Planta Med 2000; 66(7): 591-595
DOI: 10.1055/s-2000-8649
Original Paper
Georg Thieme Verlag Stuttgart · New York

Inhibition of the Transcription Factor NF-κB by Sesquiterpene Lactones from Podachaenium eminens1

Victor Castro2 , Renato Murillo2 , Christoph A. Klaas3 , Constanze Meunier3 , Gerardo Mora4 , Heike L. Pahl5 , Irmgard Merfort3,*
  • 1 Part IV in the series “Phytochemical and Biological Studies of Costa Rican Asteraceae”
  • 2 Universidad de Costa Rica, Escuela de Quimica, CIPRONA, San José, Costa Rica
  • 3 Institute of Pharmaceutical Biology, University of Freiburg, Germany
  • 4 Universidad de Costa Rica, Facultad de Farmacia, CIPRONA, San José, Costa Rica
  • 5 Department of Experimental Anaesthesiology, University Hospital, Freiburg, Germany
Further Information

Publication History

Publication Date:
31 December 2000 (online)

Abstract

Investigation of Podachaenium eminens afforded nine sesquiterpene lactones (Sls) from which costunolide, 7-hydroxycostunolide, santamarin as well as 3-chlorodehydroleucodin are new for this plant and 3,4-dehydro-4-dehydroxypodachaenin (= 3-costoyloxydehydroleucodin) is found for the first time in nature. All isolated Sls were studied for their anti-inflammatory activity using the transcription factor NF-κB as a molecular target. NF-κB is involved in the synthesis of inflammatory mediators, such as cytokines and chemokines. Except for podachaenin, all compounds completely inhibited NF-κB DNA binding in an electrophoretic mobility shift assay at concentrations between 5 and 200 μM without showing any cytotoxic effects. 3,4-Epoxydehydroleucodin possessing an α-methylene-γ-butyrolactone and a second reactive structure element by its epoxy ring α,β to a carbonyl group was most active. Although the majority of the Sls tested in this study were monofunctional only low concentrations of 50 μM were often needed for complete inhibition. Possible reasons are discussed for this result.

Abbreviations

BSA:bovine serum albuminc.p.m.:counts per minuteDTT:dithiothreitolEDTA:ethylenediaminetetraacetic acidEGTA:ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acidFCS:fetal calf serumHEPES:N-[2-hydroxyethyl]piperazine-N′-[2-ethanesul-fonic acid]NP-40:nonylphenoxypolyethoxyethanolPBS:phosphate buffered salinePMSF:phenylmethanesulfonyl fluoridePoly (dI-dC):polydeoxyinosinicdeoxycytidylic acid, double-stranded alternating copolymer

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Prof. Dr. Irmgard Merfort

Institute of Pharmaceutical Biology

Schänzlestr. 1

79104 Freiburg

Germany

Email: merfort@sun2.ruf.uni-freiburg.de

Phone: +49761-2032803