Profiling Auspicious Butyrylcholinesterase Inhibitory Activity of Two Herbal Molecules: Hyperforin and Hyuganin C

Abstract

Cholinergic therapy based on cholinesterase (ChE) inhibitory drugs is the mainstay for the treatment of Alzheimer's disease. Therefore, an extensive research has been continuing for the discovery of drug candidates as inhibitors of acetyl‐ and butyrylcholinesterase. In this study, two natural molecules, e. g. hyperforin and hyuganin C were tested in vitro for their AChE and BChE inhibitory activity. Both of the compounds were ineffective against AChE, whereas hyperforin (IC50=141.60±3.39 μm) and hyuganin C (IC50=38.86±1.69 μm) were found to be the highly active inhibitors of BChE as compared to galantamine (IC50=46.58±0.91 μm) which was used as the reference. Then, these molecules were further proceeded to molecular docking experiments in order to establish their interactions at the active site of BChE. The molecular docking results indicated that both of them are able to block the access to key residues in the catalytic triad of the enzyme, while they complement some of the hydrophobic residues of the cavity, what is consistent with our in vitro data. While both compounds were predicted as mutagenic, only hyuganin C showed hepatotoxicity in in silico analysis. According to whole outcomes that we obtained, particularly hyuganin C besides hyperforin are the promising BChE inhibitors, which can be the promising compounds for AD therapy.

Acetylcholinesterase and butyrylcholinesterase inhibitory activities of khellactone coumarin derivatives isolated from Peucedanum japonicum Thurnberg

“…The IC 50 value of PJ5 in this study was lower than those of broussonin A (7.50 µM) from Anemarrhena asphodeloides a 42 , isoacteoside (29.7 µM) from H. procumbens 52 , corenone B (10.9 μg/mL, i.e., 49.5 µM) from Niphogeton dissecta 60 , and kaempferol (62.5 µM) from Cleistocalyx operculatus 61 , but higher than that of 4′-hydroxy Pd–C-III (5.78 µM) from A. decursiva 58 . Compared to other coumarins, the IC 50 value of PJ5 for BChE inhibition was lower than those of hyuganin C (38.86 µM), from Mutellina purpurea 62 , a coumarin pteryxin (12.96 μg/mL, i.e., 33.5 µM) from M. purpurea 63 , the esculetin (9.29 µM) and the daphnetin (8.66 µM) 56 , and it might be concluded that PJ5 is the most potent BChE inhibitor in natural coumarins reported.…”

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

“…As regards other natural compounds, inhibition of BChE by GC was greater than that by boldine (IC 50 = 321 µM) [ 45 ], hyperforin and hyuganin C (IC 50 = 141.60 and 38.86 μM, respectively) [ 46 ], cremaphenanthrene F (14.62) [ 47 ], scopoletin (IC 50 = 9.11 µM) [ 48 ], and broussonin A and sagachromanol I (IC 50 = 7. 50 and 10.79 µM, respectively) [ 49 ], but less than those of norditerpenoids isograndifoliol and (1 R ,15 R )-1-acetoxycryptotanshinone (IC 50 = 0.9 and 2.4 µM, respectively) [ 50 ].…”

Evaluation of Anti‐Alzheimer Activity of Synthetic Coumarins by Combination of in Vitro and in Silico Approaches

“…SH-SY5Y cells were seeded at an initial density of 5 × 10 3 cells/well in 96-well plates and allowed to attach overnight in DMEM/F12 medium with necessary supplementation. The cells were treated with solvent (DMSO), as a control, and varying concentrations of test compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Then, the cells were incubated in humidified 5 % CO 2 atmosphere at 37 °C.…”

“…Chemical structures of the coumarin derivatives(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

“…inhibitory activity (inhibition % and IC 50 values) of the coumarins(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16).CompoundEnzyme Inhibition (Inhibition % � S.D.a ) at 100 μg/mL b and IC 50 values Selectivity index (SI) AChE BChE 1 32.18 � 0.86 40.65 � 3.15 § c 2 50.11 � 1.89 (IC 50 = 532.10 � 21.67 μM) 22.26 � 3.26 § 3 47.88 � 1.88 17.01 � 0.45 § 4 54.97 � 4.02 (IC 50 = 247.33 � 12.06 μM) 7.48 � 1.75 § 5 26.47 � 1.60 61.06 � 0.27 (IC 50 = 195.04 � 3.15 μM) § 50 = 239.70 � 11.84 μM) 93.09 � 0.76 (IC 50 = 75.14 � 1.82 μM) 0.31 10 13.06 � 0.39 7.05 � 0.95 § 11 62.68 � 0.76 (IC 50 = 109.91 � 1.56 μM) 12.50 � 2.33 § 12 70.90 � 1.88 (IC 50 = 91.62 � 7.69 μM) 16.48 � 2.63 § 13 79.41 � 1.27 (IC 50 = 37.47 � 0.87 μM) 98.77 � 0.16 (IC 50 = 16.14 � 0.43 μM) a Standard deviation (n = 3). b Final concentration, c Not applicable.…”