Metabolomics and network pharmacology based study of the potential of <i>Brassica rapa</i> L. extract BREE-Ea for the treatment of Alzheimer's disease

<i>Background</i>: Alzheimer's disease (AD) is a severe neurodegenerative disorder causing memory loss, cognitive decline, and behavioral changes. The disease mechanisms involve oxidative stress, inflammation, and abnormal protein aggregation. BREE-Ea, a bioactive compound derived from <i>Brassica rapa</i> L. (BR)-a traditional food crop indigenous to the Xinjiang Uygur Autonomous Region, where it has been cultivated as a vital local food source for centuries-has shown anti-inflammatory and antioxidant properties in <i>in vivo</i> experiments. <i>Methods</i>: An experimental study was conducted using an <i>in vivo</i> AD mouse model to evaluate the effects of BREE-Ea on memory loss and spatial discrimination deficits. Biochemical analyses were performed to assess antioxidant enzyme activities, oxidative stress markers, and inflammatory cytokines in the brains of AD mice. Metabolomics and network pharmacology approaches were used to identify blood- and brain-entry components and metabolic pathways involved. Molecular docking was also conducted to confirm the binding affinity of these components to their targets. <i>Results</i>: Treatment with BREE-Ea at a dose of 20 mg kg^-1 significantly improved memory loss and spatial discrimination deficits in AD mice. Biochemical analyses revealed that BREE-Ea enhanced antioxidant enzyme activities (SOD, GSH-Px, CAT) and reduced oxidative stress markers (MDA, AchE) and inflammatory cytokines (TNF-α, IL-6) in the brains of AD mice. Additionally, BREE-Ea decreased Aβ plaque deposition and Tau hyperphosphorylation, contributing to improved cognitive function. Metabolomics and network pharmacology approaches identified key therapeutic pathways such as serotonin synaptic transmission and neuroactive ligand-receptor interactions, targeting proteins like CASP3, APP, and PTGS2. Molecular docking confirmed the binding affinity of these components to their targets. <i>Conclusion</i>: BREE-Ea emerges as a highly promising therapeutic candidate for AD that effectively addresses the multifactorial nature of the disease and underscores its potential to alleviate the cognitive impairments associated with this debilitating condition.