title: Nerolidol exhibits antinociceptive and anti-inflammatory activity: involvement of the GABAergic system and proinflammatory cytokines.
abstract: Nerolidol, an acyclic sesquiterpene found as a major constituent of several essential oils, has several pharmacological activities, but its action in pain processes has never been studied. The purpose of our research was to evaluate the antinociceptive and anti-inflammatory activities of nerolidol, as well as possible mechanisms of action, in experimental mouse models of pain. Antinociceptive activity was evaluated using the acetic acid-induced writhing test, the formalin test, and the hot-plate test. The nerolidol-treated group showed lesser acetic acid-induced abdominal contractions than the control group in all of the three doses tested (200, 300, and 400 mg/kg, p.o.). The formalin test doses of 300 and 400 mg/kg p.o. inhibited licking time, in both the first phase and the second phase. In the hot-plate test, nerolidol did not alter latency at any of the observed time points. Motor coordination, evaluated through the rotarod test, was not hindered in animals treated with nerolidol. Regarding the mechanism of action, the antinociceptive activity of nerolidol is related to the GABAergic system, and not to the opioidergic or ATP-sensitive K(+) channels. Treatment with nerolidol reduced carrageenan-induced paw edema. In the model of carrageenan-induced peritonitis, nerolidol decreased the influx of polymorphonuclear cells and also reduced levels of tumor necrosis factor (TNF-α) in peritoneal lavage. Nerolidol reduced production of interleukin 1 beta (IL-1β) in LPS-stimulated, peritoneal macrophages. Thus, these results showed that nerolidol has antinociceptive activity with possible involvement of the GABAergic system, and anti-inflammatory activity, attributed to the suppression of TNF-α and IL-1β proinflammatory cytokines.
authors.affiliation: Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB), Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.|Laboratory of Psychopharmacology, Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.
authors.forename: Diogo V
authors.initials: DV
authors.lastname: Fonsêca
authors.affiliation: Laboratory of Psychopharmacology, Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.
authors.forename: Paula R R
authors.initials: PR
authors.lastname: Salgado
authors.affiliation: Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB), Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.|Laboratory of Psychopharmacology, Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.
authors.forename: Fabíola L
authors.initials: FL
authors.lastname: de Carvalho
authors.affiliation: Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB), Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.|Laboratory of Psychopharmacology, Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.
authors.forename: Mirian Graciela S S
authors.initials: MG
authors.lastname: Salvadori
authors.affiliation: Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB), Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.|Laboratory of Psychopharmacology, Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.
authors.forename: Antônia Rosângela S
authors.initials: AR
authors.lastname: Penha
authors.affiliation: Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB), Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.|Laboratory of Immunology, University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.
authors.forename: Fagner C
authors.initials: FC
authors.lastname: Leite
authors.affiliation: Laboratory of Psychopharmacology, Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.
authors.forename: Clóvis José S
authors.initials: CJ
authors.lastname: Borges
authors.affiliation: Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB), Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.|Laboratory of Immunology, University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.
authors.forename: Marcia R
authors.initials: MR
authors.lastname: Piuvezam
authors.affiliation: Laboratory of Psychopharmacology, Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.
authors.forename: Liana Clébia de Morais
authors.initials: LC
authors.lastname: Pordeus
authors.affiliation: Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB), Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.|Laboratory of Psychopharmacology, Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.
authors.forename: Damião P
authors.initials: DP
authors.lastname: Sousa
authors.affiliation: Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB), Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.|Laboratory of Psychopharmacology, Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.
authors.forename: Reinaldo N
authors.initials: RN
authors.lastname: Almeida
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy / Q000276:immunology; D054086:KATP Channels / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010538:Peritonitis / Q000188:drug therapy / Q000276:immunology; D011963:Receptors, GABA-A / Q000378:metabolism*; D045442:Rotarod Performance Test; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D054086:KATP Channels; D011963:Receptors, GABA-A; D012717:Sesquiterpenes; C037055:nerolidol
keywords: Nerolidol; anti-inflammatory; antinociception; sesquiterpene