Abstract
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.
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Funding
M. Lahaise received a National Sciences and Engineering Research Council of Canada Undergraduate Student Research Award. This project was funded by the National Sciences and Engineering Research Council of Canada (F. Beaudry Discovery Grant No. RGPIN-2020–05228). The laboratory equipment was funded by the Canadian Foundation for Innovation (CFI), the Fonds de Recherche du Québec (FRQ), and the Government of Quebec (F. Beaudry CFI John R. Evans Leaders grant nos. 36706 and 42043). F. Beaudry holds the Canada Research Chair in Metrology of Bioactive Molecules and Target Discovery (grant no. CRC-2021–00160). This research was partially supported by funding from the Canada Research Chairs Program.
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M. Lahaise, F. Boujenoui, and F. Beaudry conceived and designed this study. M. Lahaise and F. Boujenoui conducted the experiments. M. Lahaise, F. Boujenoui, and F. Beaudry conducted data analysis and wrote the manuscript. All the authors have read and approved the final manuscript. All authors declare that all data were generated in-house and that no paper mill was used.
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Lahaise, M., Boujenoui, F. & Beaudry, F. Cannflavins isolated from Cannabis sativa impede Caenorhabditis elegans response to noxious heat. Naunyn-Schmiedeberg's Arch Pharmacol 397, 535–548 (2024). https://doi.org/10.1007/s00210-023-02621-3
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DOI: https://doi.org/10.1007/s00210-023-02621-3