Exploring potential inhibitors from Eriobotrya japonica targeting AChE and BChE in Alzheimer's Disease through docking, ADMET profiling, and DFT analysis

Abstract Alzheimer’s disease (AD) is the most common dementia causing disease in the elderly and is strongly associated with cholinergic dysfunction. The crucial enzymes in this mechanism are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are prominent therapeutic targets. Recently, natural phytocompounds have been considered as safer substitutes to synthetic inhibitors. In this study, fifty-four phenolic compounds of Eriobotrya japonica were chosen from the literature and evaluated using in-silico methods as prospective dual AChE and BChE inhibitors. Based on molecular docking with the Schrodinger Suite, chrysin appeared to be the most promising candidate as it exhibited high binding affinity and stable interaction with the catalytic residues of both enzymes. Pharmacokinetic and ADME studies indicated that the drug would be well-absorbed and bioavailable orally with low acute toxicity. Moderate solubility, blood-brain barrier penetration and potential CYP-mediated interactions were noted. The electronic stability, antioxidant behavior, and interaction with target proteins of chrysin were also verified by density functional theory (DFT) analysis. Finally, the obtained results point to the potential of chrysin of E. japonica as a multitarget lead compound in the treatment of AD, which exerts combined enzyme inhibition and neuroprotective effects. Its therapeutic potential should be confirmed by further in-vitro and in-vivo studies.