Antinociceptive and anti-arthritic effects of kramecyne

The aim of this study was to evaluate the antinociceptive (acute assays) and anti-inflammatory (chronic assays) effects of kramecyne (KACY), a peroxide isolated from Krameria cytisoides.

The antinociceptive activity of KACY was evaluated using the hot plate, acetic acid and formalin tests. The effects of KACY on heat-induced hemolysis in rat erythrocytes were also evaluated. The in vivo anti-inflammatory assays were performed using the chronic TPA (12-O-tetradecanoylphorbol 13-acetate) method to induce ear edema and carrageenan-kaolin induced arthritis (CKIA). In the CKIA model, the hot plate test was performed, serum samples were obtained for the quantitation of pro-inflammatory (IL-1β, IL-6, IL-12 and TNF-α) and anti-inflammatory (IL-4 and IL-10) cytokines.

KACY possess antinociceptive effects with comparable activity to naproxen (NPX). KACY inhibited hemolysis (EC50 = 180 μg/mL), in comparison to the untreated group and with a higher potency than NPX (EC50 = 263 μg/mL). KACY at 50 mg/kg decreased inflammation by 38% (chronic TPA-induced edema model) and by 26% (CKIA model), in comparison with the vehicle group and with similar activity to the positive controls 8 mg/kg indomethacin (IND) and 1 mg/kg methotrexate (MTX), respectively. In the CKIA model, KACY increased the release of anti-inflammatory (IL-4 and IL-10) cytokines but reduced the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-12 and TNF-α). KACY at 50 and 100 mg/kg showed antinociceptive effects by 27% and 23%, respectively, in mice with mono-arthritis.

KACY might be a good alternative for the treatment of rheumatoid arthritis (RA) due its antinociceptive and anti-inflammatory activities.