Inhibition of Butyrylcholinesterase and Human Monoamine Oxidase-B by the Coumarin Glycyrol and Liquiritigenin Isolated from <i>Glycyrrhiza uralensis</i>

• Main Authors: Geum Seok Jeong, Myung-Gyun Kang, Joon Yeop Lee, Sang Ryong Lee, Daeui Park, MyoungLae Cho, Hoon Kim
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: Molecules
• Subjects: <i>Glycyrrhiza uralensis</i>; glycyrol; liquiritigenin; cholinesterases; human monoamine oxidases; kinetics
• Online Access: https://www.mdpi.com/1420-3049/25/17/3896

Eight compounds were isolated from the roots of <i>Glycyrrhiza uralensis</i> and tested for cholinesterase (ChE) and monoamine oxidase (MAO) inhibitory activities. The coumarin glycyrol (GC) effectively inhibited butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) with IC₅₀ values of 7.22 and 14.77 µM, respectively, and also moderately inhibited MAO-B (29.48 µM). Six of the other seven compounds only weakly inhibited AChE and BChE, whereas liquiritin apioside moderately inhibited AChE (IC₅₀ = 36.68 µM). Liquiritigenin (LG) potently inhibited MAO-B (IC₅₀ = 0.098 µM) and MAO-A (IC₅₀ = 0.27 µM), and liquiritin, a glycoside of LG, weakly inhibited MAO-B (>40 µM). GC was a reversible, noncompetitive inhibitor of BChE with a K_i value of 4.47 µM, and LG was a reversible competitive inhibitor of MAO-B with a K_i value of 0.024 µM. Docking simulations showed that the binding affinity of GC for BChE (−7.8 kcal/mol) was greater than its affinity for AChE (−7.1 kcal/mol), and suggested that GC interacted with BChE at Thr284 and Val288 by hydrogen bonds (distances: 2.42 and 1.92 Å, respectively) beyond the ligand binding site of BChE, but that GC did not form hydrogen bond with AChE. The binding affinity of LG for MAO-B (−8.8 kcal/mol) was greater than its affinity for MAO-A (−7.9 kcal/mol). These findings suggest GC and LG should be considered promising compounds for the treatment of Alzheimer’s disease with multi-targeting activities.