title: Dual inhibition of 5-lipoxygenase/cyclooxygenase by a reconstituted homeopathic remedy; possible explanation for clinical efficacy and favourable gastrointestinal tolerability.
abstract: OBJECTIVE
  In order to elucidate potential anti-inflammatory activities of Zeel comp. N and its constituents, the inhibition of the synthesis of Leukotriene B4 (LTB4) and Prostaglandin (PGE2) by 5-lipoxygenase (5-LOX) and cyclo-oxygenase 1 and 2 (COX 1 and 2) respectively were examined in vitro.
  
  
  METHODS
  Human HL-60 cells, differentiated for 6-8 days with DMSO (1.2% v/v) were used for the 5-LOX assay. The COX activity assays were carried out with purified enzymes, COX 1 (ram seminal vesicles), COX 2 (sheep placenta) and with human THP-1 cells, differentiated for 24 h with PMA (50 nM).
  
  
  METHODS
  LTB4 and PGE2 production in the 5-LOX and COX assays respectively were determined by enzyme linked immunoassays.
  
  
  RESULTS
  A reconstituted Zeel comp. N combination as well as its constituent mother tinctures of Arnica montana, Sanguinaria canadensis and Rhus toxicodendron (Toxicodendron quercifolium) showed distinct inhibitory effects on the production of LTB4 by 5-LOX (IC50 values of 10, 20, 2 and 5 microg/ml respectively) and on the synthesis of PGE2 by COX 1 (IC50 values of 50, 80, 40 and 20 microg/ml respectively) and COX 2 enzymes (IC50 values of 60, 110, 50 and 20 microg/ml respectively). The mother tincture of Solanum dulcamara inhibited the production of PGE2 by COX 1 (IC50 40 microg/ml) and COX 2 (IC50 150 microg/ml) but not production of leukotriene LTB4 by 5-LOX.
  
  
  CONCLUSIONS
  The observed dual inhibition of both LOX- and COX-metabolic pathways may offer an explanation for the reported clinical efficacy and the favorable gastrointestinal tolerability of the original remedy Zeel comp. N.
authors.affiliation: VitaPlant AG, Benkenstrasse 254, 4108 Witterswil, Switzerland. rjaeggi@vitaplant.ch
authors.forename: R
authors.initials: R
authors.lastname: Jäggi
authors.forename: U
authors.initials: U
authors.lastname: Würgler
authors.forename: F
authors.initials: F
authors.lastname: Grandjean
authors.forename: M
authors.initials: M
authors.lastname: Weiser
mesh_terms: D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004064:Digestive System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008419:Materia Medica / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D011453:Prostaglandins / Q000096:biosynthesis
chemical_list: D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D008419:Materia Medica; D011453:Prostaglandins; D007975:Leukotriene B4