백렴 추출물의 Matrix Metalloproteinase-1 발현 저해 효과

Effect of Melothria heterophylla Extract on Expression of Matrix Metalloproteinase-1 in Human Skin Fibroblasts

  • 발행 : 2004.01.01

초록

Matrix metalloproteinases (MMPs) are known to play an important role in photoaging by mediating the degradation of extracellular matrix proteins. In this study, to develop a n ew anti-aging agent, we investigated the antioxidant activity and the inhibitory effect of Melothria heterophylla extract on expression of MMP-1 in UVA-irradiated human dermal fibroblasts and MMP-1 activity. The M.heterophylla extract was found to scavenge radicals and reactive oxygen species (ROS) with the $SC_{50}$ values of $13{\mu}g/ml$ against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and $20{\mu}g/ml$ against superoxide radicals in the xanthine/xanthine oxidase system, respectively. UVA-induced MMP-1 expression was reduced about 80% by $100{\mu}g/ml$ of the M.heterophylla extract but MMP-1 Mrna expression was not inhibited. Therefore, we conclude that the M.heterophylla extract significantly inhibits MMP-1 expression at the protein level. Also, the M.heterophylla extract inhibited MMP-1 activity in a dose dependent manner. From these results, we suggest that the M.heterophylla extract can be used as a new anti-aging agent by antioxidant activity, regulation of UVA-induced MMP-1 production, and inhibition of MMP-1 activity.

키워드

참고문헌

  1. Gilchrest, B. A. : Skin aging and photoaging: an overview. J. Am. Acad. Dermatol. 21, 610 (1989)
  2. Cadenas, E. : Biochemistry of oxygen toxicity. Annu. Rev. Biochem. 58, 79 (1989) https://doi.org/10.1146/annurev.bi.58.070189.000455
  3. Lavker, R. M. and Kligman, A. M. : Chronic heliodermatitis : a morphologic evaluation of chronic actinic dermal damage with emphasis on the role of mast cells.J. Invest. Dermatol. 90, 325 (1988)
  4. Davies, K. J. : Protein damage and degradation by oxygen radicals. J. BioI. Chem. 262, 9895 (1987)
  5. Bailly, C., Dreze, S., Asselineau, D., Nusgens, B., Lapiere, C. M. and Darmon, M. : Retinoic acid inhibits the production of collagenase by human epidermal keratinocytes. J. Invest. Derm. 94, 47 (1990). https://doi.org/10.1111/1523-1747.ep12873342
  6. Yaar, M. and Gilchrest, B. A. : Aging versus photoaging : postulated mechanisms and effectors. J. Investig. Dermatol. Symp. Proc. 3, 47 (1998)
  7. Li,J.J., Dong, Z., Dawson, M. I. and Colburn, N. H. : Inhibition of tumor promoter-induced transformation by retinoids that transrepress AP-1 without transactivating retinoic acid response element. Cancer Res. 56, 483 (1996)
  8. Huang, C., Ma, W. Y., Dawson, M. I., Rincon, M., Flavell, R. A. and Dong, Z. : Blocking activator protein-1 activity, but not activation retinoic acid response element, is required for the antitumor promotion effect of retinoic acid. Proc. Natl. Acad. Sci. USA 94, 5826 (1997)
  9. Kondo, S. : The roles of cytokines in photoaging. J. Dermatol. Sci. 23, S30 (2000)
  10. Wang, Y., Johnson, A. R., Ye, Q. Z. and Dyer, R. D. : Catalytic activities and substrate specificity of the human membrane type 4 matrix metalloproteinase catalytic damain. J. BioI. Chem. 274, 33043 (1999) https://doi.org/10.1074/jbc.274.46.33043
  11. Baker, A. H., Edwards, D. R. and Murphy, G. : Metallo-proteinase inhibitors : biological actions and therapeutic opportunities. J. Cell Sci. 115, 3719 (2002)
  12. Brenneisen, P., Sies, H. and Scharffetter-Kochanek, K. : Ultraviolet-B irradiation and matrix metalloproteinases: from induction via signaling to initial events. Ann. N.Y. Acad. Sci. 973, 31 (2002)
  13. Park, J. H. : The encyclopedia of Chinese crude drugs. Shinilbooks Publications, Seoul, 310 (2002)
  14. Blois, M. S. : Antioxidant determinations by the use of a stable free radical. Nature 181, 1199 (1958) https://doi.org/10.1038/1811199a0
  15. Furuno, K., Akasako, T. and Sugihara, N. : The contribution of the pyrogallol moiety to the superoxide radical scavenging activity of flavonoids. BioI. Pharm. Bull. 25, 19 (2002) https://doi.org/10.1248/bpb.25.19
  16. Mosmann, T. : Rapid colorimetric assay for the cellular growth and survival: application to proliferation and cytotoxic assay. J. Immunol. Methods 65, 55 (1983)
  17. Dunsmore, S. E., Rubin,J.S., Kovacs, S. O., Chedid, M., Parks, W. C. and Welgus, H. G. : Mechanisms of hepatocyte growth factor stimulation of keratinocyte metalloproteinase production. J. BioI. Chem. 271, 24576 (1996) https://doi.org/10.1074/jbc.271.40.24576
  18. Kitahara, A., Matsumoto, U., Ueda, H. and Ueoka, R. : A remarkable antioxidation effect of natural phenol derivatives on the autoxidation of ${\gamma}$-irradiated methyl linolate. Chem. Pharm. BuIl. 40, 2208 (1992)
  19. Hatano, T. : Constituents of natural medicines with scavenging effects on active oxygen species-tannins and related polyphenols. Natural Medicines 49, 357 (1995)
  20. Masaki, H., Sakaki, S., Atsumi, T. and Sakurai, H. : Active oxygen scavenging activity of plant extracts. Biol. Pharm. BuII. 18, 162 (1995)
  21. Kuppusamy, P. and Zweier, J. L. : Characterization of free radical generation by xanthine oxidase. J. BioI. Chem. 264, 9880 (1989)
  22. Chun, J. H., Kang, S. W., Varani, J., Lin, J., Fisher, G. J. and Voorhees, J. J. : Decreased extracellular-signal regulated kinase and increased stress-activated MAP kinase activities in aged human skin in vivo. J. Invest. Dermatol. 115, 177 (2000) https://doi.org/10.1046/j.1523-1747.2000.00009.x
  23. Fisher, G. J., Talwar, H. S., Lin, J., Lin, P., McPhillips, P., Wang, Z. Q., Li, X., Wan, Y., Kang, S. W. and Voorhees, J.J. : Retinoic acid inhibits induction of c-Jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo. J. Clin. Invest. 101, 1432 (1998) https://doi.org/10.1172/JCI2153
  24. Seo, J. Y., Rhie, G. E. and Chung, J. H. : The effect of ultraviolet irradiation on the expression of type I procollagen and MMP-1 in human dermal fibroblast and human skin in vivo. Kor. J. Invest. Derrntaol. 8, 116 (2001)
  25. Seo, J. Y., Choi, H. R., Rhie, G. E., Youn, C. S., Choi, W. W., Kim, J. A., Chung, J. H., Kim, K. H., Cho, K. H. and Eun, H. C. : The effect of retionic acid and vitamin C on the expression of the procollagen ${\alpha}$1(l) , tropoelastin, and MMP-1 in human dermal fibroblast. Kor. J. Invest. Dermtaol. 8, 23 (2001)
  26. Kochanek, S. K., Wlaschek, M., Briviba, K. and Sies, H. : Singlet oxygen induces collagenase expression in human skin fibroblast. FEBS Lett. 331, 304 (1993) https://doi.org/10.1016/0014-5793(93)80357-Z
  27. Wlaschek, M., Brviba, K., Stricklin, G. P., Sies, H. and Scharffetter-Kochanek, K. : Singlet oxygen may mediate the ultraviolet A induced synthesis of interstitial collagenase. J. Invest. Dermatol. 104, 194 (1995) https://doi.org/10.1111/1523-1747.ep12612751