Natural Product Sciences

The Korean Society of Pharmacognosy (한국생약학회)
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Anti-Inflammatory Effect of Ixeris dentata on Ultraviolet B-Induced HaCaT Keratinocytes

  • Kim, Sung-Bae (College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University) ;
  • Kang, Ok-Hwa (College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University) ;
  • Keum, Joon-Ho (College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University) ;
  • Mun, Su-Hyun (College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University) ;
  • An, Hyun-Jin (College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University) ;
  • Jung, Hyun-Ju (College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University) ;
  • Hong, Seung-Heon (College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University) ;
  • Jeong, Dong-Myong (Department of Electronic Engineering, Wonkwang University) ;
  • Kweon, Kee-Tae (Ministry of Health and Welfare Office for Healthcare Policy Division of Traditional Korean Medicine) ;
  • Kwon, Dong-Yeul (College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University)
  • Received : 2012.02.09
  • Accepted : 2012.03.08
  • Published : 2012.03.31
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Abstract

Human skin is the first line of defense for the protection of the internal organs of the body from different stimuli. Ultraviolet B (UVB) irradiation induces skin damage and inflammation through the secretion of various cytokines, which are immune regulators produced by cells. To prevent the initiation of skin inflammation, keratinocytes that have been irreversibly damaged by radiation must be removed through the apoptotic mechanism. Ixeris dentata (family: Asteraceae) is a perennial medicinal herb indigenous to Korea. It has been used in Korea, China, and Japan to treat in digestion, pneumonia, diabetes, hepatitis, and tumors. To gain insight into the anti-inflammatory effects of I. dentata, we examined its influence on UVB-induced pro-inflammatory cytokine production in human keratinocytes (HaCaT cells), by observing cells that were stimulated with UVB in the presence or absence of I. dentata. In the present study, pro-inflammatory cytokine production was determined by performing enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and western blot analysis to measure the activation of mitogen-activated protein kinase (MAPKs). I. dentata inhibited UVBinduced production of the pro-inflammatory cytokine interleukin (IL)-6 in a dose-dependent manner. Further, I. dentata inhibited the UVB-induced expression of cyclooxygenase (COX)-2. Furthermore, I. dentata inhibited the phosphorylation of c-Jun NH2-terminal kinase and p38 MAPKs, suggesting that it inhibits the secretion of the pro-inflammatory cytokines IL-6 and IL-8, and COX-2 expression, by blocking MAPK phosphorylation. These results suggest that I. dentate can potentially protect against UVB-induced skin inflammation.

Keywords

References

  1. Arai, Y., Kusumoto, Y., Nagao, M., Shiojima, K., and Ageta, H., Composite constituents: aliphatics and triterpenoids isolated from the whole plants of Ixeris debilis and I. dentate, Yakugaku Zasshi 103, 356-359 (1983).
  2. Chen, W.Q., Tang, M.S., Gonzales, and Bowden., Role of P38 MAP kinases and ERK in mediating ultraviolet-B induced cyclooxygenase- 2 gene expression in human keratinocytes, Oncogene 20, 3921-3926 (2001).
  3. Chung, H.S., Jeong, H.J., Han, M.J., Park, S.T., Seong, K.T., Baek, S.H., Jeong, D.M., Kim, M.J., and Kim, H.M., Nitric oxide and tumor necrosis factor-alpha production by Ixeris dentata in mouse peritoneal macrophages, Journal of Ethnopharmacology 82, 217-222 (2002).
  4. Crofford, L.J., COX-1 and COX-2 tissue expression: implications and predictions, The Journal of Rheumatology Supplement 49, 15-19 (1997).
  5. De, Fabo., Edward, C., Frances, P.N., Thomas, F., and Glenn, M., Ultraviolet B but not ultraviolet A radiation initiates melanoma. Cancer Research 64, 6372-6376 (2004).
  6. Frank, R.G., Photocarcinogenesis: UVA vs. UVB radiation, Skin Pharmacology and Applied Skin Physiology 15, 316-320 (2002).
  7. Granstein, R.D., and Mary, S.M., UV radiation-induced immunosuppression and skin cancer, Cutis; Cutaneous Medicine for the Practitioner 74, 4-9 (2004).
  8. Grewe, M., Trefzer, U., Ballhorn, A., Gyufko, K., Henninger, H., and Krutmann, J., Analysis of the mechanism of ultraviolet (UV) B radiation-induced prostaglandin E2 synthesis by human epidermoid carcinoma cells, The Journal of Investigative Dermatology 101, 528-531 (1993).
  9. Heck, D.E., Vetrano, A.M., Mariano, T.M., and Laskin, J.D., UVB light stimulates production of reactive oxygen species: unexpected role for catalase. Journal of Biological Chemistry 278, 22432-22436 (2003).
  10. Johnson, G.L., and Razvan, L., Mitogen-activated protein kinase pathways mediated by ERK, JNK, and P38 protein kinases, Science 298, 1911-1912 (2002).
  11. Jung, K.H., Choe, B.K., Hong, S.J., Ban, J.Y., and Uhm, Y.K., Decrease of tumor necrosis factor alpha production by Ixeris dentata extract in RAW 264.7 macrophage cells, Journal of Meridian &Acupoint. 24, 139-148 (2007).
  12. Kamimura, D., Ishihara, K., and Hirano, T., IL-6 signal transduction and its physiological roles: the signal orchestration model. Reviews of Physiology, Biochemistry and Pharmacology 149, 1-38 (2003).
  13. Kim, H.P., Son, K.H., Chang, H.W., and Kang, S.S., Anti-inflammatory plant flavonoids and cellular action mechanisms, Journal of Pharmacological Sciences 96, 229-245 (2004).
  14. Kim, M.K., and Lee, M.S., Volatile flavor components of Ixeris dentata and Amaranthus mangostanus, Journal of the Korean Agricultural Chemical Society 31, 394-399 (1988).
  15. Kim, S.H., Inhibitory effects of Ixeris dentata on the mutagenicity of aflatoxin B1, N-methyl-N'-nitro-N-nitrosoguanidine and the growth of MG-63 human osteosarcoma cells, Journal of the Korean Society of Food and Nutrition 24, 305-312 (1995).
  16. Dagmar, K. and Zeise, E., Pöppelmann, B., and Schwarz, T., DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way, Oncogene 21, 5844-5851 (2002).
  17. Lee, J.H., Ko, W.S., Kim, Y.H., Kang, H.S., Kim, H.D., and Choi, B.T., Anti-inflammatory effect of the aqueous extract from Lonicera japonica flower is related to inhibition of NF-kappa B activation through reducing I-kappa B alpha degradation in rat liver, International Journal of Molecular Medicine 7, 79-83 (2001).
  18. Lin, S.K., Kok, S.H., Yeh, F.T., Kuo, M.P., Lin, C.C., Wang, C.C., Goldring, S.R., and Hong, C.Y., MEK/ERK and signal transducer and activator of transcription signaling pathways modulate oncostatin Mstimulated CCL2 expression in human osteoblasts through a common transcription factor, Arthritis and Rheumatism 50, 785-793 (2004).
  19. Andre, M., Wolber, R., Stäb, F., Klotz, L.O., and Sies, H., Contribution of UVB and UVA to UV-dependent stimulation of cyclooxygenase-2 expression in artificial epidermis, Photochemical & Photobiological Sciences 3, 257-262 (2004).
  20. Masferrer, J.L. and Seibert, K., Regulation of prostaglandin synthesis by glucocorticoids, Receptor 4, 25-30 (1994).
  21. Yasuhiro, M. and Ananthaswamy, H.N., Toxic effects of ultraviolet radiation on the skin, Toxicology and Applied Pharmacology 195, 298-308 (2004).
  22. Mitchell, J.A., Akarasereenont, P., Thiemermann, C., Flower, R.J., and Vane, J.R., Selectivity of nonsteroidal anti-inflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase, Proceedings of the National Academy of Sciences of the United States of America 90, 11693-11697 (1993).
  23. Muraguchi, A., Kishimoto, T., Miki, Y., Kuritani, T., Kaieda, T., Yoshizaki, K., and Yamamura, Y., T cell-replacing factor- (TRF) induced IgG secretion in a human B blastoid cell line and demonstration of acceptors for TRF, Journal of Immunology 127, 412-416 (1981).
  24. Tetsuji, N., Nishimoto, N., and Kishimoto, T., The paradigm of IL-6: from basic science to medicine, Arthritis Research 4 Suppl 3, S233-242 (2002).
  25. Juan, R., Villa, J., Ruiz, A., Armstrong, R., and Matta, J., UV dose determines key characteristics of nonmelanoma skin cancer. cancer epidemiology, biomarkers & prevention, A Publication of the American Association for Cancer Research 13, 2006-2011 (2004).
  26. Rhee, S.G., Redox signaling: hydrogen peroxide as intracellular messenger, Experimental & Molecular Medicine 31, 53-59 (1999).
  27. Seibert, K. and Masferrer, J.L., Role of inducible cyclooxygenase (COX- 2) in inflammation, Receptor 4, 17-23 (1994).
  28. Smith, W.L. and Song, I., The enzymology of prostaglandin endoperoxide H synthases-1 and -2, Prostaglandins & Other Lipid Mediators 68, 115-128 (2002).
  29. Takashima, A. and Bergstresser, P.R., Impact of UVB radiation on the epidermal cytokine network, Photochemistry and Photobiology 63, 397-400 (1996).
  30. Martine, T. and Forman, H.J., Redox signaling and the MAP kinase pathways, Biofactors 17, 287-296 (2003).