Dual inhibition of 5-lipoxygenase/cyclooxygenase by a reconstituted homeopathic remedy; possible explanation for clinical efficacy and favourable gastrointestinal tolerability.
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.
Jäggi
R
R
VitaPlant AG, Benkenstrasse 254, 4108 Witterswil, Switzerland. rjaeggi@vitaplant.ch
Würgler
U
U
Grandjean
F
F
Weiser
M
M
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
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D008419:Materia Medica; D011453:Prostaglandins; D007975:Leukotriene B4