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 B-4 (LTB4) and Prostaglandin (PGE(2)) by 5-lipoxygenase (5-LOX) and cyclooxygenase I and 2 (COX I 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 I (ram seminal vesicles), COX 2 (sheep placenta) and with human THP-1 cells, differentiated for 24 h with PMA (50 nM). Methods: LTB4 and PGE(2) 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 mug/ml respectively) and on the synthesis of PGE(2) by COX 1 (IC50 values of 50, 80, 40 and 20 mug/ml respectively) and COX 2 enzymes (IC50 values of 60, 110, 50 and 20 mug/ml respectively). The mother tincture of Solanum dulcamara inhibited the production of PGE(2) by COX 1 (lC(50) 40 mug/ml) and COX 2 (IC50 150 mug/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.