Sesquiterpene lactone containing Mexican Indian medicinal plants and pure sesquiterpene lactones as potent inhibitors of transcription factor NF-kappaB.
The potential inhibitory effect of 54 Mexican Indian medicinal plants on the activation of transcription factor NF-kappaB was studied. Band-shift experiments identified the ethanolic leaf extracts of Artemisia ludoviciana ssp. mexicana, Calea zacatechichi, and Polymnia maculata (all rich in sesquiterpene lactones) as inhibitors of NF-kappaB down to a concentration of 25 microg/ml. The sesquiterpene lactones isohelenin and parthenolide prevented NF-kappaB activation completely as low as 5 microM. Treatment of HeLa cells with leaf extract of A. ludoviciana ssp. mexicana, isohelenin and parthenolide prevented the induction of transcription on the IL-6 promoter. These experiments identify the eudesmanolide and germacranolide type of sesquiterpene lactones as potent non-antioxidant inhibitors of NF-kappaB. All plants active in the NF-kappaB assay also showed a delay in the onset of capillary reactions of the allantois membrane in a physiological model for anti-inflammatory activity - the HET-CAM assay.
Bork
P M
PM
Institute of Pharmaceutical Biology, Albert-Ludwigs University, Freiburg, Germany.
Schmitz
M L
ML
Kuhnt
M
M
Escher
C
C
Heinrich
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002196:Capillaries / Q000187:drug effects; D002642:Chick Embryo; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D051863:Host Cell Factor C1; D006801:Humans; D007198:Indians, North American; D015850:Interleukin-6 / Q000235:genetics; D007783:Lactones / Q000494:pharmacology*; D008519:Medicine, Traditional; D008800:Mexico; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D050811:Octamer Transcription Factor-1; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D012717:Sesquiterpenes / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D015850:Interleukin-6; D007783:Lactones; D016328:NF-kappa B; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D010936:Plant Extracts; D012717:Sesquiterpenes; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C103906:isohelenin; D004247:DNA