Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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WIN-34B May Have Analgesic and Anti-Inflammatory Effects by Reducing the Production of Pro-Inflammatory Mediators in Cells via Inhibition of IκB Signaling Pathways

  • Kim, Kyoung-Soo (East-West Bone & Joint Research Institute, College of Medicine, Kyung Hee University) ;
  • Choi, Hyun-Mi (East-West Bone & Joint Research Institute, College of Medicine, Kyung Hee University) ;
  • Yang, Hyung-In (Division of Rheumatology, Department of Internal Medicine, College of Medicine, Kyung Hee University) ;
  • Yoo, Myung-Chul (East-West Bone & Joint Research Institute, College of Medicine, Kyung Hee University)
  • Received : 2011.09.29
  • Accepted : 2011.11.23
  • Published : 2012.01.31
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Abstract

WIN-34B showed analgesic and anti-inflammatory effects in various animal models of pain and osteoarthritis. However, the molecular mechanism by which WIN-34B inhibits pain and inflammation in vivo remains to be elucidated. We investigated the molecular mechanisms of the actions of WIN-34B using various in vitro models using fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA FLSs), RAW264.7 cells and peritoneal macrophages. WIN-34B inhibited the level of IL-6, $PGE_2$, and MMP-13 in IL-$1{\beta}$-stimulated RA FLSs in a dose-dependent manner. The mRNA levels were also inhibited by WIN-34B. The level of $PGE_2$, NO, IL-$1{\beta}$, and TNF-${\alpha}$ were inhibited by WIN-34B at different concentrations in LPS-stimulated RAW264.7 cells. The production of NO and $PGE_2$ was inhibited by WIN-34B in a dose-dependent manner in LPS-stimulated peritoneal macrophages. All of these effects were comparable to the positive control, celecoxib or indomethacin. I${\kappa}B$B signaling pathways were inhibited by WIN-34B, and the migration of NF-${\kappa}B$ into the nucleus was inhibited, which is consistent with the degradation of $I{\kappa}B-{\alpha}$. Taken together, the results suggest that WIN-34B has potential as a therapeutic drug to reduce pain and inflammation by inhibiting the production of pro-inflammatory mediators.

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References

  1. Ameye, L. G. and Chee, W. S. (2006) Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Arthritis. Res. Ther. 8, R127. https://doi.org/10.1186/ar2016
  2. Bhatia, H. S., Candelario-Jalil, E., de Oliveira, A. C., Olajide, O. A., Martínez-Sánchez, G. and Fiebich, B. L. (2008) Mangiferin inhibits cyclooxygenase-2 expression and prostaglandin E2 production in activated rat microglial cells. Arch. Biochem. Biophys. 477, 253-258. https://doi.org/10.1016/j.abb.2008.06.017
  3. Choi, H. M., Lee, Y. A., Lee, S. H., Hong, S. J., Hahm, D. H., Choi, S. Y., Yang, H. I., Yoo, M. C. and Kim, K. S. (2009) Adiponectin may contribute to synovitis and joint destruction in rheumatoid arthritis by stimulating vascular endothelial growth factor, matrix metalloproteinase-1, and matrix metalloproteinase-13 expression in fi broblast-like synoviocytes more than proinfl ammatory mediators. Arthritis. Res. Ther. 11, R161. https://doi.org/10.1186/ar2844
  4. Choi, H. M., Oh da, H., Bang, J. S., Yang, H. I., Yoo, M. C. and Kim, K. S. (2010) Differential effect of IL-1$\beta$ and TNF$\alpha$ on the production of IL-6, IL-8 and PGE2 in fi broblast-like synoviocytes and THP-1 macrophages. Rheumatol. Int. 30, 1025-1033. https://doi.org/10.1007/s00296-009-1089-y
  5. Dat, N. T., Jin, X., Hong, Y. S. and Lee, J. J. (2010) An isoaurone and other constituents from Trichosanthes kirilowii seeds inhibit hypoxia-inducible factor-1 and nuclear factor-kappaB. J. Nat. Prod. 73, 1167-1169. https://doi.org/10.1021/np900820p
  6. dos Santos, M. D., Almeida, M. C., Lopes, N .P., de and Souza, G. E. (2006) valuation of the anti-infl ammatory, analgesic and antipyretic activities of the natural polyphenol chlorogenic acid. Biol. Pharm. Bull. 29, 2236-2240. https://doi.org/10.1248/bpb.29.2236
  7. Gottlieb, S. (2001) COX 2 inhibitors may increase risk of heart attack. BMJ. 323, 471.
  8. Hartog, A., Hougee, S., Faber, J., Sanders, A., Zuurman, C., Smit, H. F., van der Kraan, P. M., Hoijer, M. A. and Garssen, J. (2008) The multicomponent phytopharmaceutical SKI306X inhibits in vitro cartilage degradation and the production of infl ammatory mediators. Phytomedicine. 15, 313-320. https://doi.org/10.1016/j.phymed.2007.09.005
  9. Hippisley-Cox, J. and Coupland, C. (2005) Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-infl ammatory drugs: population based nested case-control analysis. BMJ. 330, 1366. https://doi.org/10.1136/bmj.330.7504.1366
  10. Huang, N., Hauck, C., Yum, M. Y., Rizshsky, L., Widrlechner, M.P , McCoy, J. A., Murphy, P. A., Dixon, P. M., Nikolau, B. J. and Birt, D. F. (2009) Rosmarinic acid in Prunella vulgaris ethanol extract inhibits lipopolysaccharide-induced prostaglandin E2 and nitric oxide in RAW 264.7 mouse macrophages. J. Agric. Food Chem. 57, 10579-10589. https://doi.org/10.1021/jf9023728
  11. Jung, K., Lee, B., Han, S. J., Ryu, J. H. and Kim, D. H. (2009) Mangiferin ameliorates scopolamine-induced learning defi cits in mice. Biol. Pharm. Bull. 32, 242-246. https://doi.org/10.1248/bpb.32.242
  12. Kang, M., Jung, I., Hur, J., Kim, S. H., Lee, J. H., Kang, J. Y., Jung, K. C., Kim, K. S., Yoo, M. C., Park, D. S., Lee, J. D. and Cho, Y. B. (2010) The analgesic and anti-infl ammatory effect of WIN-34B, a new herbal formula for osteoarthritis composed of Lonicera japonica Thunb and Anemarrhena asphodeloides BUNGE in vivo. J. Ethnopharmacol. 131, 485-496. https://doi.org/10.1016/j.jep.2010.07.025
  13. Kidd, B. L. (2006) Osteoarthritis and joint pain. Pain. 123, 6-9. https://doi.org/10.1016/j.pain.2006.04.009
  14. Kim, J. Y., Shin, J. S., Ryu, J. H., Kim, S. Y., Cho, Y. W., Choi, J. H. and Lee, K. T. (2009) Anti-infl ammatory effect of anemarsaponin B isolated from the rhizomes of Anemarrhena asphodeloides in LPSinduced RAW 264.7 macrophages is mediated by negative regulation of the nuclear factor-kappaB and p38 pathways. Food Chem. Toxicol. 47, 1610-1617. https://doi.org/10.1016/j.fct.2009.04.009
  15. Kim, K. S., Park, E. K., Ju, S. M., Jung, H. S., Bang, J. S., Kim, C., Lee, Y. A., Hong, S. J., Lee, S. H., Yang, H. I. and Yoo, M. C. (2007) Taurine chloramine differentially inhibits matrix metalloproteinase 1 and 13 synthesis in interleukin-1beta stimulated fi broblast-like synoviocytes. Arthritis. Res. Ther. 9, R80. https://doi.org/10.1186/ar2279
  16. Kwak, W. J., Han, C. K., Chang, H. W., Kim, H. P., Kang, S. S. and Son, K. H. (2003) Loniceroside C, an antiinfl ammatory saponin from Lonicera japonica. Chem. Pharm. Bull (Tokyo). 51, 333-335. https://doi.org/10.1248/cpb.51.333
  17. Lark, M. W., Bayne, E. K., Flanagan, J., Harper, C. F., Hoerrner, L. A., Hutchinson, N. I., Singer, I. I., Donatelli, S. A., Weidner, J. R., Williams, H. R., Mumford, R. A. and Lohmander, L. S. (1997) Aggrecan degradation in human cartilage. Evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic, and rheumatoid joints. J. Clin. Invest. 100, 93-106. https://doi.org/10.1172/JCI119526
  18. Lee, J. H., Park, J. H., Kim, Y. S. and Han, Y. (2008) Chlorogenic acid, a polyphenolic compound, treats mice with septic arthritis caused by Candida albicans. Int. Immunopharmacol. 8, 1681-1685. https://doi.org/10.1016/j.intimp.2008.08.002
  19. Lenzer, J. (2005) FDA advisers warn: COX 2 inhibitors increase risk of heart attack and stroke. BMJ. 330, 440. https://doi.org/10.1136/bmj.330.7489.440
  20. Park, E. K., Ryu, M. H., Kim, Y. H., Lee, Y. A., Lee, S. H., Woo, D. H., Hong, S. J., Han, J. S., Yoo, M. C., Yang, H. I. and Kim, K. S. (2006) Anti-infl ammatory effects of an ethanolic extract from Clematis mandshurica Rupr. J. Ethnopharmacol. 108, 142-147. https://doi.org/10.1016/j.jep.2006.04.025
  21. Qian, Z. M., Wen, X. D., Li, H. J., Liu, Y., Qin, S. J. and Li, P. (2008) Analysis of interaction property of bioactive components in Flos Lonicerae Japonicae with protein by microdialysis coupled with HPLC-DAD-MS. Biol. Pharm. Bull. 31, 126-130. https://doi.org/10.1248/bpb.31.126
  22. Reddivari, L., Vanamala, J., Chintharlapalli, S., Safe, S. H. and Miller, J. C. Jr. (2007) Anthocyanin fraction from potato extracts is cytotoxic to prostate cancer cells through activation of caspasedependent and caspase-independent pathways. Carcinogenesis. 28, 2227-2235. https://doi.org/10.1093/carcin/bgm117
  23. Schiavoni, G., Mauri, C., Carlei, D., Belardelli, F., Pastoris, M. C. and Proietti, E. (2004) Type I IFN protects permissive macrophages from Legionella pneumophila infection through an IFN-gammaindependent pathway. J. Immunol. 173, 1266-1275. https://doi.org/10.4049/jimmunol.173.2.1266
  24. Shan, J., Fu, J., Zhao, Z., Kong, X., Huang, H., Luo, L. and Yin, Z. (2009) Chlorogenic acid inhibits lipopolysaccharide-induced cyclooxygenase- 2 expression in RAW264.7 cells through suppressing NF-kappaB and JNK/AP-1 activation. Int. Immunopharmacol. 9, 1042-1048. https://doi.org/10.1016/j.intimp.2009.04.011
  25. Shi, S., Jiang, D., Dong, C. and Tu, P. (2006) Triterpene saponins from clematis mandshurica. J. Nat. Prod. 69, 1591-1595. https://doi.org/10.1021/np060287z
  26. Soliman, K. F. and Mazzio, E. A. (1998) In vitro attenuation of nitric oxide production in C6 astrocyte cell culture by various dietary compounds. Proc. Soc. Exp. Biol. Med. 218, 390-397. https://doi.org/10.3181/00379727-218-44309
  27. Wolfe, F. and Cathey, M. A. (1991) The assessment and prediction of functional disability in rheumatoid arthritis. J. Rheumatol. 18, 1298-1306.

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