Short Lecture "Phytochemical profiling of a cannabigerol-rich Cannabis sativa strain expands chemical and biological space of underexplored phytocannabinoids"

Phytocannabinoids represent the hallmark of the secondary metabolism of Cannabis sativa [1]. Major phytocannabinoids, like tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), biogenetically derived from cannabigerolic acid (CBGA) and their content is closely related to genetic variations, resulting in five distinguishable Cannabis chemotypes [2]. In the frame of contribution to the field of phytochemical studies on less known Cannabis chemotypes [3] [4], here we present the first phytochemical characterisation of a C. sativa chemotype IV, a B₀/B₀ homozygotic breed, resulting in the presence of CBGA, as the major phytocannabinoid, and CBD (<0.05%). A multi-step workflow developed in our studies for expeditious untargeted dereplication, extraction, fractionation and spectroscopic analysis of isolated metabolites can empower the exploration of minor phytocannabinoids, relevant for the identification of novel biological endpoints. Our analysis led to the identification of thirteen phytocannabinoids in pure form: in addition to CBGA, CBG, CBDA, CBD, nine new phytocannabinoids were obtained and structurally characterised. They resulted to be congeners of CBGA, showing different degrees of hydroxylation, double bond migration and isomerisation, or its derivatives when cyclisation occurred. Moreover, two C-1’ epimers, cannabifuranol A and B, have been isolated. They constitute an unprecedented chemotype of phytocannabinoids. All the isolated compounds have been evaluated for their profile of modulation on TRPV1, TRPA1, and TRPM8 expressed in HEK-293 (human embryonic kidney) cells, providing interesting clues on the bioactivity of this class of compounds, structure-activity relationships related to variations of the isoprenyl chain of CBGA and the enantioselectivity of the interaction on the tested endpoints.

 

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• References

• 1 Hanus LO, Meyer SM, Mufoz E, Taglialatela- OScafati, Appendino G.. Phytocannabinoids: A unified critical inventory. Nat. Prod. Rep. 2016; 33: 1357-1392
• 2 de Meijer EPM, Hammond KM.. The inheritance of chemical phenotype in Cannabis sativa L. (ll): Cannabigerol predominant plants. Euphytica 2005; 145: 189-198
• 3 Chianese G, Sirignano C, Benetti E, Marzaroli V, Collado JA, De La Vega L, Appendino G, Munoz E, Taglialatela-Scafati O.. A Nrf-2 Stimulatory Hydroxylated Cannabidiol Derivative from Hemp (Cannabis sativa). J Nat Prod 2022; 85: 1089-1097
• 4 Salamone S, Waltl L, Pompignan A, Grassi G, Chianese G, Koeberle A, Pollastro F.. That Favorably Reprogram Lipid Mediator Biosynthesis in Macrophages. Plants 2022; 11: 2130

Publikationsverlauf

Artikel online veröffentlicht:
16. November 2023