Antinociceptive and anti-inflammatory activities of curcumin diethyl disuccinate in animals

Abstract

Curcumin diethyl disuccinate (CurDD) is a succinate prodrug of curcumin. We initially determined the antinociceptive property of a range of CurDD doses in the mouse hot-plate test. Hot-plate latencies (cut-off 45 sec) were determined in male ICR mice prior to the administration of 0.9% normal saline solution (NSS; 10 ml/kg, i.p.), morphine (MO; 10 mg/kg, i.p.), 0.5% carboxymethylcellulose (CMC; 10 ml/kg, p.o.) or various doses of CurDD (25-200 mg/kg, p.o.). Hot-plate latencies were subsequently determined at 15, 30, 45, 60, 90, 120 and 240 min. The percent maximum possible effect (%MPE) was calculated and used in the determination of the area of analgesia (%MPE-min). All doses of CurDD tested except 200 mg/kg produced a significant analgesic response. CurDD 50 mg/kg produced analgesic response that was naloxone-sensitive suggesting opioid-mediated mechanism. In the mouse tail-flick test, tail-flick latencies (cut-off 4 sec) were determined prior to the administration of NSS, MO, 0.5% CMC or various doses of CurDD (25-200 mg/kg, p.o.) and were subsequently determined at 7 intervals over a 4 hr period. CurDD 25 mg/kg produced significant analgesic response. In the acetic acid-induced writhing in mice, the animals were induced with i.p. injection of 0.6% acetic acid (10 ml/kg) 1 hr after the administration of NSS, indomethacin (IND; 10 mg/kg, p.o.), 0.5% CMC or various doses of CurDD (25-200 mg/kg, p.o.) and the mean writhing response was determined for 30 min. All doses of CurDD significantly (p<0.05) decreased the mean writhing response compared to vehicle controls. Studies then determined the anti-inflammatory property of orally administered CurDD (10-80 mg/kg) using carrageenan-induced paw edema model in rats. CurDD 10, 40, and 80 mg/kg significantly reduced paw volume during the second phase of edema suggesting inhibition of prostaglandins. Taken together these results demonstrated that CurDD produced both central and peripheral analgesic activities and mechanism of analgesic action seems to be involved with the opioid pathway. The mechanism of anti-inflammatory effect of CurDD involves in the reduction of prostaglandin synthesis and inhibition of prostaglandin E1 effects.