Abstract

Arvind Kumar Shakya*, Narendra Kumar

ABSTRACT

Background: Alzheimer's disease is one of the most prominent issue of memory impairment in the 21stcentury. It hurts personal and social life, particularly among older people. The herb Bacopa monnieri (Local name Brahmi) is renowned for its therapeutic properties for the treatment of neurological disorders. Its phytochemicals can alleviate symptoms of neurological complications. This present study aims to assess the binding affinity of B. monnieri phytochemicals with the phospholipase D3 protein of Alzheimer disease. Materials and Methods: The IMPPAT database was used to retrieve 39 phytocompounds from Bacopa monnieri, and out of which 11 phytochemicals were selected for the molecular docking studies against the target protein phospholipase D3 (PLD3) based on their drug-likeness scores and ADME profile. Molecule docking analysis was performed between phytochemicals i.e. Ascorbic acid, Nicotinic acid, Luteolin, Apigenin, Betulinic acid, β-Sitosterol, Stigmasterol, Stigmastanol, Bacogenin-a1, Pseudojujubogenin, and bacosin as ligands with the receptor proteins phospholipase D3 (PLD3) (PDB ID: 8V5T). Ligand docking scores were compared with those of donepezil (a reference drug). The molecular docking, image visualisation, ADME assessment of phytochemicals were performed using the PyRex docking tool, BIOVIA Discovery Studio visualizer and Swiss ADME software respectively. Results: Docking studies showed that bioactive compounds were docked within binding pocket of PLD3 protein. Among the screened phytochemicals, bacosine exhibited the highest binding affinity (−10.2 kcal/mol), followed by pseudojujubogenin (−9.4 kcal/mol) and bacogenin A1 (−9.3 kcal/mol). Stigmasterol (−8.9 kcal/mol), Betulinic acid (−8.8 kcal/mol), beta-Sitosterol (−8.4 kcal/mol), Stigmastanol (−8.4 kcal/mol), Luteolin (−7.9 kcal/mol), Apigenin (−7.7 kcal/mol), Ascorbic acid (−5.6 kcal/mol), Nicotinic acid ((−5.1 kcal/mol) and reference drug, donepezil (−8 kcal/mol) also exhibited favorable binding patterns, indicating complementary modulatory potential against Alzheimer disease. ADME predictions suggested favorable pharmacokinetic properties, including blood–brain barrier permeability and a low risk of toxicity, for the lead compounds Conclusion: The findings of this study conclude that B. monnieri phytochemicals, Bacosine, pseudojujubogenin, and bacogenin A1 exhibit significant binding affinity with the active site of the phospholipase D3 protein which might be involved in modulation its activity to reduce plaque formation in Alzheimer's disease. These phytochemicals might be promising candidates for future investigation in the treatment of Alzheimer's disease.