DOI QR코드

DOI QR Code

Inhibitory Effects of Ginsenoside Rb1,Rg3, and Panax ginseng Head Butanol Fraction on Inflammatory Mediators from LPS-Stimulated RAW 264.7 Cells

  • Lee, Je-Hyuk (Plant Resources Research Institute, Duksung Women's University) ;
  • Jeong, Choon-Sik (Plant Resources Research Institute, Duksung Women's University)
  • Published : 2008.09.30

Abstract

Panax ginseng C.A. Mayer (Araliaceae, P. ginseng) has been used for the enhancement of vascular and immune functions in Korea and Japan for a long time. Ginsenoside $Rb_1$ and $Rg_3$ isolated from P. ginseng head-part butanolic extract (PGHB) were investigated for anti-inflammatory activity. Ginsenosides and PGHB did not affect the cell viability within $0\;-\;100\;{\mu}g/ml$ concentration to RAW 264.7 murine macrophage cells. Ginsenosides and PGHB inhibited partly lipopolysaccharide (LPS)-induced nitrite production in a dose-dependent manner. The ginsenosides and PGHB showed partially chemical nitric oxide (NO) quenching (maximum 40%) in the cell-free system. Also, ginsenoside $Rb_1$ and $Rg_3$ inhibited markedly approximately 74 and 54% of inducible nitric oxide synthase (iNOS) mRNA transcription from LPS-induced RAW 264.7 cells. Taken together, the inhibitory effect of ginsenosides and PGHB on NO production did not occur as a result of cell viability, but was caused by both the chemical NO quenching and the regulation of iNOS. Additionally, the ginsenoside $Rb_1$ and PGHB inhibited prostaglandin $E_2$ ($PGE_2$) synthesis in a concentration-dependent manner, showed approximately 70-98% inhibition at $100\;{\mu}g/ml$ concentration. And the treatment with ginsenosides and PGHB attenuated partially LPS-upregulated cyclooxygenase-2 (COX-2) gene transcription. Ginsenoside $Rg_3$ suppressed LPS-stimulated interleukin-6 (IL-6) level to the basal in RAW 264.7 cells. From these results, ginsenoside $Rb_1,\;Rg_3$, and PGHB may be useful for the relief and retardation of immunological inflammatory responses and its action may occur through the reduction of inflammatory mediators, including NO, $PGE_2$, and IL-6 production.

Keywords

References

  1. Babu, B.H., Shylesh, B.S. and Padikkala, J. (2001) Antioxidant and hepatoprotective effect of Acanthus ilicifolius. Fitoterapia 72, 272-277 https://doi.org/10.1016/S0367-326X(00)00300-2
  2. Bae, E.A., Han, M.J., Kim, E.J. and Kim, D.H. (2004A) Transformation of ginseng saponins to ginsenoside $Rh_2$ by acids and human intestinal bacteria and biological activities of their transformants. Arch. Pharm. Res. 27, 61-67 https://doi.org/10.1007/BF02980048
  3. Bae, E.A., Hyun, Y.J., Choo, M.K., Oh, J.K., Ryu, J.H. and Kim, D.H. (2004B) Protective effect of fermented red ginseng on a transient focal ischemic rats. Arch. Pharm. Res. 27, 1136-1140 https://doi.org/10.1007/BF02975119
  4. Chun, K.S., Cha, H.H., Shin, J.W., Na, H.K., Park, K.K., Chung, W.Y. and Surh, Y.J. (2004) Nitric oxide induces expression of cyclooxygenase-2 in mouse skin through activation of NF-$_{\kappa}B$. Carcinogenesis 25, 445-445 https://doi.org/10.1093/carcin/bgh021
  5. Franzotti, E.M., Santos, C.V., Rodrigues, H.M., Mourao, R.H., Andrade, M.R. and Antoniolla, A.R. (2000) Anti-inflammatory, analgesic activity and acute toxicity of Sida cordifolia L. (Malva-branca). J. Ethnopharmacol. 72, 273-277 https://doi.org/10.1016/S0378-8741(00)00205-1
  6. Gorgoni, B., Caivano, M., Arizmendi, C. and Poli, V. (2001) The transcription factor C/EBP$\beta$ is essential for inducible expression of the COX-2 gene in macrophages but not in fibroblasts. J. Biol. Chem. 276, 40769-40777 https://doi.org/10.1074/jbc.M106865200
  7. Grimble, R.F. (1998) Nutritional modulation of cytokine biology. Nutrition 14, 634-640 https://doi.org/10.1016/S0899-9007(98)00010-0
  8. Honda, S., Migita, K., Hirai, Y., Ueki, Y., Yamasaki, S., Urayama, S., Kawabe, Y., Fukuda, T., Kawakami, A., Kamachi, M., Kita, M., Ida, H., Aoyagi, T. and Eguchi, K. (2000) Induction of COX-2 expression by nitric oxide in rheumatoid synovial cells. Biochem. Biophys. Res. Commun. 268, 928-931 https://doi.org/10.1006/bbrc.2000.2228
  9. Jeong, C.S., Hyun, J.E. and Kim, Y.S. (2003) Ginsenoside $Rb_1$: the anti-ulcer constituent from the head of Panax ginseng. Arch. Pharm. Res. 26, 906-911 https://doi.org/10.1007/BF02980198
  10. Korhonen, R., Lahti, A., Kankaanranta, H. and Moilanen, E. (2005). Nitric oxide production and signaling in inflammation. Curr. Drug Targets Inflamm. Allergy 4, 471-479 https://doi.org/10.2174/1568010054526359
  11. Lee, B.H., You, H.J., Park, M.S., Kwon, B. and Ji, G.E. (2006) Transformation of the ginsenosides from food materials by probiotics and food microorganisms. J. Microbiol. Biotechnol. 16, 497-504
  12. Lian, X.Y., Zhang, Z.Z. and Stringer, J.L. (2005) Anticonvulsant activity of ginseng on seizures induced by chemical convulsants. Epilepsia 46, 15-22
  13. Lim, J.H., Wen, T.C., Matsuda, S., Tanaka, J., Maeda, N., Peng, H., Aburaya, J., Ishihara, K. and Sakanaka, M. (1997) Protection of ischemic hippocampal neurons by ginsenoside $Rb_1$, a main ingredient of ginseng root. Neurosci. Res. 28, 191-200 https://doi.org/10.1016/S0168-0102(97)00041-2
  14. Lu, Y. and Wahl, L.M. (2005) Metalloproteinase-1, cyclooxygenase- 2, and prostaglandin $E_2$ through enhancement of NF-$_{\kappa}B$ activity in lipopolysaccharide-activated human primary monocytes oxidative stress augments the production of matrix. J. Immunol. 175, 5423-5429 https://doi.org/10.4049/jimmunol.175.8.5423
  15. Nantel, F., Denis, D., Gordon, R., Northey, A., Cirino, M., Metters, K.M. and Chan, C.C. (1999) Distribution and regulation of cyclooxygenase-2 in carrageenan-induced inflammation. Br. J. Pharmacol. 128, 853-859. https://doi.org/10.1038/sj.bjp.0702866
  16. Ojewole, J.A.O. (2006) Antinociceptive, anti-inflammatory and antidiabetic properties of Hypoxis hemerocallidea Fisch. & C.A. Mey.(Hypoxidaceae) corm ['African Potato'] aqueous extract in mice and rats. J. Ethnopharmacol. 103, 126-134 https://doi.org/10.1016/j.jep.2005.07.012
  17. Park, E.K., Shin, Y.W., Lee, H.U., Kim, S.S., Lee, Y.C., Lee, B.Y. and Kim, D.H. (2005) Inhibitory effect of ginsenoside Rb1 and compound K on NO and prostaglandin $E_2$ biosynthesis of RAW 264.7 cells induced by lipopolysaccharide. Biol. Pharm. Bull. 28, 652-656 https://doi.org/10.1248/bpb.28.652
  18. Perez-Sala, D. and Lamas, S. (2001) Regulation of cyclooxygenase- 2 expression by nitric oxide in cells. Antioxid. Redox Signal 3, 231-248 https://doi.org/10.1089/152308601300185197
  19. Radad, K., Gille, G., Moldzio, R., Saito, H. and Rausch, W.D. (2004) Ginsenoside $Rb_1$ and $Rg_1$ effects on mesencephalic dopaminergic cells stressed with glutamate. Brain Res. 1021, 41-53 https://doi.org/10.1016/j.brainres.2004.06.030
  20. Saito, H., Yoshida, Y. and Takagi, K. (1974) Effect of Panax Ginseng root on exhaustive exercise in mice. Jap. J. Pharmacol. 24, 119-127 https://doi.org/10.1254/jjp.24.119
  21. Salvemini, D. (1997) Regulation of cyclooxygenase enzymes by nitric oxide. Cell. Mol. Life Sci. 53, 576-582 https://doi.org/10.1007/s000180050074
  22. Spector, W.G. and Willoughb, D.A. (1963) The inflammatory response. Bacteriol. Rev. 27, 117-154
  23. Sutherland, H., Khundkar, R., Zolle, O., McArdle, A., Simpson, A.W., Jarvis, J.C. and Salmons, S. (2001) A fluorescencebased method for measuring nitric oxide in extracts of skeletal muscle. Nitric Oxide 5, 475-481 https://doi.org/10.1006/niox.2001.0374
  24. Van Dross, R.T., Hong, X. and Pelling, J.C. (2005) Inhibition of TPA-induced cyclooxygenase-2 (COX-2) expression by apigenin through downregulation of Akt signal transduction in human keratinocytes. Mol. Carcinog. 44, 83-91 https://doi.org/10.1002/mc.20123
  25. Wei, T., Chen, C., Hau, J., Zhao, B., Xin, W. and Mori, A. (1999) The antioxidant EPC-k1 attenuates NO-induced mitochondrial disfunction, lipid peroxidation and apoptosis in cerebellar granuele cells. Toxicology 134, 117-126 https://doi.org/10.1016/S0300-483X(99)00030-X
  26. Yokota, K., Miyazaki, T., Hirano, M., Akiyama, Y. and Mimura, T. (2006). Simvastatin inhibits production of interleukin-6 (IL-6) and IL-8 and cell proliferation induced by tumor necrosis factor- $\alpha$ in fibroblast-like synoviocytes from patients with rheumatoid arthritis. J. Rheumatol. 33, 463-471

Cited by

  1. Anti-hyperlipidemic Effects of Red Ginseng Acidic Polysaccharide from Korean Red Ginseng vol.33, pp.3, 2010, https://doi.org/10.1248/bpb.33.468
  2. Alterations of Spontaneous Sleep Architecture and Cortical Electroencephalogram Power Spectra by Red Ginseng Extract via GABAAergic Systems vol.34, pp.4, 2010, https://doi.org/10.5142/jgr.2010.34.4.304
  3. Development of a rapid and convenient method to separate eight ginsenosides from Panax ginseng by high-speed counter-current chromatography coupled with evaporative light scattering detection vol.34, pp.10, 2011, https://doi.org/10.1002/jssc.201000932
  4. The effect of ultrasonication on the immunomodulatory activity of low-quality ginseng vol.29, pp.1, 2013, https://doi.org/10.1002/btpr.1645
  5. Effects of the Jinan Red Ginseng Extract Treatment on Poloxamer 407-induced Hyperlipidemia in Rabbits vol.30, pp.6, 2008, https://doi.org/10.7732/kjpr.2017.30.6.601