title: Antinociceptive activity of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone, on nociception-induced models in mice.
abstract: This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone (BHMC), using chemical- and thermal-induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose-related inhibition in the acetic acid-induced abdominal constriction test in mice with an ID(50)  of 0.15 (0.13-0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin-induced paw licking test with an ID(50)  of 0.35 (0.27-0.46) mg/kg and 0.07 (0.06-0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot-plate test. Moreover, the antinociceptive effect of the BHMC in the formalin-induced paw licking test and the hot-plate test was antagonized by pre-treatment with the non-selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID(50)  of 0.66 (0.41-1.07) mg/kg and 0.42 (0.38-0.51) mg/kg, respectively. Finally, it was also shown that BHMC-induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Lee
authors.initials: L
authors.lastname: Ming-Tatt
authors.forename: Shaik Ibrahim
authors.initials: SI
authors.lastname: Khalivulla
authors.forename: Muhammad Nadeem
authors.initials: MN
authors.lastname: Akhtar
authors.forename: Azam Shah
authors.initials: AS
authors.lastname: Mohamad
authors.forename: Enoch Kumar
authors.initials: EK
authors.lastname: Perimal
authors.forename: Mohamed Hanief
authors.initials: MH
authors.lastname: Khalid
authors.forename: Ahmad
authors.initials: A
authors.lastname: Akira
authors.forename: Nordin
authors.initials: N
authors.lastname: Lajis
authors.forename: Daud Ahmad
authors.initials: DA
authors.lastname: Israf
authors.forename: Mohd Roslan
authors.initials: MR
authors.lastname: Sulaiman
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D003512:Cyclohexanones / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D023382:Toxicity Tests, Acute
chemical_list: C548340:2,6-bis-4-(hydroxy-3-methoxybenzylidene)cyclohexanone; D000700:Analgesics; D003512:Cyclohexanones; D018836:Inflammation Mediators; D009292:Narcotic Antagonists; D009270:Naloxone; D003474:Curcumin