Am. J. Clin. Nutr. 83: 456S-460S (2006) https://doi.org/10.1093/ajcn/83.2.456S
  24. 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) https://doi.org/10.1007/s00018-016-2223-0
  25. Nam KY. The comparative understanding between red ginseng and white ginsengs, processed ginsengs (Panax ginseng CA Meyer). J. Ginseng Res. 29: 1-18 (2005) https://doi.org/10.5142/JGR.2005.29.1.001
  26. Niu J, Kolattukudy PE. Role of MCP-1 in cardiovascular disease: molecular mechanisms and clinical implications. Clin. Sci. 117: 95-109 (2009) https://doi.org/10.1042/CS20080581
  27. Rao P, Knaus EE. Evolution of nonsteroidal anti-inflammatory drugs (NSAIDs): cyclooxygenase (COX) inhibition and beyond. J. Pharm. Pharm. Sci. 11: 81s-110s (2008) https://doi.org/10.18433/J3T886
  28. Rashad S, Hemingway A, Rainsford K, Revell P, Low F, Walker F. Effect of non-steroidal anti-inflammatory drugs on the course of osteoarthritis. The Lancet 334: 519-522 (1989) https://doi.org/10.1016/S0140-6736(89)90651-X
  29. Serhan CN, Ward PA, Gilroy DW. Fundamentals of inflammation: Cambridge University Press (2010)
  30. Soares MP, Seldon MP, Gregoire IP, Vassilevskaia T, Berberat PO, Yu J, et al. Heme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation. J. Immunol. 172: 3553-3563 (2004) https://doi.org/10.4049/jimmunol.172.6.3553
  31. Swardfager W, Lanctot K, Rothenburg L, Wong A, Cappell J, Herrmann N. A meta-analysis of cytokines in Alzheimer's disease. Biol. Psychiatry 68: 930-941 (2010) https://doi.org/10.1016/j.biopsych.2010.06.012
  32. Tacke F, Randolph GJ. Migratory fate and differentiation of blood monocyte subsets. Immunobiology 211: 609-618 (2006) https://doi.org/10.1016/j.imbio.2006.05.025
  33. Tafani M, Sansone L, Limana F, Arcangeli T, De Santis E, Polese M. The interplay of reactive oxygen species, hypoxia, inflammation, and sirtuins in cancer initiation and progression. Oxid. Med. Cell Longev. 2016 (2016)
  34. Taguchi K, Motohashi H, Yamamoto M. Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells 16: 123-140 (2011) https://doi.org/10.1111/j.1365-2443.2010.01473.x
  35. Tornatore L, Thotakura AK, Bennett J, Moretti M, Franzoso G. The nuclear factor kappa B signaling pathway: integrating metabolism with inflammation. Trends Cell Biol. 22: 557-566 (2012) https://doi.org/10.1016/j.tcb.2012.08.001
  36. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J. Clin. Invest. 115: 1111-1119 (2005) https://doi.org/10.1172/JCI25102
  37. Yoon S, Joo C. Study on the preventive effect of ginsenosides against hypercholesterolemia and its mechanism. Korean J. Ginseng Sci. 17: 1-12 (1993)