Furanoligularenone, an Eremophilane from Ligularia fischeri, Inhibits the LPS-Induced Production of Nitric Oxide and Prostaglandin E₂ in Macrophage RAW264.7 Cells

Abstract

Furanoligularenone (1), a known eremophilane, was identified from Ligularia fischeri (Compositae) together with 3-oxo-8α-hydroxy-10αH-eremophila-1,7(11)-dien-12,8β-olide (2) and 3-oxo-8α-methoxy-10αH-eremophila-1,7(11)-dien-12,8β-olide (3), by its potent inhibition of LPS-induced nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in RAW 264.7 cells. Compound 1 also suppressed the expression of iNOS and COX-2 mRNA and protein in a dose-dependent manner. Taken together, compound 1 inhibits the production of NO and PGE₂ at the transcription of iNOS and COX-2 genes, and would be responsible for the anti-inflammatory activities of the Ligularia fischeri.

Key words

Ligularia fischeri - Compositae - furanoligularenone - nitric oxide - prostaglandin E₂ - inducible nitric oxide synthase - cyclooxygenase-2 - NF-κB

References

• 1 Jung B S, Shin M K. Encyclopedia of illustrated Korean natural drugs. Seoul; Young Lim Sa 1989: 1062
• 2 Wang W S, Gao K, Yang L, Jia Z J. Eremophilenolides from Ligularia fischeri .  Planta Medica. 2000;  66 189-91
• 3 Zhao Y, Peng H, Jia Z. Six new eremophilane derivatives from two Ligularia species.  Journal of Natural Products. 1994;  57 1626-30
• 4 Asada Y, Furuya T. Studies on constituents of crude drugs. XV. New pyrrolizidine alkaloids from Ligularia dentata .  Chemical and Pharmaceutical Bulletin. 1984;  32 475-82
• 5 Appleton I, Tomlinson A, Willoughby D A. Induction of cyclo-oxygenase and nitric oxide synthase in inflammation. In: Advances in pharmacology, August JT, Anders MW, Murad F, Coyle JT, editors Vol. 35 New York; Academic Press 1996: 26-78
• 6 Torres P, Ayala J, Grande C, Anaya J, Grande M. Furanoeremophilane derivatives from Senecio flavus .  Phytochemistry. 1999;  52 1507-13
• 7 Jizba J, Samek Z, Novotny L, Najdenova E, Boeva A. Components of Senecio nemorensis var. bulgaricus (Vel. Pro. Sp.)  Collection Czechoslovak Chemical Communications. 1978;  43 1113-24
• 8 Bohlmann F, Ziesche J. New sesquiterpenes from Senecio species.  Phytochemistry. 1980;  19 1851-53
• 9 Schmidt H HHW, Kelm M. Determination of Nitrite and Nitrate by the Griess Reaction. In: Methods in Nitric Oxide Research. John Wiley & Sons Ltd 1996: 491-7
• 10 Scudiero D A, Shoemaker R H, Paull K D, Monks A, Tierney S, Nofziger T H, Currens M J, Seniff D, Boyd M R. Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines.  Cancer Research. 1988;  48 4827-33
• 11 Pradelles P, Grassi J, Maclouf J. Enzyme immunoassays of eicosanoids using acetylcholine esterase as label: an alternative to radioimmunoassay.  Analytical Chemistry. 1985;  57 1170-3
• 12 Koo T H, Lee J H, Park Y J, Hong Y S, Kim H S, Kim K W, Lee J J. A sesquiterpene lactone, costunolide, from Magnolia grandiflora inhibits NF-κB by targeting IκB phosphorylation.  Planta Medica. 2001;  67 103-7
• 13 Lee S H, Soyoola E, Chanmugam P, Hart S, Sun W, Zhong H, Liou S, Simmons D, Hwang D. Selective expression of mitogen-inducible cyclooxygenase in macrophages stimulated with lipopolysaccharide.  Journal of Biological Chemistry. 1992;  267 25 934-8
• 14 Bradford M M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.  Analytical Biochemistry. 1976;  72 248-54
• 15 Erkel G, Anke T, Sterner O. Inhibition of NF-kappa B activation by panepoxydone.  Biochemical and Biophysical Research Communications. 1996;  226 214-21
• 16 Yaoita Y, and Kikuchi M. Structures of new eremophilane derivatives from the rhizomes of Petasites japonica .  Chemical and Pharmaceutical Bulletin. 1995;  43(10) 1738-43
• 17 Tobinaga S, Takeuchi N, Kasama T, Yamashita J, Aida Y, Kaneko Y. Anti-histaminic and anti-allergic principles of Petasites japonicus .  Chemical and Pharmaceutical Bulletin. 1983;  31 745-8
• 18 Park H J, Kwon S H, Yoo K O, Sohn I C, Lee K T, Lee H K. Sesquiterpenes from the leaves of Ligularia fischeri var. spiciformis .  Planta Medica. 2000;  66 783-4
• 19 Baeuerle P A, Henkel T. Function and activation of NF-kappa B in the immune system.  Annual Review of Immunology. 1994;  12 141-79
• 20 Weisz A, Oguchi S, Cicatiello L, Esumi H. Dual mechanism for the control of inducible-type NO synthase gene expression in macrophages during activation by interferon-gamma and bacterial lipopolysaccharide. Transcriptional and post-transcriptional regulation.  Journal of Biological Chemistry. 1994;  269 8324-33
• 21 Sirois J, Levy L O, Simmons D L, Richards J S. Characterization and hormonal regulation of the promoter of the rat prostaglandin endoperoxide synthase 2 gene in granulosa cells. Identification of functional and protein-binding regions.  Journal of Biological Chemistry. 1993;  268 12 199-206
• 22 Lee K Y, Chang W, Qiu D, Kao P N, Rosen G D. PG490 (triptolide) cooperates with tumor necrosis factor-α to induce apoptosis in tumor cells.  Journal of Biological Chemistry. 1999;  274 13 451-5