Antinociceptive activity of a synthetic curcuminoid analogue, 5-(3, 4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl) penta-2,4-dien-1-one in mice

Curcuminoids, including curcumin, are low in bioavailability and solubility, limiting their usage in bioassays and therapeutic interventions. Hence, curcuminoid analogues with better bioavailability and solubility were synthesized. This study was designed to evaluate the antinociceptive activities of a synthetic curcuminoid analogue, 5-(3,4- dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD) via the mouse models of induced nociception. Adult male ICR mice were administered with DHPPD (0.1, 0.3, 1 and 3mg/kg) intraperitoneally (i.p.) 30 min prior to 0.8% acetic acid injection (i.p.), and the frequencies of abdominal constrictions were recorded. Separately, mice which received DHHPD at the same doses were subjected to the hot plate test and the response latency recorded. The response of DHHPDtreated mouse to 2.5% formalin (i.p.) was recorded at 5 min interval over a period of 30 min. Possible involvements of the opioidergic, vanilloid and glutamatergic systems were evaluated through the hot plate test, capsaicin- and glutamate-induced paw licking tests, respectively. The sedative effect of DHHPD was determined through the Rotarod test. Results showed that DHHPD (0.1, 0.3, 1 and 3mg/kg, i.p.) significantly (p<0.0001) inhibited the abdominal constrictions by 45.9, 74.9, 90.7 and 97.3%, respectively, indicating a possible pain modulating activity at the peripheral level. Additionally, DHHPD at 1 and 3mg/kg (i.p.) significantly prolonged (p<0.05) the response latency of mice on the hot plate, suggesting its centrally-mediated activity. DHHPD (0.1, 0.3, 1 and 3 mg/kg, i.p.) also significantly inhibited (p<0.05) the paw licking behaviour during the neurogenic/early and inflammatory/late phases of the formalin test, thus confirming its pain modulating activity at the central and peripheral levels. The central antinociceptive activity produced by DHHPD was not antagonized by naloxone, indicating a non-involvement of the opioidergic system. Additionally, DHHPD at 0.1, 0.3, 1 and 3 mg/kg (i.p.) significantly (p<0.05) inhibited the capsaicinand glutamate-induced paw licking behaviour, suggesting involvement of the vanilloid and glutamatergic systems in DHHPD-induced analgesia. Furthermore, DHHPD (0.1,0.3, 1 and 3 mg/kg, i.p.) did not induce any sedative effects, abnormal behaviour or mortality in mice. In conclusion, DHHPD (1 and 3 mg/kg, i.p.) exerted significant (p<0.05) antinociceptive activities at the central and peripheral levels possibly through the vanilloid and glutamatergic systems.

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