Phytochemical Network Pharmacology in Alzheimer's disease: Multi-Target Neuroprotective Strategies and Emerging Drug Delivery Approaches

Abstract

Alzheimer's disease (AD) is a fatal neurodegenerative disorder, which features a host of characteristics: Aβ aggregation, tau hyperphosphorylation, neuroinflammation, oxidative stress, and synaptic loss. Most single-target drugs have proven to be inefficient in combating the disease. Phytochemical network pharmacology is a revolutionary approach in which a library of natural products from plants is systematically connected with multifaceted pathological networks in AD by use of bioinformatics tools such as Cytoscape, SwissTargetPrediction, and molecular docking. This integrated approach constructs compound target-disease-pathway interactomes, showing polypharmacological synergy in modulating key hubs involved in APP, GSK-3β, NF-κB, PI3K/Akt, and MAPK cascades, thus inhibiting Aβ plaque deposition, tau pathology, microglial activation, apoptosis, and improving neurotrophic support. Despite their encouraging neuroprotective profiles, the limiting factors associated with phytochemicals concern poor bioavailability and impermeability through the blood-brain barrier. Integration into advanced drug delivery systems such as nanoparticles, liposomes, and ligand modification of nanocarriers enables receptor-mediated transcytosis, sustained release, and targeted brain accumulation, hence surpassing such drawbacks. Such is illustrated by curcumin-loaded formulations inducing the Nrf2/HO-1 antioxidant pathways. This may support the rational design of multi-component herbal therapies through in silico simulation, preclinical models of cognitive restoration, and pathway enrichment analyses. The major challenges remain standardization and clinical translation; however, future potential in precision AD interventions could arise from AI-driven predictions and pharmacogenomics, shifting the current symptomatic palliation to disease-modifying polypharmacology.