Abstract
The anti-inflammatory activities of a prepared isoegomaketone 3a and its derivatives 3b–3f were evaluated in RAW 264.7 cells. Among these, the compound 3d was displayed the most potent inhibitory activities against production of nitric oxide, monocyte chemoattractant protein-1 and interleukin-6. Based on these results, the abilities of compounds 3a–3f to modulate NF-κB and AP-1-mediated gene transcription using a luciferase reporter assay were investigated. The transcriptional activities of NF-κB and AP-1 decreased when pretreated with 3a–3f. Interestingly, at 10 μM, compound 3d markedly suppressed the lipopolysaccharide-induced NF-κB and activator protein-1 DNA binding activities. Some preliminary structure-activity relationships were proposed that may provide a direction for further study.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abdulla, R. F. and Fuhr, K. H., An efficient conversion of ketones to α,β-unsaturated ketones. J. Org. Chem., 43, 4248–4250 (1978).
Aderem, A. and Ulevitch, R. J., Toll-like receptors in the induction of the innate immune response. Nature, 406, 782–787 (2000).
Diaz-Guerra, M. J., Velasco, M., Martin-Sanz, P., and Bosca, L., Evidence for common mechanisms in the transcriptional control of type II nitric oxide synthase in isolated hepatocytes. Requirement of NF-kappaB activation after stimulation with bacterial cell wall products and phorbol esters. J. Biol. Chem., 271, 30114–30120 (1996).
Heinrich, P. C., Behrmann, I., Haan, S., Hermanns, H. M., Muller-Newen, G., and Schaper, F., Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem. J., 374, 1–20 (2003).
Jin, C. H., Lee, H. J., Park, Y. D., Choi, D. S., Kim, D. S., Kang, S. Y., Seo, K. I., and Jeong, I. Y., Isoegomaketone inhibits lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages through the heme oxygenase-1 induction and inhibition of the interferon-beta-STAT-1 pathway. J. Agric. Food Chem., 58, 860–867 (2010).
Kristof, A. S., Marks-Konczalik, J., and Moss, J., Mitogen-activated protein kinases mediate activator protein-1-dependent human inducible nitric-oxide synthase promoter activation. J. Biol. Chem., 276, 8445–8452 (2001).
Manning, A. M. and Mercurio, F., Transcription inhibitors in inflammation. Expert Opin. Investig. Drugs, 6, 555–567 (1997).
Melgarejo, E., Medina, M. A., Sanchez-Jimenez, F., and Urdiales, J. L., Monocyte chemoattractant protein-1: a key mediator in inflammatory processes. Int. J. Biochem. Cell Biol., 41, 998–1001 (2009).
O’Neill, L. A., Targeting signal transduction as a strategy to treat inflammatory diseases. Nat. Rev. Drug Discov., 5, 549–563 (2006).
Park, Y. D., Lee, Y. M., Kang, M. A., Lee, H. J., Jin, C. H., Choi, D. S., Kim, D. S., Kang, S. Y., Kim, W. G., and Jeong, I. Y., Phytochemical profiles and in vitro anti-inflammatory properties of Perilla frutescens cv. Chookyoupjaso mutants induced by mutagenesis with γ-ray. Food Sci. Biotechnol., 19, 305–311 (2010).
Reinhart, K. and Karzai, W., Anti-tumor necrosis factor therapy in sepsis: update on clinical trials and lessons learned. Crit. Care Med., 29, S121–S125 (2001).
Shaulian, E. and Karin, M., AP-1 as a regulator of cell life and death. Nat. Cell Biol., 4, E131–E136 (2002).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Park, Y.D., Jin, C.H., Choi, D.S. et al. Biological evaluation of isoegomaketone isolated from Perilla frutescens and its synthetic derivatives as anti-inflammatory agents. Arch. Pharm. Res. 34, 1277–1282 (2011). https://doi.org/10.1007/s12272-011-0806-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-011-0806-8