“Cannabis sativa L. is a valuable agricultural crop, extensively utilized in various fields and comprising diverse chemical constituents. In preliminary experiments for rat intestinal α-glucosidase inhibition, the methanolic extract of Cannabis sativa demonstrated potential for inhibiting maltase and sucrase. Bioassay-guided isolation led to 30 metabolites, including five new cannabinoids (1, 2, 3, 4, 30) and four new spiroindans (5, 6, 10, 11). Their structures were elucidated using spectroscopic techniques such as NMR, and absolute configurations were determined by Mosher’s method. Cannabinoids were the main contributors to inhibitory potency (IC50: 0.09-0.8 mM), while spiroindans and simple phenolics showed lower activity (IC50: 1.0-2.2 mM). 8-Hydroxycannabinol (18) was the most potent inhibitor retarding the enzymes through a noncompetitive mechanism. Molecular dynamics simulations of compounds 15 and 18 showed that hydrogen bonding between phenolic hydroxyl groups and specific amino acid residues at the allosteric site was essential for strong α-glucosidase binding.”
https://pubmed.ncbi.nlm.nih.gov/40788893/
“Cannabis sativa L., a member of the Cannabaceae family derived from Western Asia, has been grown for centuries for food, fiber, and medicine.”
“This study reveals that the leaves of Cannabis sativa are a prolific source of α-glucosidase inhibitors with cannabinoids, particularly cannabinol derivatives exhibiting the most pronounced bioactivity.
Among 30 isolated compounds, 8-hydroxycannabinol demonstrated the strongest inhibitory effect, outperforming other cannabinoids through an uncompetitive inhibition mechanism. Structure–activity relationship analysis indicated that additional phenolic hydroxyl groups and extended aromatic rings substantially enhance inhibitory potency.
Molecular docking and molecular dynamics simulations confirmed that active cannabinol derivatives bind stably to an allosteric site on the α-glucosidase enzyme, supported by favorable binding energies and consistent hydrophobic interactions. However, the limited structural diversity of the isolated compounds restricts the full elucidation of SAR trends, underscoring the need for broader analog libraries.
These findings not only highlight the therapeutic potential of C. sativa leaf cannabinoids as natural antidiabetic agents but also lay a foundation for future research. In particular, the semisynthesis of novel cannabinol derivatives via rational modifications such as halogenation or esterification represents a promising strategy to enhance α-glucosidase inhibitory activity and to systematically probe the structure–activity relationship of this pharmacophore class.”
https://pubs.acs.org/doi/10.1021/acs.jafc.5c08443
“Alpha-glucosidase inhibitors are a class of medications used to treat type 2 diabetes by slowing down the digestion and absorption of carbohydrates from the small intestine.”