Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder, and multiple factors are involved in disease progression. This is why there is an urgent need to develop novel molecules with multi-target-directed ligands (MTDLs) potential. The current study explores the active phytoconstituents from traditionally used medicinal spices, namely piperine, cinnamaldehyde, eugenol, cuminaldehyde, and alpha-terpinyl acetate for the inhibition of β-secretase, monoamine oxidase, cholinesterase enzymes, anti-aggregation of amyloid β (Aβ) fibrils, and their protective effect against hydrogen peroxide (H2 O2 ) and Aβ-induced toxicity. Eugenol showed inhibitory activity against MAO-B enzyme, free radical scavenging activity, and anti-aggregation activity against Aβ peptides than other phytoconstituents. It also demonstrated a significant cytoprotective effect against H2 O2 -induced oxidative stress and Aβ-induced cytotoxicity in pheochromocytoma (PC) 12 cells. A molecular docking study of eugenol showed interactions with active site residue of the target enzymes. The study successfully demonstrated that eugenol could have an MTDLs potential better than synthesized drugs used in the treatment of AD. PRACTICAL APPLICATIONS: The present study demonstrated multi-target-directed ligand potential of eugenol and can be developed to treat complex diseases like Alzheimer's. Eugenol can bind to different Alzheimer's targets such as β-secretase (BACE1), Monoamine oxidase B (MAO-B), Cholinesterase's, and amyloid β1-42 fibrils and might have a disease-modifying potential. The other natural phytoconstituents such as piperine, cinnamaldehyde, cuminaldehyde, and alpha-terpinyl acetate also demonstrated MTDL potential could also be used for developing novel molecules for disease-modifying effect. It also protects against oxidative stress.
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