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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Oleanolic acid regulates NF-κB signaling by suppressing MafK expression in RAW 264.7 cells

  • Hwang, Yu-Jin (Department of Agrofood Resources, National Academy of Agricultural Science, RDA) ;
  • Song, Jaewhan (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Kim, Haeng-Ran (Department of Agrofood Resources, National Academy of Agricultural Science, RDA) ;
  • Hwang, Kyung-A (Department of Agrofood Resources, National Academy of Agricultural Science, RDA)
  • Received : 2014.07.17
  • Accepted : 2014.07.23
  • Published : 2014.09.30
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Abstract

Oxidative stress and inflammation are common to many pathological conditions. Defense mechanisms protect cells from oxidative stress, but can become over-activated following injury and inflammation. NF-${\kappa}B$ and Nrf2 transcription factors regulate proinflammatory and antioxidant gene expression, respectively. Studies have shown that many natural dietary compounds regulate NF-${\kappa}B$ and Nrf2, preventing inflammation and oxidative stress. Here, we report major compounds of Prunella vulgaris var. lilacina such as rosmarinic acid, oleanolic acid, ursolic acid and caffeic acid as a potential therapeutic for oxidative stress and inflammation. The major compounds exhibited high anti-inflammatory activity, inhibiting NO, PGE2 production, NF-${\kappa}B$ expression and activating Nrf2 expression. In addition, we examined the effect of major compounds on MafK expression. Among the compounds, oleanolic acid significantly decreased MafK expression and MafK-mediated p65 acetylation. These findings suggest that oleanolic acid as NF-${\kappa}B$ inhibitors can potentially be used in therapeutic applications for the treatment of oxidative stress-induced diseases.

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References

  1. Yuan, Q., Zhang, X., Liu, Z., Song, S., Xue, P., Wang, J. and Ruan, J. (2013) Ethanol extract of Adiantum capillus-veneris L. suppresses the production of inflammatory mediators by inhibiting NF-$\kappa{B}$ activation. J. Ethnopharmacol. 147, 603-611. https://doi.org/10.1016/j.jep.2013.03.046
  2. De Heredia, F. P., Gomez-Martinez, S. and Marcos, A. (2012) Obesity, inflammation and the immune system. Proc. Nutr. Soc. 71, 332-338. https://doi.org/10.1017/S0029665112000092
  3. Guha, M. and Mackman, N. (2001) LPS induction of gene expression in human monocytes. Cell Signal. 13, 85-94. https://doi.org/10.1016/S0898-6568(00)00149-2
  4. Yamamoto, Y. and Gaynor, R. B. (2001) Role of the NF-kappaB pathway in the pathogenesis of human disease states. Curr. Mol. Med. 1, 287-296. https://doi.org/10.2174/1566524013363816
  5. Bharti, A. C. and Aggarwal, B. B. (2002) Nuclear factor-kappa B and cancer: its role in prevention and therapy. Biochem. Pharmacol. 64, 883-888. https://doi.org/10.1016/S0006-2952(02)01154-1
  6. Garg, A. and Aggarwal, B. B. (2002) Nuclear transcription factor-kappaB as a target for cancer drug development. Leukemia 16, 1053-1068. https://doi.org/10.1038/sj.leu.2402482
  7. Gilroy, D. W., Lawrence, T., Perretti, M. and Rossi, A. G. (2004) Inflammatory resolution: new opportunities for drug discovery. Nat. Rev. Drug Discov. 3, 401-416. https://doi.org/10.1038/nrd1383
  8. Moi, P., Chan, K., Asunis, I., Cao, A. and Kan, Y. W. (1994) Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the b-globin locus control region. Proc. Natl. Acad. Sci. U.S.A. 91, 9926-9930. https://doi.org/10.1073/pnas.91.21.9926
  9. Motohashi, H. and Yamamoto, M. (2004) Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol. Med. 10, 549-557. https://doi.org/10.1016/j.molmed.2004.09.003
  10. Jeong, W. S., Jun, M. and Kong, A. N. (2006) Nrf2: A Potential Molecular Target for Cancer Chemoprevention by Natural Compounds. Antioxid. Redox Signal. 8, 99-106. https://doi.org/10.1089/ars.2006.8.99
  11. Kwak, M. K. and Kensler, T. W. (2010) Targeting NRF2 signaling for cancer chemoprevention. Toxicol. Appl. Pharmacol. 244, 66-76. https://doi.org/10.1016/j.taap.2009.08.028
  12. Li, W., Khor, T. O., Xu, C., Shen, G., Jeong, W. S., Yu, S. and Kong, A. N. (2008) Activation of Nrf2-antioxidant signaling attenuates NF$\kappa{B}$-inflammatory response and elicits apoptosis. Biochem. Pharmacol. 76, 1485-1489. https://doi.org/10.1016/j.bcp.2008.07.017
  13. Liu, G. H., Qu, J. and Shen, X. (2008) NF-kB/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK. Biochim. Biophys. Acta. 1783, 713-727. https://doi.org/10.1016/j.bbamcr.2008.01.002
  14. Yu, M., Li, H., Liu, Q., Liu, F., Tang, L., Li, C., Yuan, Y., Zhan, Y., Xu, W., Li, W., Chen, H., Ge, C., Wang, J. and Yang, X. (2011) Nuclear factor p65 interacts with Keap1 to repress the Nrf2-ARE pathway. Cell Signal. 23, 883-892. https://doi.org/10.1016/j.cellsig.2011.01.014
  15. Hwang, Y. J., Lee, E. W., Song, J., Kim, H. R., Jun, Y. C. and Hwang, K. A. (2013) MafK positively regulates NF-kB activity by enhancing CBP-mediated p65 acetylation. Sci. Rep. 3, 3242. https://doi.org/10.1038/srep03242
  16. Kwon, D. J., Bae, Y. S., Ju, S. M., Youn, G.S., Choi, S. Y. and Park, J. (2014) Salicortin suppresses lipopolysaccharide-stimulated inflammatory responses via blockade of NF-$\kappa{B}$ and JNK activation in RAW 264.7 macrophages. BMB Rep. 47, 318-323. https://doi.org/10.5483/BMBRep.2014.47.6.200
  17. Jeong, J. B., Hong, S. C., Jeong, H. J. and Koo, J. S. (2011) Anti-inflammatory Effect of 2-Methoxy-4-Vinylphenol via the Suppression of NF-$\kappa{B}$ and MAPK Activation, and Acetylation of Histone H3. Arch. Pharm. Res. 34, 2109-2116. https://doi.org/10.1007/s12272-011-1214-9
  18. Jeong, J. H., Ryu, D. S., Suk, D. H. and Lee, D. S. (2011) Anti-inflammatory effects of ethanol extract from Orostachys japonicus on modulation of signal pathways in LPS-stimulated RAW 264.7 cells. BMB Rep. 44, 399-404. https://doi.org/10.5483/BMBRep.2011.44.6.399
  19. Hwang, Y. J., Lee, E. J., Kim, H. R. and Hwang, K. A. (2013) In vitro antioxidant and anticancer effects of solvent fractions from prunella vulgaris var. lilacina. BMC Complement. Altern. Med. 13, 310. https://doi.org/10.1186/1472-6882-13-310
  20. Hwang, Y. J., Lee, E. J., Kim, H. R. and Hwang, K. A. (2013) NF-$\kappa{B}$-Targeted Anti-Inflammatory Activity of Prunella vulgaris var. lilacina in Macrophages RAW 264.7. Int. J. Mol. Sci. 14, 21489-21503. https://doi.org/10.3390/ijms141121489
  21. Lamaison, J. L., Petitjean-Freytet, C. and Carnat, A. (1991) Medicinal Lamiaceae with antioxidant properties, a potential source of rosmarinic acid. Pharm. Acta. Helv. 66, 185-188.
  22. Lockyer, J. M., Colladay, J. S., Alperin-Lea, W. L., Hammond, T. and Buda, A. J. (1998) Inhibition of nuclear factor-kappaB-mediated adhesion molecule expression in human endothelial cells. Circ. Res. 82, 314-320. https://doi.org/10.1161/01.RES.82.3.314
  23. Marui, N., Offermann, M. K., Swerlick, R., Kunsch, C., Rosen, C. A., Ahmad, M., Alexander, R. W. and Medford, R. M. (1993) Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. J. Clin. Invest. 92, 1866-1874. https://doi.org/10.1172/JCI116778
  24. Chen, X. L. and Kunsch, C. (2004) Induction of Cytoprotective Genes through Nrf2/Antioxidant Response Element Pathway: A New Therapeutic Approach for the Treatment of Inflammatory Diseases. Curr. Pharm. Des. 10, 879-891. https://doi.org/10.2174/1381612043452901
  25. Thimmulappa, R. K., Lee, H., Rangasamy, T., Reddy, S. P., Yamamoto, M., Kensler, T. W. and Biswal, S. (2006) Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J. Clin. Invest. 116, 984-995. https://doi.org/10.1172/JCI25790
  26. Tak, P. P. and Firestein, G. S. (2001) NF-$\kappa{B}$: a key role in inflammatory diseases. J. Clin. Invest. 107, 7-11. https://doi.org/10.1172/JCI11830
  27. Pikarsky, E., Porat, R. M., Stein, I., Abramovitch, R., Amit, S., Kasem, S., Gutkovich-Pyest, E., Urieli-Shoval, S., Galun, E. and Ben-Neriah, Y. (2004) NF-$\kappa{B}$ functions as a tumour promoter in inflammation-associated cancer. Nature 431, 461-466. https://doi.org/10.1038/nature02924
  28. Balogun, E., Hoque, M., Gong, P., Killeen, E., Green, C. J., Foresti, R., Alam, J. and Motterlini, R. (2003) Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem. J. 371, 887-895. https://doi.org/10.1042/BJ20021619
  29. Heiss, E., Herhaus, C., Klimo, K., Bartsch, H. and Gerhauser, C. (2001) Nuclear factor kappa B is a molecular target for sulforaphanemediated anti-inflammatory mechanisms. J. Biol. Chem. 276, 32008-32115. https://doi.org/10.1074/jbc.M104794200
  30. Thimmulappa, R. K., Mai, K. H., Srisuma, S., Kensler, T. W., Yamamoto, M. and Biswal, S. (2002) Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res. 62, 5196-5203.
  31. Gao, X. and Talalay, P. (2004) Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damage. Proc. Natl. Acad. Sci. U.S.A. 101, 10446-10451. https://doi.org/10.1073/pnas.0403886101
  32. Kundu, J. K., Na, H. K., Chun, K. S., Kim, Y. K., Lee, S. J., Lee, S. S., Lee, O. S., Sim, Y. C. and Surh, Y. J. (2003) Inhibition of Phorbol Ester-Induced COX-2 Expression by Epigallocatechin Gallate in Mouse Skin and Cultured Human Mammary Epithelial Cells. J. Nutr. 133, 3805S-3810S.
  33. Na, H. K. and Surh, Y. J. (2008) Modulation of Nrf2- mediated antioxidant and detoxifying enzyme induction by the green tea polyphenol EGCG. Food Chem. Toxicol. 46, 1271-1278. https://doi.org/10.1016/j.fct.2007.10.006

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