Magnolol and Luteolin Inhibition of alpha-Glucosidase Activity: Kinetics and Type of Interaction Detected by In Vitro and In Silico Studies

Magnolol and luteolin are two natural compounds recognized in several medicinal plants widely used in traditional medicine, including type 2 diabetes mellitus. This research aimed to determine the inhibitory activity of magnolol and luteolin on alpha-glucosidase activity. Their biological profile was studied by multispectroscopic methods along with inhibitory kinetic analysis and computational experiments. Magnolol and luteolin decreased the enzymatic activity in a concentration-dependent manner. With 0.075 mu M alpha-glucosidase, the IC50 values were similar for both compounds (~ 32 mu M) and significantly lower than for acarbose (815 mu M). Magnolol showed a mixed-type antagonism, while luteolin showed a non-competitive inhibition mechanism. Thermodynamic parameters suggested that the binding of magnolol was predominantly sustained by hydrophobic interactions, while luteolin mainly exploited van der Waals contacts and hydrogen bonds. Synchronous fluorescence revealed that magnolol interacted with the target, influencing the microenvironment around tyrosine residues, and circular dichroism explained a rearrangement of the secondary structure of alpha-glucosidase from the initial alpha-helix to the final conformation enriched with beta-sheet and random coil. Docking studies provided support for the experimental results. Altogether, the data propose magnolol, for the first time, as a potential alpha-glucosidase inhibitor and add further evidence to the inhibitory role of luteolin.