Limonene, a food additive, and its active metabolite perillyl alcohol improve regeneration and attenuate neuropathic pain after peripheral nerve injury: Evidence for IL-1β, TNF-α, GAP, NGF and ERK involvement

Autor: Brenda Souza Monteiro, Luana Heimfarth, Sathiyabama R. Gandhi, Jackson Roberto Guedes da Silva Almeida, Erik Willyame Menezes Pereira, Jullyana S.S. Quintans, Ray S. Almeida, Pollyana S. Siqueira-Lima, Henrique Douglas Melo Coutinho, Natália Martins, Laurent Picot, Fabiolla Rocha Santos Passos, Raphaël Grougnet, Heitor G. Araújo-Filho, Márcio R. V. Santos, Lucindo José Quintans-Júnior
Přispěvatelé: LIttoral ENvironnement et Sociétés - UMRi 7266 (LIENSs), Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
MAPK/ERK pathway
Male
Immunology
Interleukin-1beta
Anti-Inflammatory Agents
Pharmacology
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication
Peripheral Nerve Injuries
Nerve Growth Factor
medicine
Immunology and Allergy
Animals
Humans
Regeneration
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
Extracellular Signal-Regulated MAP Kinases
ComputingMilieux_MISCELLANEOUS
Motor Neurons
biology
business.industry
Tumor Necrosis Factor-alpha
Perillyl alcohol
GTPase-Activating Proteins
Nerve injury
3. Good health
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
chemistry
030220 oncology & carcinogenesis
Neuropathic pain
Hyperalgesia
Peripheral nerve injury
biology.protein
Monoterpenes
Neuralgia
Food Additives
medicine.symptom
business
Limonene
Astrocyte
Neurotrophin
Zdroj: International Immunopharmacology
International Immunopharmacology, Elsevier, 2020, 86, pp.106766. ⟨10.1016/j.intimp.2020.106766⟩
ISSN: 1567-5769
DOI: 10.1016/j.intimp.2020.106766⟩
Popis: Background Limonene (LIM) and its main metabolite perillyl alcohol (POH) are ingredients found in food with promising chemical entities due to their pharmacological profile. In this study, we hypothesized that LIM and POH are two molecules capable of accelerating the regenerative process and alleviating neuropathic pain. Methods: Animals were treated daily (LIM, POH and saline) for 28 days and during this period evaluated for mechanical hyperalgesia, astrocyte participation by immunofluorescence for GFAP, and ELISA was used to quantify IL-1β and TNF-α in the spinal cord. Western blot analysis of the following proteins was also performed: GFAP, GAP-43, NGF and ERK. For motor deficit analysis, tests were performed to assess hind paw muscle strength and footprints through gait (SFI). Results: Both POH and LIM accelerated the regenerative process and improved motor deficits comparing to positive control; however, POH was more effective, particularly between the 2nd and 3rd week after the nerve injury, increasing GAP-43, NGF and the phosphorylated ERK immunocontent. Moreover, POH and LIM were able to reduce hyperalgesia and astrocytosis. Conclusions: Both substances, LIM and POH, improved the regeneration process and sensory and motor function recovery in the PNI model in mice by mitigating the inflammatory reactions and up-regulating the neurotrophic process.
Databáze: OpenAIRE
Externí odkaz: