Outlining In Vitro and In Silico Cholinesterase Inhibitory Activity of Twenty-Four Natural Products of Various Chemical Classes: Smilagenin, Kokusaginine, and Methyl Rosmarinate as Emboldening Inhibitors

Cholinesterase (ChE) inhibition is an important treatment strategy for Alzheimer's disease (AD) as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are involved in the pathology of AD. In the current work, ChE inhibitory potential of twenty-four natural products from different chemi...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2021-04, Vol.26 (7), p.2024
Main Authors: Senol Deniz, F Sezer, Eren, Gokcen, Orhan, Ilkay Erdogan, Sener, Bilge, Ozgen, Ufuk, Aldaba, Randa, Calis, Ihsan
Format: Article
Language:English
Subjects:
Acetylcholinesterase
Alzheimer's disease
Binding sites
Cholinesterase
cholinesterase inhibition
Cholinesterase inhibitors
Enzyme-linked immunosorbent assay
Galantamine
Hydrogen bonds
Hypotheses
kokusaginine
methyl rosmarinate
Molecular docking
Natural products
smilagenin
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Summary:Cholinesterase (ChE) inhibition is an important treatment strategy for Alzheimer's disease (AD) as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are involved in the pathology of AD. In the current work, ChE inhibitory potential of twenty-four natural products from different chemical classes (i.e., diosgenin, hecogenin, rockogenin, smilagenin, tigogenin, astrasieversianins II and X, astragalosides I, IV, and VI, cyclocanthosides E and G, macrophyllosaponins A-D, kokusaginin, lamiide, forsythoside B, verbascoside, alyssonoside, ipolamide, methyl rosmarinate, and luteolin-7- -glucuronide) was examined using ELISA microtiter assay. Among them, only smilagenin and kokusaginine displayed inhibitory action against AChE (IC = 43.29 ± 1.38 and 70.24 ± 2.87 µg/mL, respectively). BChE was inhibited by only methyl rosmarinate and kokusaginine (IC = 41.46 ± 2.83 and 61.40 ± 3.67 µg/mL, respectively). IC values for galantamine as the reference drug were 1.33 ± 0.11 µg/mL for AChE and 52.31 ± 3.04 µg/mL for BChE. Molecular docking experiments showed that the orientation of smilagenin and kokusaginine was mainly driven by the interactions with the peripheral anionic site (PAS) comprising residues of hAChE, while kokusaginine and methyl rosmarinate were able to access deeper into the active gorge in hBChE. Our data indicate that similagenin, kokusaginine, and methyl rosmarinate could be hit compounds for designing novel anti-Alzheimer agents.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules26072024