Département de Biomédecine Vétérinaire, Faculté de Médecine Vétérinaire, Université de Montréal, 3200 Sicotte, Saint-Hyacinthe, Québec, J2S 2M2, Canada.
Centre interdisciplinaire de recherche sur le cerveau et l'apprentissage (CIRCA), Université de Montréal, Montréal, Québec, Canada.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Jan;397(1):535-548. doi: 10.1007/s00210-023-02621-3. Epub 2023 Jul 22.
Cannflavins, flavonoids abundantly present in Cannabis sativa, possess a distinct chemical structure comprising a vanillyl group. Notably, the capsaicin structure also contains a vanillyl group, which is considered essential for interacting with the vanilloid receptor. The vanilloid receptor plays a crucial role in the perception of pain, heat, and inflammation and mediates the analgesic effects of capsaicin. Therefore, we postulated that prolonged exposure to cannflavin A (Can A) and cannflavin B (Can B) would provoke vanilloid receptor desensitization and hinder nocifensive responses to noxious thermal stimuli. C. elegans wild-type (N2) and mutants were exposed to Can A and Can B solutions for 60 min and then aliquoted on Petri dishes divided into quadrants for thermal stimulation. We then determined the thermal avoidance index for each C. elegans experimental group. Proteomics was performed to identify proteins and pathways associated with Can A or B treatment. Prolonged exposure to Can A and Can B hindered heat avoidance (32-35 °C) in C. elegans. No antinociceptive effect was observed 6 h post Can A or B exposure. Proteomics and Reactome pathway enrichment analyses identified hierarchical differences between Can A- and B-treated nematodes. However, both treatments were related to eukaryotic translation initiation (R-CEL-72613) and metabolic processes strongly associated with pain development. Our study aids in characterizing the pharmacological activity of cannflavins isolated from Cannabis sativa and outlines a possible application as pain therapy.
大麻素，广泛存在于大麻中的黄酮类化合物，具有独特的化学结构，包含香草基基团。值得注意的是，辣椒素结构也含有香草基基团，这被认为是与香草素受体相互作用所必需的。香草素受体在疼痛、热和炎症的感知中起着至关重要的作用，并介导辣椒素的镇痛作用。因此，我们假设长时间暴露于大麻素 A（Can A）和大麻素 B（Can B）会引起香草素受体脱敏，并阻碍对有害热刺激的伤害性反应。野生型（N2）和突变体秀丽隐杆线虫暴露于 Can A 和 Can B 溶液中 60 分钟，然后分配到分为四个象限的 Petri 盘中进行热刺激。然后，我们确定了每个秀丽隐杆线虫实验组的热回避指数。进行蛋白质组学分析以鉴定与 Can A 或 B 处理相关的蛋白质和途径。长时间暴露于 Can A 和 Can B 会阻碍秀丽隐杆线虫对热的回避（32-35°C）。暴露于 Can A 或 B 后 6 小时没有观察到镇痛作用。蛋白质组学和 Reactome 途径富集分析鉴定了 Can A 和 B 处理的线虫之间的层次差异。然而，两种处理都与真核翻译起始（R-CEL-72613）和与疼痛发展密切相关的代谢过程有关。我们的研究有助于描述从大麻中分离出的大麻素的药理学活性，并概述了其作为疼痛治疗的潜在应用。
