Natural Product Sciences

The Korean Society of Pharmacognosy (한국생약학회)
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Sesquiterpene Derivatives Isolated from Cyperus rotundus L. Inhibit Inflammatory Signaling Mediated by NF-${\kappa}B$

  • Khan, Salman (Natural Products Research Institute, College of Pharmacy, Seoul National University) ;
  • Choi, Ran-Joo (Natural Products Research Institute, College of Pharmacy, Seoul National University) ;
  • Lee, Dong-Ung (Department of Biotechnology, Dongguk University) ;
  • Kim, Yeong-Shik (Natural Products Research Institute, College of Pharmacy, Seoul National University)
  • Received : 2011.06.08
  • Accepted : 2011.08.12
  • Published : 2011.09.30
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Abstract

The immune system is finely balanced by the activities of pro-inflammatory and anti-inflammatory mediators or cytokines. Unregulated activities of these mediators can lead to the development of various inflammatory diseases. A variety of safe and effective anti-inflammatory agents are available with many more drugs under development. Of the natural compounds, the sesquiterpenes (nootkatone, ${\alpha}$-cyperone, valencene and ${\alpha}$-selinene) isolated from C. rotundus L. have received much attention because of their potential antiinflammatory effects. However, limited studies have been reported regarding the influence of sesquiterpene structure on anti-inflammatory activity. In the present study, the anti-inflammatory potential of four structurally divergent sesquiterpenes was evaluated in lipopolysaccaride (LPS)-stimulated RAW 264.7 cells, murine macrophages. Among the four sesquiterpenes, ${\alpha}$-cyperone and nootkatone, showed stronger anti-inflammatory and a potent NF-${\kappa}B$ inhibitory effect on LPS-stimulated RAW 264.7 cells. Molecular analysis revealed that various inflammatory enzymes (iNOS and COX-2) were reduced significantly and this correlated with downregulation of the NF-${\kappa}B$ signaling pathway. Additionally, electrophoretic mobility shift assays (EMSA) elucidated that nootkatone and ${\alpha}$-cyperone dramatically suppressed LPS-induced NF-${\kappa}B$-DNA binding activity using 32Plabeled NF-${\kappa}B$ probe. Hence, our data suggest that ${\alpha}$-cyperone and nootkatone are potential therapeutic agents for inflammatory diseases.

Keywords

References

  1. Carson, C.F., Hammer, K.A., and Riley, T.V., Melaleuca alternifolia (Tea Tree) oil: a review of antimicrobial and other medicinal properties. Clin. Microbiol. Rev. 19, 50-62 (2006). https://doi.org/10.1128/CMR.19.1.50-62.2006
  2. Duarte, M.C., Figueira, G.M., Sartoratto, A., Rehder, V.L., and Delarmelina, C., Anti-Candida activity of Brazilian medicinal plants. J. Ethnopharmacol. 97, 305-11 (2005). https://doi.org/10.1016/j.jep.2004.11.016
  3. Jin, H.J., Lee, D.U., Kim, Y.S., and Kim, H.P., Anti-allergic activity of sesquiterpenes from the rhizome of Cyperus rotundus. Arch. Pharm. Res. 34, 223-228 (2011). https://doi.org/10.1007/s12272-011-0207-z
  4. Khan, S., Shin, E.M., Choi, R.J., Jung, Y.H., Kim, J., Tosun, A., and Kim, Y.S., Suppression of LPS-induced inflammatory and NF-kappaB responses by anomalin in RAW 264.7 macrophages. J. Cell. Biochem. doi: 10.1002/jcb.23137 (2011).
  5. Kilani, S., Ben Sghaier, M., Limem, I., Bouhlel, I., Boubaker, J., Bhouri, W., Skandrani, I., Neffatti, A., Ben Ammar, R., Dijoux-Franca, M.G., Ghedira, K., and Chekir-Ghedira, L., In vitro evaluation of antibacterial, antioxidant, cytotoxic and apoptotic activities of the tubers infusion and extracts of Cyperus rotundus. Bioresour. Technol. 99, 9004-8 (2008a). https://doi.org/10.1016/j.biortech.2008.04.066
  6. Kilani, S., Ledauphin, J., Bouhlel, I., Ben Sghaier, M., Boubaker, J., Skandrani, I., Mosrati, R., Ghedira, K., Barillier, D., and Chekir-Ghedira, L., Comparative study of Cyperus rotundus essential oil by a modified GC/MS analysis method. Evaluation of its antioxidant, cytotoxic, and apoptotic effects. Chem. Biodivers. 5, 729-42 (2008b). https://doi.org/10.1002/cbdv.200890069
  7. Lawal, O.A. and Oyedeji, A.O., Chemical composition of the essential oils of Cyperus rotundus L. from South Africa. Molecules. 14, 2909-17 (2009). https://doi.org/10.3390/molecules14082909
  8. Moon, K.Y., Ahn, K.S., Lee, J., and Kim, Y.S., Kojic acid, a potential inhibitor of NF-kappaB activation in transfectant human HaCaT and SCC-13 cells. Arch. Pharm. Res. 24, 307-11 (2001a). https://doi.org/10.1007/BF02975097
  9. Moon, K.Y., Hahn, B.S., Lee, J., and Kim, Y.S., A cell-based assay system for monitoring NF-kappaB activity in human HaCat transfectant cells. Anal. Biochem. 292, 17-21 (2001b). https://doi.org/10.1006/abio.2001.5059
  10. Morimoto, M. and Komai, K., Plant growth inhibitors: patchoulane-type sesquiterpenes from Cyperus rotundus L. Weed Biology and Management. 5, 203-209 (2005). https://doi.org/10.1111/j.1445-6664.2005.00186.x
  11. Nath, J. and Powledge, A., Modulation of human neutrophil inflammatory responses by nitric oxide: studies in unprimed and LPS-primed cells. J. Leukoc. Biol. 62, 805-16 (1997). https://doi.org/10.1002/jlb.62.6.805
  12. Noh, E.J., Ahn, K.S., Shin, E.M., Jung, S.H., and Kim, Y.S., Inhibition of lipopolysaccharide-induced iNOS and COX-2 expression by dehydroevodiamine through suppression of NF-kappaB activation in RAW 264.7 macrophages. Life. Sci. 79, 695-701 (2006). https://doi.org/10.1016/j.lfs.2006.02.020
  13. Raut, N.A. and Gaikwad, N.J., Antidiabetic activity of hydro-ethanolic extract of Cyperus rotundus in alloxan induced diabetes in rats. Fitoterapia. 77, 585-8 (2006). https://doi.org/10.1016/j.fitote.2006.09.006
  14. Sefidkon, F., Dabiri, M., and Rahimi-Bidgoly, A., The effect of distillation methods and stage of plant growth on the essential oil content and composition of Thymus kotschyanus Boiss. & Hohen. Flavour and Fragrance Journal. 14, 405-408 (1999). https://doi.org/10.1002/(SICI)1099-1026(199911/12)14:6<405::AID-FFJ853>3.0.CO;2-M
  15. Shin, E.M., Zhou, H.Y., Guo, L.Y., Kim, J.A., Lee, S.H., Merfort, I., Kang, S.S., Kim, H.S., Kim, S., and Kim, Y.S., Anti-inflammatory effects of glycyrol isolated from Glycyrrhiza uralensis in LPS-stimulated RAW264.7 macrophages. Int. Immunopharmacol. 8, 1524-32 (2008). https://doi.org/10.1016/j.intimp.2008.06.008
  16. Vuotto, M.L., Basile, A., Moscatiello, V., De Sole, P., Castaldo-Cobianchi, R., Laghi, E., and Ielpo, M.T., Antimicrobial and antioxidant activities of Feijoa sellowiana fruit. Int. J. Antimicrob Agents. 13, 197-201 (2000). https://doi.org/10.1016/S0924-8579(99)00122-3
  17. Xie, Q. and Nathan, C., The high-output nitric oxide pathway: role and regulation. J. Leukoc. Biol. 56, 576-82 (1994). https://doi.org/10.1002/jlb.56.5.576