Inhibitory effect of astragalin on expression of lipopolysaccharide-induced inflammatory mediators through NF-κB in macrophages
- 390 Downloads
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 wordsNitric oxide Nuclear factor-κB Inflammation Macrophages Astragalin Flavonoid
Unable to display preview. Download preview PDF.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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