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Anti-inflammatory Effect of Scopoletin in RAW264.7 Macrophages
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  • Journal title : Journal of Life Science
  • Volume 25, Issue 12,  2015, pp.1377-1383
  • Publisher : Korean Society of Life Science
  • DOI : 10.5352/JLS.2015.25.12.1377
 Title & Authors
Anti-inflammatory Effect of Scopoletin in RAW264.7 Macrophages
Lee, Su-Gyeong; Kim, Moon-Moo;
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Scopoletin is a component of several plant such as Erycibe obtusifolia, Aster tataricus, Foeniculum vulgare and Brunfelsia grandiflora. It was reported to have anti-angiogenesis and anti-allergy effects. In this study, the anti-inflammatory effect of scopoletin was investigated in Raw264.7 cells, mouse macrophages. The effects of scopoletin on phagocytosis and nitric oxide (NO) production were investigated in lipopolysaccharide (LPS)-induced inflammatory responses. It was observed that scopoletin exerted inhibitory effects on both phagocytosis and NO production. In addition, scopoletin decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) which were related to NO and prostaglandin E2 (PGE2) production. In particular, the expression of pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The expression levels of IL-1β, IL-6 were remarkably decreased by treatment with scopoletin. Furthermore, the content of TNFα produced by macrophage was decreased in the presence of scopoletin at 8 hr. These results indicate that the anti-inflammatory effect of scopoletin could exert by inhibiting the expression of pro-inflammatory cytokines in Raw264.7 cells stimulated with LPS. The above results suggest scopoletin could be a new remedial agent for anti-inflammation through inhibition of iNOS, COX-2, IL-1β, IL-6 and TNF-α expressions as well as supression of phagocytosis and NO production.
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Albina, J. and Reichner, J. 1995. Nitric oxide in inflammation and immunity. New Horiz 3, 46-64.

Alvarez, M. and Casadevall, A. 2006. Phagosome extrusion and host-cell survival after Cryptococcus neoformans phagocytosis by macrophages. Curr. Biol. 16, 2161-2165. crossref(new window)

Barrett, J. T. 1983. Textbook of immunology: an introduction to immunochemistry and immunobiology: Mosby.

Bradley, J. 2008. TNF mediated inflammatory disease. J. Pathol. 214, 149-160. crossref(new window)

Cheng, A. S., Cheng, Y. H. and Chang, T. L. 2012. Scopoletin attenuates allergy by inhibiting Th2 cytokines production in EL-4 T cells. Food Funct. 3, 886-890. crossref(new window)

Cheon, M., Yoon, T., Choi, G., Kim, S., Lee, A., Moon, B., Choo, B. and Kim, H. 2009. Comparative study of extracts from rhubarb on inflammatory activity in RAW 264.7 cells. Kor. J. Edicinal Crop Sci. 17. 109-114.

Cline, M. 1970. Leukocyte function in inflammation: the ingestion, killing, and digestion of microorganisms. Ser. Haematol. 3, 3.

Delgado, A. V., McManus, A. T. and Chambers, J. P. 2003. Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and interleukin 6 by rat leukocyte subpopulations after exposure to substance P. Neuropeptides 37, 355-361. crossref(new window)

Ding, C., Cicuttini, F., Li, J. and Jones, G. 2009. Targeting IL-6 in the treatment of inflammatory and autoimmune diseases. Expert Opin. Investig. Drugs 18, 1457-1466. crossref(new window)

Ding, Z., Dai, Y., Hao, H., Pan, R., Yao, X. and Wang, Z. 2008. Anti-inflammatory effects of scopoletin and underlying mechanisms. Pharm. Biol. 46, 854-860.

Dissing Olesen, L., Ladeby, R., Nielsen, H. H., Toft Hansen, H., Dalmau, I. and Finsen, B. 2007. Axonal lesion-induced microglial proliferation and microglial cluster formation in the mouse. Neuroscience 149, 112-122. crossref(new window)

Dogne, J. M., Hanson, J., Supuran, C. and Pratico, D. 2006. Coxibs and cardiovascular side-effects: from light to shadow. Curr. Pharm. Des. 12, 971-975. crossref(new window)

Filipowicz, N. and Renner, S. S. 2012. Brunfelsia (Solanaceae): A genus evenly divided between South America and radiations on Cuba and other Antillean islands. Mol. Phylogen. Evol. 64, 1-11. crossref(new window)

Gabay, C. 2006. Interleukin-6 and chronic inflammation. Arthritis Res. Ther. 8, S3.

Pathology of inflammatory bowel disease. Semin. Pediatr. Surg.; 2007. Elsevier.

Hang, D., Choi, H. S., Kang, S. C., Kim, K. R., Sohn, E. S., Kim, M. H., Pyo, S. and Son, E. 2005. Effects of fucoidan on NO production and phagocytosis of macrophages and the proliferation of neuron cells. J. Food Sci. Nutr. 10, 344-348. crossref(new window)

Hansen, M. B., Nielsen, S. E. and Berg, K. 1989. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J. Immunol. Methods 119, 203-210. crossref(new window)

Heinzmann, A. and Daser, A. 2002. Mouse models for the genetic dissection of atopy. Int. Arch. Allergy Immunol. 127, 170-180. crossref(new window)

Jeong, J. B., Hong, S. C., Jeong, H. J. and Koo, J. S. 2012. Anti-Inflammatory effects of ethyl acetate fraction from cnidium officinale makino on LPS-stimulated RAW 264.7 and THP-1 cells. Hangug Jaweon Sigmul Haghoeji 25, 299-307.

Kim, H. J., Jang, S. I., Kim, Y. J., Chung, H. T., Yun, Y. G., Kang, T. H., Jeong, O. S. and Kim, Y. C. 2004. Scopoletin suppresses pro-inflammatory cytokines and PGE 2 from LPS-stimulated cell line, RAW 264.7 cells. Fitoterapia 75, 261-266. crossref(new window)

Lee, S. J. and Lim, K. T. 2008. Phytoglycoprotein inhibits interleukin-1β and interleukin-6 via p38 mitogen-activated protein kinase in lipopolysaccharide-stimulated RAW 264.7 cells. Naunyn-Schmiedeberg’s Arch. Pharmacol. 377, 45-54. crossref(new window)

Ljung, T., Lundberg, S., Varsanyi, M., Johansson, C., Schmidt, P. T., Herulf, M., Lundberg, J. O. and Hellstrom, P. M. 2006. Rectal nitric oxide as biomarker in the treatment of inflammatory bowel disease: responders versus nonresponders. World J. Gastroenterol. 12, 3386. crossref(new window)

Makins, R. and Ballinger, A. 2003. Gastrointestinal side effects of drugs. Expert Opin. Drug Saf. 2, 421-429. crossref(new window)

Masferrer, J. L., Zweifel, B. S., Manning, P. T., Hauser, S. D., Leahy, K. M., Smith, W. G., Isakson, P. C. and Seibert, K. 1994. Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. Proc. Natl. Acad. Sci. USA 91, 3228-3232. crossref(new window)

Masters, S. L., Simon, A., Aksentijevich, I. and Kastner, D. L. 2009. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu. Rev. Immunol. 27, 621. crossref(new window)

Meydani, S. N. 1990. Dietary modulation of cytokine production and biologic functions. Nutr. Rev. 48, 361-369.

Mizel, S. B. 1989. The interleukins. FASEB J. 3, 2379-2388.

Murphy, M. P. 1999. Nitric oxide and cell death. Biochimica et Biophysica Acta (BBA)-Bioenergetics 1411, 401-414. crossref(new window)

Nathan, C. 1992. Nitric oxide as a secretory product of mammalian cells. FASEB J. 6, 3051-3064.

Pan, R., Dai, Y., Gao, X. H., Lu, D. and Xia, Y. F. 2011. Inhibition of vascular endothelial growth factor-induced angiogenesis by scopoletin through interrupting the autophosphorylation of VEGF receptor 2 and its downstream signaling pathways. Vascul. Pharmacol. 54, 18-28. crossref(new window)

Pan, R., Gao, X., Lu, D., Xu, X., Xia, Y. and Dai, Y. 2011. Prevention of FGF-2-induced angiogenesis by scopoletin, a coumarin compound isolated from Erycibe obtusifolia Benth, and its mechanism of action. Int. Immunopharmacol. 11, 2007-2016. crossref(new window)

Pan, R., Gao, X. H., Li, Y., Xia, Y. F. and Dai, Y. 2010. Anti arthritic effect of scopoletin, a coumarin compound occurring in Erycibe obtusifolia Benth stems, is associated with decreased angiogenesis in synovium. Fundam. Clin. Pharmacol. 24, 477-490.

Plowman, T. 1977. Brunfelsia in ethnomedicine. Bot Mus Lealf Harv Univ. 289-320.

Posadas, I., Terencio, M. C., Guillén, I., Ferrándiz, M. L., Coloma, J., Payá, M. and Alcaraz, M. J. 2000. Co-regulation between cyclo-oxygenase-2 and inducible nitric oxide synthase expression in the time-course of murine inflammation. Naunyn-Schmiedeberg's Arch. Pharmacol. 361, 98-106. crossref(new window)

Shih, M. F., Cheng, Y. D., Shen, C. R. and Cherng, J. Y. 2010. A molecular pharmacology study into the anti-inflammatory actions of Euphorbia hirta L. on the LPS-induced RAW 264.7 cells through selective iNOS protein inhibition. J. Nat. Med. 64, 330-335. crossref(new window)

Stuehr, D. J., Cho, H. J., Kwon, N. S., Weise, M. F. and Nathan, C. F. 1991. Purification and characterization of the cytokine-induced macrophage nitric oxide synthase: an FAD-and FMN-containing flavoprotein. Proc. Natl. Acad. Sci.USA 88, 7773-7777. crossref(new window)

Sung, Y. Y., Kim, D. S., Yang, W. K., Nho, K. J., Seo, H. S., Kim, Y. S. and Kim, H. K. 2012. Inhibitory effects of Drynaria fortunei extract on house dust mite antigen-induced atopic dermatitis in NC/Nga mice. J. Ethnopharmacol. 144, 94-100. crossref(new window)

Tsatsanis, C., Androulidaki, A., Venihaki, M. and Margioris, A. N. 2006. Signalling networks regulating cyclooxygenase-2. Int. J. Biochem. Cell Biol. 38, 1654-1661. crossref(new window)

Wang, X., Luo, Y., Liao, W. B., Zhang, J. and Chen, T. M. 2013. Effect of osteoprotegerin in combination with interleukin-6 on inhibition of osteoclast differentiation. Chin. J. Traumatol. 16, 277-280.

Willoughby, D. 1975. Heberden Oration, 1974. Human arthritis applied to animal models. Towards a better therapy. Ann. Rheum. Dis. 34, 471.

Ye, J. 2008. Regulation of PPARγ function by TNF-α. Biochem. Biophys. Res. Commun. 374, 405-408. crossref(new window)