Skip to main content
Springer Nature Link
Log in

Amentoflavone Inhibits UVB-Induced Matrix Metalloproteinase-1 Expression Through the Modulation of AP-1 Components in Normal Human Fibroblasts

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Amentoflavone is a well-known biflavonoid that has diverse biological effects. Previously, we reported that amentoflavone suppressed UVB-induced matrix metalloproteinase-1 (MMP-1) expression in normal human fibroblasts (NHF). We investigated the effects of amentoflavone on UVB-induced MMP-1 expression in order to elucidate its mode of action. NHF were treated with amentoflavone for indicated times and doses with UVB irradiation. The expressions of MMP-1 gene and protein were determined by RT-PCR and ELISA, respectively. MAP kinase phosphorylation and the expression of c-Fos protein were determined by Western blot. The treatment of amentoflavone completely blocked the upregulation of MMP-1 which is induced by UVB irradiation in HaCaT–NHF co-culture in a dose-dependent manner as well as in NHF monoculture. Also, amentoflavone inhibited UVB-induced activation of extracellular signal-regulated kinase (ERK) without changing total ERK protein level, and did not affect p38 or JNK activation. Finally, AP-1 transcription factor components, phospho-c-Jun and c-Fos protein expressions were decreased by amentoflavone treatment. The major finding of this study shows that amentoflavone inhibits intracellular cell signaling ERK pathway leading to the prevention of MMP-1 expression in human skin fibroblasts. Therefore, these results strongly suggest that amentoflavone should be investigated as a potential agent for the prevention and the treatment of skin photoaging.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

References

  1. Di Carlo, G., Mascolo, N., Izzo, A. A., & Capasso, F. (1999). Flavonoids: old and new aspects of a class of natural therapeutic drugs. Life Sciences, 65, 337–353.

    Article  Google Scholar 

  2. Kuo, Y. C., Sun, C. M., Tsai, W. J., Ou, J. C., Chen, W. P., & Lin, C. Y. (1998). Chinese herbs as modulators of human mesangial cell proliferation: preliminary studies. The Journal of Laboratory and Clinical Medicine, 132, 76–85.

    Article  CAS  Google Scholar 

  3. Banerjee, T., Valacchi, G., Ziboh, V. A., & van der Vliet, A. (2002). Inhibition of TNFalpha-induced cyclooxygenase-2 expression by amentoflavone through suppression of NF-kappaB activation in A549 cells. Molecular and Cellular Biochemistry, 238, 105–110.

    Article  CAS  Google Scholar 

  4. Suh, S. J., Chung, T. W., Son, M. J., Kim, S. H., Moon, T. C., Son, K. H., et al. (2006). The naturally occurring biflavonoid, ochnaflavone, inhibits LPS-induced iNOS expression, which is mediated by ERK1/2 via NF-kappaB regulation, in RAW264.7 cells. Archives of Biochemistry and Biophysics, 447, 136–146.

    Article  CAS  Google Scholar 

  5. Gil, B., Sanz, M. J., Terencio, M. C., Gunasegaran, R., Paya, M., & Alcaraz, M. J. (1997). Morelloflavone, a novel biflavonoid inhibitor of human secretory phospholipase A2 with anti-inflammatory activity. Biochemical Pharmacology, 53, 733–740.

    Article  CAS  Google Scholar 

  6. Lim, H., Son, K. H., Chang, H. W., Kang, S. S., & Kim, H. P. (2006). Effects of anti-inflammatory biflavonoid, ginkgetin, on chronic skin inflammation. Biological and Pharmaceutical Bulletin, 29, 1046–1049.

    Article  CAS  Google Scholar 

  7. Amellal, M., Bronner, C., Briancon, F., Haag, M., Anton, R., & Landry, Y. (1985). Inhibition of mast cell histamine release by flavonoids and biflavonoids. Planta Medica, 51, 16–20.

    Article  CAS  Google Scholar 

  8. Bronner, C., & Landry, Y. (1985). Kinetics of the inhibitory effect of flavonoids on histamine secretion from mast cells. Agents and Actions, 16, 147–151.

    Article  CAS  Google Scholar 

  9. Ito, C., Itoigawa, M., Miyamoto, Y., Rao, K. S., Takayasu, J., Okuda, Y., et al. (1999). A new biflavonoid from Calophyllum panciflorum with antitumor-promoting activity. Journal of Natural Products, 62, 1668–1671.

    Article  CAS  Google Scholar 

  10. Shinozaki, Y., Fukamiya, N., Uchiyama, C., Okano, M., Tagahara, K., Bastow, K. F., et al. (2002). Multidrug resistant cancer cells susceptibility to cytotoxic taxane diterpenes from Taxus yunnanensis and Taxus chinensis. Bioorganic & Medicinal Chemistry Letters, 12, 2785–2788.

    Article  CAS  Google Scholar 

  11. Woo, E. R., Lee, J. Y., Cho, I. J., Kim, S. G., & Kang, K. W. (2005). Amentoflavone inhibits the induction of nitric oxide synthase by inhibiting NF-kappaB activation in macrophages. Pharmacological Research, 51, 539–546.

    Article  CAS  Google Scholar 

  12. Kligman, L. H. (1989). The ultraviolet-irradiated hairless mouse: a model for photoaging. Journal of the American Academy of Dermatology, 21, 623–631.

    Article  CAS  Google Scholar 

  13. Pinnell, S. R. (2003). Cutaneous photodamage, oxidative stress, and topical antioxidant protection. Journal of the American Academy of Dermatology, 48, 1–19. quiz 20-12.

    Article  Google Scholar 

  14. Fisher, G. J., Datta, S., Wang, Z., Li, X. Y., Quan, T., Chung, J. H., et al. (2000). c-Jun-dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoic acid. The Journal of Clinical Investigation, 106, 663–670.

    Article  CAS  Google Scholar 

  15. Jung, E., Lee, J., Baek, J., Jung, K., Huh, S., Kim, S., et al. (2007). Effect of Camellia japonica oil on human type I procollagen production and skin barrier function. Journal of Ethnopharmacology, 112, 127–131.

    Article  CAS  Google Scholar 

  16. Fisher, G. J., Datta, S. C., Talwar, H. S., Wang, Z. Q., Varani, J., Kang, S., et al. (1996). Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature, 379, 335–339.

    Article  CAS  Google Scholar 

  17. Visse, R., & Nagase, H. (2003). Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circulation Research, 92, 827–839.

    Article  CAS  Google Scholar 

  18. Lauer-Fields, J. L., Juska, D., & Fields, G. B. (2002). Matrix metalloproteinases and collagen catabolism. Biopolymers, 66, 19–32.

    Article  CAS  Google Scholar 

  19. McCawley, L. J., & Matrisian, L. M. (2001). Matrix metalloproteinases: they’re not just for matrix anymore! Current Opinion in Cell Biology, 13, 534–540.

    Article  CAS  Google Scholar 

  20. Brennan, M., Bhatti, H., Nerusu, K. C., Bhagavathula, N., Kang, S., Fisher, G. J., et al. (2003). Matrix metalloproteinase-1 is the major collagenolytic enzyme responsible for collagen damage in UV-irradiated human skin. Photochemistry and Photobiology, 78, 43–48.

    Article  CAS  Google Scholar 

  21. Werb, Z., Tremble, P. M., Behrendtsen, O., Crowley, E., & Damsky, C. H. (1989). Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression. The Journal of Cell Biology, 109, 877–889.

    Article  CAS  Google Scholar 

  22. Przybylowska, K., Kluczna, A., Zadrozny, M., Krawczyk, T., Kulig, A., Rykala, J., et al. (2006). Polymorphisms of the promoter regions of matrix metalloproteinases genes MMP-1 and MMP-9 in breast cancer. Breast Cancer Research and Treatment, 95, 65–72.

    Article  CAS  Google Scholar 

  23. Maldonado, A., Game, B. A., Song, L., & Huang, Y. (2003). Up-regulation of matrix metalloproteinase-1 expression in U937 cells by low-density lipoprotein-containing immune complexes requires the activator protein-1 and the Ets motifs in the distal and the proximal promoter regions. Immunology, 109, 572–579.

    Article  CAS  Google Scholar 

  24. Doyle, G. A., Pierce, R. A., & Parks, W. C. (1997). Transcriptional induction of collagenase-1 in differentiated monocyte-like (U937) cells is regulated by AP-1 and an upstream C/EBP-beta site. Journal of Biological Chemistry, 272, 11840–11849.

    Article  CAS  Google Scholar 

  25. Reunanen, N., Westermarck, J., Hakkinen, L., Holmstrom, T. H., Elo, I., Eriksson, J. E., et al. (1998). Enhancement of fibroblast collagenase (matrix metalloproteinase-1) gene expression by ceramide is mediated by extracellular signal-regulated and stress-activated protein kinase pathways. Journal of Biological Chemistry, 273, 5137–5145.

    Article  CAS  Google Scholar 

  26. Simon, C., Goepfert, H., & Boyd, D. (1998). Inhibition of the p38 mitogen-activated protein kinase by SB 203580 blocks PMA-induced Mr 92,000 type IV collagenase secretion and in vitro invasion. Cancer Research, 58, 1135–1139.

    CAS  Google Scholar 

  27. Simon, C., Simon, M., Vucelic, G., Hicks, M. J., Plinkert, P. K., Koitschev, A., et al. (2001). The p38 SAPK pathway regulates the expression of the MMP-9 collagenase via AP-1-dependent promoter activation. Experimental Cell Research, 271, 344–355.

    Article  CAS  Google Scholar 

  28. Lee, C. W., Choi, H. J., Kim, H. S., Kim, D. H., Chang, I. S., Moon, H. T., et al. (2008). Biflavonoids isolated from Selaginella tamariscina regulate the expression of matrix metalloproteinase in human skin fibroblasts. Bioorganic & Medicinal Chemistry, 16, 732–738.

    Article  CAS  Google Scholar 

  29. Yang, J. W., Pokharel, Y. R., Kim, M. R., Woo, E. R., Choi, H. K., & Kang, K. W. (2006). Inhibition of inducible nitric oxide synthase by sumaflavone isolated from Selaginella tamariscina. Journal of Ethnopharmacology, 105, 107–113.

    Article  CAS  Google Scholar 

  30. Lin, L. C., Kuo, Y. C., & Chou, C. J. (2000). Cytotoxic biflavonoids from Selaginella delicatula. Journal of Natural Products, 63, 627–630.

    Article  CAS  Google Scholar 

  31. Li, M., Moeen Rezakhanlou, A., Chavez-Munoz, C., Lai, A., & Ghahary, A. (2009). Keratinocyte-releasable factors increased the expression of MMP1 and MMP3 in co-cultured fibroblasts under both 2D and 3D culture conditions. Molecular and Cellular Biochemistry, 332, 1–8.

    Article  CAS  Google Scholar 

  32. Park, C. H., Lee, M. J., Ahn, J., Kim, S., Kim, H. H., Kim, K. H., et al. (2004). Heat shock-induced matrix metalloproteinase (MMP)-1 and MMP-3 are mediated through ERK and JNK activation and via an autocrine interleukin-6 loop. The Journal of Investigative Dermatology, 123, 1012–1019.

    Article  CAS  Google Scholar 

  33. Xu, Y. R., & Fisher, G. J. (2005). Ultraviolet (UV) light irradiation induced signal transduction in skin photoaging. Journal of Dermatological Science, 1(2), S1–S8.

    Article  CAS  Google Scholar 

  34. Kahari, V. M., & Saarialho-Kere, U. (1997). Matrix metalloproteinases in skin. Experimental Dermatology, 6, 199–213.

    Article  CAS  Google Scholar 

  35. Kim, S., & Chung, J. H. (2008). Berberine prevents UV-induced MMP-1 and reduction of type I procollagen expression in human dermal fibroblasts. Phytomedicine, 15, 749–753.

    Article  CAS  Google Scholar 

  36. Varani, J., Perone, P., Fligiel, S. E., Fisher, G. J., & Voorhees, J. J. (2002). Inhibition of type I procollagen production in photodamage: correlation between presence of high molecular weight collagen fragments and reduced procollagen synthesis. The Journal of Investigative Dermatology, 119, 122–129.

    Article  CAS  Google Scholar 

  37. Watson, R. E., Long, S. P., Bowden, J. J., Bastrilles, J. Y., Barton, S. P., & Griffiths, C. E. (2008). Repair of photoaged dermal matrix by topical application of a cosmetic ‘antiageing’ product. British Journal of Dermatology, 158, 472–477.

    Article  CAS  Google Scholar 

  38. Moon, H. J., Lee, S. R., Shim, S. N., Jeong, S. H., Stonik, V. A., Rasskazov, V. A., et al. (2008). Fucoidan inhibits UVB-induced MMP-1 expression in human skin fibroblasts. Biological and Pharmaceutical Bulletin, 31, 284–289.

    Article  CAS  Google Scholar 

  39. Fisher, G. J., Talwar, H. S., Lin, J., & Voorhees, J. J. (1999). Molecular mechanisms of photoaging in human skin in vivo and their prevention by all-trans retinoic acid. Photochemistry and Photobiology, 69, 154–157.

    Article  CAS  Google Scholar 

  40. Kim, H. H., Shin, C. M., Park, C. H., Kim, K. H., Cho, K. H., Eun, H. C., et al. (2005). Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts. Journal of Lipid Research, 46, 1712–1720.

    Article  CAS  Google Scholar 

  41. Bae, J. Y., Choi, J. S., Choi, Y. J., Shin, S. Y., Kang, S. W., Han, S. J., et al. (2008). (-)Epigallocatechin gallate hampers collagen destruction and collagenase activation in ultraviolet-B-irradiated human dermal fibroblasts: involvement of mitogen-activated protein kinase. Food and Chemical Toxicology, 46, 1298–1307.

    Article  CAS  Google Scholar 

  42. Shim, J. S., Han, Y. S., & Hwang, J. K. (2009). The effect of 4-hydroxypanduratin A on the mitogen-activated protein kinase-dependent activation of matrix metalloproteinase-1 expression in human skin fibroblasts. Journal of Dermatological Science, 53, 129–134.

    Article  CAS  Google Scholar 

  43. Lee, J., Jung, E., Huh, S., Hwang, C. H., Lee, H. Y., Kim, E. J., et al. (2006). Emodin inhibits TNF alpha-induced MMP-1 expression through suppression of activator protein-1 (AP-1). Life Sciences, 79, 2480–2485.

    Article  CAS  Google Scholar 

  44. Huang, C., Schmid, P. C., Ma, W. Y., Schmid, H. H., & Dong, Z. (1997). Phosphatidylinositol-3 kinase is necessary for 12-O-tetradecanoylphorbol-13-acetate-induced cell transformation and activated protein 1 activation. Journal of Biological Chemistry, 272, 4187–4194.

    Article  CAS  Google Scholar 

  45. Bode, A. M., & Dong, Z. (2000). Signal transduction pathways: targets for chemoprevention of skin cancer. The Lancet Oncology, 1, 181–188.

    Article  CAS  Google Scholar 

Download references

Acknowledgement

The study was financially supported by the research fund of Hanyang University (HY-2011-N).

Author information

Authors and Affiliations

  1. Amore-Pacific Co. R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-Do, 446-729, Republic of Korea

    Chan-Woo Lee, Yongjoo Na, Nok-hyun Park, Han-Sung Kim, Soo Mi Ahn & Han-Kon Kim

  2. Department of Applied Chemistry, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do, 426-791, Republic of Korea

    Jin Woong Kim

  3. Division of Pharmacognosy, Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea

    Young Pyo Jang

  4. Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, 130-701, Republic of Korea

    Young Pyo Jang

Authors
  1. Chan-Woo Lee
    View author publications

    Search author on:PubMed Google Scholar

  2. Yongjoo Na
    View author publications

    Search author on:PubMed Google Scholar

  3. Nok-hyun Park
    View author publications

    Search author on:PubMed Google Scholar

  4. Han-Sung Kim
    View author publications

    Search author on:PubMed Google Scholar

  5. Soo Mi Ahn
    View author publications

    Search author on:PubMed Google Scholar

  6. Jin Woong Kim
    View author publications

    Search author on:PubMed Google Scholar

  7. Han-Kon Kim
    View author publications

    Search author on:PubMed Google Scholar

  8. Young Pyo Jang
    View author publications

    Search author on:PubMed Google Scholar

Corresponding authors

Correspondence to Jin Woong Kim or Young Pyo Jang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, CW., Na, Y., Park, Nh. et al. Amentoflavone Inhibits UVB-Induced Matrix Metalloproteinase-1 Expression Through the Modulation of AP-1 Components in Normal Human Fibroblasts. Appl Biochem Biotechnol 166, 1137–1147 (2012). https://doi.org/10.1007/s12010-011-9500-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-011-9500-z

Keywords