| Summary: | <i>Alpinia oxyphylla</i> Miq. (i.e., <i>A. oxyphylla</i>), a traditional Chinese medicine, can exert neuroprotective effects in ameliorating mild cognitive impairment and improving the pathological hallmarks of Alzheimer’s disease (AD). Here, 50 active compounds and 164 putative targets were collected and identified with 251 clinically tested AD-associated target proteins using network pharmacology approaches. Based on the Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway enrichments, the compound-target-pathway-disease/protein−protein interaction network constructions, and the network topological analysis, we concluded that <i>A. oxyphylla</i> may have neuroprotective effects by regulating neurotransmitter function, as well as brain plasticity in neuronal networks. Moreover, closely-related AD proteins, including the amyloid-beta precursor protein, the estrogen receptor 1, acetylcholinesterase, and nitric oxide synthase 2, were selected as the bottleneck nodes of network for further verification by molecular docking. Our analytical results demonstrated that terpene, as the main compound of <i>A. oxyphylla</i> extract, exerts neuroprotective effects, providing new insights into the development of a natural therapy for the prevention and treatment of AD.
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