Investigating the binding potential of the Melissa officinalis oil against Alzheimer’s targets by molecular docking and in vitro evaluations

چکیده مقاله

Alzheimer’s disease (AD) is a neurodegenerative disorder with limited treatment options. Melissa 
officinalis (M. officinalis) , traditionally used for its medicinal properties, contains compounds that may 
offer therapeutic benefits for AD. We extracted essential oils from M. officinalis using supercritical 
CO2 and identified 31 compounds via GC–MS, supplemented by 20 non-volatile compounds from the 
Dictionary of Natural Products. Molecular docking was performed against five AD-related targets: 
β-Secretase, γ-Secretase, amyloid-β) A(, neprilysin, and acetylcholinesterase. The oil’s antioxidant 
capacity and cytotoxicity on PC12 cells were evaluated using DPPH and MTT assays, respectively. 
Docking analysis revealed that sajerinic acid had the highest affinity for acetylcholinesterase, 
neprilysin, and γ-Secretase. Aβ and β-Secretase were most affected by 3′,4′,5,7-tetrahydroxyflavone, 
3′-O-β-D-glucuronopyranoside, γ-O-β-D-glucopyranoside and 2,3,19,23-tetrahydroxy-12-ursen-28-oic 
acid-23-sulfate, 28-O-β-D-glucopyranosyl ester, respectively. Among oil compounds, triethyl citrate 
showed the highest affinity for β-Secretase, neprilysin, and γ-Secretase, while 2,2-dimethoxybutane 
exhibited the highest potential for interaction with Aβ and acetylcholinesterase. The oil reduced PC12 
cell survival in a dose-dependent manner. The extract also displayed significant antioxidant activity, 
suggesting a potential to reduce oxidative stress. These findings suggest that M. officinalis contains 
compounds with potential anti-Alzheimer’s properties, warranting further investigation. The identified 
compounds could serve as leads for developing novel therapeutics, and the antioxidant activity of the 
extract supports its traditional use in managing neurodegenerative conditions. Further studies are 
needed to validate these findings in vivo and explore the therapeutic potential of M. officinalis in AD.