Open AccessTRPA 1 mediates the antinociceptive properties of the constituent of Crocus sativus L., safranal
Author(s) -
Li Puma Simone,
Landini Lorenzo,
Macedo Sergio J.,
Seravalli Viola,
Marone Ilaria M.,
Coppi Elisabetta,
Patacchini Riccardo,
Geppetti Pierangelo,
Materazzi Serena,
Nassini Romina,
De Logu Francesco
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14099
Subject(s) - safranal , transient receptor potential channel , chemistry , pharmacology , trpv , trpv1 , agonist , resiniferatoxin , crocus sativus , dorsal root ganglion , furocoumarin , nociception , biochemistry , medicine , biology , receptor , crocin , neuroscience , spinal cord , traditional medicine , dna
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 ( TRPA 1) channel, which in nociceptors mediates pain signals. Safranal by binding to specific cysteine/lysine residues, stimulates TRPA 1, but not the TRP vanilloid 1 and 4 channels ( TRPV 1 and TRPV 4), evoking calcium responses and currents in human cells and rat and mouse dorsal root ganglion ( DRG ) neurons. Genetic deletion or pharmacological blockade of TRPA 1 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 TRPA 1‐dependent manner, behaving as a partial agonist. After exposure to safranal the ability of allyl isothiocyanate ( TRPA 1 agonist), but not that of capsaicin ( TRPV 1 agonist) or GSK 1016790A ( TRPV 4 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 TRPA 1 channel.