In Vitro Digestive-Enzyme Inhibition and Antiglycation Activity of Cannabis sativa L. Essential Oil: Experimental Evaluation and Molecular Docking Analysis

Aim of the Study: The aim of this study was to characterize the volatile phytochemical composition of Cannabis sativa L. essential oil (CSEO) and evaluate its in vitro inhibitory activity against selected digestive enzymes and its antiglycation activity. Molecular docking and ADMET analyses were additionally performed to explore the possible interactions and predicted pharmacokinetic properties of the major identified constituents. Materials and Methods: The chemical composition of CSEO was characterized by Gas Chromatography–Mass Spectrometry (GC-MS). Its in vitro inhibitory activity was evaluated against α-amylase, α-glucosidase, and pancreatic lipase, while its antiglycation activity was assessed by monitoring the formation of glycation products at different stages of the glycation process. Molecular docking simulations were performed to investigate the potential interactions of major identified terpenes with the active sites of the investigated enzymes. In addition, ADME analysis was conducted to predict selected pharmacokinetic and drug-likeness properties of the major constituents. Results: gc-ms analysis revealed a complex terpenoid profile, with β-caryophyllene as the major constituent, followed by selina-3,7(11)-diene (8.00%), cubenol (6.62%), γ-eudesmol (6.57%), epiglobulol (6.04%), and valencene (5.80%). CSEO showed significant in vitro inhibitory activity against α-amylase, α-glucosidase, and pancreatic lipase. The essential oil also exhibited antiglycation activity, with inhibition observed at different stages of glycation-product formation. Molecular docking analysis indicated that several major sesquiterpenes could interact with the investigated enzyme targets through different binding interactions. ADME analysis provided predicted pharmacokinetic and drug-likeness profiles for the major constituents. Conclusions: The findings demonstrate that Cannabis sativa L. essential oil possesses in vitro digestive-enzyme inhibitory and antiglycation activities. The docking results provide molecular-level insights into possible interactions between major essential-oil constituents and the investigated enzyme targets. These findings support further investigation of CSEO and its major constituents using appropriate in vivo and mechanistic studies to determine their biological relevance and potential applications.