title: Alteration of anti-inflammatory activity of Harpagophytum procumbens (devil's claw) extract after external metabolic activation with S9 mix.
abstract: OBJECTIVE
  Extracts of the tubers of Harpagophytum procumbens (devil's claw, DC) inhibit different proinflammatory mediators important in the pathophysiology of osteoarthritis. Many plant-derived preparations interfere with cytochrome P450 liver enzymes, which influence their different biological activities. Therefore, the present study was designed to investigate the influence of an external metabolic activation of a DC extract on the cytotoxicity and the release of proinflammatory cytokines.
  
  
  METHODS
  A screening experiment with a panel of 12 inflammatory cytokines identified three as suitable for the study: tumour necrosis factor-α (TNF-α), interleukin (IL) IL-6 and IL-8. They were determined using enzyme-linked immunosorbent assays in lipopolysaccharide (LPS)-stimulated monocytic THP-1 cells, which were treated with rat liver S9 mix metabolically activated DC extract (DCm). For the cytotoxity experiments, a WST-1 assay was used.
  
  
  RESULTS
  DC dose-dependently suppressed the release of TNF-α, IL-6 and IL-8 in LPS-stimulated monocytic THP-1 cells at non-cytotoxic concentrations (50-250 μg/ml). The metabolic activation of the DC extract by S9 mix did not alternate its cytotoxicity and did not diminish its inhibitory effect. This effect was improved in the case of TNF-α inhibition as reflected by their EC50 values of 116 ± 8.2 μg/ml and 49 ± 3.5 μg/ml for DC and DCm (P < 0.01).
  
  
  CONCLUSIONS
  Cytokines inhibitory activity of DC was not affected after its external metabolic activation. However, the amount of harpagoside and caffeic acid derivates was decreased. Other components of the extract might have contributed to its anti-inflammatory effect.
authors.affiliation: Institute for Complementary Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Katarina
authors.initials: K
authors.lastname: Hostanska
authors.forename: Joerg
authors.initials: J
authors.lastname: Melzer
authors.forename: Matthias
authors.initials: M
authors.lastname: Rostock
authors.forename: Andy
authors.initials: A
authors.lastname: Suter
authors.forename: Reinhard
authors.initials: R
authors.lastname: Saller
mesh_terms: D065767:Activation, Metabolic; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology*; D002109:Caffeic Acids / Q000378:metabolism / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006027:Glycosides / Q000378:metabolism / Q000494:pharmacology; D031684:Harpagophytum / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000201:enzymology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology*; D035281:Plant Tubers; D011714:Pyrans / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D002109:Caffeic Acids; D016207:Cytokines; D006027:Glycosides; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D010936:Plant Extracts; D011714:Pyrans; D014409:Tumor Necrosis Factor-alpha; C033249:harpagoside; D003577:Cytochrome P-450 Enzyme System; C040048:caffeic acid
keywords: S9 mix; THP-1 cells; devil's claw extract; proinflammatory cytokines