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.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.Received 10 April 2003; returned for revision 27 May 2003; accepted by W. B. van den Berg 24 November 2003