YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Inhibitory Effect of Salvia officinalis on the Inflammatory Cytokines and Inducible Nitric Oxide Synthasis in Murine Macrophage RAW264.7

RAW 264.7 Cell에서 세이지에 의한 염증성 Cytokine 및 iNOS억제 효과

  • 현은아 (제주대학교 의과대학 약리학교실) ;
  • 이혜자 (제주대학교 의과대학 약리학교실) ;
  • 윤원종 (제주대학교 의과대학 약리학교실) ;
  • 박수영 (제주대학교 의과대학 약리학교실) ;
  • 강희경 (제주대학교 의과대학 약리학교실) ;
  • 김세재 (제주대학교 자연과학대학 생명과학과) ;
  • 유은숙 (제주대학교 의과대학 약리학교실)
  • Published : 2004.04.01
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Abstract

Primary pro-inflammatory cytokines are a trio: tumor necrosis- $\alpha$ (TNF-$\alpha$), interleukine-$\beta$ (IL-$\beta$), and interleukine-6 (IL-6). These cytokines initiate and regulate the acute-phase inflammatory response during infection, trauma, or stress and appear to play an important role in the immune process. Nitric oxide (NO) is a multi-functional mediator, which plays an important role in regulating various biological functions in vivo. NO production by inducible nitric oxide synthase (iNOS) in macrophages is essential for the defense mechanisms against microorganisms and tumor cells. However, over-expression of iNOS by various stimuli, resulting in over-production of NO, contributes to the pathogenesis of septic shock and some inflammatory and auto-immune disease. Solvent fractions of sage ( Salvia officinalis L.), which is cultivated in Jeju-Do, was assayed for their effects on TNF-$\alpha$ and IL-6 production in LPS-stimulated RAW 264.7 macrophages. Hexane and ethylacetate (EtOAc) fraction of sage inhibited the protein and mRNA expression of TNF-$\alpha$ and IL-6 in LPS stimulated RAW 264.7 cells at the concentration of 100 $\mu\textrm{g}$/$m\ell$. Also, incubation of RAW 264.7 cells with the fraction of hexane or EtOAc (50 $\mu\textrm{g}$/$m\ell$) inhibited the LPS induced nitrite accumulation and the LPS/IFN-${\gamma}$ induced iNOS protein. And this inhibition of iNOS protein is concordant with the inhibition of iNOS mRNA expression. Above results suggest that extract of sage may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines (TNF-$\alpha$, IL-1$\beta$, IL-6), iNOS and NO.

Keywords

References

  1. Park, S. Y., Lee, H. J., Hyun, E, A., Moon, J, Y., Yang, H. C., Lee, N. H., Kim, S. J., Kang, H. K. and Yoo, E. S. : Inhibitory effect of eurya emarginata on the production of proinflammatory cytokines in murine macrophage RAW264.7. Yakhak Hoeji 47, 5 (2003)
  2. Willoughby, D. A. : Human arthritis applied to animal models. Towards a better therapy. Ann. Rheum. Dis. 34 (1971)
  3. Scott, M. G. and Hancock, R. E. : Cationic antimicrobial peptides and their multifunctional role in the immune system. Crit. Rev. Immunol. 20 (2000)
  4. An, S. J., Pae, H. O., Oh, G. S., Choi, B. M., Jeong, S., Jang, S. I., Oh, H., Kwon, T. O., Song, C. E. and Chung, H. T. : Inhibition of TNF-${\alpha}$, IL-1${\beta}$ and IL-6 productions and NF-${\kappa}$B activation in lipopolysaccharide-activated RAW 264.7 macrophages by catalposide, an iridoid glycoside isolated from Catalpa ovata G. Don (Bignoniaceae). Int. Immunopharmacol . 2 (2002)
  5. Lee, H. J., Jeong, Y. S., Ryu, S. Y. and Ryu, J. H. : Inhibition of nitric oxide synthesis by 8-epi-xanthatin in activated RAW 264.7 cells. Yakhak Hoeji 42, 5 (1998)
  6. Axtelle, T. and Pribble, J. : IC14, a CD14 specific monoclonal antibody is a potential treatment for patients with severe sepsis. J. Endotoxin Res. 7 (2001)
  7. MukIS, N., Ishikawa, Y, Ikeda, N., Fujioka, N., Watanabe, S. and Kuno, K. : Novel insight into molecular mechanism of endotoxin shock; biochemical analysis of LPS receptor signaling in a cell-free system targeting NF-kapperB and regulation of cytokine production/action through beta2 integrin in vivo. J. Leukoc. Biol. 59 (1995)
  8. Ryoo, J. W. and Cha, B. C. : Mineral content and antioxidative activity in some herb plants. Kor. J. Med. Crop Sci. 6, 1 (1998)
  9. Chung, H. Y and Kim, H. B. : In vitro studies on the superoxide scavenging activities, the cytotoxic and the immunomodulatingeffects of thirteen kinds of herbal extracts. Korean J. Food Sci. Technol, 32, 3 (2000)
  10. 최영전 : 허브와 스파이스 가이드북. 도서출판 예가 p.258 (1998)
  11. Song, E. S., Ku, C. S., Mun, S. P., Ryu, J. S., Kim, D. H., Choi, J. S. and Choi, Y. G. : Volatile aroma compounds and their characteristics of Labiatae by soild-phase microextraction (SPME). Kor. J. Med. Crop Sci. 10, 2 (2002)
  12. Dorman, H. J. D., Peltoketo, A., Hiltunen, R. and Tikkanen, M. J. : Characterisation of the antioxidant properties of deodourised aqueous extracts from selected Lamiaceae herbs. Food Chemistry 83 (2003)
  13. Cuppett, S. L. and Hall, C. A. : Antioxidant activity of the Labiatae. Adv. Food Nutr. Res. 42 (1998)
  14. Bandonien, D., Venskutonis, P. R., Gruzdien, D. and Murkovic, M. : Antioxidative activity of sage (Salvia officinalis L.), savory (Satureja hortenis L.) and borage (Borago officinalis L.) extracts in rapeseed oil. Eur. J. Lipid Sci. Technol. 104 (2002)
  15. Santos-Gomes, P. C., Seabra, R. M., Andrade, P. B. 2nd Fernandes-Ferreira, M. : Phenolic antioxidant compounds produced by in vitro shoots of sage (Salvia officinalis). Plant Science 162 (2002).
  16. Hohmann, J., Rdei, D., Mth, I. and Blunden, G. : Phenylpropanoid glycosides and diterpenoids from Salvia Officidnalis. Biochem. Syst. Ecol. 31 (2003)
  17. Ashutosh, K. M., Amita, A. and Sita, N. : Gold sodium thimalaate (GSTM) inhibits lipopolysaccaride stimulated tumor necrosis factor-${\alpha}$ through ceramide pathway. Cell. Immunol. 219 (2002)
  18. Groves, R. W., Allen, M. H. and Ross, E. L. : Tumour necrosis factor alpha is pro-inflammatory in normal human skin and modulates cutaneous adhesion molecule expression. Br. J. Dermatol. 32 (1994)
  19. Wakefield, P. E., James, W. D., Samlaska, C. P. and Mettzes, M. S. : Tumour necrosis factor. J. Am. Acad. Dermatol. 24 (1991)
  20. Ishii, R., Horie, M., Saito, K., Arisawa, M. and Kitanaka, S. : Inhibition of lipopolysaccharide induced pro-inflammatory cytokine expression via suppression of nuclear factor-${\kappa}$B activation by Mallotus japonicus phloroglucinol derivatives. Biochim. Biophys. ACTA 1620 (2003)
  21. Korean society of medical biochemistry and molecular biology : Trends in medical research. Korean Society of Medical Biochemistry and Molecular Biology 64 (1998)
  22. Tezuka, Y., Irikawa, S., Kaneko, T., Banskota, A. H., Nagaoka, T., Xiong, Q., Hase, K. and Kadota, S. : Screening of chinese herval drug extracts for inhibitory activity on nitric oxide production and identification of an active compound of Zanthoxylum bugeanum. J. Ethnopharmacol. 77 (2001)
  23. Feldmann, M., Brennan, F. M. and Maini. R. N. : Role of cytokine in rheumatoid arthritis. Annu. Rev. Immunol. 14 (1996)
  24. Harada, A., Sekido, N., Akahoshi, T., Wada, T., Mukaida, N. and Matsushima, K. J. : Essential involvement of interleukin-8 in acute inflammation. J. Leukoc. Biol. 56, 5 (1994)
  25. Kim, R. G., Shin, K. M., Chun, S. K., Ji, S. Y., Seo, S. H., Park, H. J., Choi, J. W. and Lee, K. T. : In vitro antiinflammatory activity of the essential oil from Ligularia fischeri var. spiciformis in murine macrophage RAW 264.7 cells. Yakhak Hoeji 46, 5 (2002)