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Article Publish Status: FREE
Abstract Title:

TRPA1 mediates the antinociceptive properties of the constituent of Crocus sativus L., safranal.

Abstract Source:

J Cell Mol Med. 2019 Jan 12. Epub 2019 Jan 12. PMID: 30636360

Abstract Author(s):

Simone Li Puma, Lorenzo Landini, Sergio J Macedo, Viola Seravalli, Ilaria M Marone, Elisabetta Coppi, Riccardo Patacchini, Pierangelo Geppetti, Serena Materazzi, Romina Nassini, Francesco De Logu

Article Affiliation:

Simone Li Puma

Abstract:

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.

Study Type : Animal Study
Additional Links
Pharmacological Actions : Antinoceceptive : CK(492) : AC(153)

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