Probing Latent Targets of Acanthopanax Trifoliatus for Alzheimer's Disease: A Prototype Discovery Using Network Pharmacology

Abstract

Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning, presents a significant challenge in healthcare, urging the exploration of novel therapeutic avenues. Currently utilized drugs for treatment of AD includes donepezil, rivastigmine and galantamine. Research is underway to find novel compounds that will target the exact pathogenesis in AD. Acanthopanax trifoliatus, a ginseng-like plant, stands out as a potential candidate due to its traditional use in managing cognitive function. The aim of presented study is to utilize network pharmacologybased tactics to explore the potential of Acanthopanax trifoliatus as a therapeutic intervention for Alzheimer's disease via finding its related active constituents, latent targets and potential molecular mechanisms. Through active constituent prescreening and target prediction, combined with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, this study identified potential molecular pathways and targets involved in Acanthopanax trifoliatus therapeutic effects. Molecular docking experiments were further conducted to validate these findings. Five main active constituents were identified—Acantrifoic acid A, Acankoreoside A, Acankoreoside D, Acantrifoside A, and Impressic Acid—each exhibiting positive drug likeness, suggesting their potential suitability for therapeutic development. Subsequent network construction and gene ontology (GO) and KEGG pathway analyses unveiled key genes involved in AD metabolic pathways, including TLR4, PI3K, NF-κB, ADAM17, CDK5, CK2 and NMDA. Molecular docking studies further revealed promising insights, with Acanthopanax trifoliatus' active constituents demonstrating notably lower binding energies compared to the cocrystal ligand of TLR4 is better across various target genes. The results unveil a spectrum of active constituents within the plant and illuminate potential gene targets associated with Alzheimer's disease pathology. Network analysis showed that A. trifoliatus exerted a promising effect on treatment of Alzheimer's disease by acting on several signaling pathways. Therefore, this study offers insights into the molecular mechanisms underlying the efficacy of the plant against AD, paving the way for future therapeutic developments in neurodegenerative diseases. Such insights are crucial for advancing research and potential clinical applications in the field of Alzheimer's disease therapeutics.