Microbiology and Biotechnology Letters (한국미생물·생명공학회지)

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Red Ginseng Ethanol Extract Suppressed Ag I/II-induced Up-expression of Inflammatory Mediators in RAW 264.7 Macrophages

홍삼에탄올추출물의 염증유발인자에 대한 억제효과

  • Choi, Kyung-Min (Department of Research Development, Institute of Jinan Red Ginseng) ;
  • Hwang, Seung-Mi (Department of Research Development, Institute of Jinan Red Ginseng) ;
  • Lim, Ji-Ye (Department of Research Development, Institute of Jinan Red Ginseng) ;
  • Ko, Eun-Sil (Department of Research Development, Institute of Jinan Red Ginseng) ;
  • Park, Jong-Hyuk (Imsil Research Institute of Cheese Science) ;
  • Moon, Jung-Hye (Imsil Research Institute of Cheese Science) ;
  • Lee, Min-Jung (Berry&Bio Food Research Institute) ;
  • Jang, Ji-Eun (Berry&Bio Food Research Institute) ;
  • Cha, Jeong-Dan (Department of Research Development, Institute of Jinan Red Ginseng)
  • Received : 2015.02.04
  • Accepted : 2015.06.01
  • Published : 2015.06.28
Download PDF
⟨ Previous Next ⟩

Abstract

In this study, we investigated the effects of 40% ethanol extract of Red Ginseng (RGE) on the productions of inflammatory proteins in Antigen I/II (Ag I/II)-N, a recombinant protein isolated from Streptococcus mutans -stimulated in RAW 264.7 cells. RGE inhibited the expression of Ag I/II-N-induced pro-inflammatory mediators, both mRNA and protein synthesis levels, without any cytotoxic effects. Moreover, RGE significantly inhibited Ag I/II-N induced NF-κB translocation into the nucleus by preventing the degradation of inhibitor κB-α. In conclusion, RGE down regulates the expression of pro-inflammatory genes involved in the synthesis of NO and iNOS in Ag I/II-N-stimulated RAW 264.7 cells by suppressing NF-κB activity.

본 연구에서, 우리는 S. mutans Ag I/II 재조합단백질에 의해 유도되어진 염증유발 단백질의 발현에 홍삼 40% 에탄올 추출물의 효과를 알아보고자 하였다. 홍삼에탄올추출물은 Ag I/II 재조합단백질에 의해 유도되어진 염증유발물질들의 mRNA와 단백질의 발현을 억제하였다. 더불어 홍삼에탄올 추출물은 NF-κΒ p65가 핵내로 이용하는 것이 억제하였다. 결론적으로 홍삼 40%에탄올추출물은 NF-κB의 활성에 의해 NO 생성과 iNOS 발현이 조절되어지는 것으로 생각되어지며, 염증유발 관련 유전자들의 낮은 발현을 유도하는 것으로 관찰되어졌다.

Keywords

References

  1. Ahmadi-Ashtiani H, Allameh A, Rastegar H, Soleimani M, Barkhordari E. 2012. Inhibition of cyclooxygenase-2 and inducible nitric oxide synthase by silymarin in proliferating mesenchymal stem cells: comparison with glutathione modifiers. J. Nat. Med. 66: 85-94. https://doi.org/10.1007/s11418-011-0554-6
  2. Aktan, F. 2004. iNOS-mediated nitric oxide production and its regulation. Life Sci. 75: 639-653. https://doi.org/10.1016/j.lfs.2003.10.042
  3. Attele AS, Wu JA, Yuan CS. 1999. Ginseng pharmacology; multiple constituents and multiple actions. Biochem. Pharmacol. 58: 1685-1693. https://doi.org/10.1016/S0006-2952(99)00212-9
  4. Bae EA, Han MJ, Shin YW, Kim DH. 2006. Inhibitory effects of Korean red ginseng and its genuine constituents ginsenosides Rg3, Rf, and Rh2 in mouse passive cutaneous anaphylaxis reaction and contact dermatitis models. Biol. Pharm. Bull. 29: 1862-1867. https://doi.org/10.1248/bpb.29.1862
  5. Bowers LW, Maximo IX, Brenner AJ, Beeram M, Hursting SD, Price RS, et al. 2014. NSAID use reduces breast cancer recurrence in overweight and obese woman: role of prostaglandin-aromatase interactions. Cancer Res. 74: 4446-4457. https://doi.org/10.1158/0008-5472.CAN-13-3603
  6. Chawla A, Nguyen KD, Goh YP. 2011. Macrophage mediated inflammation in metabolic disease. Nat. Rev. Immunol. 11: 738-749. https://doi.org/10.1038/nri3071
  7. Cheng YJ, Yang BC, Liu MY. 2006. Lead increases lipopoly-saccharide-induced liver injury through tumor necrosis factor-α overexpression by monocytes/macrophages: role of protein kinase C and p42/44 mitogen-activated protein kinase. Environ. Health Perspect 114: 507-513.
  8. Chepurnov SA, Chepurnova NE, Park JK, Buzinova EV, Lubinov II, Kabanova NP, et al. 1994. The central effects of saponin components and polysaccharides fraction from korea red ginseng. Korean J. Ginseng Sci. 18: 165-174.
  9. Cho CW, Kim SW, Rho JH, Rhee YK, Kim KT. 2008. Extraction characteristics of saponin and acidic polysaccharide based on the red ginseng particle size. J. Ginseng Res. 32: 179-186. https://doi.org/10.5142/JGR.2008.32.3.179
  10. Choi KS, Song H, Kim EH, Choi JH, Hong H, Han YM, et al. 2012. Inhibition of hydrogen sulfide-induced angiogenesis and inflammation in vascular endothelial cells: potential mechanisms of gastric cancer prevention by Korean red ginseng. Ginseng Res. 36: 135-145. https://doi.org/10.5142/jgr.2012.36.2.135
  11. Choi WY, Lee CG, Seo YC, Song CH, Lim HW, Lee HY. 2012. Effect of high pressure and steaming extraction processes on ginsenosides Rg3 and Rh2 contents of cultured-root in wild ginseng (Panax ginseng C. A. Meyer). Korean J. Med. Crop Sci. 20: 270-276. https://doi.org/10.7783/KJMCS.2012.20.4.270
  12. Chu S, Gu J, Feng L, Liu J, Zhang M, Jia X, et al. 2014. Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses. Int. Immunopharmacol. 19: 317-326. https://doi.org/10.1016/j.intimp.2014.01.018
  13. Dean JLE, Brook M, Clark AR, Saklatavala J. 1999. P38 mitogen activated protein kinase regulates cycloxygenase-2 mRNA stability and transcription in lipopolysaccharide-treated human monocytes. J. Biol. Chem. 274: 264-269. https://doi.org/10.1074/jbc.274.1.264
  14. Duan Y, Chen F, Zhang A, Zhu B, Sun J, Xie Q, et al. 2014. Aspirin inhibits lipopolysaccharide-induced COX-2 expression and PGE2 production in porcine alveolar macrophages by modulating protein kinase C and protein tyrosine phosphatase activity. BMB Rep. 47: 45-50. https://doi.org/10.5483/BMBRep.2014.47.1.089
  15. Du YJ, Dong JC. 2009. Changes of cytokines, inflammatory mediators and signal pathways in patients of asthma at attack and remission stage respectively and influence of Chinese medicinal on them. Zhongguo Zhong Xi Yi Jie He Za Zhi. 29: 1141-1144.
  16. Gabay C. 2006. Interleukin-6 and chronic inflammation. Arthritis Res. Ther. 8: S3.
  17. Han JH, Baik BJ, Yang YM, Park JY, Kim JG. 2006. Generation of antibodies against N-terminus fragment of Ag I/II protein from Streptococcus mutans GS-5. J. Korean Acad. Ped. Dent. 33: 401-410.
  18. Huang GJ, Deng JS, Liao JC, Hou WC, Wang SY, Sung PJ, et al. 2012. Inducible nitric oxide synthase and cyclooxygenase-2 participate in anti-inflammatory activity of imperatorin from Glehnia littoralis. J. Agric. Food Chem. 60: 1673-1681. https://doi.org/10.1021/jf204297e
  19. In JG, Lee BS, Kim EJ, Park MH, Yang DC. 2006. Increase of functional saponin by acidic treatement and temperature of red ginseng extract. Korean J. Plant Res. 19: 139-143.
  20. Kang YS, Han MH, Hong SH, Park C, Hwang HJ, Kim BW, et al. 2014. Anti-inflammatory effects of Schisandra chinensis (Turcz.) Baill fruit through the inactivation of nuclear factor-κB and mitogen-activated protein kinases signaling pathways in lipopolysaccharide-stimulated murine macrophages. J. Cancer Prev. 19: 279-287. https://doi.org/10.15430/JCP.2014.19.4.279
  21. Kim MA, Jeon HS, Shin SY, Baik BJ, Yang YM, Lee KY, et al. 2013. Rapid detection of S. mutans surface antigen I/II using a sensitive monoclonal anti-Ag I/II antibody by ELISA. Monoclon. Antib. Immunodiagn Immunother. 32: 336-340. https://doi.org/10.1089/mab.2013.0017
  22. Kitagawa I, Taniyama T, Shibuya H, Noda T, Yoshikawa M. 1987. Chemical studies on crude drug processing. V. On the constituents of ginseng radix rubra (2): comparison of the constituents of white ginseng and red ginseng prepared from the same Panax ginseng root. Yakugaku. Zasshi. 107: 495-505. https://doi.org/10.1248/yakushi1947.107.7_495
  23. Lee DC, Lau AS. 2011. Effects of Panax ginseng on tumor necrosis factor-α-mediated inflammation: a mini-review. Molecules. 16: 2802-2816. https://doi.org/10.3390/molecules16042802
  24. Lee SE, Park YS. 2014. Korean red ginseng water extract inhibits COX-2 expression by suppressing p38 in acrolein-treated human endothelial cells. Ginseng Res. 38: 34-39. https://doi.org/10.1016/j.jgr.2013.11.004
  25. Lee SY, Kwon HK, Lee SM. 2011. Shinbaro, a new herbal medicine with multifunctional mechanism for joint disease: first therapeutic application for the treatment of osteoarthritis. Arch. Pharm. Res. 34: 1773-1777. https://doi.org/10.1007/s12272-011-1121-0
  26. Medzhitov R. 2008. Origin and physiological roles of inflammation. Nature 454: 24. https://doi.org/10.1038/454024a
  27. Miyataka M, Rich KA, Ingram M, Yamamoto T, Bing RJ. 2002. Nitric oxide, anti-inflammatory drugs on renal prostaglandins and cyclooxygenase-2. Hypertension 39: 785-789. https://doi.org/10.1161/hy0302.105689
  28. Muller N, Myint AM, Schwarz MJ. 2011. Inflammatory biomarkers and depression. Neurotox. Res. 19: 308-318. https://doi.org/10.1007/s12640-010-9210-2
  29. Nam KY. 2005. The comparative understanding between red ginseng and white ginsengs, processed ginsengs (Panax ginseng C.A. Meyer). J. Ginseng Res. 29: 1-18. https://doi.org/10.5142/JGR.2005.29.1.001
  30. Park CM, Jin KS, Lee YW, Song YS. 2011. Luteolin and chicoric acid synergistically inhibited inflammatory responses via inactivation of PI3K-Akt pathway and impairment of NF-κB translocation in LPS stimulated RAW 264.7 cells. Eur. J. Pharmacol. 660: 454-459. https://doi.org/10.1016/j.ejphar.2011.04.007
  31. Park CM, Park JY, Noh KH, Shin JH, Song YS. 2011. Taraxacum officinale Weber extracts inhibit LPS induced oxidative stress and nitric oxide production via the NF-κB modulation in RAW 264.7 cells. J. Ethnopharmacol. 133: 834-842. https://doi.org/10.1016/j.jep.2010.11.015
  32. Park HM, Kim SJ, Go HK, Kim GB, Kim SZ, Kim JS, et al. 2011. Korean red ginseng prevents ethanol-induced hepato-toxicity in isolated perfused rat liver. Korean J. Vet. Res. 51: 159-164.
  33. Park HM, Kim SJ, Mun AR, Go HK, Kim GB, Kim SZ, et al. 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
  34. Salvemini D, Milko TP, Masferrer JL, Seibert K, Currie MG, Needleman P. 1993. Nitric oxide activates cyclooxygenase enzymes. Proc. Natl. Acad. Sci. USA. 90: 7240-7244. https://doi.org/10.1073/pnas.90.15.7240
  35. Sung HS. 1986. Present and future on the processing of ginseng. Korean J. Ginseng Sci. 10: 218-232.
  36. Swierkosz TA, Mitchell JA, Warner TD, Botting RM, Vane JR. 1995. Co-induction of nitric oxide synthase and cyclo-oxygenase: interactions between nitric oxide and prostanoids. Br. J. Pharmacol. 114: 1335-1342. https://doi.org/10.1111/j.1476-5381.1995.tb13353.x
  37. Tak PP, Firestein GS. 2001. NF-κB: a key role in inflammatory diseases. J. Clin. Invest. 107: 7-11. https://doi.org/10.1172/JCI11830
  38. Vogler BK, Pittler MH, Ernst E. 1999. The efficacy of ginseng. A systematic review of randomised clinical trials. Eur. J. Clin. Pharmacol. 55: 567-575. https://doi.org/10.1007/s002280050674
  39. Xu X, Yin P, Wan C, Chong X, Liu M, Cheng P, et al. 2014. Punicalagin inhibits inflammation in LPS-induced RAW 264.7 macrophages via the suppression of TLR4-mediated MAPKs and NF-κB activation. Inflammation 37: 956-965. https://doi.org/10.1007/s10753-014-9816-2
  40. Yang Y, Yang WS, Yu T, Sung GH, Park KW, Yoon K, et al. 2014. ATF-2/CREB/IRF-3-targeted anti-inflammatory activity of Korean red ginseng water extract. J. Ethnopharmacol. 154: 218-228. https://doi.org/10.1016/j.jep.2014.04.008

Cited by

  1. 항염증 물질 생산 능력이 우수한 야생효모의 선별 및 이들의 균학적 특성 vol.45, pp.3, 2017, https://doi.org/10.4489/kjm.20170025
  2. Lipopolysaccharide로 유도한 RAW 264.7 세포에 대한 Meyerozyma guilliermondii YJ34-2와 Rhodotorula graminis YJ36-1의 항염활성과 Nitric Oxide 생성 저해물질의 생산 vol.45, pp.4, 2015, https://doi.org/10.4489/kjm.20170039