title: Effects of 20-hydroxyecdysone, Leuzea carthamoides extracts, dexamethasone and their combinations on the NF-κB activation in HeLa cells.
abstract: OBJECTIVE
  The plant steroid 20-hydroxyecdysterone (20E) and 20E-containing extracts from Leuzea carthamoides (Willd.) DC are sold with claims of anabolic and immunomodulatory effects. Yet their effect on the activation of nuclear factor kappa B (NF-κB), a key player in immune response and cell fate, and their influence on the NF-κB-inhibiting activity of steroidal anti-inflammatory drugs is still unknown.
  
  
  METHODS
  The ability of 20E, Leuzea extracts and selected steroidal/non-steroidal anti-inflammatory drugs to influence the activation of NF-κB was explored using, as the experimental model, human cervical cancer HeLa-IL-6 cells stably transfected with an IL-6-bound reporter gene. Effects on cell viability and proliferation were monitored (MTT assay). HPLC-DAD was used to establish links between chemical patterns of Leuzea extracts and their bioactivities.
  
  
  RESULTS
  20E inhibited NF-κB activation (IC50 31.8 µm) but was less active than other plant metabolites (xanthohumol 3.8 µm, withaferin A 1.4 µm). Leuzea extracts with high content in 20E had a fair activating effect, but in contrast, some extracts with low 20E content significantly inhibited NF-κB activation at IC50s ranging from 3.5 to 6.2 µg/ml. Combination tests confirmed that 20E does not explain the NF-κB modulation achieved by Leuzea extracts. The extracts but not 20E itself showed a significant modulation of the NF-κB inhibitory effect of dexamethasone.
  
  
  CONCLUSIONS
  20E is unlikely a major player in the NF-κB inhibitory effects displayed by some Leuzea extracts in vitro. If confirmed in vivo, caution should prevail towards marketed Leuzea extracts that are non-standardised or standardised on 20E only, since different starting materials and extracts may even cause opposite effects. More importantly, our results indicate the interaction potential of Leuzea with steroidal anti-inflammatory drugs.
authors: Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London, London, UK. wieland.peschel@ema.europa.eu
authors: Wieland
authors: W
authors: Peschel
authors: Alfred
authors: A
authors: Kump
authors: José Maria
authors: JM
authors: Prieto
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004338:Drug Combinations; D004441:Ecdysterone / Q000494:pharmacology*; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D043843:Leuzea / Q000737:chemistry*; D016328:NF-kappa B / Q000378:metabolism*; D028321:Plant Preparations / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D016328:NF-kappa B; D028321:Plant Preparations; D004441:Ecdysterone; D003907:Dexamethasone