Agastache rugosa Leaf Extract Inhibits the iNOS Expression in ROS 17/2.8 Cells Activated with TNF-$\alpha$ and IL-$\beta$

  • Oh Hwa Min (Department of Pharmacology, College of Medicine, and Institute of Health Sciences, Gyeongsang National University) ;
  • Kang Young Jin (Department of Pharmacology, College of Medicine, and Institute of Health Sciences, Gyeongsang National University) ;
  • Kim Sun Hee (Department of Pharmacology, College of Medicine, and Institute of Health Sciences, Gyeongsang National University) ;
  • Lee Young Soo (Department of Pharmacology, College of Medicine, and Institute of Health Sciences, Gyeongsang National University) ;
  • Park Min Kyu (Department of Pharmacology, College of Medicine, and Institute of Health Sciences, Gyeongsang National University) ;
  • Heo Ja Myung (Department of Pharmacology, College of Medicine, and Institute of Health Sciences, Gyeongsang National University) ;
  • Sun Jin Ji (Department of Pharmacology, College of Medicine, and Institute of Health Sciences, Gyeongsang National University) ;
  • Kim Hyo Jung (Department of Pharmacology, College of Medicine, and Institute of Health Sciences, Gyeongsang National University) ;
  • Kang Eun Sil (Department of Pharmacology, College of Medicine, and Institute of Health Sciences, Gyeongsang National University) ;
  • Kim Hye Jung (Department of Pharmacology, College of Medicine, and Institute of Health Sciences, Gyeongsang National University) ;
  • Sea Han Geuk (Department of Pharmacology, College of Medicine, and Institute of Health Sciences, Gyeongsang National University) ;
  • Lee Jae Heun (Department of Pharmacology, College of Medicine, and Institute of Health Sciences, Gyeongsang National University) ;
  • YunChoi Hye Sook (Natural Products Research Institute, Seoul National University)
  • 발행 : 2005.03.01

초록

It has been suggested that nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) may act as a mediator of cytokine-induced effects on bone turn-over. NO is also recognized as an important factor in bone remodeling, i.e., participating in osteoblast apoptosis in an arthritic joint. The components of Agastache rugosa are known to have many pharmacological activities. In the present study, we investigated the effects of Agastache rugosa leaf extract (ELAR) on NO production and the iNOS expression in ROS 17/2.8 cells activated by a mixture of inflammatory cytokines including TNF-$alpha$ and IL-1$\beta$. A preincubation with ELAR significantly and concentration-dependently reduced the expression of iNOS protein in ROS 17/2.8 cells activated with the cytokine mixture. Consequently, the NO production was also significantly reduced by ELAR with an IC$_{50}$ of 0.75 mg/mL. The inhibitory mechanism of iNOS induction by ELAR prevented the activation and translocation of NF-$\kappa$B (p65) to the nucleus from the cytosol fraction. Furthermore, ELAR concentration-dependently reduced the cellular toxicity induced by sodium nitroprusside, an NO-donor. These results suggest that ELAR may be beneficial in NO-mediated inflammatory conditions such as osteoporosis.

키워드

참고문헌

  1. Armour, K. J., Armour, K. E., VanT Hof, R. J., Reid, D. M., Wei, X. Q., Liew, F. Y., and Ralston, S. H., Activation of the inducible nitric oxide synthase pathway contributes to inflammation induced osteoporosis by suppressing bone formation and causing osteoblast apoptosis. Arthritis Rheum., 44, 2790-2796 (2001) https://doi.org/10.1002/1529-0131(200112)44:12<2790::AID-ART466>3.0.CO;2-X
  2. Armour, K. E., VanT Hof, R. J., Grabowski, P. S., Reid, D. H., and Ralston, S. H., Evidence for a pathogenic role of nitric oxide in inflammation-induced osteoblast. J. Bone Miner. Res., 14, 2137-2142 (1999) https://doi.org/10.1359/jbmr.1999.14.12.2137
  3. Bertolini, D. R., Nedwin, G. E., Bringman, T. S., Smith, D. D., and Mundy, G. R., Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors. Nature, 319, 6-8 (1986) https://doi.org/10.1038/319006a0
  4. Boileau, C., Martel-Pelletier, J., Moldovan, F., Jouzeau, J. Y., Netter, P., Manning, P. T., and Pelletier, J. P., The in situ upregulation of chondrocyte interleukin-1-converting enzyme and interleukin-18 levels in experimental osteoarthritis is mediated by nitric oxide. Arthritis Rheum., 46, 2637-2647 (2002) https://doi.org/10.1002/art.10518
  5. Chae, H. J., Chae, S. W., Kang, J. S., Bang, B. G., Cho, S. B., Park, R. K., So, H. S., Kim, Y. K., Kim, H. M., and Kim, H. R., Dexamethasone suppresses tumor necrosis factor-alphainduced apoptosis in osteoblasts: possible role for ceramide. Endocrinology, 141, 2904-2913 (2000a) https://doi.org/10.1210/en.141.8.2904
  6. Chae, H. J., Kang, J. S., Byun, J. O., Han, K. S., Kim, D. U., Oh, S. M., Kim, H. M., Chae, S. W., and Kim, H. R., Molecular mechanism of staurosporine-induced apoptosis in osteoblasts. Pharmacol. Res., 42, 373-381 (2000b) https://doi.org/10.1006/phrs.2000.0700
  7. Gowen, M., Wood, D. D., Ihrie, E. J., McGuire, M. K., and Russell, R. G., An interleukin 1 like factor stimulates bone resorption in vitro. Nature, 306, 378-380 (1983) https://doi.org/10.1038/306378a0
  8. Grabowski, P. S., England, A. J., Dykhuizen, R., Copland, M., Benjamin, N., Reid, D. M., and Ralston, S.H., Elevated nitric oxide production in rheumatoid arthritis. Detection using the fasting urinary nitrate:creatinine ratio. Arthritis Rheum., 39, 643-647 (1996) https://doi.org/10.1002/art.1780390416
  9. Green, L. C., De Luzuriaga, K. R., Wagner, D. A., Rand, W., Istfan, N., Young, V. R., and Tannenbaum, S. R., Nitrate biosynthesis in the germfree and conventional rat. Science (Wash DC), 212, 56-68 (1981) https://doi.org/10.1126/science.6451927
  10. Hukkanen, M., Hughes, F. J., Buttery, L. D., Gross, S. S., Evans, T. J., Seddon, S., Riveros-Moreno, V., Macintyre, I., and Polak, J. M., Cytokine-stimulated expression of inducible nitric oxide synthase by mouse, rat, and human osteoblastlike cells and its functional role in osteoblast metabolic activity. Endocrinology, 136, 5445-5453 (1995) https://doi.org/10.1210/en.136.12.5445
  11. Ihbe, A., Baumann, G., Heinzmann, U., and Atkinson, M. J., Loss of the differentiated phenotype precedes apoptosis of ROS 17/2.8 osteoblast-like cells. Calcif. Tissue Int., 63, 208- 213 (1998) https://doi.org/10.1007/s002239900516
  12. Jilka, R. L., Weinstein, R. S., Bellido, T., Parfitt, A. M., and Manolagas, S. C., Osteoblast programmed cell death (apoptosis): modulation by growth factors and cytokines. J.Bone Miner. Res., 13, 793-802 (1998) https://doi.org/10.1359/jbmr.1998.13.5.793
  13. Kang, Y. J., Koo, E. B., Lee, Y. S., Yun-Choi, H. S., and Chang, K. C., Prevention of the expression of inducible nitric oxide synthase by a novel positive inotropic agent, YS 49, in rat vascular smooth muscle and RAW 264.7 macrophages. Br. J. Pharmacol., 128, 357-364 (1999) https://doi.org/10.1038/sj.bjp.0702787
  14. Kitajima, I., Nakajima, T., Imamura, T., Takasaki, I., Kawahara, K., Okano, T., Tokioka, T., Soejima, Y., Abeyama, K., and Maruyama, I., Induction of apoptosis in murine clonal osteoblasts expressed by human T-cell leukemia virus type I tax by NF-kappa B and TNF-alpha. J. Bone Miner. Res., 11, 200-210 (1996)
  15. Kim, H. K., Lee, H. K., Shin, C. G., and Huh, H., HIV integrase inhibitory activity of Agastache rugosa. Arch. Pharm. Res., 22, 520-523 (1999) https://doi.org/10.1007/BF02979163
  16. Lee, C. H , Kim, H. N., and Kho, K. E., Agastinol and agastenol, novel ligans from Agastache rugosa and their evaluation in an apoptosis inhibition assay. J. Nat. Prod., 65, 414-416 (2002) https://doi.org/10.1021/np010425e
  17. Lin, S. K., Kok, S. H., Kuo, M. Y,. Lee, M. S., Wang, C. C., Lan, W. H., Hsiao, M., Goldring, S. R., and Hong, C. Y., Nitric oxide promotes infectious bone resorption by enhancing cytokin-stimulated interstitial collagenase synthesis in osteoblasts. J. Bone Miner. Res., 18, 39-46 (2003) https://doi.org/10.1359/jbmr.2003.18.1.39
  18. Niederberger, E., Tegeder, I., Schafer, C., Seegel, M., Grosch, S., and Geisslinger, G., Opposite effects of rofecoxib on nuclear factor-kappaB and activating protein-1 activation. J. Pharmacol. Exp. Ther., 304, 1153-1160 (2003) https://doi.org/10.1124/jpet.102.044016
  19. Marpherson, H., Noble, B. S., and Ralston, S. H., Expression and functional role of nitric oxide synthase isoforms in human osteoblast-like cells. Bone, 24, 179-185 (1999) https://doi.org/10.1016/S8756-3282(98)00173-2
  20. Mcsheehy, P. M. and Chambers, T. J., Osteoblastic cells mediate osteoclastic responsiveness to parathyroid hormone. Endocrinology, 118, 824-828 (1986) https://doi.org/10.1210/endo-118-2-824
  21. Mogi, M., Kinpara, K., Kondo, A., and Togari, A., Involvement of nitric oxide and biopterin in proinflammatory cytokineinduced apoptotic cell death in mouse osteoblastic cell line MC3T3-E1. Biochem. Pharmacol., 58, 649-654 (1999) https://doi.org/10.1016/S0006-2952(99)00131-8
  22. Mogi, M., Kondo, A., Kinpara, K., and Togari, A., Anti-apoptotic action of nerve growth factor in mouse osteoblastic cell line. Life Sci., 67, 1197-1206 (2000) https://doi.org/10.1016/S0024-3205(00)00705-0
  23. Pelletier, J. P., Fernande,s J. C., Jovanovic, D. V., Reboul, P., and Martel-Pelletier, J., Chondrocyte death in experimental osteoarthritis is mediated by MEK 1/2 and p38 pathways: role of cyclooxygenase-2 and inducible nitric oxide synthase. J. Rheumatol., 11, 2509-2519 (2001)
  24. Rodan, G. A. and Noda, M., Gene expression in osteoblastic cells. Crit. Rev. Eukaryot. Gene Expr., 1, 85-98 (1991)
  25. Sandhu, J. K., Robertson, S., Birnboim, H. C., and Goldstein, R., Distribution of protein nitrotyrosine in synovial tissues of patients with rheumatoid arthritis and osteoarthritis. J. Rheumatol., 30, 1173-1181 (2003)
  26. Shin, S., Essential oil compounds from Agastache rugosa as antifungal agents against Trichophyton species. Arch. Pharm. Res., 27, 295-299 (2004) https://doi.org/10.1007/BF02980063
  27. Wang, E. A., Rosen, V., DAlessandro, J. S., Bauduy, M., Cordes, P., Harada, T., Israel, D. I., Hewick, R. M., Kerns, K. M., LaPan, P., Luxenberg, D. P., McQuaid, D., Moutsatsos, K. I., Nove, J., and Wozney, J. M., Recombinant human bone morphogenetic protein induces bone formation. Proc. Natl. Acad. Sci. U.S.A., 87, 2220-2224 (1990) https://doi.org/10.1073/pnas.87.6.2220
  28. Wetterwald, A., Hoffstetter, W., Cecchini, M. G., Lanske, B., Wagner, C., Fleisch, H., and Atkinson, M., Characterization and cloning of the E11 antigen, a marker expressed by rat osteoblasts and osteocytes. Bone, 18, 125-132 (1996) https://doi.org/10.1016/8756-3282(95)00457-2
  29. Yamaguchi, A., Katagiri, T., Ikeda, T., Wozney, J. M., Rosen, V., Wang, E. A., Kahn, A. J., Suda, T., and Yoshiki, S., Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro. J. Cell Biol., 113, 681-687 (1991) https://doi.org/10.1083/jcb.113.3.681