Cyane-carvone, a Synthetic Derivative of Carvone, Inhibits Inflammatory Response by Reducing Cytokine Production and Oxidative Stress and Shows Antinociceptive Effect in Mice Thiago Henrique Costa Marques, 1 Maria Leonildes Boavista Gomes Castelo Branco Marques, 1 Jand-Venes R. Medeiros, 2 Renan Oliveira Silva, 2 André Luiz dos Reis Barbosa, 2 Tamires Cardoso Lima, 3 Damião Pergentino de Sousa, 4 and Rivelilson Mendes de Freitas 1,5 Abstract—Cyane-carvone (CC) was studied to elucidate its anti-inflammatory, antinociceptive, and a- ntioxidant effects in Mus musculus. Anti-inflammatory (bradykinin, histamine, prostaglandin E 2 , sero- tonin, and carrageenan) and antinociceptive (acetic acid and formalin) models were utilized. Myelope- roxidase activity, interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), and glutathione (GSH) le- vels were evaluated. Analysis of variance followed by Student-Newman-Keuls’ test was done. Results were compared with control groups (significantly when p <0.05). In bradykinin, histamine, prostaglan- din E 2 , and serotonin tests, 75 mg/kg CC decreased significantly paw edema (t =30, 60, 90, and/or 12- 0 min). In carrageenan test, 50 and 75 mg/kg CC (t =3 h and t =4 h) and 25 mg/kg CC (t =4 h) decreased significantly paw edema. CC (75 mg/kg) inhibited significantly mieloperoxidase activity and decreased IL-1β and TNF-α, and all doses increased GSH levels. CC (75 mg/kg) decreased significantly the nu- mber of contortions of animals and time of licking (phase 2). CC showed anti-inflammatory, antinoci- ceptive, and antioxidant effects in mice. KEY WORDS: anti-inflammatory; antinociceptive; cyane-carvone; mice. INTRODUCTION Inflammation is a response of the body to injury that occurs in an organism, detecting threats and dam- ages [1]. This process occurs as a defensive response, which induces profound physiological adaptations trig- gered in an attempt to limit tissue damage and remove the pathogenic insult. Mechanisms of inflammation involve dilatation of arterioles, venules, and capillaries; exudation of fluids; and leukocyte migration into the inflammatory area [2]. Myeloperoxidase (MPO) is stored in azurophilic granules of polymorphonuclear neutrophils and macro- phages, and this enzyme is involved in the oxidative stress and inflammation [3]. Cytokines are proteins that control inflammatory responses. Two cytokines, tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1, are involved in rheumatoid diseases, such as arthritis. The most studied of the IL-1 proteins are IL-1α and IL-1β, regulated by transcriptional and posttranslational mechanisms or natural competitive antagonist [4]. Several studies associate brain and chronic pain. Neuroimaging modified knowledge of how pain affects the brain. The new notion is that chronic pain as a very complex state in which patterns of sensory system activation are integrated aberrantly with activity in 1 Laboratório de Pesquisa em Neuroquímica Experimental, Curso de Farmácia, Universidade Federal do Piauí, Campus Universitário Ministro Petrônio Portella, Bairro Ininga, 64049-550 Teresina, Piauí, Brazil 2 Laboratory of Experimental Physiopharmacology, Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí (UFPI), Campus of Parnaíba, 64202-020 Parnaíba, PI, Brazil 3 Post-Graduate Program in Pharmaceutics Sciences, Federal University of Sergipe, 49100-000 São Cristóvão, SE, Brazil 4 Department of Pharmaceutical Science, Federal University of Paraiba, University Campus I, Castelo Branco District, 58051-900 João Pessoa, PB, Brazil 5 To whom correspondence should be addressed at Laboratório de Pesquisa em Neuroquímica Experimental, Curso de Farmácia, Universidade Federal do Piauí, Campus Universitário Ministro Petrônio Portella, Bairro Ininga, 64049-550 Teresina, Piauí, Brazil. E-mail: rivmendes@hotmail.com 0360-3997/14/0300-0966/0 # 2014 Springer Science+Business Media New York Inflammation, Vol. 37, No. 3, June 2014 ( # 2014) DOI: 10.1007/s10753-014-9817-1 966