Antiinflammatory profile of Harpagophytum procumbens crude extract and after its external metabolic activation in THP-1 monocytic cells in vitro

Harpagophytum procumbens (Devil's Claw; DCE) has demonstrated anti-inflammatory effects in animal models and clinical efficacy in osteoarthritis. In the present investigations we used an in vitro model based on human THP-1 cells to evaluate the effect of crude DCE and after metabolic activation (DCEm) with S9 mix from Aroclor-induced rat livers on a panel of 12 inflammatory cytokine/chemokine using Multi-Analyte ELISArray Kits (SABiosciences, Frederick, USA) and the single cytokine ELISAs (TNF-α, IL-6, IL-8). Cytokine productions were induced in THP-1 cells by 25µg/ml LPS and the effect of DCE dry extract (DER 1.5–3:1; 60% ethanol, Bioforce AG) at concentrations (0–250µg/ml) was investigated after 24h treatment. In addition, the effect of DCE after simulated liver metabolism by S9 mix was compared. As positive controls 10–7M dexamethasone and 10µg/ml cyclophosphamide were used. All concentrations of DCE exerted no cytotoxicity as measured by WST-1 assay (IC50=1.25mg/ml). Both DCE extracts inhibited dose-dependently the secretion of TNF-α. The highest concentration (250µg/ml) inhibited the release of TNF-α by about 80%. IC50 beeing 98µg/ml and 47µg/ml for DCE and DCEm. IL-8 and IL-6 secretion were moderately inhibited by about 25% at concentration of 50–100µg/ml of DCE. The inhibitory effect on TNF- α release in THP-1 cells have been increased in the presence of metabolic activated DCEm as mirrored in their IC50 values. Our data suggest that proprietary DCE is an inhibitor of proinflammatory cytokines and that metabolic activation seems to play an important role in this effect.