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Inflammation

, Volume 40, Issue 2, pp 511–522 | Cite as

Physio-pharmacological Investigations About the Anti-inflammatory and Antinociceptive Efficacy of (+)-Limonene Epoxide

  • Antonia Amanda Cardoso de Almeida
  • Renan Oliveira Silva
  • Lucas Antonio Duarte Nicolau
  • Tarcísio Vieira de Brito
  • Damião Pergentino de Sousa
  • André Luiz dos Reis Barbosa
  • Rivelilson Mendes de Freitas
  • Luciano da Silva Lopes
  • Jand-Venes Rolim Medeiros
  • Paulo Michel Pinheiro Ferreira
ORIGINAL ARTICLE

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.

KEY WORDS

semisynthetic compound cell migration inhibition cytokine reduction analgesia opioid system involvement 

Notes

ACKNOWLEDGEMENTS

We wish to thank the Federal Brazilian agency “Conselho Nacional de Desenvolvimento Científico e Tecnológico” (CNPq) for financial support in the form of grants (#473167/2012-3) and fellowships.

COMPLIANCE WITH ETHICAL STANDARDS

All procedures were approved by the Committee on Animal Research at the UFPI (Process no. 091/2014) and followed the Brazilian (Colégio Brasileiro de Experimentação Animal—COBEA) and International Standards on the care and use of experimental animals (Directive 2010/63/EU of the European Parliament and of the Council).

Conflict of Interest

The authors declare that there are no conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Antonia Amanda Cardoso de Almeida
    • 1
  • Renan Oliveira Silva
    • 2
  • Lucas Antonio Duarte Nicolau
    • 2
  • Tarcísio Vieira de Brito
    • 1
    • 3
  • Damião Pergentino de Sousa
    • 4
  • André Luiz dos Reis Barbosa
    • 1
    • 3
  • Rivelilson Mendes de Freitas
    • 1
    • 5
  • Luciano da Silva Lopes
    • 6
  • Jand-Venes Rolim Medeiros
    • 1
    • 3
  • Paulo Michel Pinheiro Ferreira
    • 1
    • 6
  1. 1.Postgraduate Program in BiotechnologyFederal University of PiauíTeresinaBrazil
  2. 2.Laboratory of Pharmacology of Inflammation and Cancer, Faculty of MedicineFederal University of CearáFortalezaBrazil
  3. 3.Biotechnology and Biodiversity Center Research (BIOTEC)Federal University of PiauíParnaíbaBrazil
  4. 4.Department of PharmacyFederal University of ParaíbaJoão PessoaBrazil
  5. 5.Department of PharmacyFederal University of PiauíTeresinaBrazil
  6. 6.Department of Biophysics and PhysiologyFederal University of PiauíTeresinaBrazil

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