Cholinergic dysfunction is a key feature of cognitive impairment, and currently available acetylcholinesterase (AChE) inhibitors provide limited symptomatic benefit and are often associated with adverse effects. This study evaluated the cognitive-protective effects of bavachin (BVC), a prenylated flavonoid from Psoralea corylifolia, and its interaction with Donepezil (DNP) in a scopolamine (SCP)-induced amnesia model. Male Swiss albino mice were pretreated with BVC (10-40 mg/kg), DNP (2.5 mg/kg), or their combination for 7 days prior to SCP challenge, followed by assessment using multiple behavioral paradigms, including novel object recognition, elevated plus maze, passive avoidance, Y-maze, and Morris water maze. BVC attenuated SCP-induced memory deficits in a dose-dependent manner, with the 40 mg/kg dose producing performance statistically comparable to, though not formally demonstrated to be equivalent to, the normal control across tests. Bliss independence analysis of behavioral endpoints indicated predominantly additive interactions, with occasional greater-than-additive trends. Biochemical evaluation demonstrated that BVC inhibits AChE in vitro (IC50 = 27.7 µM) and attenuates SCP-induced elevations of AChE activity ex vivo in the frontal cortex and hippocampus. Combination treatment showed a greater-than-additive interaction in the frontal cortex (ΔBliss = 0.054) and an approximately additive effect in the hippocampus (ΔBliss = 0.013). Molecular docking and molecular dynamics simulations further suggested stable binding of BVC within the active sites of AChE and butyrylcholinesterase (BChE). Collectively, these findings indicate that BVC attenuates cognitive deficits, at least in part, through cholinesterase inhibition, and exhibits additive effects with DNP, supporting its potential as an adjunctive candidate for cognitive disorders.
The severe neurodegenerative disease known as Alzheimer's disease (AD) is typified by a progressive loss of memory and cognitive function. The prevalence of AD is rising due to an aging global population, calling for novel treatment strategies. A potential treatment option for AD that shows promise is the use of functionalized nanoparticles (NPs). Recent developments in the synthesis, design, and use of functionalized NPs in AD therapy are examined in this review. An outline of the pathophysiological mechanisms underlying AD is given in the first section, focusing on the roles played by tau protein aggregates and amyloid-beta plaques in the development of the illness. We then explore the many approaches used to functionalize NPs, such as surface alterations and bioconjugation methods, which enable accurate drug administration, targeted delivery, and enhanced biocompatibility. The review also emphasizes the therapeutic potential of functionalized NPs, highlighting their capacity to improve neuroprotection, lower amyloid-beta aggregation, and improve blood-brain barrier penetration. The potential of NPs as a tool for disease modification and symptom relief is highlighted by recent pre-clinical and clinical research. Concerns about toxicity and safety are also covered, underscoring the significance of thorough testing and the field's future directions. Functionalized NPs have great promise as a multimodal strategy to treat AD, offering patients hope for better quality of life, early diagnosis, and efficient disease treatment. This study highlights the growing role of nanotechnology in the search for novel and potent therapies for AD.