Molecular Docking, Drug-Likeness Score Prediction, and Adme Evaluation of Bacopa Monnieri Phytochemicals as Potential Human Phospholipase D3 Modulator Against Alzheimer's Disease: In Silico Approach

Background: Alzheimer's disease has emerged as one of the most prominent issues 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 in the treatment of neurological disorders. Its phytochemicals can alleviate symptoms of neurological complications. This study aims to examine the binding affinity of B. monnieri phytochemicals against phospholipase D3protein of Alzheimer disease. Materials and Methods: The IMMPAT database was used to retrieve 40 phytocompounds from Bacopa monnieri, and 10 were selected for molecular docking against the target protein phospholipase D3 (PD3) based on drug-likeness scores and ADME profile of phytochemicals except nicotinic acid (a known carcinogenic agent). Molecule docking analysis were performed between phytochemicals i.e. Ascorbic 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 (reference drug). The molecular docking, image visualisation, ADME and organ toxicity analyses, as well as the molecular dynamics simulation, were performed using the PyRex docking tool, Discovery Studio, Swiss ADME and Protox 3.0 respectively. Results: Docking studies showed that bioactive compounds were docked against the crystal structure of PLD3. 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), and donepezil drug (−8 kcal/mol) also exhibited favorable binding patterns, indicating complementary inhibitory potential. ADME predictions suggested favorable pharmacokinetic properties, including blood–brain barrier permeability and a low risk of toxicity, for the lead compounds. Conclusion: This study concludes that B. monnieri phytochemicals, Bacosine, pseudojujubogenin, and bacogenin A1 exhibit significant binding affinity for the active site of the phospholipase D3 protein which might be involved in modulation its activity to reduce plaque formation in Alzheimer's disease. Phytochemicals derived from B. monnieri might be promising candidates for future investigation in the treatment of Alzheimer's disease.