Korean Journal of Pharmacognosy (생약학회지)

The Korean Society of Pharmacognosy (한국생약학회)
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Anti-inflammatory Effect of Unripe Fruit of Citrus grandis Osbeck in RAW 264.7 and HaCaT Cells

RAW 264.7 및 HaCaT Cell에서 당유자 미숙과의 염증억제 효과

  • Lee, Hye-Ja (Department of Pharmacology, College of Medicine, Cheju National University) ;
  • Kang, Gyeoung-Jin (Department of Pharmacology, College of Medicine, Cheju National University) ;
  • Yoon, Weon-Jong (Department of Pharmacology, College of Medicine, Cheju National University) ;
  • Kang, Hee-Kyoung (Department of Pharmacology, College of Medicine, Cheju National University) ;
  • Kim, Young-Suk (Department of Food and Nutritional Sciences, Ewha Womans University) ;
  • Kim, So-Mi (Faculty of Biotechnology, College of Applied Life Science, Cheju National University) ;
  • Yoo, Eun-Sook (Department of Pharmacology, College of Medicine, Cheju National University)
  • 이혜자 (제주대학교 의과대학 약리학교실) ;
  • 강경진 (제주대학교 의과대학 약리학교실) ;
  • 윤원종 (제주대학교 의과대학 약리학교실) ;
  • 강희경 (제주대학교 의과대학 약리학교실) ;
  • 김영석 (이화여자대학교 식품영양학과) ;
  • 김소미 (제주대학교 생명자원과학대학 생명공학부) ;
  • 유은숙 (제주대학교 의과대학 약리학교실)
  • Published : 2006.06.30
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Abstract

We investigated the anti-inflammatory activities of unripe fruit of Citrus grandis Osbeck growing at Jeju Island, through the evaluation of their inhibitory effect on the production of inflammatory markers (IL-6, iNOS, COX, TARC and MDC) in RAW264.7 murine macrophage cells and HaCaT human keratinocyte cells. Among the sequential solvent fractions obtained from crude extract, hexane and chloroform $(CHCI_3)$ fractions showed potential inhibitory activity on the mRNA expressions of IL-6, iNOS and COX-2 at the concentration of $100\;{\mu}g/ml$ in RAW264.7 cells. Also, EtOAc fraction showed inhibitory activity on the thymus and activation-regulated chemokine (TARC)/CCL17 and macrophage-derived chemokine (MDC)/CCL22 at the concentration of $50\;{\mu}g/ml$ in HaCaT cells. These results suggest that the unripe fruit of C. grandis may have anti-inflammatory activity through the suppression of inflammatory markers (IL-6, iNOS, COX, TARC and MDC).

Keywords

References

  1. 고정삼 (2001) 감귤산업. 104. 제주문화. 제주
  2. Oh, H. S., Park, W. B., An, Y. S., Oh, M. C., Oh, C. K. and Kim, S. H. (2003) Antimicrobial Activity of Extracts from Citrus Seeds. 한국조리학회지. 9: 69-80
  3. Mokbel, M. S. and Hashinaga, F. (2006) Evaluation of the antioxidant activity of extracts from buntan (Citrus grandis Osbeck) fruit tissues. Food chemistry. 94: 529-534 https://doi.org/10.1016/j.foodchem.2004.11.042
  4. Willoughby, D. A. (1975) Human arthritis applied to animal models. Towards a better therapy. Ann. Rheum. Dis. 34: 471-478 https://doi.org/10.1136/ard.34.6.471
  5. Axtelle, T. and Pribble, J. (2001) IC14, a CD14 specific monoclonal antibody is a potential treatment for patients with severe sepsis. J. Endotoxin. Res. 7: 310-314 https://doi.org/10.1177/09680519010070040201
  6. Lee, E. S., Ju, H. K., Moon, T. C., Lee, E., Jahng, Y, Lee S. H., Son, J. K., Baek, S. H. and Chang, H. W. (2004) Inhibition of nitric oxide and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) production by propenone compound through blockade of nuclear factor (NF)-KB activation in cultured murine macrophages. BioI. Pharm. Bull. 27: 617-620 https://doi.org/10.1248/bpb.27.617
  7. MuklS, N., Ishikawa, Y., Ikeda, N., Fujioka, N., Watanabe, S. and Kuno, K. (1996) 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: 145- 151e https://doi.org/10.1002/jlb.59.2.145
  8. Lazarov, S., Balutsov, M. and Ianev, E. (2000) The role of bacterial endotoxins, receptors and cytokines in the pathogenesis of septic(endotoxin) shock. Vutr. Boles. 32: 33-40
  9. Scott, M. G and Hancock, R. E. (2000) Cationic antimicrobial peptides and their multifunctional role in the immune system. Crit. Rev. Immunol. 20: 407-431
  10. Vane, J. A. (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like durgs. Nat. New. Biol. 23: 232-235
  11. Funk, C. D., Frunk, L. B., Kennedy, M. E., Pong, A. S. and Fitzgerald, G. A. (1991) Human platelet/erythroleukemia cell prostaglandin G/H synthase: eDNA cloning, expression, and gene chromosomal assignment. FASEB J. 5: 2304-23 I2 https://doi.org/10.1096/fasebj.5.9.1907252
  12. Weis, Z. A., Cicatiello, L. and Esumi, H. (1996) Regulation of the mouse inducible -type nitric oxide synthase gene promoter by interferon-gamma, bacterial lipopolysaccharide and $N^G$-monomethyl-L-arginine. Biochem J. 316: 209-215 https://doi.org/10.1042/bj3160209
  13. Ryu, J. H. Ahn, H. Kim, J. Y. and Kim, Y. K. (2003) Inhibitory activity of plant extracts on nitric oxide synthesis in LPS-activated macrophage. Phytother Res. 17: 485-489 https://doi.org/10.1002/ptr.1180
  14. Mu, M. M., Chakravortty, D., Sugiyama, T.,Koide, N., Takahashi, K., Mori, I., Yoshida, T. and Yokochi, T. (2001) The inhibitory action of quercetin on lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophage cells. J. Endotoxin Res. 7: 431-438 https://doi.org/10.1177/09680519010070060601
  15. 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. (2002) In vitro antiinflammatory activity of the essential oil from Ligularia fischeri var. spiciformis in murine macrophage RAW 264.7 cells. Yakhak Hoeji. 46: 343-347
  16. Seibert, K., Zhang, Y., Leahy, K., Hauser, S, Masferrer, J., Perkins, W., Lee, L. and Isakson, P. (1994) Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci USA. 91: 12013-12017
  17. Kim, J. Y., Jung, K. S. and Jeong, H. G (2004) Suppressive effects of the kahweol and cafestol on cycloocygenase-2 expression in macrophages. FEBS Letters. 569: 321-326 https://doi.org/10.1016/j.febslet.2004.05.070
  18. Yoshie, O., Imai, T. and Nomiyama, H. (2001) Chemokines in immunity. Adv. Immunol. 78: 57-110 https://doi.org/10.1016/S0065-2776(01)78002-9
  19. Rha, Y H. (2005) Role of chemokines in the pathogenesis of atopic. Pediatr Allergy Respir Dis. 15: 238-241
  20. Fujii-Maeda, S., Kajiwara, K., Ikizawa, K., Shinazawa, M., Yu, B., Koga, T., Fume, M. and Yanagihara, Y. (2004) Reciprocal regulation of thymus and activation-regulated chemokine/ macrophage-derived chemokine production by interleukin (IL)-4/IL-13 and interferon-gamma in HaCaT keratinocytes is mediated by alternations in E-cadherin distribution. J. Invest. Dermatol. 122: 20-28 https://doi.org/10.1046/j.0022-202X.2003.22103.x
  21. Campbell, J. J., Haraldsen, G., Pan, J., Rottman, J., Qin, S. and Ponath, P. (1999) The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells. Nature 400: 776-780 https://doi.org/10.1038/23495
  22. Vestergaard, C., Bang, K., Gesser, B., Yoneyama, H., Matsushima, K. and Larsen, C. C. (2000) A Th2 chmokine, TARC, produced by keratinocytes may recruit CLA+ CCR4+ lymphocytesinto lesional atopic dermatitis skin. J. Invest. Dermatol. 115: 640-646 https://doi.org/10.1046/j.1523-1747.2000.00115.x
  23. Leung, T. F., Wong, C. K., Chan, I. H., Lam, C. W. and Wong, G. W. (2002) Plasma concentration of thymus and activation-regulated chemokine is elevated in childhood asthma J. Allergy Clin Immunol. 110: 404-409 https://doi.org/10.1067/mai.2002.126378
  24. Sugawara, N., Yamashita, T., Ote, Y., Miura, M., Terada, N. and Kurosawa, M. (2002) TARC in allergic disease. Allergy. 57: 180-181
  25. 김승화 (2000) 유자 기능성 물질을 이용한 가공적성 향상 방안. 제주농업시험장. 제주
  26. Dorman, H. J., Bachmayer, O., Kosar, M. and Hiltunen, R. (2004) Antioxidant properties of aqueous extracts from selected lamiaceae species grownin Turkey. J. Agric Food Chem 25: 762-770
  27. Santos-Gomes, P. C., Seabra, R. M., Andrade, P. B. and Fernandes-Ferreira. M. (2003) Determination of phenolic antioxidant compounds produced by calli and cell suspensions of sage (Salvia officinalis L.). J. Plant Physiol. 160: 1025-1032 https://doi.org/10.1078/0176-1617-00831
  28. Tesuka, Y, Irikawa, S., Kaneko, T., Banskota, A.H., Nagaoka, T., Xiong, Q., Rase, K. and Kadota, S. (2001) Screening ofchinese herval drug extracts for inhibitory activity on nitric oxide production and identification of an active compound of Zanthoxylum bugeanum. Journal of Ethnopharmacology. 77: 209-217 https://doi.org/10.1016/S0378-8741(01)00300-2
  29. Masferrer, J., Zweifel B. S., Manning, P. T., Hauser, S. D., Leahy, K. M., Smith, W. G., Isakson. P. C. and Seibert, K. (1994) Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. Proc. Natl. Acad. Sci. 91: 3228-3232
  30. Hyun, E. A., Lee, H. J., Yoon, W. J., Park, S. Y., Kang, H. K., Kim, S. J. and Yoo, E. S. (2004) Inhibitory Effect of Salvia officinalis on the Inflammatory Cytokines and Inducible Nitric Oxide Synthesis in Murine Macrophage RAW264.7. YAKHAK HOEJI. 48: 159-164232
  31. Kim, S. D., Lee, J. Y., Lee, W. J. and Koo, D. W. (2001) Comparative study on the expression of ICAM-l of preimmune state keratinocytes induced by trichophyton antigen. Korean J. Dermatol. 39: 39-42
  32. Horikawa, T., Nakayama, T., Hikita, I., Yamada, H., Fujisawa, R., Bito, T.,Harada, S., Fukunaga, A, Chantry, D., Gray, P. W, Morita, A, Suzuki, R., Tezuka, T., Ichihashi, M. and Yoshie, O. (2002) IFN-gamma-inducible expression of thymus and activation-regulated chemokine/CCLl7 and macrophage-derived chemokine/CCL22 in epidermal keratinocytes and their roles in atopic dermatitis. Int. Immunol. 14: 767-773 https://doi.org/10.1093/intimm/dxf044
  33. Yu, B., Koga, T., Urabe, K., Maroi, Y., Maeda, S., Yanagihara, Y and Fume, M. (2002) Differential regulation of thymus- and activation-regulated chemokine induced by IL-4, IL-13, TNF-alpha and lFN-gamma in human keratinocyte and fibroblast. J. Dermatol. Sci. 30: 29-36 https://doi.org/10.1016/S0923-1811(02)00046-4