Together, the present results suggested that EOZZ-induced antinociceptive activity was possibly related to its ability to inhibit glutamatergic system, TRPV1 receptors as well as through activation of l-arginine/nitric oxide/cGMP/protein kinase C/ATP-sensitive K(+) channel pathway.
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.
Pain is one of the most common cause for hospital visits. It plays an important role in inflammation and serves as a warning sign to avoid further injury. Analgesics are used to manage pain and provide comfort to patients. However, prolonged usage of pain treatments like opioids and NSAIDs are accompanied with undesirable side effects. Therefore, research to identify novel compounds that produce analgesia with lesser side effects are necessary. The present study investigated the antinociceptive potentials of a natural compound, cardamonin, isolated from Boesenbergia rotunda (L) Mansf. using chemical and thermal models of nociception. Our findings showed that intraperitoneal and oral administration of cardamonin (0.3, 1, 3, and 10 mg/kg) produced significant and dose-dependent inhibition of pain in abdominal writhing responses induced by acetic acid. The present study also demonstrated that cardamonin produced significant analgesia in formalin-, capsaicin-, and glutamate-induced paw licking tests. In the thermal-induced nociception model, cardamonin exhibited significant increase in response latency time of animals subjected to hot-plate thermal stimuli. The rota-rod assessment confirmed that the antinociceptive activities elicited by cardamonin was not related to muscle relaxant or sedative effects of the compound. In conclusion, the present findings showed that cardamonin exerted significant peripheral and central antinociception through chemical- and thermal-induced nociception in mice through the involvement of TRPV1, glutamate, and opioid receptors.
The possible mechanisms of action in the antinociceptive activity induced by systemic administration (intraperitoneal, i.p.) of flavokawin B (FKB) were analysed using chemical models of nociception in mice. It was demonstrated that i.p. administration of FKB to the mice at 0.3, 1.0, 3.0 and 10 mg ⁄ kg produced significant dose-related reduction in the number of abdominal constrictions. The antinociception induced by FKB in the acetic acid test was significantly attenuated by i.p. pretreatment of mice with L-arginine, the substrate for nitric oxide synthase or glibenclamide, the ATP-sensitive K + channel inhibitor, but was enhanced by methylene blue, the non-specific guanylyl cyclase inhibitor. FKB also produced dose-dependent inhibition of licking response caused by intraplantar injection of phorbol 12-myristate 13-acetate, a protein kinase C activator (PKC). Together, these data indicate that the NO ⁄ cyclic guanosine monophosphate ⁄ PKC ⁄ ATP-sensitive K + channel pathway possibly participated in the antinociceptive action induced by FKB.Chalcones or 1,3-diaryl-2-propen-1-ones are a well-known class of flavonoids that have been reported to possess both in vitro and in vivo biological activities including antimicrobial, anticancer, antiprotozoal, antiplatelet, antinociceptive and anti-inflammatory [1][2][3][4][5][6]. It has been reported elsewhere that chalcones and their derivatives inhibited the synthesis of nitric oxide (NO), lipoxygenase as well as cyclo-oxygenase activities which constitute the major pro-inflammatory pathways and remain most targeted for anti-inflammatory and antinociceptive drug development [7][8][9][10].In attempts to obtain active derivatives from chalcone that possesses anti-inflammatory and antinociceptive activities, our group previously isolated 6¢-hydroxy-2¢,4¢-dimethoxychalcone or flavokawin B (FKB) from Alpinia nutans Rosc. along with other chalcones such as cardamonin (6), 5,6-dehydrokawain, (-)-pinocembrin, (-)-pinostrobin and 2¢,3¢,4¢,6¢-tetrahydroxychalcone [11]. Recently, we chemically synthesized FKB and demonstrated that systemic administration of FKB exerted potent dose-dependent antinociceptive activity when assessed in the chemical and thermal models of nociception in mice, indicating involvement of the peripheral and central antinociceptive activities [12]. Moreover, in the same study, we demonstrated that the central antinociceptive activity of FKB was not mediated by the activation of opioid receptors. Besides, we also demonstrated that FKB produced marked inhibition of the nociceptive response caused by intraplantar injection of glutamate into mouse hind paw in the glutamate-induced nociception test and perhaps the inhibition of peripheral N-Methyl-D-aspartic acid (NMDA) receptors contributes to the antinociceptive effect of FKB [12]. As activation of the NO cascade is known to take place secondary to NMDA receptor activation and a great deal of evidence has demonstrated the role of NO in various models of nociception [13][14][15][16], this has led to the ...
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