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.
Centre de recherche sur le cerveau et l'apprentissage (CIRCA), Université de Montréal, Montréal, QC, Canada.
Neurochem Res. 2021 Feb;46(2):252-264. doi: 10.1007/s11064-020-03159-z. Epub 2020 Oct 29.
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.
丁香酚是一种已知的香草醛，在牙科中常被用作局部镇痛药，此外，它还具有抗菌和神经保护作用。丁香酚、辣椒素和许多香草醛与哺乳动物中的瞬时受体电位香草醛 1（TRPV1）相互作用，TRPV1 被有害热激活。TRPV1 的药理学操作已被证明具有治疗价值。秀丽隐杆线虫（C. elegans）表达 TRPV 同源物（例如 OCR-2、OSM-9），它是一种常用的动物模型系统，用于研究伤害感受，因为它表现出明确且可重复的伤害性行为。在接触香草醛溶液后，将野生型（N2）和突变体秀丽隐杆线虫放在分为四个象限的培养皿上进行热刺激。热回避指数用于表型分析每个测试的秀丽隐杆线虫实验组。结果表明，丁香酚、香草醛和姜酮可以阻止秀丽隐杆线虫对有害热（32-35°C）的伤害性反应，持续暴露后。此外，暴露后 6 小时，这种作用会逆转。此外，丁香酚和香草醛并非专门针对 OCR-2 或 OSM-9，而是类似于辣椒素，专门针对 OCR-2。进一步进行了结构和物理化学分析。定量构效关系（QSAR）和前沿轨道分析的关键参数表明，在所测试的香草醛和辣椒素之间存在相似性和差异性，这与观察到的相对抗伤害作用一致。
