Eugenol and Other Vanilloids Hamper Caenorhabditis elegans Response to Noxious Heat
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ORIGINAL PAPER
Eugenol and Other Vanilloids Hamper Caenorhabditis elegans Response to Noxious Heat Bruno Nkambeu1,2 · Jennifer Ben Salem1,2,3 · Francis Beaudry1,2 Received: 16 September 2020 / Revised: 19 October 2020 / Accepted: 22 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Eugenol, a known vanilloid, was frequently used in dentistry as a local analgesic in addition, antibacterial and neuroprotective effects were also reported. Eugenol, capsaicin and many vanilloids are interacting with the transient receptor potential vanilloid 1 (TRPV1) in mammals and the TRPV1 is activated by noxious heat. The pharmacological manipulation of the TRPV1 has been shown to have therapeutic value. Caenorhabditis elegans (C. elegans) express TRPV orthologs (e.g. OCR-2, OSM-9) and it is a commonly used animal model system to study nociception as it displays a well-defined and reproducible nocifensive behavior. After exposure to vanilloid solutions, C. elegans wild type (N2) and mutants were placed on petri dishes divided in quadrants for heat stimulation. Thermal avoidance index was used to phenotype each tested C. elegans experimental groups. The results showed that eugenol, vanillin and zingerone can hamper nocifensive response of C. elegans to noxious heat (32–35 °C) following a sustained exposition. Also, the effect was reversed 6 h post exposition. Furthermore, eugenol and vanillin did not target specifically the OCR-2 or OSM-9 but zingerone did specifically target the OCR-2 similarly to capsaicin. Further structural and physicochemical analyses were performed. Key parameters for quantitative structure-property relationships (QSPR), quantitative structure-activity relationships (QSAR) and frontier orbital analyses suggest similarities and dissimilarities amongst the tested vanilloids and capsaicin in accordance with the relative anti-nociceptive effects observed. Keywords Caenorhabditis elegans · Eugenol · Vanillin · Zingerone · Vanilloids · Nociception · Transient receptor potential cation channel
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11064-020-03159-z) contains supplementary material, which is available to authorized users. * Francis Beaudry [email protected] 1
Groupe de Recherche en Pharmacologie Animal du Québec (GREPAQ), Département de Biomédecine Vétérinaire, Faculté de Médecine Vétérinaire, Université de Montréal, 3200 Sicotte, Saint‑Hyacinthe, QC J2S 2M2, Canada
2
Centre de recherche sur le cerveau et l’apprentissage (CIRCA), Université de Montréal, Montréal, QC, Canada
3
Institut des Maladies Métaboliques et Cardiovasculaires, INSERM UMR1048, Université de Toulouse, Toulouse, France
Caenorhabditis elegans (C. elegans) is a commonly used animal model system to study neuronal communication and more recently neurodegenerative diseases [1]. Adult self-fertilizing hermaphrodite C. elegans consists of 959 cells, of which 302 are neurons, making this model very attractive to
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