TRPA1 mediates the antinociceptive properties of the constituent of Crocus sativus L., safranal.
Analgesics
/ pharmacology
Animals
Calcium Channels
/ metabolism
Cell Line
Crocus
/ chemistry
Cyclohexenes
/ pharmacology
Ganglia, Spinal
/ drug effects
HEK293 Cells
Humans
Isothiocyanates
/ pharmacology
Mice
Mice, Inbred C57BL
Neurons
/ drug effects
Nociception
/ drug effects
Sesquiterpenes
/ pharmacology
TRPA1 Cation Channel
/ metabolism
TRPV Cation Channels
/ metabolism
Terpenes
/ pharmacology
calcitonin gene-related peptide
neurogenic inflammation
pain
safranal
transient receptor potential ankyrin 1
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
11
10
2018
revised:
26
11
2018
accepted:
29
11
2018
pubmed:
14
1
2019
medline:
26
6
2020
entrez:
14
1
2019
Statut:
ppublish
Résumé
Safranal, contained in Crocus sativus L., exerts anti-inflammatory and analgesic effects. However, the underlying mechanisms for such effects are poorly understood. We explored whether safranal targets the transient receptor potential ankyrin 1 (TRPA1) channel, which in nociceptors mediates pain signals. Safranal by binding to specific cysteine/lysine residues, stimulates TRPA1, but not the TRP vanilloid 1 and 4 channels (TRPV1 and TRPV4), evoking calcium responses and currents in human cells and rat and mouse dorsal root ganglion (DRG) neurons. Genetic deletion or pharmacological blockade of TRPA1 attenuated safranal-evoked release of calcitonin gene-related peptide (CGRP) from rat and mouse dorsal spinal cord, and acute nociception in mice. Safranal contracted rat urinary bladder isolated strips in a TRPA1-dependent manner, behaving as a partial agonist. After exposure to safranal the ability of allyl isothiocyanate (TRPA1 agonist), but not that of capsaicin (TRPV1 agonist) or GSK1016790A (TRPV4 agonist), to evoke currents in DRG neurons, contraction of urinary bladder strips and CGRP release from spinal cord slices in rats, and acute nociception in mice underwent desensitization. As previously shown for other herbal extracts, including petasites or parthenolide, safranal might exert analgesic properties by partial agonism and selective desensitization of the TRPA1 channel.
Identifiants
pubmed: 30636360
doi: 10.1111/jcmm.14099
pmc: PMC6378183
doi:
Substances chimiques
Analgesics
0
Calcium Channels
0
Cyclohexenes
0
Isothiocyanates
0
Sesquiterpenes
0
TRPA1 Cation Channel
0
TRPV Cation Channels
0
Terpenes
0
Trpa1 protein, mouse
0
parthenolide
2RDB26I5ZB
safranal
4393FR07EA
allyl isothiocyanate
BN34FX42G3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1976-1986Informations de copyright
© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
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