Analgesic Effect of 5-(3,4-Dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one in Experimental Animal Models of Nociception

Abstract

Curcuminoids derived from turmeric rhizome have been reported to exhibit antinociceptive, antioxidant and anti-inflammatory activities. We evaluated the peripheral and central antinociceptive activities of 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD), a novel synthetic curcuminoid analogue at 0.1, 0.3, 1 and 3 mg/kg (intraperitoneal), through chemical and thermal models of nociception. The effects of DHHPD on the vanilloid and glutamatergic systems were evaluated through the capsaicin- and glutamate-induced paw licking tests. Results showed that DHHPD significantly (p < 0.05) attenuated the writhing response produced by the 0.8% acetic acid injection. In addition, 1 and 3 mg/kg of DHHPD significantly (p < 0.05) reduced the licking time spent by each mouse in both phases of the 2.5% formalin test and increased the response latency of mice on the hot-plate. However, the effect produced in the latter was not reversed by naloxone, a non-selective opioid receptor antagonist. Despite this, DHHPD decreased the licking latency of mice in the capsaicin- and glutamate-induced paw licking tests in a dose response manner. In conclusion, DHHPD showed excellent peripheral and central antinociceptive activities possibly by attenuation of the synthesis and/or release of pro-inflammatory mediators in addition to modulation of the vanilloid and glutamatergic systems without an apparent effect on the opioidergic system.

Anti-Edematogenic and Anti-Granuloma Activity of a Synthetic Curcuminoid Analog, 5-(3,4-Dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one, in Mouse Models of Inflammation

“…No mortalities were recorded over the 7-day test period and the vital organs were normal upon post mortem examination. The results of the acute toxicity study for DHHPD corroborates the findings reported by Kamarudin et al [15].…”

“…), which was used as the reference drug, only caused significant inhibition from 2 h onwards. In addition, DHHPD has been shown to reduce the frequency of abdominal constrictions in the 0.6% acetic acid test and the latency of paw licking in the 2.5% formalin test in mice, suggesting its peripheral mechanism in inhibiting the release of inflammatory mediators responsible for pain [15]. These results indicate that DHHPD may act on the COX enzymes or prostaglandin synthesis from arachidonic acid through a mechanism similar to that of aspirin.…”

“…However, the suppressive effect on edema produced by curcumin alone and by the curcumin–morphine combination was not antagonized by naloxone, indicating a non-opioid-dependent anti-edema effect. In addition, the analgesia induced by DHHPD in the mice models of induced anti-nociception did not involve the opioidergic system [15]. Thus, it appears that curcumin and its analog DHHPD both present anti-edema activity, possibly through a non-opioidergic mechanism.…”

Analgesic potential of dichloromethane leaf extracts of Eucalyptus globulus (Labill) and Senna didymobotrya (Fresenius) in mice models

“…The E. globulus and S. didymobotrya leaf extracts showed significant analgesic effects by reducing pain in mice in the early and late phases. The demonstrated effects were both peripheral and central (23). The central analgesic activity could have been due to inhibition of the nociceptive effects of noradrenaline, bradykinin, prostaglandins, adrenaline, adenosine, serotonin, and acetylcholine.…”

Usnic Acid Potassium Salt: Evaluation of the Acute Toxicity and Antinociceptive Effect in Murine Model

“…Each animal received an intraperitoneal injection of 0.85% ( v / v ) acetic acid in saline and was then placed in a polyethylene box to record the latency period (time until the first writhing) and the number of writhes in the interval corresponding to 5–15 min after the injection of acetic acid (CEEA process N o . 23076.015163/2017-65) [59].…”