Dual inhibition of 5-lipoxygenase/cyclooxygenase by a reconstituted homeopathic remedy; possible explanation for clinical efficacy and favourable gastrointestinal tolerability
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- Jäggi, R., Würgler, U., Grandjean, F. et al. Inflamm. res. (2004) 53: 150. doi:10.1007/s00011-003-1236-y
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.
Materials: 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 µg/ml respectively) and on the synthesis of PGE2 by COX 1 (IC50 values of 50, 80, 40 and 20 µg/ml respectively) and COX 2 enzymes (IC50 values of 60, 110, 50 and 20 µg/ml respectively). The mother tincture of Solanum dulcamara inhibited the production of PGE2 by COX 1 (IC50 40 µg/ml) and COX 2 (IC50 150 µg/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.