Phytochemical Characterization and TRPA1/TRPM8 Modulation Profile of the Cannabigerol-Rich Cannabis sativa L. Chemotype IV

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2024-04, Vol.87 (4), p.722-732
• Main Authors: Gargiulo, Ernesto, Moriello, Aniello Schiano, Benetti, Emanuele, Pagni, Luca, Arnoldi, Lolita, De Petrocellis, Luciano, Chianese, Giuseppina, Vitale, Rosa Maria, Taglialatela-Scafati, Orazio
• Format: Article
• Language: English
• ISSN: 0163-3864; 1520-6025; 1520-6025
• DOI: 10.1021/acs.jnatprod.3c00831

The first detailed phytochemical analysis of the cannabigerol (CBG)-rich chemotype IV of Cannabis sativa L. resulted in the isolation of the expected cannabigerolic acid/cannabigerol (CBGA/CBG) and cannabidiolic acid/cannabidiol (CBDA/CBD) and of nine new phytocannabinoids (5–13), which were fully characterized by HR-ESIMS and 1D and 2D NMR. These included mono- or dihydroxylated CBGA/CBG analogues, a congener with a truncated side chain (10), cyclocannabigerol B (11), and the CBD derivatives named cannabifuranols (12 and 13). Cyclocannabigerol B and cannabifuranols are characterized by a novel phytocannabinoid structural architecture. The isolated phytocannabinoids were assayed on the receptor channels TRPA1 and TRPM8, unveiling a potent dual TRPA1 agonist/TRPM8 antagonist profile for compounds 6, 7, and 14. Chiral separation of the two enantiomers of 5 resulted in the discovery of a synergistic effect of the two enantiomers on TRPA1.