DOI QR코드

DOI QR Code

Cardamonin Inhibits the Expression of Inducible Nitric Oxide Synthase Induced by TLR2, 4, and 6 Agonists

  • Kim, Ah-Yeon (Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University) ;
  • Shim, Hyun-Jin (Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University) ;
  • Kim, Su-Yeon (Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University) ;
  • Heo, Sung-Hye (Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University) ;
  • Youn, Hyung-Sun (Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University)
  • Received : 2018.04.16
  • Accepted : 2018.06.15
  • Published : 2018.06.30

Abstract

Toll-like receptors (TLRs) play an important role for host defense against invading pathogens. The activation of TLRs signaling leads to the activation of $NF-{\kappa}B$ and the expression of pro-inflammatory gene products such as cytokines and inducible nitric oxide synthase (iNOS). To evaluate the therapeutic potential of cardamonin, which is a naturally occurring chalcone from Alpinia species (zingiberaceous plant species), $NF-{\kappa}B$ activation and iNOS expression induced by MALP-2 (TLR2 and TLR6 agonist) or LPS (TLR4 agonist) were examined. Cardamonin inhibited the activation of $NF-{\kappa}B$ induced by MALP-2 or LPS. Cardamonin also suppressed the iNOS expression induced by MALP-2 or LPS. These results suggest that cardamonin has the specific mechanism for anti-inflammatory responses by regulating of TLRs signaling pathway.

Keywords

References

  1. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004. 4: 499-511. https://doi.org/10.1038/nri1391
  2. Chow YL, Lee KH, Vidyadaran S, Lajis NH, Akhtar MN, Israf DA, Syahida A. (Cardamonin from Alpinia rafflesiana inhibits inflammatory responses in IFN-gamma/LPS-stimulated BV2 microglia via NF-kappaB signalling pathway. Int Immunopharmacol. 2012. 12: 657-665. https://doi.org/10.1016/j.intimp.2012.01.009
  3. Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE. Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation. Clin Exp Immunol. 2007. 147: 227-235.
  4. Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell. 2002. 109 Suppl: S81-96. https://doi.org/10.1016/S0092-8674(02)00703-1
  5. Goncalves LM, Valente IM, Rodrigues JA. An overview on cardamonin. J Med Food. 2014. 17: 633-640. https://doi.org/10.1089/jmf.2013.0061
  6. Green SJ, Meltzer MS, Hibbs JB Jr, Nacy CA. Activated macrophages destroy intracellular Leishmania major amastigotes by an L-arginine-dependent killing mechanism. J Immunol. 1990. 144: 278-283.
  7. Hanafy KA, Krumenacker JS, Murad F. NO, nitrotyrosine, and cyclic GMP in signal transduction. Med Sci Monit. 2001. 7:801-819.
  8. Jantan I, Raweh SM, Sirat HM, Jamil S, Mohd Yasin YH, Jalil J, Jamal JA. Inhibitory effect of compounds from Zingiberaceae species on human platelet aggregation. Phytomedicine. 2008. 15: 306-309. https://doi.org/10.1016/j.phymed.2007.08.002
  9. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010. 11: 373-384. https://doi.org/10.1038/ni.1863
  10. Lim HJ, Lee HS, Ryu JH. Suppression of inducible nitric oxide synthase and cyclooxygenase-2 expression by tussilagone from Farfarae flos in BV-2 microglial cells. Arch Pharm Res. 2008. 31: 645-652. https://doi.org/10.1007/s12272-001-1207-4
  11. Lin YM, Zhou Y, Flavin MT, Zhou LM, Nie W, Chen FC. Chalcones and flavonoids as anti-tuberculosis agents. Bioorg Med Chem. 2002. 10: 2795-2802. https://doi.org/10.1016/S0968-0896(02)00094-9
  12. Moncada S. Nitric oxide: discovery and impact on clinical medicine. J R Soc Med. 1999. 92: 164-169. https://doi.org/10.1177/014107689909200402
  13. Murakami A, Ohigashi H. Targeting NOX, INOS and COX-2 in inflammatory cells: chemoprevention using food phytochemicals. Int J Cancer. 2007. 121: 2357-2363. https://doi.org/10.1002/ijc.23161
  14. Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene. 1999. 18: 6853-6866. https://doi.org/10.1038/sj.onc.1203239
  15. Palmer RM, Hickery MS, Charles IG, Moncada S, Bayliss MT. Induction of nitric oxide synthase in human chondrocytes. Biochem Biophys Res Commun. 1993. 193: 398-405. https://doi.org/10.1006/bbrc.1993.1637
  16. Park S, Gwak J, Han SJ, Oh S. Cardamonin suppresses the proliferation of colon cancer cells by promoting beta-catenin degradation. Biol Pharm Bull. 2013. 36: 1040-1044. https://doi.org/10.1248/bpb.b13-00158
  17. Turini ME, DuBois RN. Cyclooxygenase-2: a therapeutic target. Annu Rev Med. 2002. 53: 35-57. https://doi.org/10.1146/annurev.med.53.082901.103952
  18. Vallance P. Nitric oxide: therapeutic opportunities. Fundam Clin Pharmacol. 2003. 17: 1-10. https://doi.org/10.1046/j.1472-8206.2003.00124.x
  19. Youn HS. The Anti-Inflammatory Effects of Phytochemicals by the Modulation of Innate Immunity. J Exp Biomed Sci. 2012. 18: 181-192.
  20. Youn HS, Lee JY, Fitzgerald KA, Young HA, Akira S, Hwang DH. Specific inhibition of MyD88-independent signaling pathways of TLR3 and TLR4 by resveratrol: molecular targets are TBK1 and RIP1 in TRIF complex. J Immunol. 2005. 175: 3339-3346. https://doi.org/10.4049/jimmunol.175.5.3339
  21. Youn HS, Lee JY, Saitoh SI, Miyake K, Hwang DH. Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of TLR4. Biochem Biophys Res Commun. 2006a. 350: 866-871. https://doi.org/10.1016/j.bbrc.2006.09.097
  22. Youn HS, Lee JY, Saitoh SI, Miyake K, Kang KW, Choi YJ, Hwang DH. Suppression of MyD88- and TRIF-dependent signaling pathways of Toll-like receptor by (-)-epigallocatechin-3-gallate, a polyphenol component of green tea. Biochem Pharmacol. 2006b. 72: 850-859. https://doi.org/10.1016/j.bcp.2006.06.021
  23. Youn HS, Saitoh SI, Miyake K, Hwang DH. Inhibition of homodimerization of Toll-like receptor 4 by curcumin. Biochem Pharmacol. 2006c. 72: 62-69. https://doi.org/10.1016/j.bcp.2006.03.022