title: Physio-pharmacological Investigations About the Anti-inflammatory and Antinociceptive Efficacy of (+)-Limonene Epoxide.
abstract: D-limonene epoxidation generates (+)-limonene epoxide, an understudied compound in the pharmacologically point of view. Herein, we investigated the anti-inflammatory and antinociceptive potentialities of (+)-limonene epoxide and suggested a mechanism of action. The anti-inflammatory potential was analyzed using agents to induce paw edema, permeability, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines and cell migration of peritoneal cells were also assessed. Antinociceptive effects were evaluated by writhing test induced by acetic acid, formalin, and hot plate assays and contribution of opioid pathways. Pretreated animals with (+)-limonene epoxide showed reduced carrageenan-induced paw edema in all doses (25, 50, and 75 mg/kg) (P < 0.05). At 75 mg/kg, it suppressed edema provoked by compound 48/80, histamine, prostaglandin E2, and serotonin and reduced permeability determined by Evans blue and MPO activity. It also reduced leukocytes, neutrophils, and IL-1β levels in the peritoneal cavity in comparison with carrageenan group (P < 0.05). (+)-Limonene epoxide diminished abdominal contortions induced by acetic acid (78.9%) and paw licking times in both 1 (41.8%) and 2 (51.5%) phases and a pretreatment with naloxone (3 mg/kg) reverted the antinociceptive action in morphine- and (+)-limonene epoxide-treated groups (P < 0.05). Additionally, it enlarged response times to the thermal stimulus after 60 and 90 min. In conclusion, (+)-limonene epoxide inhibited release/activity of inflammatory mediators, vascular permeability, migration of neutrophils and displayed systemic and peripheral analgesic-dependent effects of the opioid system.
authors.affiliation: Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Brazil.
authors.forename: Antonia Amanda Cardoso
authors.initials: AA
authors.lastname: de Almeida
authors.affiliation: Laboratory of Pharmacology of Inflammation and Cancer, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Renan Oliveira
authors.initials: RO
authors.lastname: Silva
authors.affiliation: Laboratory of Pharmacology of Inflammation and Cancer, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Lucas Antonio Duarte
authors.initials: LA
authors.lastname: Nicolau
authors.affiliation: Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Brazil.|Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, Brazil.
authors.forename: Tarcísio Vieira
authors.initials: TV
authors.lastname: de Brito
authors.affiliation: Department of Pharmacy, Federal University of Paraíba, João Pessoa, Brazil.
authors.forename: Damião Pergentino
authors.initials: DP
authors.lastname: de Sousa
authors.affiliation: Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Brazil.|Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, Brazil.
authors.forename: André Luiz Dos Reis
authors.initials: AL
authors.lastname: Barbosa
authors.affiliation: Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Brazil.|Department of Pharmacy, Federal University of Piauí, Teresina, Brazil.
authors.forename: Rivelilson Mendes
authors.initials: RM
authors.lastname: de Freitas
authors.affiliation: Department of Biophysics and Physiology, Federal University of Piauí, Teresina, Brazil.
authors.forename: Luciano da Silva
authors.initials: LD
authors.lastname: Lopes
authors.affiliation: Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Brazil.|Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Parnaíba, Brazil.
authors.forename: Jand-Venes Rolim
authors.initials: JR
authors.lastname: Medeiros
authors.affiliation: Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Brazil. pmpf@ufpi.edu.br.|Department of Biophysics and Physiology, Federal University of Piauí, Teresina, Brazil. pmpf@ufpi.edu.br.
authors.forename: Paulo Michel Pinheiro
authors.initials: PM
authors.lastname: Ferreira
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D000081005:Cyclohexane Monoterpenes; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D018836:Inflammation Mediators; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D009504:Neutrophils / Q000166:cytology; D010146:Pain / Q000188:drug therapy
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000081005:Cyclohexane Monoterpenes; D018836:Inflammation Mediators; D039821:Monoterpenes; C028940:limonene-1,2-epoxide
keywords: analgesia; cell migration inhibition; cytokine reduction; opioid system involvement; semisynthetic compound