Stylopine from Chelidonium mrajus Inhibits LPS-Induced Inflammatory Mediators un RAW 264.7 Cells

  • Seon Il, Jang (Department of Skin & beauty, Seojeong College) ;
  • Byung Hee, Kim (Department of Bionanochemistry and Basic Sciences Research Institute, Wonkwang University) ;
  • Woo-Yiel, Lee (Department of Bionanochemistry and Basic Sciences Research Institute, Wonkwang University) ;
  • Sang Jin, An (Department of Bionanochemistry and Basic Sciences Research Institute, Wonkwang University) ;
  • Han Gil, Choi (Division of Biological Science, College of Natural Sciences, Wonkwang University) ;
  • Byung Hun, Jeon (Department of Pathology, College of Oriental Medicine, Wonkwang University) ;
  • Hun-Taeg, Chung (Department of Immunology, Institute of Immtec Korea, Medicinal Resources Research Center of Wonkwang University) ;
  • Jung-Rae, Rho (Department of Oceanography, Kunsan National University)
  • Published : 2004.09.01

Abstract

Stylopine is a major component of the leaf of Chelidonium majus L. (Papaveraceae), which has been used for the removal of warts, papillomas and condylomas, as well as the treatment of liver disease, in oriental countries. Stylopine per se had no cytotoxic effect in unstimulated RAW 264.7 cells, but concentration-dependently reduced nitric oxide (NO), prostaglandin E$_2$ (PGE$_2$), tumor necrosis factor-a (TNF-$\alpha$) and interleukin-1$\beta$(IL-1$\beta$), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. The levels of inducible nitric oxide synthase (iNOS) and COX-2 protein expressions were markedly suppressed by stylopine in a concentration dependent manner. These results suggest that stylopine suppress the NO and PGE$_2$ production in macrophages by inhibiting the iNOS and COX-2 expressions. These biological activities of stylopine may contribute to the anti-inflammatory activity of Cheli-donium majus.

Keywords

References

  1. Ahmad, N., Chen, L. C., Gordon, M. A., Laskin, J. D., and Laskin, D. L., Related Articles, Links regulation of cycolooxygenase- 2 by nitric oxide in activated hepatic macrophages during acute endotoxemia. J. Leukoc. Biol., 71, 1005-1011 (2002)
  2. Barnes, P. J. and Karin, M., Nuclear factor-kappaB: a pivotal transcription factorin chronic inflammatory diseases. N. Engl. J. Med., 336,1066-1071 (1997) https://doi.org/10.1056/NEJM199704103361506
  3. Biswas, S. J. and Khuda-Bukhsh, A. R., Effect of a homeopathic drug, Chelidonium, in amelioration of p-DAB induced hepatocarcinogenesis in mice. BMC Complement Altem. Med., 10;2(1): 4. (2002)
  4. Coker, P. K. and Laurent, G. J., Pulmonary fibrosis: cytokines in the balance. Eur. Resp. J, 11, 1218(1998) https://doi.org/10.1183/09031936.98.11061218
  5. Colombo, M. L. and Bosisio, E., Pharmacological activities of Chelidonium majus L. Pharmacol. Res., 33, 127-134 (1996) https://doi.org/10.1006/phrs.1996.0019
  6. De Nardin, E., The role of inflammatory and immunological mediators in periodontitis and cardiovascular disease. Ann. Periodontol., 6, 30-40 (2001) https://doi.org/10.1902/annals.2001.6.1.30
  7. Dinarello, C. A., Cytokines as endogenous pyrogens. J Infect. Dis., 179, Suppl 2, S294-304(1999) https://doi.org/10.1086/513856
  8. Feldmann, M., Brennan, F. M., and Maini, R. N., Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol., 14, 397-440 (1996) https://doi.org/10.1146/annurev.immunol.14.1.397
  9. Haberlein, H., Tschiersch, K. P., Boonen, G., and Hiller, K. O. Chelidonium majus L.: components with in vitro affinity for the FABAA receptor. Planta Med., 62, 227- 231 (1996) https://doi.org/10.1055/s-2006-957865
  10. Hu, S., Cai. W, Ye, J., Qian, Z., and Sun. Z., Influence of medicinal herbs on phagocytosis by bovine neutrophils. Zentralbl. Veterinarmed A., 39, 593-599 (1992) https://doi.org/10.1111/j.1439-0442.1992.tb00222.x
  11. Ikezawa, N., Tanaka, M., Nagayoshi, M., Shinkyo, R., Sakaki, T., Inouye, K., and Sato, F., J. Biol. Chem., 278, 38557-38565 (2003) https://doi.org/10.1074/jbc.M302470200
  12. Isomaki, P. and Punnonen, J., Pro- and anti-inflammatory cytokines inrheumatoid arthritis. Ann. Med., 29(6), 499-507 (1997)
  13. Kotake, Y., Sang, H., Miyajima, T., and Wallis, G. L., Inhibition of NF-kappaB, iNOS mRNA, COX-2 mRNA, and COX catalytic activity by phenyl-N-tert-butylnitrone (PBN). Biochim. Biophys. Acta, 1448, 77-84 (1998) https://doi.org/10.1016/S0167-4889(98)00126-8
  14. Kroncke, K. D., Fehsel, K., and Kolb-Bachofen. V., Nitric oxide: cytotoxicity versus cytoprotectionohow, why, when, and where? Nitric Oxide, 1, 107-120 (1997) https://doi.org/10.1006/niox.1997.0118
  15. Lee, S. H., Soyoola, E., Chanmugam, P., Hart, S., Sun, W., Zhong, H., Liou, S., Simmons, D., and Hwang, D., Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide. J. Biol. Chem., 267, 25934-25938 (1992)
  16. Lenfeld, J., Kroutil, M., Marsalek, E., Slavik, J., Preininger, V., and Simanek, V., Anti-inflammatory activity of quaternary benzophenanthridine alkaloids from Chelidonium majus. Planta Med., 43,161-165 (1981) https://doi.org/10.1055/s-2007-971493
  17. Mannel, D. N. and Echtenacher, B., TNF in the inflammatory response. Chem. lmmunol., 74,141-161 (2000)
  18. Mojena, M., Hortelano, S., Castrillo, A., Diaz-Guerra, M. J., Garcia-Barchino, M. J., Saez, G. T., and Bosca, L., Protection by nitric oxide against liver inflammatory injury in animals carrying a nitric oxide synthase-2 transgene. FASEB J, 15, 583-585 (2001) https://doi.org/10.1096/fj.00-0509fje
  19. Moncada, S., Palmer, R. M., and Higgs, E. A., Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol. Rev., 43,109-142. (1991)
  20. Penglis, P. S., Cleland, L. G., Demasi, M., Caughey, G. E., and James, M. J., Differential regulation of prostaglandin E2 and thromboxane A2 production in human monocytes: implications for the use of cyclooxygenase inhibitors. J. Immunol., 165, 1605-1611. (2000) https://doi.org/10.4049/jimmunol.165.3.1605
  21. Recio, M. C., Giner, R. M., Manez, S., and Rios, J. L., Structural considerations on the iridoids as anti-inflammatory agents. Planta Med., 60, 232-234 (1994) https://doi.org/10.1055/s-2006-959465
  22. Roshak, A. K., Jackson, J. R., McGough, K., Chabot-Fletcher, M., Mochan, E., and Marshall, L. A., Manipulation of distinct NFkappaB proteins alters interleukin-1beta-induced human rheumatoid synovial fibroblast prostaglandin E2 formation. J. Biol. Chem., 271, 31496-31501 (1996) https://doi.org/10.1074/jbc.271.49.31496
  23. Satou, T., Koga, M., Matsuhashi, R., Koike, K., Tada, I., and Nikaido, T., Characterisation of the 33kDa piroplasm surface antigen of Theileria orientalls/ sergenti/ buffeliisolates from West Java. Indonesia Veterinary Parasitology, 104, 117-131 (2002)
  24. Sautebin L., Prostaglandins and nitric oxide as molecular targets for anti-inflammatory therapy. Fitoterapia, 71, S48-S57 (2000) https://doi.org/10.1016/S0367-326X(00)00181-7
  25. Seibert, K., Zhang, Y., Leahy, K., Hauser, S., Masferrer, J., Perkins, W., Lee, L., and Isakson, P., Pharmacolagical and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc. Natl. Acad. Sci. U.S.A., 91, 12013-12017 (1994) https://doi.org/10.1073/pnas.91.25.12013
  26. Shapira, L., Soskolne, W. A., Houri, Y., Barak, V., Halabi, A., and Stabholz, A., Protection against endotoxic shock and lipopolysaccharide-induced local inflammation by tetra cyclin: correlation with inhibition of cytokine secretion. Infect. Immun., 64, 825-828 (1996)
  27. Straub, R. H., Linde, H. J., Mannel, D. N., Scholmerich, J., and Falk, W., A bacteria-induced switch of sympathetic effector mechanisms augments local inhibition of TNF-alpha IL-6 secretion in the spleen. FASEB J., 14, 1380-1388 (2000) https://doi.org/10.1096/fj.14.10.1380
  28. Suau R., Cabezudo B., Rico R., and Najera F., Direct determination of alkaloid contents in Fumaria species by GCMS. Phytochem. Anal., 13, 363-367 (2002) https://doi.org/10.1002/pca.669
  29. Wheeler, A. P. and Bemard, G. R., Treating patients with sever sepsis. N. Engl. J. Med., 340, 207-214 (1999) https://doi.org/10.1056/NEJM199901213400307
  30. Yamashita, T., Kawashima, S., Ohashi, Y., Ozaki, M., Ueyama, T., Ishida, T., Inoue, N., Hirata, K., Akita, H., and Yokoyama, M., Resistance to endotoxin shock in transgenic mice overex endothelial nitric oxide synthase. Circulation, 101, 931-937 (2000) https://doi.org/10.1161/01.CIR.101.8.931