Flavonoids are naturally occurring polyphenolic compounds known for their extensive range of biological activities. This review focuses on the inhibitory effects of flavonoids on acetylcholinesterase (AChE) and their potential as therapeutic agents for cognitive dysfunction. AChE, a serine hydrolase that plays a crucial role in cholinergic neurotransmission, is a key target in the treatment of cognitive impairments due to its function in acetylcholine hydrolysis. Natural polyphenolic compounds, particularly flavonoids, have demonstrated significant inhibition of AChE, positioning them as promising alternatives or adjuncts in neuropharmacology. This study specifically examines flavonoids such as quercetin, apigenin, kaempferol, and naringenin, investigating their inhibitory efficacy, binding mechanisms, and additional neuroprotective properties, including their antioxidant and anti-inflammatory effects. In vitro, in vivo, and in silico analyses reveal that these flavonoids effectively interact with both the active and peripheral anionic sites of AChE, resulting in increased acetylcholine levels and the stabilization of cholinergic signaling. Their mechanisms of action extend beyond mere enzymatic inhibition, as they also exhibit antioxidant and anti-amyloidogenic properties, thereby offering a multifaceted approach to neuroprotection. Given these findings, flavonoids hold considerable therapeutic potential as modulators of AChE, with implications for enhancing cognitive function and treating neurodegenerative diseases. Future studies should prioritize the enhancement of flavonoid bioavailability, evaluate their efficacy in clinical settings, and explore their potential synergistic effects when combined with established therapies to fully harness their potential as neurotherapeutic agents.

Acetylcholinesterase (AChE) has emerged not only as a cholinergic enzyme but also as a modulator of β-amyloid (Aβ) aggregation via its peripheral anionic site (PAS), making it a dual-purpose target in Alzheimer’s disease. While classical AChE inhibitors provide symptomatic relief, they lack efficacy against the amyloidogenic cascade. This review highlights recent advances in multifunctional AChE pharmacophores that inhibit enzymatic activity while simultaneously interfering with Aβ aggregation, oxidative stress, metal dyshomeostasis, and neuroinflammation. Particular emphasis is placed on dual-site inhibitors targeting both catalytic and peripheral domains, multi-target-directed ligands (MTDLs) acting on multiple neurodegenerative pathways, and metal-chelating hybrids that address redox-active metal ions promoting Aβ fibrillization. We also discuss enabling technologies such as AI-assisted drug design, high-resolution structural tools, and human induced pluripotent stem cell (iPSC)-derived neuronal models that support physiologically relevant validation. These insights reflect a paradigm shift towards disease-modifying therapies that bridge molecular pharmacology and pathophysiological relevance.

This study evaluated a novel methodology for assessing food safety vulnerabilities in shopping malls by integrating Hazard Analysis and Critical Control Points (HACCP), Threat Assessment and Critical Points (TACCP), and Failure Mode and Effects Analysis (FMEA). Inspections were conducted in nine shopping centers across Poland, the Czech Republic, Slovakia, and Spain to identify the risk of intentional/unintentional contamination with chemical, biological, radiological, and nuclear agents. The assessment considered key operational areas, including food delivery, transportation, staff security, back-office access, product handling, and inspection protocols. Risk levels were quantified using FMEA parameters. The findings revealed an overall high to average risk score with the most critical vulnerabilities linked to back-office access, unauthorized personnel entry, and susceptibility to fraudulent inspections. Observations also highlighted infrastructural shortcomings, insufficient monitoring, and procedural gaps that could facilitate contamination. The proposed methodology offers a structured, quantitative framework for identifying and prioritizing food safety hazards in public environments. Implementing targeted countermeasures—such as enhanced surveillance, strict access control, staff training, and dedicated food handling protocols—can substantially reduce risks, thereby strengthening public health protection and operational resilience. This approach may serve as a promising framework for integrating food defense and safety assessments for food defense in high-density commercial facilities.