Planta Medica, Table of Contents Planta Med 2012; 78(16): 1725-1730DOI: 10.1055/s-0032-1315241 Original Papers Georg Thieme Verlag KG Stuttgart · New YorkActivation of Antioxidant Response Element in Mouse Primary Cortical Cultures with Sesquiterpene Lactones Isolated from Tanacetum parthenium Authors Author Affiliations Justin T. Fischedick 1 PRISNA BV, Leiden, The Netherlands 2 Natural Products Laboratory, Institute of Biology, Leiden University, Leiden, The Netherlands Miranda Standiford 3 Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin, Madison, WI, USA Delinda A. Johnson 3 Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin, Madison, WI, USA Ric C. H. De Vos 4 Plant Research International, BU Biosciences, Wageningen University and Research Centre, Wageningen, The Netherlands 5 Centre for BioSystems Genomics, Wageningen, The Netherlands 6 Netherlands Metabolomics Centre, Leiden, The Netherlands Slađana Todorović 7 Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia Tijana Banjanac 7 Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia Rob Verpoorte 2 Natural Products Laboratory, Institute of Biology, Leiden University, Leiden, The Netherlands Jeffrey A. Johnson 3 Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin, Madison, WI, USA Recommend Article Abstract Buy Article(opens in new window) Abstract Tanacetum parthenium produces biologically active sesquiterpene lactones (SL). Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to activate a series of genes termed the antioxidant response element (ARE). Activation of Nrf2/ARE may be useful for the treatment of neurodegenerative disease. In this study we isolated 11 SL from T. parthenium with centrifugal partition chromatography and semipreparative HPLC. Compounds were screened in vitro for their ability to activate the ARE on primary mouse cortical cultures as well as for their toxicity towards the cultures. All SL containing the α-methylene-γ-lactone moiety were able to activate the ARE and cause cellular toxicity. The structure–activity relationship among the SL isolated indicates that the guaianolides were more active and when lacking the endoperoxide functionality less toxic then the germacranolides. Key words Key words Tanacetum parthenium - Asteraceae - nuclear factor E2-related factor 2 - antioxidant response element - sesquiterpene lactones - parthenolide - centrifugal partition - chromatography Full Text References References 1 Abad MJ, Bermejo P, Villar A. An approach to the genus Tanacetum L. (Compositae): phytochemical and pharmacological review. Phytother Res 1995; 9: 79-92 2 Hwang DR, Wu YS, Chang CW, Lien TW, Chen WC, Tan UK, Hsu JTA, Hsieh HP. Synthesis and anti-viral activity of a series of sesquiterpene lactones and analogues in the subgenomic HCV replicon system. Bioorg Med Chem 2006; 14: 83-91 3 Tiuman TS, Ueda-Nakamura T, Cortez DAG, Filho BPD, Morgado-Díaz JA, Souza WD, Nakamura CV. Antileishmanial activity of parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium . Antimicrob Agents Chemother 2005; 49: 176-182 4 Salminen A, Lehtonen M, Suuronen T, Kaarniranta A, Huuskonen J. Terpenoids: natural inhibitors of NF-κB signaling with anti-inflammatory and anticancer potential. Cell Mol Life Sci 2008; 65: 2979-2999 5 Ghantous A, Gali-Muhtasib H, Vuorela H, Saliba NA, Darwiche N. What made sesquiterpene lactones reach cancer clinical trials?. Drug Discov Today 2010; 15: 668-678 6 Calkins MJ, Johnson DA, Townsend JA, Vargas MR, Dowell JA, Williamson TP, Kraft AD, Lee JM, Li J, Johnson JA. The Nrf2/ARE pathway as a potential therapeutic target in neurodegenerative disease. Antioxid Redox Signal 2009; 11: 497-508 7 de Vries HE, Witte M, Hondius D, Rozemuller AJM, Drukarch B, Hoozemans J, van Horssen J. Nrf2-induced antioxidant protection: a promising target to counteract ROS-mediated damage in neurodegenerative disease?. Free Radic Biol Med 2008; 45: 1375-1383 8 Zhang DD, Hannink M. Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol Cell Biol 2003; 23: 8137-8151 9 Itoh K, Tong KI, Yamamoto M. Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles. Free Radic Biol Med 2004; 36: 1208-1213 10 Mathema VB, Koh YS, Thakuri BC, Sillanpää M. Parthenolide, a sesquiterpene lactone, expresses multiple anti-cancer and anti-inflammatory activities. Inflammation 2012; 35: 560-565 11 Jeong WS, Keum YS, Chen C, Jain MR, Shen G, Kim JH, Li W, Kong AN. Differential expression and stability of endogenous nuclear factor E2-related factor 2 (Nrf2) by natural chemopreventive compounds in HepG2 human hepatoma cells. J Biochem Mol Biol 2005; 38: 167-176 12 Umemura K, Itoh T, Hamada N, Fujita Y, Akao Y, Nozawa Y, Matsuura N, Iinuma M, Ito M. Preconditioning by sesquiterpene lactone enhances H2O2-induced Nrf2/ARE activation. Biochem Biophys Res Commun 2008; 368: 948-954 13 Kim SK, Cho SB, Moon HI. Neuroprotective effects of a sesquiterpene lactone and flavanones from Paulownia tomentosa Steud. against glutamate-induced neurotoxicity in primary cultured rat cortical cells. Phytother Res 2010; 24: 1898-1900 14 Tukov FF, Anand S, Gadepalli RS, Gunatilaka AA, Matthews JC, Rimoldi JM. Inactivation of the cytotoxic activity of repin, a sesquiterpene lactone from Centaurea repens . Chem Res Toxicol 2004; 17: 1170-1176 15 Bohlmann F, Zdero C. Naturally-occurring terpene derivatives 454. Sesquiterpene lactones and other constituents from Tanacetum parthenium . Phytochemistry 1982; 21: 2543-2549 16 Johnson DA, Andrews GK, Xu W, Johnson JA. Activation of the antioxidant response element in primary cortical neuronal cultures derived from transgenic reporter mice. J Neurochem 2002; 81: 1233-1241 17 Foucault AP. Centrifugal partition chromatography. New York: Marcel Dekker; 1995 18 Kraft AD, Johnson DA, Johnson JA. Nuclear factor E2-related factor 2-dependent antioxidant response element activation by tert-butylhydroquinone and sulforaphane occurring preferentially in astrocytes conditions neurons against oxidative insult. J Neurosci 2004; 24: 1101-1112 19 Majdi M, Liu Q, Karimzadeh G, Malboobi MA, Beekwilder J, Cankar K, de Vos R, Todorovic S, Simonovic A, Bouwmeester H. Biosynthesis and localization of parthenolide in glandular trichomes of feverfew (Tanacetum parthenium L. Schulz Bip.). Phytochemistry 2011; 72: 1739-1750 20 Milbrodt M, Schröder F, König WA. 3,4-β-Epoxy-8-deoxycumambrin B, A sesquiterpene lactone from Tanacetum parthenium . Phytochemistry 1997; 44: 471-474 21 Rey J-P, Levesque J, Louis Pousset J. Extraction and high-performance liquid chromatographic methods for the γ-lactones parthenolide (Chrysanthemum parthenium Bernh.), marrubiin (Marrubium vulgare L.) and artemisinin (Artemisia annua L.). J Chromatogr A 1992; 605: 124-128 22 El-Feraly FS, Chan YM. Isolation and characterization of the sesquiterpene lactones costunolide, parthenolide, costunolide diepoxide, santamarine, and reynosin from Magnolia grandiflora L. J Pharm Sci 1978; 67: 347-350 23 Parodi FJ, Fronczek FR, Fischer NH. Biomimetic transformations of 11, 13-dihydroparthenolide and oxidative rearrangements of a guai-1(10)-en-6, 12-olide. J Nat Prod 1989; 52: 554-566 24 Sanz JF, Barbera O, Marco JA. Sesquiterpene lactones from Artemisia hispanica . Phytochemistry 1989; 28: 2163-2167 25 Romo De Vivar A, Jiménez H. Structure of santamarine, a new sesquiterpene lactone. Tetrahedron 1965; 21: 1741-1745 26 Yoshioka H, Renold W, Fischer NH, Higo A, Mabry TJ. Sesquiterpene lactones from Ambrosia confertiflora (compositae). Phytochemistry 1970; 9: 823-832 27 Asakawa Y, Toyota M, Takemoto T. Two guaiane-type sesquiterpene lactones and their related sesquiterpene lactones from Porella japonica . Phytochemistry 1981; 20: 257-261 28 El-Feraly FS, Chan YM. Peroxycostunolide and peroxyparthenolide: two cytotoxic germacranolide hydroperoxides from Magnolia grandiflora. Structural revision of verlotorin and artemorin. Tetrahedron Lett 1977; 23: 1973-1976 29 Geissman TA. Sesquiterpene lactones of Artemisia – A. verlotorum and A. vulgaris . Phytochemistry 1970; 9: 2377-2381 30 Begley MJ, Hewlett MJ, Knight DW. Revised structures for guaianolide α-methylenebutyrolactones from feverfew. Phytochemistry 1989; 28: 940-943 31 Castaneda-Acosta J, Fischer NH. Biomimetic transformations of parthenolide. J Nat Prod 1993; 56: 90-98 32 Neukirch H, Kaneider NC, Wiedermann CJ, Guerriero A, DʼAmbrosio M. Parthenolide and its photochemically synthesized 1(10)Z isomer: chemical reactivity and structure–activity relationship studies in human leucocyte chemotaxis. Bioorg Med Chem 2003; 11: 1503-1510 Supplementary Material Supplementary Material Supporting Information (PDF)
