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

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.