Inhibition of Matrix Metalloproteinases-12 (MMP-12) and Anti-oxidant Effect of Xanthohumol from Hop (Humulus lupulus L.)

  • Received : 2012.11.10
  • Accepted : 2012.12.09
  • Published : 2012.12.31


Xanthohumol was isolated from hops (Humulus lupulus L.), and then investigated anti-oxidant effect by AAPH-induced LLC-PK1 cell and oxygen radical absorbance capacity (ORCA) assays and MMP-12 inhibitory effect by direct MMP-12 inhibition assay. The treatment of xanthohumol protected LLC-PK1 cells from AAPH-induced cell damage such as cell viability, SOD and GSH-px reduction in a dose dependant manner (0.1, 1, and $5{\mu}M$), the SOD value was 2.98, 4.51, and 5.77 U/mg protein, and GSH-px value was 30.12, 49.32, and 60.11 U/mg protein. ORAC value of xanthohumol was showed as 4320, 12004, and $14209{\mu}M$ TE/g at the concentration 0.1, 1, and $5{\mu}M$, respectively. The change of SOD and GSH-px values was significantly correlated with the results of ORAC assay, that is, AAPH-induced cell and ORCA assays. In addition, inhibition of MMP-12 that is known to play an important role in skin aging was 14%, 37%, 46%, and 79% at the concentration of 0.01, 0.1, 1, and $5{\mu}M$, respectively. On the basis of these results, xanthohumol from hops (Humulus lupulus L.) showed interesting biological and pharmacological activity such as anti-oxidant effect and anti-aging.


Supported by : Seoil University


  1. Alptekin, N., Seckin, S., Dogru-Abbasoglu, S., Yelkenci, F., Kocak-Toker, N., Toker, G., and Uysal, M., Lipid peroxides, glutathione, gammaglutamylcysteine synthetase and gamma-glutamyltranspeptidase activities in several tissues of rats following water-immersion stress. Pharmacol. Res. 34, 167-169 (1996).
  2. Braverman, I.M. and Fonferko, E., Studies in cutaneous aging: I. The elastic fiber network. Dermatol. 78, 434-443 (1982).
  3. Buckwold, V.E., Wilson, R.J.H., Nalca, A., Beer, B.B., Voss, T.G., Yurpin, J.A., Buckheit, III R.W., Wei, J.Y., Wenzel-Mathers, M., Walton, E.M., Smith, R.J., Pallansch, M., Ward, P., Wells, J., Chuvala, L., Sloane, S., Paulman, R., Russell, J., Hartman, T., and Ptak, R., Antiviral activity of hop constituents against a series of DNA and RNA viruses. Antiviral. Res. 61, 57-62 (2004).
  4. Carmichael, J., DeGraff, W.G., Gazdar, A.F., Minna, J.D., and Mitchell, J.B., Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res. 47, 936-942 (1987).
  5. Chung, J.H., Seo, J.Y., Lee, M.K., Eun, H.C., Lee, J.H., Kang, S., Fisher, G.J., and Voorhees, J.J., Ultraviolet modulation of human macrophage metalloelastase in human skin in vivo. J. Invest. Dermatol. 119, 507-512 (2002).
  6. Gilchrest, B.A., Skin aging and photoaging: an overview. J. Am. Acad. Dermatol. 21, 610-613 (1989).
  7. Hautamaki, R.D., Kobayashi, D.K., Senior, R.M., and Shapiro, S.D., Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science 277, 2002-2004 (1997).
  8. Husain, K. and Somani, S.M., Interaction of exercise training and chronic ethanol ingestion on testicular antioxidant system in rat. J. Appl. Toxicol. 18, 421-429 (1998).<421::AID-JAT532>3.0.CO;2-R
  9. Jimenez, I., Garrido, A., Bannach, R., Gotteland, M., and Speiskg, H., Protective effects of boldine against free radical-induced erythrocyte lysis. Phytother. Res. 14, 339-343 (2000).<339::AID-PTR585>3.0.CO;2-T
  10. Lawrence, R.A. and Burk, R.F., Glutathione peroxidase activity in selenium-deficient rat liver. Biochem. Biophys. Res. Commun. 71, 952-958 (1976).
  11. Marklund, S. and Marklund, G., Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem. 47, 469-474 (1974).
  12. Mera, S.L., Lovell, C.R., Jones, R.R., and Davies, J.D., Elastic fibres in normal and sun-damaged skin: an immunohistochemical study. Br. J. Dermatol. 117, 21-27 (1987).
  13. Miranda, C.L., Stevens, J.F., Helmrich, A., Henderson, M.C., Rodriguez, R.J., Yang, Y.H., Deinzer, M.L., Barnes, D.W., and Buhler, D.R., Antiproliferative and cytotoxic effects of prenylated flavonoids from hops (Humulus lupulus) in human cancer cell lines. Food Chem. Toxicol. 37, 271-285 (1999).
  14. Montagna, W., Kirchner, S., and Carlisle, K., Histology of sun-damaged human skin. J. Am. Acad. Dermatol. 21, 907-918 (1989).
  15. Philips, N., Auler, S., Hugo, R., and Gonzalez, S., Beneficial regulation of matrix metalloproteinases for skin health. Enzyme Res. 2011, Article ID 427285, 1-4 (2010).
  16. Philips, N., Samuel, M., Arena, R., Chen, Y.J., Conte, J., Natarajan, P., Haas, G., and Gonzalez, S., Direct inhibition of elastase and matrixmetalloproteinases and stimulation of biosynthesis of fibrillar collagens, elastin, and fibrillins by xanthohumol. J. Cosmet. Sci. 61, 125-132 (2010).
  17. Piao, X.L., Park, I.H., Baek, S.H., Kim, H.Y., Park, M.K., and Park, J.H., Antioxidative activity of furanocoumarins isolated from Angelicae dahuricae. J. Ethnopharmacol. 93, 243-246 (2004).
  18. Prior, R.L., Hoang, H., Gu, L., Wu, X., Bacchiocca, M., Howard, L., Hampsch-Woodill, M., Huang, D., Ou, B., and Jacob, R., Assays for hydrophilic and lipophilic antioxidant capacity (oxygen radical absorbance capacity (ORAC(FL))) of plasma and other biological and food samples. J. Agric. Food Chem. 51, 3273-3279 (2003).
  19. Seo, J.Y. and Chung, J.H., Thermal aging: A new concept of skin aging. J. Dermatol. Sci. Suppl. 2, S13-22 (2006).
  20. Shapiro, S.D., Kobayashi, D.K., and Ley, T.J., Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. J. Biol. Chem. 268, 23824-23829 (1993).
  21. Tabata, N., Ito, M., Tomoda, H., and Omura, S., Xanthohumols, diacylglycerol acyltransferase inhibitors, from Humulus lupulus. Phytochemistry 4, 683-687 (1997).
  22. Varani, J., Warner, R.L., Gharaee-Kermani, M., Phan, S.H., Kang, S., Chung, J.H., Wang, Z.Q., Datta, S.C., Fisher, G.J., and Voorhees, J.J., Vitamin A antagonizes decreased cell growth and elevated collagendegrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin. J. Invest. Dermatol. 114, 480-486 (2000).
  23. Vogel, S. and Heilmann, J., Synthesis, cytotoxicity, and antioxidative activity of minor prenylated chalcones from Humulus lupulus. J. Nat. Prod. 71, 1237-1241 (2008).
  24. Weingarten, H. and Feder, J., Spectrophotometric assay for vertebrate collagenase. Anal. Biochem. 47, 437-440 (1985).