Bacopa monnieri: A promising herbal approach for neurodegenerative disease treatment supported by in silico and in vitro research

Neurodegenerative disorders, caused by progressive neuron loss, are a global health issue. Among the various factors implicated in their pathogenesis, dysregulation of acetylcholinesterase activity has been recognized as a key contributor. Acetylcholinesterase breaks down the neurotransmitter acetylcholine, important for neural transmission. Evaluating phyto-compounds from Bacopa monnieri Linn. through in vitro and in silico analysis may expand their role as alternative therapeutic agents by modulating the function of acetylcholinesterase and complementing existing treatments. To accomplish this objective, chemical structures of phyto-compounds were retrieved from PubChem database and subjected to in silico and in vitro approaches. Virtual screening was performed through molecular docking and molecular dynamic simulation resulting in four top hit compounds including quercetin, apigenin, wogonin, and bacopaside X (novel lead compound for acetylcholinesterase inhibitor) with least binding score. Further, dose dependent acetylcholinesterase inhibition biochemical assay depicted that bacopaside X, apigenin, quercetin, and wogonin exhibited strong potential against acetylcholinesterase with IC50 values of 12.78 μM, 13.83 μM, 12.73 μM and 15.48 μM respectively, in comparison with the donepezil (IC50: 0.0204 μM). The in silico and in vitro research suggests that B. monnieri phyto-compounds have the potential to modulate molecular targets associated with neurodegenerative diseases and have a role in neuroprotection. •Novel Compound: Bacopaside X - promising for neural modulation.•Potent Inhibitors: Bacopa phyto-compounds - combat neurodegeneration.•Compared to Donepezil: Similar efficacy with lower IC50 values.•Validated In Silico: Molecular simulations bolster findings.•Therapeutic Promise: Opens new treatment avenues.