Unraveling potential neuroprotective mechanisms of herbal medicine for Alzheimer’s diseases through comprehensive molecular docking analyses

Abstract

Alzheimer's disease (AD) continues to be a worldwide health concern, demanding innovative therapeutic approaches. This study investigates the neuroprotective potential of herbal compounds by scrutinizing their interactions with Beta-Secretase-1 (BACE1). Through comprehensive molecular docking analyses, three compounds, Masticadienonic acid (ΔG: −9.6 kcal/mol), Hederagenin (ΔG: −9.3 kcal/mol), and Anthocyanins (ΔG: −8.1 kcal/mol), emerge as promising BACE1 ligands, displaying low binding energies and strong affinities. ADME parameter predictions, drug-likeness assessments, and toxicity analyses reveal favorable pharmacokinetic profiles for these compounds. Notably, Masticadienonic Acid exhibits optimal drug-likeness (−3.3736) and negligible toxicity concerns. Hederagenin (drug-likeness: −5.3272) and Anthocyanins (drug-likeness: −6.2041) also demonstrate promising safety profiles. Furthermore, pharmacophore modeling elucidates the compounds' unique interaction landscapes within BACE1′s active site. Masticadienonic acid showcases seven hydrophobic interactions and a hydrogen bond acceptor interaction with Thr232. Hederagenin exhibits a specific hydrogen bond acceptor interaction with Trp76, emphasizing its selective binding. Anthocyanins reveal a multifaceted engagement, combining hydrophobic contacts and hydrogen bond interactions with key residues. In conclusion, Masticadienonic acid, Hederagenin, and Anthocyanins stand out as promising candidates for further experimental validation, presenting a synergistic balance of efficacy and safety in combating AD through BACE1 inhibition.