SCREENING AND IN SILICO ANALYSIS OF HYPTIS SUAVEOLENS METABOLITES FOR ACETYLCHOLINESTERASE INHIBITION
Abstract
Objective: Current drugs to Alzheimer's disease (AD) are targeted to delay the breakdown of acetylcholine, thereby increasing the concentration
of acetylcholine released into synaptic cleft and enhancing cholinergic neurotransmission. This paper deals with screening and identification of
acetylcholinesterase (AChE) inhibitors in solvent extracts of Hyptis suaveolens (HS).
Methods: In search of natural inhibitors of AChE, this study is focused on extract of HS, a member of Lamiaceae. 1:4 ratio of methanolic extract
is prepared with shade dried areal parts of HS plant. The extract was assayed by Ellman's method for inhibition activity and then purified using
ammonium sulfate precipitation and chromatography techniques. Gas chromatography-mass spectrometry (GC-MS) identified compounds were
analyzed by docking studies.
Results: Methanolic extract showed maximum percentage inhibition of 75.00±4.30 (2.1 mg/ml) with an IC
value of 1.020±0.026 mg/ml.
However, saturated ammonium sulfate precipitation of methanolic extract and further fractionation by gel permeation chromatography showed
86.00±1.30% AChE inhibition (AChEI) activity. Reverse phase high-performance liquid chromatography (RP-HPLC) fraction (retention time [RT]
5.170) showed significant inhibition when compared to the other peak (RT 6.643). RP-HPLC fraction (RT 5.170) with significant inhibition was
identified as Eugenol by GC-MS analysis. In silico analysis of all the GC-MS identified molecules revealed Eugenol as possessing preeminent absorption,
distribution, metabolism, elimination properties and a glide (docking) score of −9.14 kcal/mole with AChE enzyme of pacific electric ray (Torpedo
californica - TcAChE) (PDB ID: 1EVE).
Conclusion: Screening, purification and identification, and identification of diverse phytochemicals of the HS plant, as potent source of AChEI.
Keywords: Acetylcholinesterase, Acetylcholnesterase inhibitor, Hyptis suaveolens, Alzheimer's disease, Dementia.
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