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Planta Med 2012; 78(16): 1725-1730
DOI: 10.1055/s-0032-1315241
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Activation of Antioxidant Response Element in Mouse Primary Cortical Cultures with Sesquiterpene Lactones Isolated from Tanacetum parthenium

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
› Author Affiliations
Further Information

Publication History

received 09 June 2012
revised 19 July 2012

accepted 23 July 2012

Publication Date:
24 August 2012 (online)

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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

Tanacetum parthenium - Asteraceae - nuclear factor E2-related factor 2 - antioxidant response element - sesquiterpene lactones - parthenolide - centrifugal partition - chromatography

Supporting Information

 

  • References

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