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TRPA1 mediates the antinociceptive properties of the constituent of Crocus sativus L., safranal.
J Cell Mol Med. 2019 03; 23(3):1976-1986.JC

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.

Authors+Show Affiliations

Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Brazil.Department of Health Sciences, Section of Paediatrics, Midwifery, Gynaecology and Nursing, University of Florence, Florence, Italy.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.Department of Neuroscience, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy.Department of Pharmacology, Chiesi Farmaceutici SpA, Parma, Italy.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30636360

Citation

Li Puma, Simone, et al. "TRPA1 Mediates the Antinociceptive Properties of the Constituent of Crocus Sativus L., Safranal." Journal of Cellular and Molecular Medicine, vol. 23, no. 3, 2019, pp. 1976-1986.
Li Puma S, Landini L, Macedo SJ, et al. TRPA1 mediates the antinociceptive properties of the constituent of Crocus sativus L., safranal. J Cell Mol Med. 2019;23(3):1976-1986.
Li Puma, S., Landini, L., Macedo, S. J., Seravalli, V., Marone, I. M., Coppi, E., Patacchini, R., Geppetti, P., Materazzi, S., Nassini, R., & De Logu, F. (2019). TRPA1 mediates the antinociceptive properties of the constituent of Crocus sativus L., safranal. Journal of Cellular and Molecular Medicine, 23(3), 1976-1986. https://doi.org/10.1111/jcmm.14099
Li Puma S, et al. TRPA1 Mediates the Antinociceptive Properties of the Constituent of Crocus Sativus L., Safranal. J Cell Mol Med. 2019;23(3):1976-1986. PubMed PMID: 30636360.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TRPA1 mediates the antinociceptive properties of the constituent of Crocus sativus L., safranal. AU - Li Puma,Simone, AU - Landini,Lorenzo, AU - Macedo,Sergio J,Jr AU - Seravalli,Viola, AU - Marone,Ilaria M, AU - Coppi,Elisabetta, AU - Patacchini,Riccardo, AU - Geppetti,Pierangelo, AU - Materazzi,Serena, AU - Nassini,Romina, AU - De Logu,Francesco, Y1 - 2019/01/12/ PY - 2018/10/11/received PY - 2018/11/26/revised PY - 2018/11/29/accepted PY - 2019/1/14/pubmed PY - 2020/6/26/medline PY - 2019/1/14/entrez KW - calcitonin gene-related peptide KW - neurogenic inflammation KW - pain KW - safranal KW - transient receptor potential ankyrin 1 SP - 1976 EP - 1986 JF - Journal of cellular and molecular medicine JO - J Cell Mol Med VL - 23 IS - 3 N2 - 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. SN - 1582-4934 UR - https://www.unboundmedicine.com/medline/citation/30636360/TRPA1_mediates_the_antinociceptive_properties_of_the_constituent_of_Crocus_sativus_L__safranal_ DB - PRIME DP - Unbound Medicine ER -