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.
Highlights
Crocus sativus L., known as saffron crocus, belongs to the family of Iridaceas[1] and is commonly used for flavouring and colouring food preparations
In IMR90 cells, which constitutively express the native human transient receptor potential ankyrin 1 (TRPA1) receptor,[34] safranal and picrocrocin evoked concentration‐dependent calcium responses (EC50s 9 ± 0.2 μmol/L and 44 ± 0.4 μmol/L respectively) that were attenuated by HC‐030031, alike the response evoked by allyl isothiocyanate (AITC) (Figure 1E)
The lower potency of picrocrocin compared to safranal may depend on various factors
Summary
Crocus sativus L., known as saffron crocus, belongs to the family of Iridaceas[1] and is commonly used for flavouring and colouring food preparations. Constituents: the carotenoid crocin, responsible for its typical colour, the monoterpene aldehyde picrocrocin, and the volatile compound safranal, which accounts for its special flavour.[2] Saffron has been reported to possess beneficial effects against depression, sexual dysfunction, premenstrual syndrome and weight loss.[1,3] clinical trials reported headache as one possible adverse effect of saffron,[4] in Indian traditional medicine saffron has been. Safranal induces selective desensitization of the TRPA1 channel, attenuating neuronal excitation that results in nociception and CGRP release This unforeseen TRPA1‐desensitization mechanism could possibly explain the analgesic effects attributed to saffron
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