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.
Animals
Anti-Inflammatory Agents
/ therapeutic use
Disease Models, Animal
Extracellular Signal-Regulated MAP Kinases
/ metabolism
Food Additives
/ therapeutic use
GTPase-Activating Proteins
/ metabolism
Humans
Interleukin-1beta
/ metabolism
Limonene
/ therapeutic use
Male
Mice
Monoterpenes
/ therapeutic use
Motor Neurons
/ physiology
Nerve Growth Factor
/ metabolism
Neuralgia
/ diet therapy
Peripheral Nerve Injuries
/ therapy
Regeneration
/ drug effects
Tumor Necrosis Factor-alpha
/ metabolism
D-limonene
Monoterpenes
Natural products
Nerve regeneration
Neuropathic pain
Perillyl alcohol
Journal
International immunopharmacology
ISSN: 1878-1705
Titre abrégé: Int Immunopharmacol
Pays: Netherlands
ID NLM: 100965259
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
18
05
2020
revised:
25
06
2020
accepted:
29
06
2020
pubmed:
12
7
2020
medline:
28
5
2021
entrez:
12
7
2020
Statut:
ppublish
Résumé
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. 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). 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 32652504
pii: S1567-5769(20)31617-9
doi: 10.1016/j.intimp.2020.106766
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Food Additives
0
GTPase-Activating Proteins
0
Interleukin-1beta
0
Monoterpenes
0
Tumor Necrosis Factor-alpha
0
perillyl alcohol
319R5C7293
Nerve Growth Factor
9061-61-4
Limonene
9MC3I34447
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
106766Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.