Abstract
Stylopine is a major component of the leaf ofChelidonium 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. Stylopineper se had no cytotoxic effect in unstimulated RAW 264.7 cells, but concentration-dependently reduced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-a (TNF-α) and interleukin-1 β (IL-1β), 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 PGE2 production in macrophages by inhibiting the iNOS and COX-2 expressions. These biological activities of stylopine may contribute to the anti-inflammatory activity ofChelidonium majus.
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Ahmad, N., Chen, L. C., Gordon, M. A., Laskin, J. D., and Laskin, D. L., Related Articles, Links regulation of cycolooxy- genase-2 by nitric oxide in activated hepatic macrophages during acute endotoxemia.J. Leukoc. Biol., 71, 1005–1011 (2002).
Barnes, P. J. and Karin, M., Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases.N. Engl. J. Med., 336, 1066–1071 (1997).
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 Altern. Med., 10; 2(1): 4 (2002).
Coker, P. K. and Laurent, G. J., Pulmonary fibrosis: cytokines in the balance.Eur. Resp. J., 11, 1218 (1998).
Colombo, M. L. and Bosisio, E., Pharmacological activities ofChelidonium majus L.Pharmacol. Res., 33, 127–134 (1996).
De Nardin, E., The role of inflammatory and immunological mediators in periodontitis and cardiovascular disease.Ann. Periodontol., 6, 30–40 (2001).
Dinarello, C. A., Cytokines as endogenous pyrogens.J. Infect. Dis., 179, Suppl 2, S294–304 (1999).
Feldmann, M., Brennan, F. M., and Maini, R. N., Role of cytokines in rheumatoid arthritis.Annu. Rev. Immunol., 14, 397–440 (1996).
Haberlein, H., Tschiersch, K. P., Boonen, G., and Hiller, K. O.Chelidonium majus L: components within vitro affinity for the FABAA receptor.Planta Med., 62, 227–231 (1996).
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).
Ikezawa, N., Tanaka, M., Nagayoshi, M., Shinkyo, R., Sakaki, T., Inouye, K., and Sato, F.,J. Biol. Chem., 278, 38557–38565 (2003).
Isomaki, P., and Punnonen, J., Pro- and anti-inflammatory cytokines inrheumatoid arthritis.Ann. Med., 29(6), 499–507 (1997).
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).
Kroncke, K. D., Fehsel, K., and Kolb-Bachofen, V., Nitric oxide: cytotoxicity versus cytoprotectionóhow, why, when, and where?Nitric Oxide, 1, 107–120 (1997).
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).
Lenfeld, J., Kroutil, M., Marsalek, E., Slavik, J., Preininger, V., and Simanek, V., Anti-inflammatory activity of quaternary benzophenanthridine alkaloids fromChelidonium majus.Planta Med., 43, 161–165 (1981).
Mannel, D. N. and Echtenacher, B., TNF in the inflammatory response.Chem. Immunol., 74, 141–161 (2000).
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).
Moncada, S., Palmer, R. M., and Higgs, E. A., Nitric oxide: physiology, pathophysiology, and pharmacology.Pharmacol. Rev., 43, 109–142. (1991).
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).
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).
Roshak, A. K., Jackson, J. R., McGough, K., Chabot-Fletcher, M., Mochan, E., and Marshall, L. A., Manipulation of distinct NFkappaB proteins alters interleukin-1 beta-induced human rheumatoid synovial fibroblast prostaglandin E2 formation.J. Biol. Chem., 271, 31496–31501 (1996).
Satou, T., Koga, M., Matsuhashi, R., Koike, K., Tada, I., and Nikaido, T., Characterisation of the 33kDa piroplasm surface antigen of Theileria orientalis/ sergenti/ buffeliisolates from West Java.Indonesia Veterinary Parasitology., 104, 117–131 (2002).
Sautebin, L., Prostaglandins and nitric oxide as molecular targets for anti-inflammatory therapy.Fitoterapia, 71, S48-S57 (2000).
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).
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).
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).
Suau R., Cabezudo B., Rico R., and Najera F., Direct determination of alkaloid contents in Fumaria species by GC-MS.Phytochem. Anal., 13, 363–367 (2002).
Wheeler, A. P., and Bernard, G. R., Treating patients with sever sepsis.N. Engl. J. Med., 340, 207–214 (1999).
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).
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Jang, S., Kim, B.H., Lee, WY. et al. Stylopine fromChelidonium majus inhibits LPS-Induced inflammatory mediators in RAW 264.7 cells. Arch Pharm Res 27, 923–929 (2004). https://doi.org/10.1007/BF02975845
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DOI: https://doi.org/10.1007/BF02975845