Advertisement

Archives of Pharmacal Research

, Volume 34, Issue 12, pp 2101–2107 | Cite as

Inhibitory effect of astragalin on expression of lipopolysaccharide-induced inflammatory mediators through NF-κB in macrophages

  • Mi-Sun Kim
  • Sang-Hyun KimEmail author
Research Articles Drug Actions

Abstract

Astragalin (kaempferol-3-O-glucoside), a newly found flavonoid from leaves of persimmon or Rosa agrestis, is known to have antiatopic dermatitis and antioxidant activity. However, the effect of astragalin on the inflammatory response is not well defined. Nitric oxide (NO) produced from the activated macrophages is well known as a mediator of inflammation. Transcription factor (NF)-κB mediates the inducible expression of a variety of genes involved in immune and inflammatory responses including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and cytokines/chemokines. In the present study, we examined the inhibitory effects of astragalin on the lipopolysaccharide (LPS)-induced inflammatory mediators. Astragalin significantly reduced LPS-induced expression of iNOS, COX-2 and cytokines/chemokines, and production of NO in J774A.1 mouse macrophages. Astragalin inhibited LPSinduced activation of NF-κB as indicated by inhibition of degradation of IκBα, nuclear translocation of NF-κB, and NF-κB dependent gene reporter assay. The inhibitory effects of astragalin on the inflammatory mediators are comparable with quercetin, a well known flavonoid possessing antioxidant and anti-inflammatory activity. Using the mouse peritoneal macrophages, we confirmed the inhibitory effect of astragalin on NO production and NF-κB activation. Taken together, our results indicate that astragalin inhibits expression of proinflammatory mediators through the inhibition of NF-κB in macrophages.

Key words

Nitric oxide Nuclear factor-κB Inflammation Macrophages Astragalin Flavonoid 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abad, M. J., Bessa, A. L., Ballarin, B., Aragon, O., Gonzales, E., and Bermejo, P., Anti-inflammatory activity of four Bolivian Baccharis species (Compositae). J. Ethnopharmacol., 103, 338–344 (2006).PubMedCrossRefGoogle Scholar
  2. Altinoz, M. A. and Korkmaz, R., NF-kappaB, macrophage migration inhibitory factor and cyclooxygenase-inhibitions as likely mechanisms behind the acetaminophen- and NSAID-prevention of the ovarian cancer. Neoplasma, 51, 239–247 (2004).PubMedGoogle Scholar
  3. Bitis, L., Kultur, S., Melikoglu, G., Ozsoy, N., and Can, A., Flavonoids and antioxidant activity of Rosa agrestis leaves. Nat. Prod. Res., 24, 580–589 (2010).PubMedCrossRefGoogle Scholar
  4. Cho, S. Y., Park, S. J., Kwon, M. J., Jeong, T. S., Bok, S. H., Choi, W. Y., Jeong, W. I., Ryu, S. Y., Do, S. H., Lee, C. S., Song, J. C., and Jeong, K. S., Quercetin suppresses proinflammatory cytokines production through MAP kinases and NF-kappaB pathway in lipopolysaccharide-stimulated macrophage. Mol. Cell. Biochem., 243, 153–160 (2003).PubMedCrossRefGoogle Scholar
  5. Eads, D., Hansen, R., Oyegunwa, A., Cecil, C., Culver, C., Scholle, F., Petty, I., and Laster, S., Terameprocol, a methylated derivative of nordihydroguaiaretic acid, inhibits production of prostaglandins and several key inflammatory cytokines and chemokines. J. Inflamm. (Lond), 6, 2 (2009).CrossRefGoogle Scholar
  6. Gross, S. S. and Wolin, M. S., Nitric oxide: pathophysiological mechanisms. Annu. Rev. Physiol., 57, 737–769 (1995).PubMedCrossRefGoogle Scholar
  7. Hamalainen, M., Nieminen, R., Vuorela, P., Heinonen, M., and Moilanen, E., Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm., 2007, 45673 (2007).PubMedCrossRefGoogle Scholar
  8. Higa, S., Hirano, T., Kotani, M., Matsumoto, M., Fujita, A., Suemura, M., Kawase, I., and Tanaka, T., Fisetin, a flavonol, inhibits TH2-type cytokine production by activated human basophils. J. Allergy Clin. Immunol., 111, 1299–1306 (2003).PubMedCrossRefGoogle Scholar
  9. Hirano, T., Arimitsu, J., Higa, S., Naka, T., Ogata, A., Shima, Y., Fujimoto, M., Yamadori, T., Ohkawara, T., Kuwabara, Y., Kawai, M., Kawase, I., and Tanaka, T., Luteolin, a flavonoid, inhibits CD40 ligand expression by activated human basophils. Int. Arch. Allergy Immunol., 140, 150–156 (2006).PubMedCrossRefGoogle Scholar
  10. Inaba, H., Tagashira, M., Honma, D., Kanda, T., Kou, Y., Ohtake, Y., and Amano, A., Identification of hop polyphenolic components which inhibit prostaglandin E2 production by gingival epithelial cells stimulated with periodontal pathogen. Biol. Pharm. Bull., 31, 527–530 (2008).PubMedCrossRefGoogle Scholar
  11. Jung, C. H., Kim, J. H., Hong, M. H., Seog, H. M., Oh, S. H., Lee, P. J., Kim, G. J., Kim, H. M., Um, J. Y., and Ko, S. G., Phenolic-rich fraction from Rhus verniciflua Stokes (RVS) suppress inflammatory response via NF-kappaB and JNK pathway in lipopolysaccharide-induced RAW 264.7 macrophages. J. Ethnopharmacol., 110, 490–497 (2007).PubMedCrossRefGoogle Scholar
  12. Kameda, K., Takaku, T., Okuda, H., Kimura, Y., Okuda, T., Hatano, T., Agata, I., and Arichi, S., Inhibitory effects of various flavonoids isolated from leaves of persimmon on angiotensin-converting enzyme activity. J. Nat. Prod., 50, 680–683 (1987).PubMedCrossRefGoogle Scholar
  13. Kim, M. S., Park, S. B., Suk, K., Kim, I. K., Kim, S. Y., Kim, J. A., Lee, S. H., and Kim, S. H., Gallotannin isolated from Euphorbia species, 1,2,6-tri-O-galloyl-beta-D-allose, decreases nitric oxide production through inhibition of nuclear factor-kappa>B and downstream inducible nitric oxide synthase expression in macrophages. Biol. Pharm. Bull., 32, 1053–1056 (2009).PubMedCrossRefGoogle Scholar
  14. Kim, S. H., Johnson, V. J., and Sharma, R. P., Mercury inhibits nitric oxide production but activates proinflammatory cytokine expression in murine macrophage: differential modulation of NF-kappaB and p38 MAPK signaling pathways. Nitric Oxide, 7, 67–74 (2002).PubMedCrossRefGoogle Scholar
  15. Kim, S. H. and Sharma, R. P., Mercury-induced apoptosis and necrosis in murine macrophages: role of calciuminduced reactive oxygen species and p38 mitogen-activated protein kinase signaling. Toxicol. Appl. Pharmacol., 196, 47–57 (2004).PubMedCrossRefGoogle Scholar
  16. Kim, S. H., Jun, C. D., Suk, K., Choi, B. J., Lim, H., Park, S., Lee, S. H., Shin, H. Y., Kim, D. K., and Shin, T. Y., Gallic acid inhibits histamine release and pro-inflammatory cytokine production in mast cells. Toxicol. Sci., 91, 123–131 (2006).PubMedCrossRefGoogle Scholar
  17. Kim, S. H., Lee, S., Suk, K., Bark, H., Jun, C. D., Kim, D. K., Choi, C. H., and Yoshimura, T., Discoidin domain receptor 1 mediates collagen-induced nitric oxide production in J774A.1 murine macrophages. Free Radic. Biol. Med., 42, 343–352 (2007).PubMedCrossRefGoogle Scholar
  18. Kotani, M., Matsumoto, M., Fujita, A., Higa, S., Wang, W., Suemura, M., Kishimoto, T., and Tanaka, T., Persimmon leaf extract and astragalin inhibit development of dermatitis and IgE elevation in NC/Nga mice. J. Allergy Clin. Immunol., 106, 159–166 (2000).PubMedCrossRefGoogle Scholar
  19. Lee, S., Suk, K., Kim, I. K., Jang, I. S., Park, J. W., Johnson, V. J., Kwon, T. K., Choi, B. J., and Kim, S. H., Signaling pathways of bisphenol A-induced apoptosis in hippocampal neuronal cells: role of calcium-induced reactive oxygen species, mitogen-activated protein kinases, and nuclear factor-kappaB. J. Neurosci. Res., 86, 2932–2942 (2008).PubMedCrossRefGoogle Scholar
  20. 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).PubMedGoogle Scholar
  21. Liu, P. T. and Modlin, R. L., Human macrophage host defense against Mycobacterium tuberculosis. Curr. Opin. Immunol., 20, 371–376 (2008).PubMedCrossRefGoogle Scholar
  22. Maier, J. A., Hla, T., and Maciag, T., Cyclooxygenase is an immediate-early gene induced by interleukin-1 in human endothelial cells. J. Biol. Chem., 265, 10805–10808 (1990).PubMedGoogle Scholar
  23. Metcalfe, D. D., Baram, D., and Mekori, Y. A., Mast cells. Physiol. Rev., 77, 1033–1079 (1997).PubMedGoogle Scholar
  24. Nhiem, N. X., Tai, B. H., Quang, T. H., Kiem, P. V., Minh, C. V., Nam, N. H., Kim, J. H., Im, L. R., Lee, Y. M., and Kim, Y. H., A new ursane-type triterpenoid glycoside from Centella asiatica leaves modulates the production of nitric oxide and secretion of TNF-alpha in activated RAW 264.7 cells. Bioorg. Med. Chem. Lett., 21, 1777–1781 (2011).PubMedCrossRefGoogle Scholar
  25. Park, H. H., Lee, S., Son, H. Y., Park, S. B., Kim, M. S., Choi, E. J., Singh, T. S., Ha, J. H., Lee, M. G., Kim, J. E., Hyun, M. C., Kwon, T. K., Kim, Y. H., and Kim, S. H., Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells. Arch. Pharm. Res., 31, 1303–1311 (2008).PubMedCrossRefGoogle Scholar
  26. Shen, S. C., Lee, W. R., Lin, H. Y., Huang, H. C., Ko, C. H., Yang, L. L., and Chen, Y. C., In vitro and in vivo inhibitory activities of rutin, wogonin, and quercetin on lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production. Eur. J. Pharmacol., 446, 187–194 (2002).PubMedCrossRefGoogle Scholar
  27. Xie, Q. W., Kashiwabara, Y., and Nathan, C., Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase. J. Biol. Chem., 269, 4705–4708 (1994).PubMedGoogle Scholar
  28. Yasukawa, K., Takido, M., Takeuchi, M., Sato, Y., Nitta, K., and Nakagawa, S., Inhibitory effects of flavonol glycosides on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion. Chem. Pharm. Bull. (Tokyo), 38, 774–776 (1990).CrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea and Springer Netherlands 2011

Authors and Affiliations

  1. 1.Department of Pharmacology, School of MedicineKyungpook National UniversityDaeguKorea

Personalised recommendations