QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.077107v1 312/3/1187    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kang, J. S. Articles by Kim, H. M. Search for Related Content PubMed PubMed Citation Articles by Kang, J. S. Articles by Kim, H. M.

INFLAMMATION AND IMMUNOPHARMACOLOGY

Glabridin, an Isoflavan from Licorice Root, Inhibits Inducible Nitric-Oxide Synthase Expression and Improves Survival of Mice in Experimental Model of Septic Shock

Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Taejon, Korea

(R)-4-(3,4-Dihydro-8,8-dimethyl)-2H,8H-benzo[1,2-b:3,4-b']dipyran-3yl)-1,3-benzenediol (glabridin), a flavonoid present in licorice extract, is known to have antimicrobial, anti-inflammatory, and cardiovascular protective activities. In the present study, we report the inhibitory effect of glabridin on nitric oxide (NO) production and inducible nitric oxide (iNOS) gene expression in murine macrophages. Glabridin attenuated lipopolysaccharide (LPS)-induced NO production in isolated mouse peritoneal macrophages and RAW 264.7 cells, a mouse macrophage-like cell line. Moreover, iNOS mRNA expression was also blocked by glabridin treatment in LPS-stimulated RAW 264.7 cells. Further study demonstrated that the LPS-induced nuclear factor (NF)-B/Rel DNA binding activity and NF-B/Rel-dependent reporter gene activity were significantly inhibited by glabridin in RAW 264.7 cells and that this effect was mediated through the inhibition of inhibitory factor-B degradation and p65 nuclear translocation. Moreover, reactive oxygen species generation was also suppressed by glabridin treatment in RAW 264.7 cells. In contrast, the activity of mitogen-activated protein kinases was unaffected by glabridin treatment. In animal model, in vivo administration of glabridin increased the rate of survival of LPS-treated mice and inhibited LPS-induced increase in plasma concentrations of nitrite/nitrate and tumor necrosis factor-. Collectively, these data suggest that glabridin inhibits NO production and iNOS gene expression by blocking NF-B/Rel activation and that this effect was mediated, at least in part, by inhibiting reactive oxygen species generation. Furthermore, in vivo anti-inflammatory effect of glabridin suggests a possible therapeutic application of this agent in inflammatory diseases.

Address correspondence to: Hwan Mook Kim, Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Taejon, 305-333, Korea. E-mail: hwanmook{at}kribb.re.kr

This article has been cited by other articles:

				H.-M. Kwon, Y.-J. Choi, J.-S. Choi, S.-W. Kang, J.-Y. Bae, I.-J. Kang, J.-G. Jun, S.-S. Lee, S. S. Lim, and Y.-H. Kang Blockade of Cytokine-Induced Endothelial Cell Adhesion Molecule Expression by Licorice Isoliquiritigenin Through NF-{kappa}B Signal Disruption Experimental Biology and Medicine, February 1, 2007; 232(2): 235 - 245. [Abstract] [Full Text] [PDF]

				J. Hong, S. Sang, H.-J. Park, S. J. Kwon, N. Suh, M.-T. Huang, C.-T. Ho, and C. S. Yang Modulation of arachidonic acid metabolism and nitric oxide synthesis by garcinol and its derivatives Carcinogenesis, February 1, 2006; 27(2): 278 - 286. [Abstract] [Full Text] [PDF]