Selective in vitro and in silico butyrylcholinesterase inhibitory activity of diterpenes and rosmarinic acid isolated from Perovskia atriplicifolia Benth. and Salvia glutinosa L.
Cholinesterase inhibition is one of the most treatment strategies against Alzheimer's disease (AD) where metal accumulation is also strongly associated with pathology of the disease. In the current study, we assessed inhibitory effect against acetyl- (AChE) and butyrylcholinesterase (BChE) and metal-chelating capacity of twelve diterpenes: arucadiol, miltirone, tanshinone IIa, 1-oxomiltirone, cryptotanshinone, 1,2-didehydromiltirone, 1,2-didehydrotanshinone IIa, 1β-hydroxycryptotanshinone, 15,16-dihydrotanshinone, tanshinone I, isotanshinone II, 1(S)-hydroxytanshinone IIa, and rosmarinic acid, isolated from Perovskia atriplicifolia and Salvia glutinosa. The compounds were tested at 10 μg/mL using ELISA microtiter assays against AChE and BChE. QSAR and molecular docking studies have been also performed on the active compounds. All of the compounds showed higher [e.g., IC50= 1.12 ± 0.07 μg/mL for 1,2-didehydromiltirone, IC50= 1.15 ± 0.07 μg/mL for cryptotanshinone, IC50= 1.20 ± 0.03 μg/mL for arucadiol, etc.)] or closer [1,2-didehydrotanshinone IIa (IC50= 5.98 ± 0.49 μg/mL) and 1(S)-hydroxytanshinone IIa (IC50= 5.71 ± 0.27 μg/mL)] inhibition against BChE as compared to that of galanthamine (IC50= 12.56 ± 0.37 μg/mL), whereas only 15,16-dihydrotanshinone moderately inhibited AChE (65.17 ± 1.39%). 1,2-Didehydrotanshinone IIa (48.94 ± 0.26%) and 1(S)-hydroxytanshinone IIa (47.18 ± 5.10%) possessed the highest metal-chelation capacity. The present study affords an evidence for the fact that selective BChE inhibitors should be further investigated as promising candidate molecules for AD therapy.
Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey.
F Sezer
FS
Senol
Department of Pharmaceutical Biology and Botany, Wroclaw Medical University, Wroclaw, Poland; Bioinformatics and High Performance Computing Research Group, Universidad Católica San Antonio de Murcia (UCAM), Spain.
Sylwester
S
Ślusarczyk
Department of Pharmaceutical Biology and Botany, Wroclaw Medical University, Wroclaw, Poland.
Adam
A
Matkowski
Bioinformatics and High Performance Computing Research Group, Universidad Católica San Antonio de Murcia (UCAM), Spain.
Alfonso
A
Pérez-Garrido
Department of Food and Nutrition Technology, Universidad Católica San Antonio de Murcia (UCAM), Spain.
Francisco
F
Girón-Rodríguez
Bioinformatics and High Performance Computing Research Group, Universidad Católica San Antonio de Murcia (UCAM), Spain.
José P
JP
Cerón-Carrasco
Bioinformatics and High Performance Computing Research Group, Universidad Católica San Antonio de Murcia (UCAM), Spain.
Helena
H
den-Haan
Bioinformatics and High Performance Computing Research Group, Universidad Católica San Antonio de Murcia (UCAM), Spain.
Jorge
J
Peña-García
Bioinformatics and High Performance Computing Research Group, Universidad Católica San Antonio de Murcia (UCAM), Spain. Electronic address: hperez@ucam.edu.
Horacio
H
Pérez-Sánchez
Department of Weed Science and Soil Tillage Systems, IUNG-Institute of Soil Science and Plant Cultivation, Wroclaw, Poland.
Krzysztof
K
Domaradzki
Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey. Electronic address: iorhan@gazi.edu.tr.
Ilkay Erdogan
IE
Orhan
D045784:Abietanes / Q000737:chemistry; D000544:Alzheimer Disease / Q000188:drug therapy; D002091:Butyrylcholinesterase / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002934:Cinnamates / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D053630:Depsides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019686:Lamiaceae / Q000737:chemistry* / Q000235:genetics; D010616:Phenanthrenes / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D027544:Salvia / Q000737:chemistry* / Q000235:genetics; D000097123:Rosmarinic Acid
D045784:Abietanes; D002091:Butyrylcholinesterase; D002800:Cholinesterase Inhibitors; D002934:Cinnamates; D053630:Depsides; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D010616:Phenanthrenes; D000097123:Rosmarinic Acid; C442707:1-oxomiltirone; C021751:tanshinone; C068880:miltirone; C037886:cryptotanshinone
Butyrylcholinesterase; Cholinesterase inhibition; Diterpenes; Molecular modeling; Perovskia atriplicifolia (Lamiaceae); QSAR; Salvia glutinosa (Lamiaceae); Tanshinones