Selective in vitro and in silico butyrylcholinesterase inhibitory activity of diterpenes and rosmarinic acid isolated from Perovskia atriplicifolia Benth. and Salvia glutinosa L

• Published in: Phytochemistry (Oxford) Vol. 133; pp. 33 - 44
• Main Authors: Senol, F. Sezer, Ślusarczyk, Sylwester, Matkowski, Adam, Pérez-Garrido, Alfonso, Girón-Rodríguez, Francisco, Cerón-Carrasco, José P., den-Haan, Helena, Peña-García, Jorge, Pérez-Sánchez, Horacio, Domaradzki, Krzysztof, Orhan, Ilkay Erdogan
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-01-2017
• Subjects: Abietanes - chemistry; Alzheimer Disease - drug therapy; Butyrylcholinesterase; Butyrylcholinesterase - drug effects; Cholinesterase inhibition; Cholinesterase Inhibitors - pharmacology; Cinnamates - chemistry; Cinnamates - isolation & purification; Cinnamates - pharmacology; Depsides - chemistry; Depsides - isolation & purification; Depsides - pharmacology; Diterpenes; Diterpenes - chemistry; Diterpenes - isolation & purification; Diterpenes - pharmacology; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - isolation & purification; Drugs, Chinese Herbal - pharmacology; Lamiaceae - chemistry; Lamiaceae - genetics; Molecular modeling; Perovskia atriplicifolia (Lamiaceae); Phenanthrenes - chemistry; QSAR; Quantitative Structure-Activity Relationship; Rosmarinic Acid; Salvia - chemistry; Salvia - genetics; Salvia glutinosa (Lamiaceae); Tanshinones; Cholinesterase inhibition; QSAR; Molecular modeling; Diterpenes; Salvia glutinosa (Lamiaceae); Perovskia atriplicifolia (Lamiaceae); Tanshinones; Butyrylcholinesterase
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2016.10.012

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.
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•Diterpenes and rosmarinic acid were tested against cholinesterase enzymes.•QSAR and molecular docking studies have been also performed on the active compounds.•All of the compounds showed higher or closer inhibition against BChE.•In silico data well-matched with the in vitro outcomes of the present study.•15,16-Dihydrotanshinone is promising due to its dual inhibition toward both enzymes.