In silico exploration the phenolic compound of olive leaves as acetylcholinesterase enzyme (AChE) inhibitor for Alzheimer’s disease therapy

Abstract

Olive (Olea europaea) have been cultivated and grown well in tropical climates such as Indonesia. Indonesia local community have used olive as herbal medicines due to its active compounds known as oleuropein that has many biological activities including as neurotherapy in Alzheimer's disease. The purpose of this study is to explore the potential phenolic compounds of olive and examine the acetylcholinesterase (AChE) inhibitory activity displayed by different olive polyphenols through a silico approach. The bioactive compounds of olive which had been analyzed in this study were phenolic compound included oleuropein, demethyl-oleuropein, ligstroside, oleoside, verbascoside, luteolin 7-glucoside, and hydroxytyrosol. Interaction of bioactive compounds with acetylcholinesterase (AChE) was analyzed through molecular specific docking using AutoDock Vina with Pyrx Software. The result elucidate that olive contain potential biological activities as antioxidant, anti-inflammatory, antineoplastic, free radical scavenger, antibacterial, antifungal, expression TP53 enhancer, caspase 8 stimulant, platelet adhesion inhibitor, treatment for lipoprotein disorder, antiviral and dementia treatment/Alzheimer disease. The highest bioactivity percentage of olive phenolic compound are as an antioxidant of 82%, anti-inflammatory of 73%, and anti-cancer (antineoplastic) of 70% respectively. Based on molecular docking analysis show one of olive phenolic compound of the dimethyl-oleuropein has strong interaction with AChE as pointed in the binding affinity of demethyl-oleuropein +AChE of-8.9 kcal/mol has closed to galanthamine binding affinity of-10.3 kcal/mol. Along with glutamate acid 202, tyrosine 133 and tyrosine 124 are the major contributors in the target-ligand interactions. The selected demethyl-oleuropein ought to be tested in clinical studies to discover new neuro-therapeutic candidates.

Neuroprotective effects of oleuropein: Recent developments and contemporary research

“…Several in vivo studies have shown that OL is one of the most actively investigated biophenols that are potent amyloid inhibitors (Casamenti et al., 2015; Cordero et al., 2018). The major mechanism behind this action of OL is that it inhibits the formation of Aβ toxic aggregates and also causes a marked reduction in neuroinflammation and ROS/RNS production by mitochondria (Mubarakati et al., 2019; Omar et al., 2019). OLA has been found to interfere with the formulation of Aβ aggregates (Rigacci et al., 2011), amylin (Rigacci et al., 2010), and Tau (Daccache et al., 2011).…”

Myricetin Amorphous Solid Dispersions—Antineurodegenerative Potential

“…This structural difference may contribute to the higher affinity of myricetin towards BChE. Molecular docking (MD) is a key technique in structural molecular biology, as confirmed by numerous literature reports [96][97][98][99][100]. MD was used to observe and confirm possible interactions between MYR and AChE/BChE, which are important targets for neuroprotection.…”

Investigation of Excellent ACE Inhibitor Agents from Scurrula atropurpure and Dendrophthoe pentandra for Anti-Hypertension

“…Simple phenolic acids, such as gallic acid, also inhibit platelet aggregation and activation via the inhibition of the phosphorylation of PKCα/p38 MAPK and Akt/GSK3β (Oh et al, 2012). Besides, Mubarakati et al, (2019) showed that based on molecular docking analysis, phenolic compounds such as dimethyl-oleuropein in olives have acetylcholinesterase (AChE) inhibitory activity for the treatment of Alzheimer's disease. CMUJ.…”

“…Theoretically, the application of the methods of virtual screening is limited to the structures of the compounds that can be counted and to compounds known to have ties with other compounds. There are a lot of studies doing computer screening and active compound molecular docking to a target protein (Kumar, et al, 2017;Mubarakati, et al, 2019;Sarkar, et al, 2021). Nevertheless, these predictive results require validation through in vitro and in vivo toxicological and pharmacological assays and experimental bioavailability tests for this main compound concerning hypertension prevention.…”