In Silico Identification of Potential BACE1 Inhibitors from Ruta graveolens Essential Oil Targeting Alzheimer's Disease

Alzheimer's disease (AD) is the most common cause of neurodegenerative disease dementia in individuals above 65. Dementia is characterized by the accumulation of amyloid‐beta (Aβ) plaques and tau tangles, which disrupt neural communication and contribute to the decline of memory. The most pathogenic of the Aβ species, Aβ42, is vital for the formation of plaque and neuroinflammation in the brain. Ruta graveolens ( R. graveolens ) essential oil (EO) (RGEO), an herbal medicine that has been recognized for many ailments, contains a lot of bioactive phytochemicals like alkaloids, coumarins, flavonoids, and terpenoids, which are considered to have antioxidants and neuroprotective properties. Further, its neuroprotective efficacy in the management of AD is supported by initial evidence, which suggests that it can reduce oxidative stress and brain inflammation. The presence of R. graveolens EO phytochemicals might be the reason why the potential to manage Alzheimer's disease is being researched currently. Initially, 57 different phytoconstituents were considered by GC‐MS results, and after ADMET profiling, only 19 compounds were handpicked for further molecular target docking cascade. The present research focused on the interaction between BACE1 (PDB ID: 7D2V) and RGEO ligands through molecular docking and molecular dynamics simulations (MDS). High binding affinities and stable interactions with the protein were shown by the two compounds, BACE1‐ANT and BACE1‐TRI. The interaction between ligand and protein was mainly due to stacking of π‐type and hydrophobic interactions, as revealed by docking analysis. The simulations of molecular dynamics (MD) verified these complexes' stability by the existence of hydrogen bonds and very small structural fluctuations. The results indicated that these two compounds are hopeful BACE1 inhibitors and should be studied more to see whether they can be used as therapeutic agents for Alzheimer's disease.