Gallotannins are uncompetitive inhibitors of pancreatic lipase activity

• Published in: Biophysical chemistry Vol. 264; p. 106409
• Main Authors: Moreno-Córdova, Elena N., Arvizu-Flores, Aldo A., Valenzuela-Soto, Elisa M., García-Orozco, Karina D., Wall-Medrano, Abraham, Alvarez-Parrilla, Emilio, Ayala-Zavala, J. Fernando, Domínguez-Avila, J. Abraham, González-Aguilar, Gustavo A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-09-2020
• Subjects: Animals; Enzyme Inhibitors - pharmacology; Enzyme kinetics; Fluorescence; Hydrogen Bonding; Hydrolyzable Tannins - pharmacology; Hydroxyl group; Kinetics; Lipase - antagonists & inhibitors; Lipase - metabolism; Molecular docking; Molecular Docking Simulation; Pancreas - drug effects; Pancreas - enzymology; Phenolic compound; Substrate Specificity; Swine; Hydroxyl group; Phenolic compound; Enzyme kinetics; Molecular docking
• ISSN: 0301-4622; 1873-4200
• DOI: 10.1016/j.bpc.2020.106409

Inhibition of pancreatic lipase (PL) is used to treat dyslipidemias and obesity. Phenolic compounds are highly bioactive molecules that can inhibit various enzymes. Our aim was to evaluate the inhibitory activity of selected phenolic compounds of increasing molecular complexity, namely, phenolic acids, mangiferin, penta-O-galloyl-β-d-glucose (PGG) and tannic acid (TA) against porcine PL, according to in vitro and in silico methodologies. TA and PGG were effective inhibitors (IC50 22.4 and 64.6 μM, respectively), with strong affinity towards the enzyme-substrate complex (uncompetitive inhibition). Fluorescence quenching suggested phenolic-enzyme interactions, which may occur at the PL-colipase complex interface, according to molecular docking. Interactions are likely between hydroxyl groups and polar amino acid residues. We conclude that TA and PGG, but not simple phenolic acids, are effective PL inhibitors, likely due to their numerous hydroxyl groups, which promote phenolic-enzyme interactions. Thus, their consumption may exert health benefits derived from their effects on this digestive enzyme.
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•Inhibition of phenolic compounds against pancreatic lipase (PL) was analyzed.•Polymeric compounds (gallotannins) were effective PL inhibitors.•Compounds preferentially bound to the enzyme-substrate complex.•Hydroxyl groups of gallotannins formed hydrogen bonds with polar aminoacid residues.•Complexity and number of hydroxyl groups on phenolics promote PL inhibition