Chemical profile and biological activities of coffee-bean oil: In vitro and computational studies

Coffee is widely researched for its health benefits, but the specific pharmacological agents within coffee oil and their multi-target mechanisms are not fully understood. This lack of mechanistic understanding limits the therapeutic application of coffee oil. Our study comprehensively investigated the chemical profile and mechanisms of action of coffee oil, focusing on its antioxidant, antidiabetic, and anti-obesity properties, using an integrated in vitro and computational approach. The in vitro analysis included the DPPH, FRAP, and OH* radical scavenging assays for antioxidant activity; α-glucosidase, α-amylase, and pancreatic lipase inhibitory assays for metabolic enzyme inhibition; and the yeast cell model for glucose uptake. Gas chromatography-mass spectrometry (GC–MS) was used to identify the phytochemical constituents. Computational studies, including molecular docking, Density Functional Theory (DFT), and ADME analysis, were employed to predict binding interactions, electronic properties, and drug-likeness. The results demonstrated potent, concentration-dependent bioactivity. Coffee oil exhibited significant free radical scavenging activity and strongly inhibited α-glucosidase, α-amylase, and pancreatic lipase, while also enhancing glucose uptake in yeast. GC–MS profiling identified key bioactive compounds, including fatty acids, alkaloids, and phenolic acids. Molecular docking confirmed their strong binding affinities to the enzymes' active sites, which were further validated by DFT and ADME studies. These findings provide a robust mechanistic explanation for the efficacy of coffee oil, revealing it to be a rich source of multifunctional compounds. This work solidifies coffee oil's potential as a safe and effective natural therapeutic or functional food ingredient for managing metabolic syndromes, such as diabetes and obesity.