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

Pharmaceuticals

Francine Medjiofack Djeujo¹  Guglielmina Froldi¹  Eugenio Ragazzi¹  Miriana Urettini¹  Beatrice Sauro¹  Elena Cichero²  Michele Tonelli² 

[1] Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35122 Padova, Italy;Department of Pharmacy, University of Genova, 16128 Genova, Italy;

关键词: natural polyphenols;    α-glucosidase inhibitors;    magnolol;    luteolin;    enzymatic kinetics;    circular dichroism;   

DOI  :  10.3390/ph15020205

来源: DOAJ

【 摘 要 】

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 α-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 µM α-glucosidase, the IC₅₀ values were similar for both compounds (~ 32 µM) and significantly lower than for acarbose (815 μM). 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 α-glucosidase from the initial α-helix to the final conformation enriched with β-sheet and random coil. Docking studies provided support for the experimental results. Altogether, the data propose magnolol, for the first time, as a potential α-glucosidase inhibitor and add further evidence to the inhibitory role of luteolin.

【 授权许可】

Unknown