Abstract
Curcumin and its analogues exhibited anti-inflammatory activity in different experimental models. Recently, we synthesized (2E,3E)-3-buten-2-one-4-(4-hydroxy-3-methoxyphenyl)-2-(4-(4-methoxyphenyl)-2-thiazolyl)hydrazone (RI75), a curcumin analogue with a thiazolyl hydrazone moiety. In the present study, we investigated the effects induced by RI75 in different models of inflammation and pain in mice, as well as some underlying mechanisms. Pre-treatment with RI75 (40 mg/kg, intraperitoneal; i.p.) or curcumin (40 mg/kg, i.p.) reduced the mechanical allodynia and paw edema induced by intraplantar (i.pl) injection of carrageenan. RI75 antiallodynic activity was reduced by pre-treatment with naltrexone (5 and 10 mg/kg, i.p.) and cyproheptadine (10 mg/kg, i.p.), but not glibenclamide (20 and 40 mg/kg, i.p.). In a model of neuropathic pain, a single i.p. administration of RI75 (40 mg/kg) or curcumin (40 mg/kg) attenuated the ongoing mechanical allodynia induced by repeated administrations of paclitaxel. Pre-treatment with RI75 (40 mg/kg, i.p.) or curcumin (40 mg/kg, i.p.) also reduced tumor necrosis factor-α and interleukin-6 production and myeloperoxidase activity induced by carrageenan. The results of the present study demonstrate that RI75, a synthetic curcumin analogue, exhibits antiallodynic and antiedematogenic activities. Activation of opioidergic and serotonergic mechanisms and reduced production of inflammatory mediators and neutrophil recruitment may underlie RI75 activities.
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We thank Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; 303307/2018-8), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; Finance Code 001), and Pró-Reitoria de Pesquisa/UFMG for financial support and scholarship.
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Costa, S.O.A.M., Rodrigues, I.B., Braga, A.V. et al. RI75, a curcumin analogue, inhibits tumor necrosis factor-α and interleukin-6 production and exhibits antiallodynic and antiedematogenic activities in mice. Inflammopharmacol 30, 505–515 (2022). https://doi.org/10.1007/s10787-021-00913-9
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DOI: https://doi.org/10.1007/s10787-021-00913-9